Facts & Resources

Acute lymphoblastic leukemia (ALL) is one type of cancer of the bone marrow and blood. It is also called acute lymphocytic leukemia or acute lymphoid leukemia.

Acute myeloid leukemia (AML) is one type of cancer of the bone marrow and blood. It is also called acute myelogenous leukemia or acute myelocytic leukemia.

Acute promyelocytic leukemia (APL), is a subtype of acute myeloid leukemia (AML). Cells in the bone marrow that produce blood cells (red cells, white cells and platelets) do not develop and function normally.

Amyloidosis is a potentially serious and very rare disease that involves abnormal protein (amyloid) building up in your tissues and organs.

Anemia occurs when there are too few red blood cells in the body. At Fred Hutch, our team of experts provides comprehensive diagnostic and medical care for people with this blood condition. 

What Is Anemia?

Anemia is not a disease per se, but rather an indicator of an underlying disorder that was either inherited or acquired after birth. The causes of anemia include:

• Impaired red blood cell production
• Red blood cell destruction (hemolysis)
• Increased red blood cell loss (such as from bleeding)

Anemia can be reversible or chronic.

Red blood cells contain hemoglobin — an iron-rich protein that gives blood its red color. Hemoglobin enables the blood cells to carry oxygen from your lungs to the rest of your body and to carry carbon dioxide from other parts of your body back to your lungs to be exhaled. When your level of red blood cells is low, this process is impaired, and your body doesn’t get as much oxygen as it needs.

Decreased red blood cells can occur in isolation or in combination with a decrease in other types of blood cells.

Symptoms and Diagnosis of Anemia

When your blood cannot deliver enough oxygen to the rest of your body, you may feel weak, dizzy, or short of breath. You may notice chest pain, a rapid or irregular heartbeat, headaches, cold hands and feet, or pale skin. If anemia is mild or develops slowly over a long period, you may have no symptoms at all.

Fred Hutch offers a full array of services to diagnose anemia and determine the cause. 

Your physician will ask about your medical history and examine you. The presence of anemia is established by a blood test, called a complete blood count (CBC) and differential, which measures the number of red blood cells and other types of cells in the blood. When investigating the cause of anemia, it’s important for your doctor to measure the number of young red blood cells your body is making (reticulocyte count). This will help your doctor interpret the CBC and direct additional testing.

Another option to help determine the cause of anemia is a bone marrow aspiration and biopsy, in which a doctor uses a hollow needle to extract tiny samples of bone marrow while you are under local anesthesia. This allows your doctor to study your blood cell development.

Anemia Treatment

Red blood cell transfusion can increase the number of red blood cells in patients with symptomatic anemia. Additional treatments are directed at the underlying cause of the low red blood cell level.

Fred Hutch’s team of physicians provides a comprehensive range of treatment options for anemia and the conditions that may lead to it. To find detailed information on treatments for specific types of anemia, click on any of the following disorders:

• Aplastic anemia 
• Diamond-Blackfan anemia 
• Fanconi anemia
• Hemolytic anemia
• Iron-deficiency anemia 
• Pernicious anemia (B12 deficiency)
• Sickle cell disease

In aplastic anemia, the bone marrow stops producing new blood cells at the same rate resulting in deficits of all blood cell types. White blood cells fight germs and platelets help blood clot. Without these, the body is at risk for infection and uncontrolled bleeding.

Autoimmune thrombocytopenic purpura is a blood disease that leads to an abnormally low level of platelets in your blood. It is also called immune thrombocytopenia (ITP).

Fred Hutch offers a full array of services to diagnose and treat this disease and to rule out other causes of low platelets.

What Is Itp?

ITP usually occurs because antibodies produced by your immune system mistakenly attack and destroy your platelets. Platelets are small cells in your blood that are the first step in forming a clot to stop bleeding. 

Most often, ITP occurs without any known trigger, although it may follow a viral infection or be associated with other autoimmune disorders. It sometimes occurs along with lymphoma and may be caused by some medications.  

There are two forms of the condition: acute and chronic. The acute form is more common in children and rarely lasts more than six months. Treatment is often not needed unless your platelet count is very low or you are bleeding.

The chronic form is more common in adults. It is considered chronic if it lasts for at least 1 year. Chronic ITP may go away and then recur, even after a long remission. 

Symptoms and Diagnosis of ITP

People with ITP often bleed and bruise easily. You might have spontaneous nosebleeds or gum bleeding when you brush or floss or during dental visits. 

Small blood vessels may break, causing purple bruises to appear on your skin. These bruises are called purpura. Sometimes the only evidence of low platelets is the appearance of tiny bruises, or reddish-purple dots called petechiae, usually on the lower legs and ankles. In other cases, the disease can cause more severe bleeding or internal bleeding that’s difficult to stop.

Many patients report fatigue when their platelet counts are low. 

Women with ITP may notice unusually heavy menstrual flow. 

To diagnose the disease, your physician will review your personal and family medical history and do a thorough physical exam. They will order blood tests, including a complete blood count (CBC), and other tests to rule out other causes of your symptoms. If other causes seem likely or if your condition doesn’t respond to treatment for ITP, your doctor may order a bone marrow biopsy to learn more about how your body is making blood cells.

ITP Treatment

Treatment for ITP depends on many factors, including your age and overall health, the severity of your symptoms, your platelet count and your personal preferences. Mild cases may not need any treatment. 

First-line treatment is often corticosteroids, like prednisone, or if your platelet count is very low, intravenous gamma globulin, a blood component that can help to raise your platelet count quickly.

If these treatments don’t control the condition, your doctor may suggest other medicines, including thrombopoietin receptor agonists, which can help increase platelet production, or immunosuppressant therapy, such as rituximab (Rituxan, Truxima) or mycophenolate (CellCept, Myfortic). 

In very severe cases, doctors may consider surgery to remove your spleen (splenectomy) if other treatments don’t work. 

Chronic lymphocytic leukemia (CLL) is one type of cancer of the bone marrow and blood. It is also called chronic lymphoid leukemia or small lymphocytic lymphoma.

Chronic myeloid leukemia (CML) is one type of cancer of the bone marrow and blood. It is also called chronic myelogenous leukemia or chronic myelocytic leukemia.

Deep vein thrombosis (DVT) is a blood clot that forms in a vein deep in your body. It happens most often in the lower leg or thigh but can happen in other parts of the body as well. 

DVT can occur for several reasons, including damage to a vein, such as from a fracture or surgery, or slow blood flow, such as from lying in bed or sitting for long periods. Other risk factors include:

• Being pregnant
• Taking birth control pills or hormone replacement for menopause
• Being overweight
• Having cancer
• Having an inherited condition that increases your tendency to form clots or decreases your ability to dissolve them

Many patients with DVT have more than one risk factor, but some patients can have DVT without any known risk factors.

If a blood clot in a deep vein breaks loose, it can travel through your bloodstream. A clot that’s moving is called an embolus. Clots in veins travel toward your lungs. If a clot reaches your lungs and blocks blood flow there, the condition is called pulmonary embolism (PE). PE can damage your lungs or be fatal.

Diamond-Blackfan anemia (DBA) occurs when your bone marrow cannot make red blood cells as it should. Red blood cells are essential for carrying oxygen from your lungs to the rest of your body.

At Fred Hutch, our team of experts provides comprehensive diagnostic and medical care for adults with DBA. We also work closely with our colleagues at Seattle Children’s Hospital to care for children with DBA and to transition them from pediatric care to adult care when they are ready. 

What Is Diamond-Blackfan Anemia?

DBA is a genetic blood disorder that causes anemia and other abnormalities. It belongs to a group of disorders called inherited bone marrow failure syndromes. In these disorders, the bone marrow cannot make enough healthy blood cells. People with DBA are at increased risk for certain cancers. They also can be born with malformations of the heart, genitourinary system and other parts of the body.

DBA results from a problem with ribosomes, structures in your cells that play an important role in building proteins in your body. Mutations in ribosomal protein genes account for many DBA cases. Most often, people with the disorder inherit the abnormal gene from a parent. In other cases, a gene mutation happens in a person with no family history of DBA.

Symptoms and Diagnosis of Diamond-Blackfan Anemia

Most people with DBA are diagnosed before age 1. However, DBA is increasingly being diagnosed in older children and adults. 

People with DBA typically have symptoms of anemia, such as fatigue or decreased energy, shortness of breath and pale skin. Some are short in stature, and they may be born with traits such as thumb abnormalities, characteristic facial appearance and congenital heart disease. In some people with DBA, a physical exam and lab tests reveal no signs or only subtle signs of the disease.

Fred Hutch offers a full array of services to diagnose DBA. Your physician may order some or all of the following:

• Blood tests — A complete blood count (CBC) and reticulocyte (immature red blood cell) count can help find the cause of the anemia. In DBA, these tests show an abnormally low number of red blood cells. Occasionally, white blood cell and platelet numbers are also low. A low reticulocyte count indicates that your bone marrow is not making new red blood cells and releasing them into your bloodstream as it should in response to anemia.
• Bone marrow aspiration and biopsy — Using a hollow needle, tiny samples of bone marrow are taken under local anesthesia. This allows your physician to study your blood cell development. In DBA, physicians look for a low level of red blood cell precursors in your bone marrow. Precursor cells are stem cells that will divide to form one specific type of blood cell, such as a red blood cell.
• Other tests — You might have genetic testing to find mutations in DBA genes and to rule out mutations in genes linked with other inherited types of anemia. Your doctor may recommend other blood tests as well.

Diamond-Blackfan Anemia Treatment

Fred Hutch’s team of physicians provides a comprehensive range of treatment options for DBA.

Corticosteroids

An initial course of corticosteroid therapy increases red blood cell production in many people with DBA. The dose is gradually lowered to maintain enough red blood cells while limiting side effects, like high blood pressure, diabetes, slowed growth, low bone density and increased risk of infections.

Red Blood Cell Transfusions

If you do not respond to corticosteroid therapy or you have significant side effects from steroids, the main therapy is red blood cell transfusions. If you receive repeated transfusions, you can develop iron overload and may need medicine to remove the excess iron from your body (chelation therapy), as well as testing to check for organ damage from excess iron.

Bone Marrow Transplant

For some people with DBA, doctors consider blood or bone marrow transplantation (also called stem cell or hematopoietic cell transplantation), a procedure that replaces your hematopoietic (blood-forming) stem cells with the cells of a healthy donor. A transplant cures the blood-related abnormalities of DBA.

The Fred Hutch Blood and Marrow Transplant Program at Fred Hutch has performed more bone marrow transplants than any other institution in the world. 

Multidisciplinary Care

Because DBA and its treatments can impact many organ systems and affect your lifestyle, care at Fred Hutch involves a multidisciplinary team. Based on your health needs, your team may include hematologists, internists, psychiatrists, psychologists, surgeons, cardiologists, endocrinologists, nurses, social workers and physical and occupational therapists.

Dyskeratosis congenita (DKC) is a genetic disorder. It can cause low levels of red blood cells, white blood cells and platelets as well as other abnormalities, including skin and nail changes and a predisposition to cancer.

At Fred Hutch, our team of experts provides comprehensive diagnostic and medical care for people with DKC.

What Is Dyskeratosis Congenita?

DKC belongs to a group of disorders called inherited bone marrow failure syndromes. In these disorders, your bone marrow cannot make enough healthy blood cells. DKC can affect many other parts of your body too. It is caused by a problem with your body’s ability to maintain telomeres, structures at the ends of your chromosomes. 

Symptoms and Diagnosis of Dyskeratosis Congenita

DKC can be difficult to diagnose because people with the disorder experience different symptoms that show up at different times in their lives. Most people with DKC have cytopenias, low levels of blood cells, because their bone marrows doesn’t produce enough blood cells. This can worsen over time and lead to bone marrow failure.

You may also experience premature hair graying, hair loss, tooth abnormalities and problems with your lungs (like pulmonary fibrosis) or digestive system. Some people may have learning difficulties or mild to moderate developmental delay.

Other signs and symptoms may include:

• A lacy-looking rash on your face, neck and chest
• Ridged, fissured and weakened nails
• White patches inside your mouth and upper throat (leukoplakia) 

People with DKC are at increased risk for cancers of the tongue, mouth, throat, stomach, colon, rectum, and blood and bone marrow.

Fred Hutch has experts in recognizing this disorder and offers a full array of services to diagnose it. Your physician will ask about your medical history and perform a physical exam looking for signs of DKC. Next, the doctor may order some of the following:

• Blood tests — A complete blood count (CBC) is done to check your level of each kind of blood cell.
• Bone marrow aspiration and biopsy — Using a hollow needle, tiny samples of bone marrow are taken under local anesthesia. This allows your doctor to study your blood cell development. 
• Other tests — You might have genetic testing to find mutations in DKC genes and to rule out mutations in genes linked with other inherited bone marrow failure syndromes. Your doctor may recommend other blood tests to measure the length of your telomeres. Telomeres are unusually short in many people with DKC.

Dyskeratosis Congenita Treatment

Fred Hutch’s team of physicians provides a comprehensive range of treatment options for DKC and has expertise in the medical monitoring that people with DKC need.

Care is aimed at managing health problems associated with DKC; monitoring for complications, such as lung problems or cancer; and caring for bone marrow failure or cancer, if it occurs.

Medicines

Physicians may treat bone marrow failure with medications that help increase your levels of blood cells. These include:

• Oxymethalone (Anadrol) — an anabolic steroid used to improve your red blood cell count
• Erythropoietin (Epogen, Eprex, Procrit) — a medicine that helps your bone marrow make more red blood cells
• Filgrastim (Neupogen) — also called granulocyte colony-stimulating factor, or G-CSF, a medicine that helps your bone marrow make more white blood cells

Blood and Marrow Transplant

So far, the only cure for bone marrow failure is blood or bone marrow transplantation (also called stem cell or hematopoietic cell transplantation). Transplants can cure bone marrow failure, but they do not cure other problems caused by DKC, like problems with the digestive system and lungs.

The Fred Hutch Blood and Marrow Transplant Program at Fred Hutch has performed more bone marrow transplants than any other institution in the world. For people with DKC, our team uses reduced-intensity conditioning regimens that we developed specifically to reduce transplant complications.   

Multidisciplinary Care

Because DKC can impact many organ systems and affect your lifestyle, care at Fred Hutch involves a multidisciplinary team. Based on your health needs, your team may include hematologists, internists, psychiatrists, psychologists, surgeons, cardiologists, endocrinologists, nurses, social workers and physical and occupational therapists.

Eosinophilic disorders are blood conditions typically characterized by too many eosinophils — a type of white blood cell — in the bloodstream and sometimes by the presence of eosinophils in organs or tissues where they are not normally found. At Fred Hutch, our team of experts provides comprehensive diagnostic and medical care for people with eosinophilic disorders.

What Is Eosinophilia?

Eosinophils generally account for less than 5 percent of white blood cells circulating in the bloodstream. They help fight off certain infections, and they are involved in hypersensitivity reactions of the immune system. The number of eosinophils in the blood can rise during a normal response to allergic reactions, fungal and parasitic infections, medications, and some types of cancer.

An abnormal increase in eosinophils, called eosinophilia, can result from an acquired genetic defect in the cells that make eosinophils (bone marrow precursor cells), or it can occur as an inappropriate response by the body to immune cells called T lymphocytes (T-cells). Eosinophilia also can occur in conjunction with myeloproliferative neoplasms and lymphoproliferative disorders.

What Is Hypereosinophilic Syndrome?

Conditions in the group of disorders known as hypereosinophilic syndrome (HES) develop when the body consistently and inappropriately produces a high number of eosinophils with no apparent underlying allergic or drug reaction or other trigger. Though it can affect anyone, HES is more common in men over 50.

A needless surplus of eosinophils can infiltrate and affect any organ in the body, especially the gastrointestinal tract, skin, lungs, heart, and liver.

Symptoms and Diagnosis of Eosinophilia & Hypereosinophilic Syndrome

Symptoms of HES depend largely on the organs affected, the severity of the disease, and any associated medical conditions. Common red flags include fever, rash, itching, coughing, wheezing, shortness of breath, diarrhea, abnormal blood counts, and enlarged lymph nodes or organs.

Because many different problems can cause high numbers of eosinophils in the blood, eosinophilia alone is not enough to diagnose of HES. Instead, doctors consider several factors, including the degree and duration of eosinophilia and the affect on organs.

Fred Hutch offers a full array of services to diagnose eosinophilia and HES. Physicians use blood tests, biopsies of affected organs, and sometimes a bone marrow biopsy (examining a small sample of marrow taken with a hollow needle) to try to identify the underlying cause of the high eosinophil level.

To rule out allergic or drug reactions that might be affecting eosinophil levels in your blood, your physician may ask you to temporarily stop taking certain medications or supplements. You might also undergo allergy testing.

If these steps don’t reveal an underlying cause and your physician suspects you have HES, you may have genetic tests to look for abnormal bone marrow precursor cells and abnormal T-cells.

Eosinophilia & Hypereosinophilic Syndrome Treatment

Fred Hutch’s team of physicians provides a comprehensive range of treatment options for eosinophilia and HES. While treatments vary depending on the organs involved and the severity of symptoms, the goals remain the same:

• To decrease the number of eosinophils
• To prevent organ damage
• To slow disease progression

Your physician may prescribe drugs that suppress the growth of eosinophils, the action of eosinophils, or abnormal T-cells, if present. Systemic corticosteroids are often needed to combat severe rash, fluid retention, and other systemic symptoms. In some patients, corticosteroids alone are enough to manage the condition; others need stronger immunosuppressive therapies.

In essential thrombocythemia (ET), your body has too many platelets — fragments of cells that help your blood to clot.

At Fred Hutch, our team of experts provides comprehensive diagnostic and medical care along with ongoing monitoring and support for people with ET and related blood disorders.

What Is Essential Thrombocythemia?

ET is a type of myeloproliferative neoplasm (MPN) — the name for a group of diseases in which a bone marrow problem leads to increased levels of blood cells circulating in the bloodstream.

In ET, your bone marrow has too many immature cells (precursors) that turn into platelets. Your levels of white blood cells and red blood cells (hemoglobin/hematocrit on a blood test) may also be high in ET. Excess platelets can lead to health issues, such as bleeding problems and blood clots. Clots increase your risk of stroke and heart attack.

About 5 in 100 people with ET later develop acute leukemia. About 15 in 100 develop scarring in their bone marrow, called myelofibrosis.

Essential thrombocythemia is sometimes called primary thrombocythemia or idiopathic thrombocythemia.

Symptoms and Diagnosis of Essential Thrombocythemia

Many people with ET have no symptoms when their disease is diagnosed. But a routine blood test may show high levels of platelets. Symptoms may develop as the number of platelets increases.

ET symptoms may include:

• Headaches
• Changes in vision
• Feeling dizzy or lightheaded
• Cold fingers or toes
• Burning, pain and redness in the hands and feet
• Easy bruising or bleeding

If ET leads to blood clots, it can cause stroke, transient ischemic attack, heart attack, deep vein thrombosis or pulmonary embolism.

Besides detecting abnormal blood counts during routine testing, your doctor might suspect ET if you have noticeable signs or symptoms. To confirm the diagnosis, you may need additional blood tests — including tests to check for gene mutations, like JAK2 or CALR, that are common in ET — and tests of your bone marrow.

Essential Thrombocythemia Treatment

If you don’t have any symptoms, you may not need any active treatment right now. But it’s important to see your doctor regularly to monitor your condition. This approach is called watchful waiting. ET is a chronic disease can get worse over time.

Fred Hutch’s team of physicians provides a comprehensive range of treatment options for ET including:

• Aspirin — used at low doses to reduce clot risk
• Hydroxyurea — a mild chemotherapy drug used to reduce your chance of blood clots if you are at high risk 
• Anagrelide (Agrylin) — a medicine that can reduce platelet counts if hydroxyurea is not right for you
• Interferon — another medicine that can reduce platelets

A blood or bone marrow transplant may be an option for people with severe or advanced MPNs, like ET. This is currently the only type of treatment that has the potential to cure MPNs. The Fred Hutch Bone Marrow Transplant Program has performed more bone marrow transplants than any other institution in the world.

Fanconi anemia (FA) is a rare, inherited blood disorder that causes your bone marrow to stop making enough new blood cells for your body to work normally. It can also cause your bone marrow to make many abnormal blood cells, which can lead to serious health problems, such as cancer. FA can affect many of your body's organs, tissues, and systems. Children who inherit FA are at higher risk of being born with birth defects. People with FA are at higher risk for some cancers and other serious health problems. As an inherited disease, children can be tested if one of their brothers or sisters has the disease.

Symptoms include:

• Anemia
• Bone marrow failure
• Birth defects in the bones, eyes, ears, skin, kidneys, heart
• Developmental or eating problems

Other symptoms of FA are related to physical and mental development:

• Low birth weight
• Poor appetite
• Slower growth than other children
• Lower than normal height
• Small head size
• Mental retardation or learning disabilities

Symptoms of adult FA in women include:

• Female sex organs that are less developed than normal
• Menstruation starts later than women who don't have FA
• Menopause starts earlier than women who don't have FA
• Difficulty becoming pregnant and carrying a pregnancy to full term

Symptoms of adult FA in men:

• Male sex organs are less developed
• May be less fertile than men who don't have the disease.

Gaucher (pronounced “go-SHAY”) disease leads to deficiency of an enzyme that breaks down a certain fatty substance (lipid) in the body. The deficiency in turn leads to a build-up of cells swollen with the fatty substance. These swollen cells crowd out normal cells in some organs and tissues.

At Fred Hutch, our team of experts provides comprehensive diagnostic and medical care along with ongoing monitoring and support for people with Gaucher disease.

What Is Gaucher Disease?

Gaucher disease is an inherited genetic disorder caused by a mutation in the GBA gene. The abnormal gene reduces or stops the effect of an enzyme called beta-glucocerebrosidase. Normally this enzyme breaks down a fatty substance (glucosylceramide) and converts it to two components (glucose and ceramide) that we can easily process. Without enough of the enzyme, high levels of the fatty substance build up in cells of the spleen and liver, which become enlarged.

Both parents must carry the abnormal gene in order to pass Gaucher disease on to their child.

Symptoms and Diagnosis of Gaucher Disease

There are three types of Gaucher disease. The most common, known as type 1 Gaucher disease, can cause an enlarged spleen and liver, anemia, easy bruising, impaired blood clotting, lung disease, bone pain and fractures. Types 2 and 3 cause the same symptoms as type 1, but they also affect the central nervous system (brain and spinal cord) and can affect eye movement and cause seizures and brain damage.

To diagnose Gaucher disease, doctors perform a blood test to assess enzyme activity. After the initial diagnosis, many people have genetic testing to identify specific mutations in the GBA gene. This helps doctors create an effective treatment plan, and it helps families build a history of genetic traits.

Gaucher Disease Treatment

Treatment of Gaucher disease focuses on replacing the deficient enzyme or reducing the formation of the fatty substance that builds up. In most cases, people with Gaucher disease receive long-term enzyme replacement therapy by intravenous infusion every two weeks. In addition, some people respond well to medicines taken by mouth (miglustat [Zavesca] and eliglustat [Cerdelga]) that reduce the formation of glucosylceramide.

More Information at the National Gaucher Foundation

Hemochromatosis is a disease in which too much iron builds up in your body. Primary hemochromatosis, also called hereditary hemochromatosis (HHC), is an inherited disease in which your body absorbs extra iron and cannot get rid of it. Secondary hemochromatosis, commonly known as secondary iron overload, may develop after repeated red blood cell transfusions or as a complication of certain inherited or acquired anemias.

At Fred Hutch, our team of experts provides comprehensive diagnostic and medical care, along with ongoing monitoring and support, for people with HHC or secondary iron overload.

What Is Hemochromatosis?

Your body needs iron to make red bloods cells. Iron is a critical component of hemoglobin, the molecule in red bloods cells that carries oxygen to your tissues. Iron is also involved in enzymes that help convert blood sugars into energy within your cells, particularly muscle cells. It plays a vital role in producing new cells and recovering from illness.

In HHC, a genetic defect causes your body to absorb more iron from food than you need — many times more. The excess is stored in your body, especially in your liver. Your heart, pancreas, joints, skin and endocrine glands can also store extra iron.

Secondary iron overload usually develops along with or as a complication of the following disorders, especially when they require frequent red blood cell transfusions:

• Severe aplastic anemia
• Myelodysplastic syndromes
• Moderate to severe thalassemia
• Sickle cell disease
• Chronic inherited bone marrow failure syndromes 
• Chronic acquired bone marrow disorders

If iron overload rises to toxic levels, it causes organ damage. Iron overload may make you susceptible to conditions like cirrhosis, heart arrhythmia, heart attack, diabetes, bone and joint abnormalities and hormone deficiencies or even cause organs to fail.

Symptoms and Diagnosis of Hemochromatosis

HHC does not always cause signs, symptoms or serious problems. Even so, it’s important to diagnose the condition early so doctors can monitor any effects that develop and prevent or manage organ damage. 

Joint pain and chronic fatigue are the most common symptoms of hemochromatosis. Other symptoms include:

• Abdominal pain
• Memory lapses
• Heart palpitations
• Decreased sex drive

To definitively diagnose hereditary hemochromatosis doctors check both your iron storage levels and your iron saturation percentage. Doctors also perform genetic testing to confirm or rule out hereditary hemochromatosis in patients who have symptoms or who have unexplained high iron levels. 

Hemochromatosis Treatment

The goal of treatment for hereditary hemochromatosis and secondary iron overload is to lower the level of iron in your body to avoid organ complications. 

With HHC, this is usually done by removing blood through therapeutic phlebotomy (TP), which is the same process used when you donate blood, except that it is done under a doctor’s care. The number of times you might need TP depends on your iron levels.

Because secondary iron overload is often linked with severe anemia and repeated blood transfusions, TP cannot be used to remove excess iron in these cases. Instead, you might need iron-binding medicine to help your body excrete iron, a treatment called chelation therapy. Rarely, chelation therapy may also be used for HHC.

Once your iron level has come down to normal, your doctor will develop a personalized ongoing plan for you that may include getting your iron level tested regularly, having TP and limiting the amount of iron you get through your diet.

For detailed information on hemochromatosis research and support groups, visit the hemochromatosis website of the Iron Disorders Institute.

Hemochromatosis Website

Hemolytic is a condition in which are destroyed before they reach the end of their normal lifespan. At Fred Hutch, our team of experts provides comprehensive diagnostic and medical care for people with this and other forms of anemia.

What is Hemolytic Anemia?

Red blood cells are essential for carrying oxygen from the lungs to the rest of the body. Normally, these cells survive for about four months. The makes new red blood cells as needed and releases them into the bloodstream.

In hemolytic anemia, the lifespan of red blood cells is significantly shortened because a mechanism either within the red blood cells or elsewhere in the body destroys the cells. (Destruction of red blood cells is called hemolysis.) As a result, the bone marrow must work harder than usual to replace these cells.

Usually in hemolytic anemia, the bone marrow makes and releases red blood cells as it normally would, but these cells are later destroyed in the bloodstream, or liver.

Hemolytic anemias can be divided into immune and nonimmune forms.

• Immune hemolytic anemias are caused by generated by the patient’s own immune system.
• Nonimmune hemolytic anemias may be caused either by defects in the red blood cells (as in thalassemia, sickle cell disease, and hereditary spherocytosis) or by factors outside the red blood cells (as when cells are destroyed by a mechanical heart valve).

Symptoms and Diagnosis of Hemolytic Anemia

A physician may suspect hemolytic anemia based on typical anemia, such as fatigue or decreased energy, shortness of breath, and pale skin, and the results of a complete physical exam.

The condition is usually confirmed through blood tests. However, diagnosing the type and specific cause of the anemia requires clinical expertise and sophisticated testing methods, some of which are only offered at institutions like Fred Hutch, where you have access to world-class physicians and laboratory testing.

Because hemolytic anemia can occur along with an underlying disease, such as, physicians may include additional studies, like studies and a bone marrow (examining a small sample of marrow taken with a hollow needle), to detect underlying disease.

Hemolytic Anemia Treatment

Fred Hutch’s team of doctors provides a comprehensive range of treatment options for all forms of hemolytic anemia.

The goal of therapy is to increase the count to a safe level. Treatment varies depending on the cause of the hemolysis. For example, when the hemolysis is due to an immune system attack on red blood cells, doctors may use, intravenous immune globulin, or surgical removal of the spleen (splenectomy) to slow or stop red blood cell destruction.

Hemophilia is a genetic disease that prevents blood from clotting normally.

At Fred Hutch, our expert team of doctors works closely with Bloodworks Northwest to provide comprehensive diagnostic and treatment options for people with hemophilia.

What is hemophilia?

Hemophilia is a deficiency of factor VIII (8) or factor IX (9). These proteins, or clotting factors, activate blood clotting. People born with too little factor VIII have hemophilia A. Those without enough factor IX have hemophilia B.

Hemophilia ranges from mild disease, which may be diagnosed in later childhood or adulthood if there is no family history, to severe disease, which is usually diagnosed by age 2.

The genes for both factor VIII and factor IX are on the X Males, who typically have an X and a Y chromosome, and females, who typically have two Xs, can both carry the that causes the disease. Males are usually more severely affected. Females usually have milder and may have no symptoms at all. Anyone with a hemophilia gene can pass it on to their children.

Symptoms and Diagnosis of Hemophilia

People with mild hemophilia bleed more than expected during surgery or dental procedures or after an injury. They rarely have bleeding for no obvious reason.

Patients with moderate and severe hemophilia (factor levels less than 5 percent of normal) can have recurrent bleeding into their joints and life-threatening internal bleeding, including into the brain — even in situations that wouldn’t cause bleeding in a person with healthy clotting.

Physicians most often diagnose hemophilia after a bleeding episode or due to a family history of the condition. In some cases, a pre-surgical blood test (partial thromboplastin time, PTT) might detect it. This test measures how long blood takes to clot. More specific tests can determine whether a long clotting time is due to hemophilia.

A more common, usually milder, bleeding disorder called von Willebrand disease may resemble hemophilia. It is caused by problems with a clotting protein called von Willebrand factor. If your physician suspects you might have von Willebrand disease, they will order tests to confirm it because treatment for bleeding disorders depends on which protein is missing or defective.

Hemophilia treatment

The main treatment for hemophilia is replacement therapy with concentrated clotting factors. Regular infusions of blood clotting factor, which can be done at home, allow people with severe hemophilia to lead normal, active lives. For people with milder disease who do not need regular infusions, replacement therapy is given before surgeries and other procedures that might cause bleeding or in response to bleeding episodes.

If you have mild hemophilia A, physicians may prescribe the medicine desmopressin acetate (DDAVP). It causes cells in the lining of your blood vessels to release stored factor VIII, increasing the level in your blood. You may also need medicines that prevent the breakdown of blood clots (antifibrinolytic therapy).

Some people with hemophilia develop antibiodies to transfused clotting factors. The antibodies destroy the factors, making them less effective. If physicians detect antibodies to factor VIII in your blood, they may prescribe a special high-dose regimen of factor to decrease the antibody response and use alternative treatments to treat bleeding.

Hereditary spherocytosis is a genetic disease that causes your (RBCs) to change shape and become less flexible. These changes hinder the cells’ ability to travel through your bloodstream and can lead to, jaundice and an enlarged.

At Fred Hutch, our team of experts provides comprehensive diagnostic and medical care for people with hereditary spherocytosis.

What is Hereditary Spherocytosis?

Hereditary spherocytosis is caused by changes in genes that control important proteins in and on the membranes around your. The mutated genes give instructions that weaken the cell membranes, changing your RBCs from flat discs to rounder spheres.

The new shape makes it hard for your RBCs to pass from large arteries into narrow blood vessels, especially tiny capillaries. Your spleen captures and destroys the misshaped cells. As a result, you have fewer red blood cells in circulation and you may develop anemia.

Symptoms and Diagnosis of Hereditary Spherocytosis

Hereditary spherocytosis can be mild, moderate or severe. Most people with the condition develop hemolytic anemia, and people with the moderate to severe forms can experience jaundice (yellowing of the skin), gallstones and an enlarged spleen (splenomegaly).

Physicians diagnose hereditary spherocytosis by testing your blood to check the number, shape and maturity of your RBCs. If more information is needed, your doctor may order a flow cytometry analysis of your RBCs or an osmotic fragility test to measure the fragility of the cell membranes.

Hereditary Spherocytosis Treatment

Since there is currently no known cure for hereditary spherocytosis, doctors treat the condition by focusing on ways to limit symptoms and to ensure your body makes enough red blood cells. Fred Hutch's team of physicians provides a comprehensive range of treatment options.

Anemia, the most common symptom of the condition in its mildest form, is often treated with folic acid supplements that facilitate RBC production. For more severe anemia, you may need blood transfusions. People with a very enlarged spleen may need surgery to remove their spleen (splenectomy).

Hodgkin lymphoma is caused by malfunctioning lymphocytes, white blood cells that usually help our bodies fight infection.

What Are the Inherited Bone Marrow Failure Syndromes (IMBFS)?

The IBMFS are a group of rare inherited diseases with varying defects in the production of red blood cells, white blood cells, and/or platelets leading to low blood counts. Patients with some of the IBMFS are at risk for developing both blood and solid tumor cancers. Many of these patients also have typical changes in their physical appearance and dysfunction in multiple organ systems apart from the bone marrow. There are several different types of IBMFS, for example, Diamond-Blackfan Anemia, Dyskeratosis Congenita, Fanconi Anemia, and Schwachman-Diamond Syndrome.

The IBMFS were traditionally diagnosed in children, however, with the advent of new laboratory and genetic testing, hematologists are now recognizing these disorders in adult patients presenting with abnormal blood counts or other findings. Additionally, children with these inherited disorders now survive to adulthood and transition their care to adult hematologists.

Diagnosis and Work-Up

The diagnosis of any of the IBMFS is made through careful consideration of a patient’s history, including a detailed family history of any problems in blood counts, typical physical findings, or cancer predisposition, together with a thorough physical exam to assess for clinical findings seen in IBMFS. In those patients with a suggestive history and physical exam, bone marrow examination and additional laboratory testing are important elements of the diagnostic workup; the results guide the appropriate selection of additional tests. All results should be interpreted carefully within the context of the entire clinical picture of the patient and the patient’s family. Importantly, the new diagnosis of any of the IBMFS in adult patients requires that adult hematologists remain thoughtful of the possibility that an inherited disease may first come to medical attention when the patient reaches adulthood.

Anemia occurs when your body has too few red blood cells. Iron-deficiency anemia is the most common form of the condition.

At Fred Hutch, our team of experts provides comprehensive diagnostic and medical care for people with many types of anemia, including this type.

What Is Iron-Deficiency Anemia?

Iron-deficiency anemia happens if your body loses more iron than normal or you’re not getting enough iron through your diet. Your body can lose iron if:

• You’re bleeding — even if the blood loss is slow and you’re not aware of it.
• Your body has trouble absorbing iron because of an intestinal surgery you’ve had or because of another condition, such as celiac disease.
• Some diets, such as vegetarian diets, may be low in iron and lead to iron deficiency if followed strictly over many years.

Red blood cells contain hemoglobin, an iron-rich protein that gives blood its red color. Hemoglobin enables the blood cells to carry oxygen from your lungs to the rest of your body. When your iron level is low, this process is impaired, and your tissues don’t get as much oxygen as they need.

Symptoms and Diagnosis of Iron-Deficiency Anemia

When your blood cannot deliver enough oxygen throughout your body, you may feel weak, dizzy or short of breath with activities that would normally not be challenging for you, such as walking up stairs.

In iron-deficiency anemia specifically, people often notice unusual symptoms, most commonly craving for ice chips, burning in the mouth, hair loss or restless leg syndrome.

If your anemia is mild or develops slowly over a long period, you might not notice any symptoms at all.

Fred Hutch offers a full array of services to diagnose anemia and determine the cause.

Your physician will ask about your medical history and examine you. They can diagnose low iron with simple blood tests, including a complete blood count with blood smear and iron studies (iron, iron binding capacity, transferrin saturation and ferritin). A bone marrow biopsy can help doctors assess your iron stores, but this is rarely needed to diagnose iron deficiency.

If you’re low on iron, your doctor will look further to determine the cause. You may need more blood tests or gastrointestinal procedures, such as an endoscopy or colonoscopy, to check for internal bleeding from an ulcer, polyp or other condition.

Iron-Deficiency Anemia Treatment

To rebuild your body’s iron stores, you’ll need iron supplements in pill form. There’s also an option to get supplemental iron through an intravenous (IV) line, if you cannot absorb enough iron from pills.

If your physician finds a cause for your iron deficiency, such as bleeding, you’ll need treatment to correct that as well. SCCA’s team of doctors provides a full range of treatment options for anemia and the conditions that may lead to it.

What Is Langerhans Cell Histiocytosis?

Langerhan cell histiocytosis is a rare blood disease that is caused by an excess of white blood cells called histiocytes, which cluster together and attack the skin, bones, lung, liver, spleen, gums, ears, eyes, and/or brain. The disease can range from limited involvement that spontaneously regresses to progressive multi-organ involvement that can be chronic and debilitating. In some cases, the disease can be life-threatening.

Who Gets LCH?

Histiocytosis is more common in children than adults and affects 1 in 200,000 children born each year in the United States, though it can affect adults of any age. The cause is in most cases is not known. However, in cases where only the lungs are involved, smoking has been strongly implicated.

Symptoms and Diagnosis of LCh

LCH can present increased thirst and urination (diabetes insipidus) due to involvement of an area in the brain called the pituitary gland. Other symptoms may be bone pain, particular lower jaw, skin rash, cough or shortness of breath, weight loss, fever, and enlarged lymph nodes or spleen. The diagnosis of LCH requires a biopsy of an affected area. The biopsy is best reviewed by large academic centers since it is rare and the findings can be subtle.

Treatment of LCh

LCH is best treated at a large institution like Fred Hutch where there will be physicians who have experience in treating this rare disease. Since it is so rare in adults, there is little research about its cause and treatment and no standard treatment is available. Many adult treatments are based on what has been successful in treating children, but the results have not been good. When the disease is localized to one or two areas, surgery and/or radiation therapy have been used. Patients with mild symptoms may be managed with steroids and some will improve without treatment. When only the lungs are involved, smoking cessation has resulted in some cures. For patients with more extensive disease and/or severe symptoms, chemotherapy is required. Hematopoietic stem cell transplant should also be considered for patients who have a poor response to chemotherapy.

Large granular lymphocytic (LGL) leukemia is a type of chronic leukemia affecting white blood cells.

At Fred Hutch, our team of experts provides comprehensive diagnostic and medical care for people with LGL.

In people with leukemia, the bone marrow produces abnormal (leukemic) blood cells.

What Is Mastocytosis?

Mastocytosis is a group of rare disorders caused by the presence of too many mast cells, or (mastocytes), which are part of the immune system. They are located in connective tissue, including the skin and other areas. They release histamines in the body that alert other immune defenses and are thought to play a role in wound healing. No one with too few or no mast cells has been found, which leads doctors to believe that people cannot survive without mast cells. In rare cases chemicals released by mast cells cause changes in the immune system leading to typical allergy symptoms such as: itching, abdominal cramping, or anaphylaxis (shock from allergic or immune causes). The increased number of mast cells in the tissues in mastocytosis is due to acquired genetic mutations in a protein called c-kit. Since this disease is an abnormal increased growth of genetically abnormal blood cells, mastocytosis is classified as a myeloproliferative neoplasm (MPN).

Symptoms and Diagnosis

When too many mast cells exist in the body, skin lesions can occur, as can abdominal discomfort, low blood pressure, faintness, bone or muscle pain, nausea, and vomiting. The diagnosis can be expected from the clinical history and physical exam findings. Blood and urine tests are helpful for making the diagnosis and detecting the proteins produced by the mast cells call tryptase and histamine. Biopsies of affected tissue are needed to make the diagnosis. A bone marrow biopsy is commonly done to demonstrate more wide spread, or systemic, disease. Specific tests on biopsy samples are performed to detect the common mutation in the c-kit protein.

Treatment

Most cases of mastocytosis in adults are systemic (involving multiple sites) but are mild and do not require much therapy. Treatments are aimed at preventing the effects of the released disease mediators such as anti-histamines. Other medications stabilize the mast cells. Rarely do patients have more aggressive disease with organ involvement that causes low blood counts, liver failure, and malnutrition. For these patients, steroids and chemotherapy may be used but there are currently no good treatments. Newer drugs are being developed that act on the mutated c-kit or similar proteins. Physicians at Fred Hutch are participating in clinical trials to test these drugs.

In monoclonal gammopathy of undetermined significance (MGUS), your body makes an abnormal protein that circulates in your blood. This protein rarely causes problems. But it may be a sign that you have another condition that does need treatment. Over time, MGUS can give rise to a serious disease, like multiple myeloma.

At Fred Hutch, our team of experts provides comprehensive diagnostic and medical care, including ongoing monitoring and support, for people with MGUS and related blood disorders.

What Is MGUS?

MGUS is a condition in which plasma cells, a type of white blood cell in your bone marrow, begin making an abnormal monoclonal protein, or M protein. About 3 percent of people over 50 have MGUS.

It can occur along with a range of other conditions, such as osteoporosis, neuropathy and blood clots. In about 1 percent of cases per year, MGUS progresses to multiple myeloma or another malignant blood disorder.

Symptoms and Diagnosis of Monoclonal Gammopathy

Typically, MGUS doesn’t cause symptoms. Physicians usually discover it during routine blood work or testing to investigate another condition you have.

If initial tests show M protein, your doctor will order further blood tests and possibly urine tests to see how M protein is affecting your body and to check for associated conditions.

Fred Hutch offers a full array of services to diagnose MGUS and any related health problems you may have.

When symptoms of MGUS do arise, they differ depending on the effects of the M protein and any associated condition. Symptoms can include:

• Anemia-related symptoms, like fatigue and weakness
• Bone or soft tissue pain
• Tingling or numbness in your feet or hands
• Recurring infections
• Increased bruising or bleeding
• Weight loss
• Swelling
• Headache
• Vision problems

Mgus Treatment

MGUS by itself is not harmful, so it usually doesn’t warrant treatment if it isn’t causing symptoms.

But because MGUS may progress to a more serious condition, it’s important to closely monitor your health and level of M protein to detect and treat any problems that might arise. This approach, called watchful waiting, usually means seeing your doctor regularly for physical exams and blood work. It’s also important to let your health care team know between checkups if you develop any new symptoms.

SCCA’s team of doctors provides regular monitoring for people with MGUS, as well as a comprehensive range of treatment options for related conditions, including malignant diseases like multiple myeloma.

Multiple myeloma is a blood, or hematologic, cancer that can affect your bones and kidneys as well as your levels of healthy blood cells.

Myelodysplastic syndromes (MDS) is not a single disease but a group of diseases that affect blood-cell formation. In all subtypes of MDS, a chronic bone marrow problem leads to low levels of blood cells circulating in your bloodstream.

Myelofibrosis (MF) is a blood disorder in which fibers and blasts (abnormal stem cells) build up in your bone marrow.

At Fred Hutch, our team of experts provides comprehensive diagnostic and medical care along with ongoing monitoring and support for people with primary MF or MF that develops due to another condition.

What Is Myelofibrosis?

Myelofibrosis is a type of myeloproliferative neoplasm (MPN) — the name for a group of diseases in which a bone marrow problem leads to increased levels of blood cells circulating in the bloodstream.

In MF, an excess of cells in your bone marrow causes scarring (fibrosis). This makes it hard for your marrow to produce the healthy blood cells your body needs. As a result, your body may make some blood cells in your spleen or liver to try to keep up. This can enlarge these organs.

MF can arise as a result of another condition that affects your marrow, like essential thrombocythemia or polycythemia vera, or it can happen on its own. Physicians use the name primary myelofibrosis when there is no other underlying disease that causes the scarring.

In about 20 in 100 patients, MF can lead to acute myeloid leukemia.

Symptoms and Diagnosis of Myelofibrosis

Some people with MF have no symptoms when their disease is diagnosed. But a routine blood test may show abnormal levels of blood cells. Or your doctor may notice signs of MF during an exam, even if you don’t feel ill.

Your spleen might be enlarged. Your physician might feel this when they examine your abdomen. You might notice abdominal pain or fullness.
You might develop anemia (low red blood cells), which can lead to weakness and fatigue. Your physician might notice signs like paler-than-usual color to your skin or mucous membranes (such as inside your mouth or the lining around your eyes).

MF can lead to a range of other signs or symptoms, like easy bleeding or bruising (if you have low platelets), frequent infections (if you have low white blood cells), fever, night sweats, pain, itching and loss of weight or muscle mass.

To confirm the diagnosis, you may need blood tests — including tests to check for gene mutations, like JAK2 or CALR, that are common in MF — and tests of your bone marrow.

Myelofibrosis Treatment

If you don’t have any symptoms, you may not need any active treatment right now. But it’s important to see your doctor regularly to monitor your condition. This approach is called watchful waiting. MF is a chronic disease that may get worse over time.

Fred Hutch’s team of physicians provides a comprehensive range of treatment options for MF, including JAK-inhibitors, such as ruxolitinib (Jakafi) and fedratinib (Inrebic). These medicines reduce overactive signaling by proteins that may cause your body to make too many blood cells. We also provide therapies you may need to relieve MF-related signs or symptoms, like anemia or bleeding or clotting problems. At Fred Hutch, we also have clinical trials testing new treatments for people with MF.

A blood or bone marrow transplant may be an option for people with severe or advanced MPNs, like MF. This is currently the only type of treatment that has the potential to cure MPNs. The Fred Hutch Blood and Marrow Transplant Program has performed more bone marrow transplants than any other institution in the world.

For more information about primary MF, visit the MPN Research Foundation website.

MPN Research Foundation

Myeloproliferative neoplasms (MPN) are a group of diseases that affect blood-cell formation. In all forms of MPN, a bone marrow problem leads to increased levels of blood cells circulating in the bloodstream.

Non-Hodgkin lymphoma (NHL) is cancer that begins in lymphocytes, white blood cells that are an important part of the body’s infection-fighting immune system.

Paroxysmal nocturnal hemoglobinuria (PNH) may cause unpredictable episodes of acute red blood cell destruction (hemolysis). This occurs when a part of your immune system called complement attacks red blood cells that lack certain protective proteins.

At Fred Hutch, our team of experts provides comprehensive diagnostic services, including flow cytometry, bone marrow evaluation, and other special testing, as well as treatment options, such as eculizumab (Soliris), a monoclonal antibody therapy, for people with PNH.

What Is Paroxysmal Nocturnal Hemoglobinuria?

PNH is a rare, acquired blood disease that affects just one to two people per million. It’s caused by an acquired genetic mutation in a subset of the hematopoietic (blood-forming) stem cells. Hematopoietic stem cells are found mainly in the bone marrow. In PHN, the stem cells affected by the mutation and the blood cells they produce (red blood cells, white blood cells, and platelets) gradually become the dominant cells in your marrow.

PNH is a complex disease characterized by hemolytic crises — periods in which large numbers of red blood cells are destroyed. Red blood cells are essential for carrying oxygen from the lungs to the rest of the body. Stem cells with the PNH mutation can also lead to ineffective production of white blood cells, which fight infection, and platelets, which help the blood to clot.

Sometimes, PNH arises after healthy hematopoietic stem cells have been damaged, such as by exposure to toxins, radiation, or chemotherapy, or after the bone marrow has been suppressed by a virus or by a person’s own immune system. These insults to the bone marrow can cause aplastic anemia, and PNH can arise as an outgrowth of recovery from aplastic anemia. In fact, up to 30 percent of newly diagnosed cases of PNH develop from aplastic anemia.

Alternatively, PNH can arise spontaneously without prior marrow damage. In this case, excessive and unexpected breakdown of red blood cells may be the only sign of the disorder, with otherwise normal blood counts.

PNH can lead to inappropriate blood clotting (thrombosis), bone marrow failure, and aplastic anemia. It increases the risk for preleukemia (myelodysplastic syndrome, MDS) and can lead to leukemia.

PNH is most common in adults age 35 to 40, but occasionally it affects children and adolescents or older adults.

Symptoms and Diagnosis of Paroxysmal Nocturnal Hemoglobinuria

Hemolysis in PNH can cause acute, severe anemia associated with severe abdominal spasms, headaches, back pain, weakness, occasionally blood clots in unusual places in the body, and extreme fatigue. However, some people with PNH experience no discomfort.

The classic symptom of bloody red or brown urine (hemoglobinuria) actually happens in less than half of those diagnosed with PNH. People with this symptom tend to describe their urine as tea or cola colored. Their urine is usually darker in the morning, because it became concentrated in the bladder overnight, and clearer during the day. The discoloration happens because damaged red blood cells leak the protein hemoglobin into the bloodstream, and this ends up in the urine.

Fred Hutch offers a full array of services to diagnose PNH and related problems that may affect the bone marrow or blood cells.

If your physician suspects you have PNH, he or she may order a variety of blood tests. Flow cytometry, a very sensitive blood test, has become the standard for detecting PNH. Results from flow cytometry are usually not affected by recent blood transfusions or other factors that can alter results of some other types of tests. In addition to flow cytometry, bone marrow biopsy (examining a small sample of marrow taken with a hollow needle) is important to understand the full nature of PNH and possible associated diseases, such as aplastic anemia or MDS.

Paroxysmal Nocturnal Hemoglobinuria Treatment

Fred Hutch's team of physicians provides a comprehensive range of treatment options for PNH. Treatment depends largely on the severity of symptoms.

Supplements and Medicines

Some people with PNH experience no discomfort and require no treatment beyond folic acid or iron supplements to increase their red blood cell production.

For those requiring more support, doctors may prescribe:

• Prednisone to slow red blood cell destruction
• Anticoagulation drugs to help prevent or treat complications from blood clots
• Eculizumab to help lessen the severity of hemolysis in the bloodstream, reduce the symptoms of PNH, and lower the risk of complications from blood clots

Blood and Marrow Transplant

If you develop bone marrow failure or MDS, your physician may recommend considering a bone marrow transplant (also called a stem cell or hematopoietic cell transplant). This procedure replaces your blood-forming stem cells with the cells of a donor. Few people with PNH need a transplant, but it is the only cure.

The Fred Hutch Blood and Marrow Transplant Program has performed more bone marrow transplants than any other institution in the world and consistently achieves higher-than-expected survival rates.

Anemia occurs when your body has too few red blood cells. Pernicious anemia is low red blood cell level due to low levels of vitamin B12 (also called cobalamin).

At Fred Hutch, our team of experts provides comprehensive diagnostic and medical care for people with many types of anemia, including this type.

What Is Pernicious Anemia?

Vitamin B12 is important for many processes in your body, including cell multiplication. Red blood cell production is particularly sensitive to low B12 levels.

In pernicious anemia, your body makes antibodies that attack cells in your stomach called parietal cells. Normally, parietal cells make intrinsic factor, a protein that has to bind to B12 so your intestines can absorb this vitamin from your diet. If your parietal cells are destroyed, you don’t have intrinsic factor, and you can’t absorb enough B12 to maintain a healthy red blood cell count.

Red blood cells carry oxygen from your lungs to the rest of your body. When your red blood cell count is low, this process is impaired, and your tissues don’t get as much oxygen as they need.

There are other reasons your body might be low in B12, such as an imbalance of bacteria in your intestine, another disease in your stomach or gut or a medicine that limits how much B12 you can absorb. You could also be low in B12 if you don’t get enough through your diet — for instance, if you are vegan (eating no animal-based products) and you do not take B12 supplements. Low B12 for any reason can lead to anemia. Sometimes the term “pernicious anemia” is used for any anemia caused by B12 deficiency; some sources use this term only for anemia that stems from problems with intrinsic factor.

Symptoms and Diagnosis of Pernicious Anemia

When your blood cannot deliver enough oxygen throughout your body, you may feel weak, dizzy or short of breath. You may notice chest pain, a rapid or irregular heartbeat, headaches, cold hands and feet or pale skin.

Without treatment, pernicious anemia can lead to other health concerns, including sores or chapping in the corners of the mouth; a smooth, red tongue with reduced sensation of taste; tingling or numbness from nerve damage; memory loss, dementia or other neurologic conditions; and heart or digestive problems. Lack of vitamin B12 can also lead to a decrease in other types of blood cells, such as white blood cells and platelets.

Fred Hutch offers a full array of services to diagnose anemia and determine the cause.

Your doctor will ask about your medical and family history and examine you. You will have a blood test (complete blood count) to check the levels of your blood cells, the volume of space your red blood cells take up in your blood (hematocrit) and the size of your red blood cells.

B12 deficiency causes fewer red blood cells and a lower volume of red blood cells in the blood, but typically each individual red blood cell is larger than normal. This is called macrocytosis, so this type of anemia is called macrocytic.

If you have anemia, additional blood tests can help your doctor tell which type you have. For instance, blood tests can be used to check your B12 level, evaluate your body’s use of B12 and look for antibodies that may be present if you have pernicious anemia. Endoscopy may also be used to check for problems in your stomach and gut that can explain decreased B12 absorption.

To learn more about your body’s ability to make healthy red blood cells, you may need other tests too. You may have a bone marrow biopsy — removing a small sample of bone marrow to examine under a microscope. Bone marrow makes young blood-forming cells, called hematopoietic stem cells, that develop into mature white or red blood cells or platelets. You may hear doctors mention the term “megaloblastic anemia.” This refers to changes in your stem cells that result in larger red blood cells if you are low in B12.

Pernicious Anemia Treatment

Treatment of pernicious anemia requires building up and then maintaining your vitamin B12 stores. Typically, pernicious anemia prevents normal absorption of B12 taken by mouth, so it is very likely you’ll need B12 supplements by injection. But some people with pernicious anemia can absorb some vitamin B12 orally and may take B12 in pill form.

Pernicious anemia can become severe enough to require blood transfusions to increase your red blood cell level.

If another condition is causing your lack of intrinsic factor or poor absorption of B12, you’ll need treatment to correct that as well. The type and duration of treatment will depend on the underlying problem.

Fred Hutch’s team of physicians provides a full range of treatment options for anemia and the conditions that may lead to it.

In polycythemia vera (PV), your bone marrow makes too many red blood cells.

At Fred Hutch, our team of experts provides comprehensive diagnostic and medical care along with ongoing monitoring and support for people with PV and related blood disorders.

What Is Polycythemia Vera?

PV is a type of myeloproliferative neoplasm (MPN) — the name for a group of diseases in which a bone marrow problem leads to increased levels of blood cells. In PV, extra red blood cells circulate in your bloodstream, making your blood thicker than usual. This usually shows up on results of blood tests as a high hemoglobin or hematocrit level.

You may also have more white blood cells and platelets than normal. These can collect in your spleen, causing it to enlarge.

Excess blood cells can lead to health issues, such as bleeding problems and blood clots. In people over 65, PV increases the risk of stroke and heart attack.

PV can lead to acute myeloid leukemia in about 5 in 100 patients or myelofibrosis in 15 in 100 patients.

Symptoms and Diagnosis of Polycythemia Vera

Some people with PV have no symptoms when their disease is diagnosed. But a routine blood test may show high levels of blood cells. Symptoms may develop as the number of blood cells increases.

Symptoms may include:

• A feeling of pressure or fullness below the ribs on the left side (spleen)
  Headaches
• Double vision or seeing dark or blind spots that come and go
• Itching all over the body, especially after being in warm or hot water
• Reddened face that looks like a blush or sunburn
• Weakness
• Dizziness
• Weight loss for no known reason

Besides detecting abnormal blood counts during routine testing, your physician might suspect PV if you have noticeable signs or symptoms. To confirm the diagnosis, you may need additional blood tests, including tests to check for the JAK2 gene mutation that’s common in PV, and tests of your bone marrow.

Polycythemia Vera Treatment

If you don’t have any symptoms, you may not need any active treatment right now. But it’s important to see your doctor regularly to monitor your condition. This approach is called watchful waiting. PV is a chronic disease that tends to get worse over time.

Fred Hutch's team of physicians provides a comprehensive range of treatment options for PV including:

Phlebotomy — removing blood from your body to decrease your red blood cell counts, relieve symptoms and reduce clot risk
Aspirin — used at low doses to reduce clot risk
Hydroxyurea — a medicine to decrease your production of blood cells or the release of blood cells from your bone marrow if you who have had or are at high risk for a blood clot and have very high non-red blood cell counts
Ruxolitinib (Jakafi) — a medicine that reduces overactive signaling by proteins that may cause your body to make too many blood cells
Interferon — which stimulates your immune system to help control your blood counts

A blood or bone marrow transplant may be an option for people with severe or advanced MPNs, like PV. This is currently the only type of treatment that has the potential to cure MPNs. The Fred Hutch Blood and Marrow Transplant Program has performed more bone marrow transplants than any other institution in the world.

For more information about PV, visit the MPN Research Foundation website.

MPN Research Foundation

Porphyria is a group of different disorders caused by abnormalities in the chemical steps leading to the production of heme, a substance that is important in the body. The largest amounts of heme are in the blood and bone marrow, where it carries oxygen. Heme is also found in the liver and other tissues.

Multiple enzymes are needed for the body to produce heme. If any one of the enzymes is abnormal, the process cannot continue and the intermediate products, porphyrin or its precursors, may build up and be excreted in the urine and stool.

The porphyria disorders can be grouped by symptoms—whether they affect the skin or the nervous system. The cutaneous porphyrias affect the skin. People with cutaneous porphyria develop blisters, itching, and swelling of their skin when it is exposed to sunlight. The acute porphyrias affect the nervous system. Symptoms of acute porphyria include pain in the chest, abdomen, limbs, or back; muscle numbness, tingling, paralysis, or cramping; vomiting; constipation; and personality changes or mental disorders. These symptoms appear intermittently.

The porphyrias are inherited conditions, and the genes for all enzymes in the heme pathway have been identified. Some forms of porphyria result from inheriting an abnormal gene from one parent (autosomal dominant). Other forms are from inheriting an abnormal gene from each parent (autosomal recessive). The risk that individuals in an affected family will have the disease or transmit it to their children is quite different depending on the type.

Attacks of porphyria can develop over hours or days and last for days or weeks. Porphyria can be triggered by drugs (barbiturates, tranquilizers, birth control pills, sedatives), chemicals, fasting, smoking, drinking alcohol, infections, emotional and physical stress, menstrual hormones, and exposure to the sun.

Porphyria is diagnosed through blood, urine, and stool tests. Diagnosis may be difficult because the range of symptoms is common to many disorders and interpretation of the tests may be complex. Each form of porphyria is treated differently. Treatment may involve treating with heme, giving medicines to relieve the symptoms, or drawing blood. People who have severe attacks may need to be hospitalized.

Post-transplant lymphoproliferative disorder (PTLD) spans from indolent polyclonal proliferations to aggressive lymphomas that complicate solid organ or hematopoietic transplantation.

At Fred Hutch, our team of experts provides comprehensive diagnostic and medical care for people with PTLD

Venous thromboembolism (VTE) is an umbrella term that includes two conditions, pulmonary embolism (PE) and deep vein thrombosis (DVT).

PE symptoms include:

• Shortness of breath
• Fast heart rate or breathing
• Chest pain, made worse by taking a deep breath or coughing
• Coughing up blood
• Feeling lightheaded or fainting

Treatment

The usual treatment is anti-clotting medicine (anticoagulants) — such as heparin, enoxaparin (Lovenox), apixaban (Eliquis), dabigatran (Pradaxa), rivaroxaban (Xarelto), edoxaban (Savaysa) and warfarin (Coumadin) — given by injection or taken in tablet form. Doctors can also give medicines that dissolve clots (thrombolytics) into your bloodstream or even directly into a clot. Some people need surgery in order to inject medicine into a clot, remove a clot or place a filter in a vein to keep clots from reaching the lungs.

Experts at Fred Hutch can provide information and advice to help you decide about ongoing treatment.

Shwachman-Diamond syndrome (SDS) is an inherited condition that can affect the bone marrow, pancreas, skeletal system, and other organ systems. Children with this disease typically have a shortage of neutrophils (a condition called neutropenia) which makes them more prone to pneumonia, ear infections, and skin infections. SDS can also lead to decreased numbers of red blood cells, called anemia, or decreased numbers of platelets, called thrombocytopenia. A gene mutation in a majority of patients recently discovered reveals new information about the molecular make-up and progression of this disorder.

Sickle cell disease is a group of inherited blood disorders that cause people to have an abnormal protein in their red blood cells (RBCs).

Thalassemia is a type of anemia, which means your body makes fewer healthy red blood cells and less hemoglobin than normal. At SCCA, our team of experts provides comprehensive diagnostic and medical care for people with all types of thalassemia.

What Are Thalassemias?

Thalassemias are inherited blood disorders that cause your body to make less hemoglobin than normal. Hemoglobin is the red protein that fills your red blood cells. It enables the blood cells to carry oxygen from your lungs to the rest of your body and to carry carbon dioxide from other parts of your body back to your lungs to be exhaled.

To make a molecule of hemoglobin, your body first needs to make specific parts called globin chains. There are two main types of chains, alpha and beta. Each molecule of hemoglobin needs 2 alpha chains and 2 beta chains. In thalassemias, your body can’t make enough of 1 of these chains. As a result, you can’t make a normal amount of hemoglobin.

Without making enough hemoglobin, your body can’t fill as many healthy red blood cells as usual. You may develop anemia, which means your tissues don’t get as much oxygen as they need.

Thalassemias happen because of a mutation in the genes used to make globins. These diseases can be passed down in families. In fact, they are the most commonly inherited diseases in the world.

Types of Thalassemia

There are two main types of thalassemia, named after the globin you have less of: alpha thalassemia and beta thalassemia.

Alpha Thalassemias

Four genes can cause alpha thalassemia. Your thalassemia depends on how many of these genes have mutations.

• Hemoglobin Bart’s hydrops fetalis syndrome: This is the most severe type of alpha thalassemia. It affects people who inherit mutations in all 4 genes. It causes severe anemia even before birth.
• Hemoglobin H disease: This affects people who inherit mutations in 3 out of the 4 genes. It causes moderate anemia.
• Alpha thalassemia trait: This affects people who inherit mutations in 2 out of the 4 genes. It causes mild anemia.
• Alpha thalassemia carrier: This affects people who inherit mutations in 1 out of the 4 genes. It usually causes no symptoms.

Beta Thalassemias

Beta thalassemias are divided into these groups:

• Beta thalassemia major: This affects people who inherit an abnormal gene from both parents. It causes severe anemia, usually diagnosed in the first year of life. People with beta thalassemia major need blood transfusions.
• Beta thalassemia minor (or trait): This affects people who inherit only 1 abnormal gene from 1 parent. It leads to very mild anemia that usually doesn’t cause any symptoms.
• Beta thalassemia intermedia: This affects people who inherit an abnormal gene from both parents. It causes anemia, but the severity varies from person to person. You may not know you have it until sometime in adulthood.

An important subtype of thalassemia is caused by a specific gene mutation that makes a form of hemoglobin called hemoglobin E. Hemoglobin E is common in southeastern Asia. Combined with mutations that cause beta thalassemia, it can cause severe thalassemia.

Symptoms and Diagnosis of Thalassemia

Thalassemia symptoms can range from mild to severe.

If you have anemia, meaning your blood cannot deliver enough oxygen throughout your body, you may feel weak, dizzy or short of breath when you exercise, and you may have a pale skin. If anemia is severe, you may notice chest pain or a rapid or irregular heartbeat.

Your spleen may be working overtime to help make more red blood cells. This can cause your spleen get larger. Your doctor might notice this during an exam, and you might feel unusually full after meals.

If you have no symptoms or only mild symptoms, you might not find out you have thalassemia unless abnormal results appear on a blood test that you have for another reason.

Some people with thalassemia are diagnosed in childhood because:

• Their symptoms are severe enough to cause concern.
• They have family members with the condition.
• Anemia shows up on a routine blood test.
• Their pediatrician notices something unusual, such as not growing as expected, having an enlarged spleen or having bone abnormalities.

Fred Hutch offers a full array of services to diagnose thalassemia. Along with examining you and asking about your health history and family history, your doctor may order blood tests. These tests can check your level of hemoglobin and the number and size of your red blood cells. Specific tests to study your hemoglobin and genetic tests can also be done to tell whether you (and your family members) have thalassemia.

Thalassemia Treatment

Fred Hutch’s hematologists provide care for adults with all types of thalassemia. We tailor a treatment plan to you. Your plan may include several different approaches, such as:

• Folic acid supplements to support your body in making red blood cells
• Blood transfusions to boost your red blood cell level and fight the effects of anemia
• Chelation therapy — taking medicine to remove excess iron from your body
• Medicines that increase the production of red blood cells by your bone marrow
• Bone marrow transplant to give you stem cells that make normal hemoglobin
• New medicines, gene therapy or other treatments available in clinical trials
• Genetic counseling if you plan to have children

It’s also important to receive regular care to check for and treat complications that can arise from anemia or iron overload. These can include:

• Heart and blood vessel problems, such as irregular heartbeat, congestive heart failure and pulmonary hypertension
• Liver problems, such as scarring (fibrosis or cirrhosis), due to too much iron
• Skin complications, such as leg ulcers and changes in the elastic fibers in your skin (pseudoxanthoma elasticum)
• Early bone thinning (osteopenia and osteoporosis)
• Problems related to hormones, such as diabetes, hypothyroidism and fertility concerns

Your team works closely with you to support you in living a healthy life and to make sure you receive the care you may need from a variety of specialists.

Thrombotic thrombocytopenic purpura (TTP) is a rare blood condition that causes blood clots to form in small blood vessels throughout the body, which can cause serious problems if they block blood vessels and limit blood flow to the brain, kidneys, or heart.

There are two main types of TTP: inherited and acquired. Acquired TTP is the more common type that occurs mostly in adults, but it sometimes affects children. The causes are unknown, but it can be triggered by conditions such as pregnancy or infection or diseases such as cancer, HIV, and lupus. Medical procedures such as surgery and bone marrow transplant and certain medications and hormone replacement therapies may induce TTP as well.

In TTP, when blood clots form, there are fewer platelets in the blood. This can cause bleeding into the skin (purpura), prolonged bleeding from cuts, and internal bleeding. It also causes small blood clots to form suddenly throughout the body, including in the brain and kidneys. Symptoms are due to blood clots, a low platelet count, and damaged red blood cells, purplish spots called purpura on the skin or in the mouth, paleness or jaundice, feeling tired or weak, fever, fast heart rate or feeling short of breath, headache, speech changes, confusion, coma, stroke, or seizure, a low amount of urine, or protein or blood in the urine.

Venous thromboembolism (VTE) is a blood clot that starts in a vein. Blood clots occur when your blood thickens and blocks flow through a vessel.

At Fred Hutch, our team of experts provides comprehensive diagnostic and medical care for people who’ve had venous thromboembolism. Fred Hutch hematologists work closely with all of our doctors to care for people who are at risk, including people being treated for cancer or bone marrow disorders.

What Is Venous Thromboembolism?

VTE is an umbrella term that includes two conditions: Deep vein thrombosis (DVT) and pulmonary embolism (PE).

DVT is a blood clot that forms in a vein deep in your body. It happens most often in the lower leg or thigh but can happen in other parts of the body as well.

DVT can occur for several reasons, including damage to a vein, such as from a fracture or surgery, or slow blood flow, such as from lying in bed or sitting for long periods. Other risk factors include:

• Being pregnant
• Taking birth control pills or hormone replacement for menopause
• Being overweight
• Having cancer
• Having an inherited condition that increases your tendency to form clots or decreases your ability to dissolve them

Many patients with DVT have more than one risk factor, but some patients can have DVT without any known risk factors.

If a blood clot in a deep vein breaks loose, it can travel through your bloodstream. A clot that’s moving is called an embolus. Clots in veins travel toward your lungs. If a clot reaches your lungs and blocks blood flow there, the condition is called pulmonary embolism (PE). PE can damage your lungs or be fatal.

Symptoms and Diagnosis of Venous Thromboembolism

Not everyone with DVT has symptoms. When symptoms do arise, they may include:

• Swelling of the leg
• Pain or tenderness in the leg, often similar to the symptoms of a muscle cramp (or injury) that does not resolve
• Increased warmth in the area
• Red or discolored skin

Typically, DVT affects only one leg at a time, not both.

PE symptoms include:

• Shortness of breath
• Fast heart rate or breathing
• Chest pain, made worse by taking a deep breath or coughing
• Coughing up blood
• Feeling lightheaded or fainting

To diagnose venous thromboembolism, your doctor will examine you and ask about your health history and family history. You will have blood tests to check your clotting activity, and you may need an imaging test, such as an ultrasound of your leg for DVT or a computed tomography (CT) scan of your lungs for PE.

Venous Thromboembolism Treatment

Both DVT and PE are serious conditions that can damage your lungs and other organs. They need medical treatment right away.

The usual treatment is anti-clotting medicine (anticoagulants) — such as heparin, enoxaparin (Lovenox), apixaban (Eliquis), dabigatran (Pradaxa), rivaroxaban (Xarelto), edoxaban (Savaysa) and warfarin (Coumadin) — given by injection or taken in tablet form. Doctors can also give medicines that dissolve clots (thrombolytics) into your bloodstream or even directly into a clot. Some people need surgery in order to inject medicine into a clot, remove a clot or place a filter in a vein to keep clots from reaching the lungs.

After the first few months of treatment for DVT or PE, the decision about whether to continue anti-clotting medicine can be complex. Venous thromboembolism experts at Fred Hutch can provide information and advice to help you decide about ongoing treatment.

The von Willebrand factor is a protein that helps blood clot. Von Willebrand disease (VWD) is the most common of all the inherited bleeding disorders, occurring in about 1 out of every 100 to 1,000 people. This disease decreases levels of this protein, or makes it work improperly, affecting your blood's ability to clot. If your blood doesn't clot, you can have heavy, hard-to-stop bleeding after an injury. The bleeding can damage your internal organs and in rare cases may be life-threatening.

Under normally circumstance, if you get a cut, you start to bleed. Small blood cells called platelets clump together (clot) to stop the bleeding. Von Willebrand factor acts like glue to help the platelets stick together and form a blood clot. Von Willebrand factor also carries another important protein, factor VIII, that helps your blood clot. People with hemophilia are missing this protein, or it doesn’t work properly. VWD is more common and usually milder than hemophilia. VWD affects both males and females, while hemophilia mainly affects males.

There are three major types of VWD. In type 1 VWD, you have a low level of the von Willebrand factor, and you may have lower levels of factor VIII than normal. This is the mildest and most common form of the disease. About 3 out of 4 people who have VWD have type 1. Type 2, the von Willebrand factor doesn’t work the way it's supposed to. Type 2 has four subtypes for the different gene mutations that cause each type. Each is treated differently. This makes knowing the exact type of VWD that you have very important. Type 3 VWD patients have no von Willebrand factor and low levels of factor VIII. Type 3 is the most serious form of VWD, but it’s very rare. Early diagnosis is important. With the right treatment plan, even people with type 3 VWD can be helped to live normal, active lives.

Waldenström macroglobulinemia (WM), also known as lymphoplasmacytic lymphoma, is one type of cancer of the lymph system.