What Are Blood Dyscrasias?

The term "blood dyscrasia" is used frequently by physicians but can be confusing (and sometimes alarming) to patients. In general, it is a non-specific term that can refer to any blood-related disease. That said, it tends to be used when a diagnosis is uncertain (during diagnosis) or in specific situations.

Blood dyscrasias are medical conditions (hematologic disorders) that may affect the cellular or plasma components of the blood, the bone marrow, or the lymph tissue. Examples of blood dyscrasias include anemias, cancers such as leukemias and lymphomas, conditions that cause the blood to clot or bleed too readily, and more.

Blood dyscrasias may be common or uncommon, malignant (cancerous) or benign, and range from conditions that are very mild or asymptomatic, to those that are life-threatening. We will look at causes or mechanisms responsible for blood dyscrasias, the different types, common symptoms, and what you may expect when it comes to diagnosis and treatment.

Definition and Basics

The medical term blood dyscrasia literally means "bad mixture," and can be traced back to the Greek physician Galen (A.D. 130 to 199). At that time, this bad mixture (dyscrasia) was felt to be an imbalance in the four body humors—blood, black bile, yellow bile, and water. When these humors were all in balance, the term used was "eucrasia."

When is The Term Blood Dyscrasia Used in Medicine?

Part of the confusion surrounding the term blood dyscrasias is that it is used in a number of different and conflicting ways.

Collectively: Sometimes the term is used to describe any disorder of the blood, bone marrow, clotting proteins, or lymph tissue. In clinical trials, the term may be used to describe any side effect related to an investigational drug that affects these tissues.

When a diagnosis is uncertain: Often times the term blood dyscrasia is used during the process of diagnosis before a precise diagnosis is made. In this case, the term implies that a disorder involves the blood in some way, but further work-up is needed.

When risk factors may be present (especially with clotting disorders): The term may also be used when a workup for risk factors is needed, for example, to look for underlying causes of blood clots. In this case, it may imply that a physician suspects an underlying condition (such as factor V Leiden) in a person who has blood clots or a stroke without an obvious predisposing condition.

With specific concerns: The term blood dyscrasia is sometimes used very specifically. For example, it may be used to describe blood conditions related to an adverse drug reaction, or a specific diagnostic category, such as plasma cell dyscrasias.

Blood Components

Before looking at specific diagnoses, it's helpful to look at the components of blood and lymph tissues. Blood is made up of both plasma (the liquid component) and cells.

Cells

There are three types of blood cells (or parts of cells) found circulating in the blood.

Red blood cells (RBCs) are responsible for picking up oxygen in the lungs and transporting it to all of the cells in the body.

White blood cells (WBCs) function as the body's first defense against infections with bacteria, viruses, and parasites. There are two primary categories of white blood cells.

• The lymphoid cell line includes T and B lymphocytes (T cells and B cells) and natural killer cells
• The myeloid cell line includes neutrophils, basophils, and eosinophils

Platelets (thrombocytes) are important in blood clotting (along with clotting factors). Platelets accumulate at the site of an injury to the skin or a blood vessel and are the platform upon which a clot forms during coagulation.

Plasma

Plasma accounts for around 55% of the blood volume and contains a number of different substances, including:

• Clotting proteins, such as fibrinogen, thrombin, and clotting factors such as von Willebrand factor (vWF) and Factor VIII
• Albumin
• Immunoglobulins (antibodies) to fight infections
• Electrolytes
• Hormones
• Nutrients
• Waste products

Bone Marrow

Bone marrow is distributed within large bones such as the iliac crest and sternum. It is the site where blood cells are "born and raised" before entering the circulation and tissues of the body.

All of the different types of blood cells are all derived from a single type of "progenitor" cell in the bone marrow called a hematopoietic stem cell. In a process called hematopoiesis these "pluripotential cells" differentiate into the different types of cells.

Within the bone marrow, cells at all stages of differentiation are present (for example, a neutrophil begins as a promyelocyte, then becomes a myelocyte, a metamyelocyte, a band neutrophil, and finally a mature neutrophil).

Ordinarily, these younger forms of white blood cells (with the exception of some bands) are not seen in the blood other than in some forms of leukemia, myelodysplastic disorders, and severe infections.

Lymphoid Tissue

It is important to include lymphoid tissue such as the lymph nodes and spleen as they may be involved in a number of blood dyscrasias.

Causes

The causes of blood dyscrasias are not always known. When this is the case, physicians often use the term idiopathic, which essentially means the cause is uncertain or even totally unknown at the time. Causes and risk factors can fall into several categories which sometimes overlap.

Malignancies

Cancers, such as leukemias, lymphomas, and multiple myeloma are characterized by the out-of-control growth of one of the types of white blood cells. This can lead to problems related to the specific type of cell, but may also affect other blood cells, such as when leukemic cells crowd the bone marrow resulting in lower production of other types of blood cells.

Drug-Induced

Adverse drug reactions are a very common cause of blood dyscrasias and may occur with both prescription and illicit drugs as well as vitamin and nutritional supplements. These reactions may occur by a number of several different mechanisms.

Environmental Exposures

There are a number of exposures in the environment that may result in blood dyscrasias, such as certain chemicals and radiation.

Infections

Blood cells are not only important in fighting infections, but may be damaged by infections as well.

Vitamin and Mineral Deficiencies

A deficiency in essential nutrients may interfere with the proper formation of blood cells. Examples include anemias caused by iron, vitamin B12, or folate deficiencies.

Autoimmune

Autoimmune conditions may result in antibodies that are directed against different blood cells.

Genetics

Genetics can play a role win blood dyscrasias through either specific gene mutations (such as sickle cell disease) or a hereditary predisposition (such as with some cases of B12 deficiency anemia).

Combination

A combination of the above causes may result in a single type of blood dyscrasia. For example, aplastic anemia may occur due to viral infections, medications, exposure to chemicals or radiation, and more.

Types and Classification

Blood dyscrasias can be broken down into a number of different categories. There are many ways in which this is done, but is often easiest to understand by looking at a few specific cell types and mechanisms.

Some conditions affect only one type of blood cell, and commonly involve either an increase or a decrease in the type of blood cell. If all the major types of blood cells are affected, it is referred to as pancytopenia.

The suffix "cytosis" (or "philia") refers to an excess of a type of blood cell, while "penia" refers to a reduced level of the cell.

Terminology for an Increase or Decrease in Blood Cells
Cell type	Excess	Deficiency
Red blood cells	Erythrocytosis or polycythemia	Anemia
White blood cells	Leukocytosis	Leukopenia
Platelets	Thrombocytosis	Thrombocytopenia

These principles can be followed with more specific cells as well. For example, an excess number of neutrophils would be called neutrophilia and a reduced number of neutrophils would be called neutropenia.

Red Blood Cell and Hemoglobin Disorders

Red blood cells may be abnormal in a number of different ways. In addition to an excess or deficiency, red cells may structurally abnormal or contain abnormal hemoglobins. When a low number of red blood cells are present (anemia) it may be due to decreased production, increased destruction, loss (such as with bleeding), or redistribution.

Some red blood cell disorders include:

• Nutritional deficiencies: These include iron deficiency anemia or macrocytic (large cell) anemias due to vitamin B12 or folate deficiency.
• Hemoglobinopathies: Hemoglobin disorders (disorders in either heme or globin) may be hereditary, such as with sickle cell disease or thalassemia, or acquired, such as with sideroblastic anemia.
• Aplastic anemia: In some cases, very few red blood cells are produced due to damage to the bone marrow. The term aplastic refers to "absence of."
• 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 hereditary or acquired, and include conditions such as hereditary spherocytosis and elliptocytosis.
• Hemolytic anemias: In these conditions, red blood cells are broken down, such as with cold agglutinin disease.
• Polycythemia: An excess number of red blood cells may be hereditary, or occur secondarily as a response to high altitude, lung disease, and more (the body makes more red blood cells to compensate for a lack of oxygen). An example is polycythemia vera.

White Blood Cell Disorders

White blood cell disorders may also include an excess or deficiency of all or one type of white blood cell as well as abnormal functioning of a normal number. Some white blood cell disorders include:

• Proliferative disorders: Leukemias are cancers in which cancerous white blood cells are found primarily in the blood and bone marrow, whereas lymphomas involve the same cells but primarily in lymphoid tissue (eg. lymph nodes). Leukemias may be acute or chronic, and may involve cells at any point in development from blasts to mature white blood cells.
• Leukocytosis: An elevated white blood cell count is common with many types of infections. One type of white blood cell, eosinophils, is often elevated with parasitic infections.
• Leukopenia: A deficiency of white blood cells may occur for many reasons, such as due to chemotherapy, other medications that result in destruction of white blood cells, and with some infections (especially after the acute period of infection).
• Other: There are a number of non-cancerous conditions that may affect white blood cells that are uncommon (and often hereditary due to a single gene mutation). Examples include MPO and LAD deficiency, Job syndrome, and chronic granulomatous disease.

Platelet Disorders

Platelet disorders may also be related to an excess (thrombocytosis) or deficiency (thrombocytopenia) of platelets or abnormal functioning of a normal number of platelets, and may be either hereditary or acquired. Since platelets are an essential part of the clotting process, there is some overlap with bleeding disorders and clotting disorders.

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

• Decreased production of platelets (with bone marrow disorders, some medications such as chemotherapy, some viral infections, etc)
• Increased destruction of platelets (with immune disorders (immune thrombocytopenia) such as idiopathic thrombocytopenic purpura)
• Loss (such as with bleeding)
• Sequestration (seen with an enlarged spleen due to alcoholic liver disease, etc.)

Thrombocytosis (thrombocythemia), an elevated platelet count, can be seen with some cancers and inflammatory conditions, but may also be hereditary, such as with essential thrombocythemia.

Platelet disorders that affect normal functioning can be caused by liver or kidney disease, as well as inherited conditions such as Wiskott-Aldrich syndrome. These conditions may affect the ability of platelets to come together (aggregate) or stick together (adhesion defects), as well as other mechanisms.

Bleeding Disorders

Bleeding disorders may be broken down into four major categories:

• Platelet disorders (discussed above)
• Coagulation factor deficiencies
• Fibrinolytic defects
• Vascular defects

Coagulation factor deficiencies, such as hemophilia, result from a hereditary deficiency in clotting factors that are needed in order for blood to clot normally. These may be rare or common and be mild or life-threatening. These can involve a deficiency in:

• Fibrinogen (afibrogenemia)
• Factor V (parahemophilia)
• Factor VII
• Factor VIII (hemophilia A)
• Factor IX (hemophilia B)
• Factor X
• Factor XI (Rosenthal's syndrome)
• Factor XII
• Factor XIII
• von Willebrand's factor (von Willebrand disease), a common condition affecting up to 1% of the US population

Clotting factor issues may also be acquired, as with liver disease, vitamin K deficiency, and the use of blood thinners.

Even when a clot forms properly, it may be broken down prematurely (fibrinolytic defects). This is seen with the medication streptokinase (the "clot" busting drug sometimes used with strokes or heart attacks) or in a condition known as disseminated intravascular coagulation (DIC).

DIC is a dreaded complication most often seen in people who are seriously ill. It involves a combination of both bleeding and clotting at the same time, making it challenging to treat.

Vascular defects involve bleeding as a result of inflammation or damage to the blood vessels. These may be seen with autoimmune conditions, or with the use of angiogenesis inhibitors, which are drugs used for cancer that interfere with the growth and repair of blood vessels.

Clotting Disorders (Thrombosis)

Instead of bleeding, some blood dyscrasias cause the blood to clot too easily. These conditions may be hereditary, or instead related to conditions such as cancer, kidney disease, medications such as estrogen, or autoimmune conditions, such as antiphospholipid syndrome.

Some hereditary clotting disorders include:

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

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, thus limiting the production of normal blood cells. This often leads to a deficiency of all of the types of blood cells (pancytopenia), and may be seen with:

• Blood-related cancers (eg. leukemia and myelodysplastic syndromes) in the bone marrow
• 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 due to medications, environmental exposures, severe infections, and other causes may also occur, such as with aplastic anemia.

Symptoms

Many of the symptoms related to blood dyscrasias are related to an excess or deficiency of the different types of blood cells or due to build-up of these cells within the lymph nodes or spleen.

Red Blood Cells

The most common symptoms related to blood cells occur when anemia is present (a reduced number of red blood cells or a low hemoglobin level). Symptoms of anemia can include lightheadedness or fainting (syncope), fatigue, palpitations or a rapid heart rate, shortness of breath, and pale skin.

When red blood cells are malformed (for example, with sickle cell anemia) they may get "stuck" in blood vessels in various tissues, causing cell death and subsequent pain (often severe).

An increase of red blood cells (and subsequent increase in blood viscosity) can result in a red facial complexion and headaches.

White Blood Cells

When levels of the various white blood cells 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

A low level of platelets (thrombocytopenia) can cause symptoms depending on the severity. These may include:

• Bruising (ecchymosis)
• 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 and depend on the severity of the disease. With mild conditions, people may notice increased bleeding after surgery or dental procedures, With more serious disorders, spontaneous bleedings, such as into joints may occur.

Clotting Disorders

Risk factors for blood clots include bed rest, recent surgery, cancer, travel, and more. When blood clots occur without these risk factors, such in someone who is otherwise healthy and has not been sedentary, the possibility of a clotting disorder is often considered.

Bone Marrow Disorders and Malignancies

Since bone marrow disorder may affect all types of blood cells, symptoms related to all of these may be present. Blood-related cancers are an important cause, and may include symptoms such as:

• Enlarged lymph nodes
• Night sweats
• Fever of unknown origin
• An enlarged spleen and/or liver
• Unintentional weight loss

Other Symptoms

There is a wide range of symptoms that may be seen with different blood dyscrasias, and many of these may not seem obvious. A few examples include:

• Pica: Pica is translated as meaning to "eat dirt" and children who have iron deficiency anemia indeed sometimes eat dirt, presumably due to an instinctual iron craving.
• Neurological symptoms: With vitamin B12 deficiency, in addition to developing anemia people may have symptoms that can be indistinguishable from multiple sclerosis.

Diagnosis

The diagnosis of blood dyscrasias may involve a number of steps depending on symptoms, family history, physical findings, and more. A blood dyscrasia is often suspected when a person sees a primary care physician.

A work-up may be started with your family doctor or internist, or you may instead be referred to a hematologist/oncologist. A hematologist is a physician who specializes in the diagnosis of blood dyscrasias, whether benign or cancerous.

History

The diagnosis of blood dyscrasias begins with a careful history, with questions regarding symptoms, potential exposures, medications, past medical history, and family history.

Sometimes early symptoms of blood dyscrasias (such as heavy menstrual periods) may be overlooked, and it's important to mention anything in your history that seems abnormal to you.

Physical Examination

Symptoms of blood dyscrasias such as pale skin or bruising may be noted. A careful evaluation of lymph nodes (not only those in your neck, but those under your collarbone and in your armpits) will be done as well.

Evaluation of Blood Cells

The initial evaluation of most blood dyscrasias begins with an examination of a blood sample. A complete blood count (CBC) will provide the number of red blood cells, white blood cells, and platelets present, and a differential will also indicate 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 can be very helpful for learning more about 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. Indices include:

• Mean corpuscular volume (MCV)
• Mean corpuscular hemoglobin concentration (MCHC)
• Red cell distribution width (RDW)
• Mean platelet volume (MPV)

A reticulocyte count can be very helpful in evaluating different causes of anemia, for example, whether it is due to decreased production of red blood cells or increased breakdown of an adequate number of cells.

An extremely important test is a peripheral blood smear for morphology. This test may note abnormal findings in any of the types of blood cells or the presence of cells not ordinarily found in the bloodstream.

Supplemental Tests

Based on a CBC, other tests that may be recommended include:

• 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, and is essential in diagnosing some types of leukemia. When a cancer is suspected, further tests (such as biomarker testing) will be done on the cells.

Coagulation Studies

If a bleeding disorder is suspected, your doctor may have clues from your history and physical exam as to whether you may have a platelet disorder or another type of bleeding disorder.

Tests to evaluate platelet function may include bleeding time, a platelet function assay, and 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 (such as Von Willebrand factor antigen) will be done.

If, on the other hand, your doctor suspects that your blood clots more easily than usual, she may recommend tests such as antiphospholipid antibodies, protein C activity, homocysteine levels, and more.

Treatment

The treatment of blood dycrasias depends on the cause. Sometimes treating the the underlying condition alone will be a solution, whereas other times, a deficiency in blood cells or 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. Platelet transfusions may be needed to stop or prevent bleeding if your platelet count is very low.

With a very low white blood cell count, a medication that stimulates the production of white blood cells (such as Neulasta) may be needed. Since the most important complications related to a low white count are infections, taking measures to reduce infection risk is critical.

Certainly, treatments that help the blood clot (in the case of bleeding disorders) or help reduce the risk of clotting (with clotting disorders) are important. With bleeding disorders, fresh frozen plasma and/or replacing missing clotting factors is often needed.

A Word From Verywell

If your doctor believes you have a blood dyscrasia, you may be feeling anxious as well as downright impatient. Diagnosing a blood dyscrasia can take time and is sometimes similar to putting together a large jigsaw puzzle (but without a picture).

Make sure to ask a lot of questions so that you understand why any recommended tests are being done. With such a diverse array of conditions and causes, many doctors are hesitant to bring up all possibilities, especially worst-case scenarios. Yet our minds sometimes fill in answers by going straight to those possibilities.

Learning about your condition can not only help you feel more in control of your journey, but may even help you recall important symptoms that could otherwise be easily overlooked.