Blood Dyscrasias: Symptoms, Causes, and Treatment

Red Blood Cell and Hemoglobin Disorders

Red blood cells may be abnormal in a number of different ways. When there are too few of them, it’s called anemia. It is also possible to have too many red blood cells, cells with abnormal structure, or cells that contain abnormal hemoglobins.

Some red blood cell disorders include:

• Nutritional deficiencies: These include iron deficiency anemia or macrocytic (large cell) anemias caused by vitamin B12 or folate deficiency.
• Aplastic anemia: In some cases, damage to bone marrow results in the production of very few red blood cells. The term aplastic means “unformed.”
• Hemolytic anemias: In these conditions, red blood cells are broken down. Cold agglutinin disease is an example of this type of condition.
• Red blood cell enzyme deficiencies: These include glucose-6-phosphate dehydrogenase deficiency and pyruvate kinase deficiency.
• Red cell membrane diseases (leading to abnormal shapes): These can be inherited or may develop later in life. They include conditions such as hereditary spherocytosis and elliptocytosis.
• Hemoglobinopathies: Hemoglobin is a protein found in red blood cells. Some hemoglobin disorders, like sickle cell disease and thalassemia, are hereditary. Others, like acquired sideroblastic anemia, can develop later in life.
• Polycythemia: An excess number of red blood cells may be hereditary, but sometimes it can occur as a response to other factors, such as lung disease, heart disease, or high altitude. This happens because the body makes more red blood cells to compensate for a lack of oxygen.

White Blood Cell Disorders

In white blood cell disorders, there may be too much or too little of all or one type of white blood cell. There could also be a normal number of abnormally functioning cells.

Some white blood cell disorders include:

• Proliferative disorders: Leukemias are cancers in which abnormal white blood cells are found primarily in the blood and bone marrow. Lymphomas involve the same cells, but they are found primarily in lymphoid tissue such as the lymph nodes. Leukemias may be acute, which means they grow quickly, or chronic, which means they grow more slowly. They may involve cells at any point in development. Myeloma and other plasma cell neoplasms involve producing too much of a type of white blood cell.
• Leukocytosis: An elevated white blood cell count is common with many types of infections. One type of white blood cell, eosinophils, is often elevated when there is a parasitic infection.
• Leukopenia: A deficiency of white blood cells may occur for many reasons. Some examples include chemotherapy, other medications that cause the destruction of white blood cells, and some infections, especially after the acute period of infection.
• Other: A few noncancerous conditions that affect white blood cells are uncommon. These conditions are often caused by a single gene mutation. Examples include myeloperoxidase (MPO) deficiency, leukocyte adhesion deficiency (LAD), hyperimmunoglobulin E syndrome (“Job syndrome”), and chronic granulomatous disease.

Platelet Disorders

Platelet disorders may be caused by too many (thrombocytosis) or too few (thrombocytopenia) platelets. They can also be caused by a normal number of platelets that function abnormally. They can be genetic or they may develop later in life.

Platelets are an essential part of the clotting process, so there is some overlap with bleeding disorders and clotting disorders.

Thrombocytopenia (a low platelet count) may be caused by:

• Decreased production of platelets. Examples include bone marrow disorders, some medications such as chemotherapy, certain viral infections, etc.
• Increased destruction of platelets. This can be caused by immune disorders such as immune thrombocytopenia (also called idiopathic thrombocytopenic purpura).
• Blood loss, such as from bleeding

Thrombocytosis (thrombocythemia) is an elevated platelet count. It can be seen with some cancers and inflammatory conditions, such as essential thrombocythemia.

Platelet disorders that affect normal functioning can be caused by liver or kidney disease. They can also be caused by inherited conditions such as Wiskott-Aldrich syndrome. These conditions may affect the ability of platelets to come together or stick together.

Bleeding Disorders

Bleeding disorders can be broken down into four major categories:

• Platelet disorders: (discussed above)
• Coagulation factor deficiencies: Coagulation factor deficiencies such as hemophilia are inherited conditions. They are caused by a deficiency of substances in the blood called clotting factors. Clotting factors are needed in order for blood to clot normally. These conditions may be rare or common and can be mild or life-threatening. Coagulation factor issues that develop later in life include liver disease, vitamin K deficiency, and conditions caused by blood thinners.
• Fibrinolytic defects: Even when a clot forms properly, it may be broken down prematurely. This happens with the medication streptokinase, a drug sometimes used for strokes or heart attacks.
• Vascular defects: Vascular defects involve bleeding from inflammation or damage to the blood vessels. These may be seen with autoimmune conditions. They may also be seen with angiogenesis inhibitors, which are cancer drugs that interfere with the growth and repair of blood vessels.

Clotting Disorders (Thrombosis)

Some types of blood dyscrasias cause the blood to clot too easily. Some of these conditions are hereditary, such as:

• Factor V Leiden mutation
• Prothrombin gene mutation
• Protein C deficiency
• Protein S deficiency
• Antithrombin deficiency
• Hyperhomocysteinemia

Others are related to conditions like:

Medications like estrogen can also cause this type of blood dyscrasia.

Bone Marrow Disorders

Diseases related to the bone marrow are another important cause of blood dyscrasias.

In some cases, the bone marrow is infiltrated with abnormal cells. This limits the production of normal blood cells and often leads to a deficiency of all blood cell types. It may be seen with:

• Blood-related cancers in the bone marrow such as leukemia and myelodysplastic syndromes
• Solid tumors, such as breast cancer, that spread to the bone marrow
• Myelofibrosis, when the bone marrow is replaced with fibrous/scar tissue
• Some connective tissue diseases

Failure of the bone marrow can occur for other reasons, too, such as:

• Medications
• Environmental exposures
• Severe infections
• Aplastic anemia

Symptoms

Many of the symptoms of blood dyscrasias are related to having too much or too little of the different types of blood cells. Symptoms can also be caused by the build-up of these cells within the lymph nodes or spleen.

Red Blood Cells

Anemia can cause a number of symptoms, including:

• Lightheadedness or fainting
• Fatigue
• Palpitations or a rapid heart rate
• Shortness of breath
• Pale skin

When red blood cells are the wrong shape, such as in sickle cell anemia, they may get “stuck” in blood vessels in various tissues. This can cause cell death and pain that is often severe.

An increase of red blood cells can result in a red facial complexion and headaches.

White Blood Cells

When white blood cells levels are low, infections may develop. Symptoms are usually related to the site of infection, such as:

• Lungs: Cough or coughing up blood, shortness of breath
• Upper respiratory tract: Sore throat, difficulty swallowing, sinus pain, nasal drainage
• Urinary tract: Pain with urination, frequency of urination
• Abdomen: Nausea, vomiting, or diarrhea, abdominal pain
• Central nervous system: Headaches, neck stiffness, confusion

Platelets

Depending on the severity, a low level of platelets can also cause symptoms. These may include:

• Bruising
• Red dots on the skin that don’t blanch with pressure (petechiae)
• Nosebleeds
• Heavy menstrual periods
• Bleeding from the bladder or with bowel movements

Bleeding Disorders

The symptoms of bleeding disorders overlap with platelet conditions. Specific symptoms often depend on the severity of the disease. If the condition is mild, you may notice increased bleeding after surgery or dental procedures. With more serious disorders you may have spontaneous bleedings.

Clotting Disorders

Risk factors for blood clots include bed rest, recent surgery, cancer, travel, and more. Sometimes blood clots occur without these risk factors in someone who is otherwise healthy and has not been sedentary. When this happens, your healthcare provider will consider the possibility of a clotting disorder.

Bone Marrow Disorders and Malignancies

Bone marrow disorders may affect all types of blood cells. Symptoms of these conditions can be similar to those of blood cell disorders. Blood-related cancers may produce symptoms such as:

Other Symptoms

A wide range of symptoms may be seen with different blood dyscrasias. Many of these are not obvious. A few examples include:

• Pica: Pica is the desire to eat non-food items, like dirt, hair, or paint chips. Children who have iron deficiency anemia indeed sometimes eat dirt, presumably because of an instinctual craving for iron.
• Pagophagia: Pagophagia is a craving for ice. This is a more common symptom of iron deficiency than pica.
• Neurological symptoms: When you have a vitamin B12 deficiency, you may develop anemia and symptoms that are similar to those of multiple sclerosis.

Diagnosis

Blood dyscrasias are often diagnosed with multiple steps. These depend on symptoms, family history, physical findings, and more. A blood dyscrasia is often suspected when a person sees a primary care provider.

A workup may be started with your healthcare provider, or you may be referred to a hematologist/oncologist. A hematologist is a physician who specializes in the diagnosis of blood dyscrasias, whether benign or cancerous.

Your healthcare provider will start by asking you about your family and medical history, symptoms, medications, and possible exposures. Make sure to mention anything abnormal in your history, such as heavy menstrual periods.

During your medical exam, your healthcare provider will evaluate your lymph nodes and look for signs of blood dyscrasias like pale skin or bruising. After the initial exam, you may be referred for testing.

Tests to Evaluate Blood Dyscrasias

• Complete blood count (CBC): This test provides the number of red blood cells, white blood cells, and platelets present. A differential will show the proportion of different types of white blood cells in your blood. A larger-than-normal number of immature white blood cells may suggest a serious infection or blood-related cancer.
• Blood cell indices: This test can be very helpful for learning more about your blood cells. For example, small red blood cells tend to be seen with iron deficiency anemia, whereas red blood cells tend to be large with anemia related to vitamin B12 deficiency.
• Reticulocyte count: A reticulocyte count is used to find the cause of anemia. For example, it can help your healthcare provider determine whether your anemia is caused by decreased production of red blood cells or increased breakdown of cells.
• Peripheral blood smear for morphology: This is an extremely important test that may note abnormal findings in any of the types of blood cells. It can also detect the presence of cells not ordinarily found in the bloodstream.

Supplemental Tests

Based on your CBC results, other tests may be recommended:

• Hemoglobin electrophoresis, to look for thalassemias
• Iron studies, such as serum iron, iron binding capacity, or serum ferritin
• Vitamin B12 and folic acid levels

Evaluation of Bone Marrow

A bone marrow biopsy and aspiration can provide a lot of information about the health of the bone marrow. This test is essential in diagnosing some types of leukemia. When cancer is suspected, further tests such as biomarker testing will be done on the cells.

Coagulation Studies

Your history and physical exam may provide clues as to whether you have a platelet disorder or another type of bleeding disorder.

Tests to evaluate platelet function may include:

• Bleeding time
• Platelet function assay
• Platelet aggregation testing

Coagulation studies may include a prothrombin time (and INR) and partial thromboplastin time. If a clotting factor abnormality is suspected, specific testing will be done.

If your healthcare provider suspects your blood clots more easily than usual, you may be referred for tests such as:

• Antiphospholipid antibodies
• Protein C activity
• Homocysteine levels

Treatment

The treatment of blood dyscrasias depends on the cause. Sometimes it’s sufficient to just treat the underlying condition. Other times, a deficiency in blood cells or the absence of clotting factors will need to be treated directly.

For severe anemia, a blood transfusion may be needed until the underlying cause can be addressed. If your platelet count is very low, platelet transfusions may be needed to stop or prevent bleeding.

If you have a very low white blood cell count, you may be prescribed a medication that stimulates the production of white blood cells. Since the most important complications related to a low white count are infections, it’s also important to take steps to reduce infections.

Clotting disorders require treatments that help reduce the risk of clotting. Bleeding disorders require treatments that help the blood clot. Fresh frozen plasma and/or replacement of missing clotting factors are also often needed.