209 Blood Diseases and Disorders

Hemostasis Disorders

The most common blood disorders involve defects in the amount or activity of factors involved in coagulation.

Learning Objectives

Differentiate among the hemostasis disorders of Von Willebran disease, hemophilia, and factor V Leiden thrombophilia

Key Takeaways

Key Points

  • Von Willebrand disease is the most common inherited bleeding disorder. People with type 1 and type 2 von Willebrand disease may have mild-to-moderate bleeding symptoms, while those with type 3 can have severe bleeding episodes.
  • Hemophilia is a disease where there is a low level of, or are no, blood proteins important for clotting, causing an inability to produce blood clots. There are two types: Type A, which is a deficiency in factor VIII, and Type B, also known as Christmas disease, which is a deficiency in factor IX.
  • The opposite of hemophilia is Factor V Leiden thrombophilia, a disorder of human factor V blood protein that causes a hypercoagulability disorder or overactive clotting resulting in dangerous blood clots.
  • In sickle- cell disease, red blood cells undergo a change in shape upon deoxygenation because of polymerization of the abnormal sickle hemoglobin.
  • Polycythemia is a condition in which there is a net increase in the total circulating erythrocyte (red blood cell).
  • Leukemia is a cancer of the blood or bone marrow characterized by an abnormal proliferation of blood cells, usually white blood cells (leukocytes).

Key Terms

  • Hemophilia: A group of hereditary genetic disorders that impair the body’s ability to control blood clotting or coagulation, which is used to stop bleeding when a blood vessel is broken.
  • coagulation: The process by which blood forms solid clots.
  • thrombophilia: The tendency to develop thrombosis (blood clots) due to an abnormality in the system of coagulation.

The most common blood disorders, Von Willebrand disease, hemophilia, and Factor V Leiden thrombophilia, all involve defects in the amount or activity of factors involved in coagulation.

Von Willebrand Disease

Von Willebrand disease is the most common inherited bleeding disorder, and it affects both men and women equally. Von Willebrand disease is similar to hemophilia in that it involves a deficiency in the ability of blood to clot properly. Those affected by von Willebrand disease will have low levels of von Willebrand factor, a protein that helps the blood to clot, and/or their von Willebrand factor does not work properly.

There are three types of von Willebrand disease: type 1, type 2, and type 3. People with type 1 and type 2 von Willebrand disease may have the following mild-to-moderate bleeding symptoms: easy bruising, nosebleeds, bleeding from the gums after a dental procedure, heavy menstrual bleeding in women, blood in their stools or urine, and excessive bleeding after a cut or other accident or surgery.

Type 1 von Willebrand disease is the mildest and most common form of the disease. In this type of disease, there is a low level of von Willebrand factor. The level of factor VIII, another protein involved in clotting, may also be lower than normal. About 3 out of 4 people diagnosed with von Willebrand disease have type 1.

Type 2 von Willebrand disease has four subtypes and ranges from mild to moderate in severity. In this type of disease, there is a defect in von Willebrand factor resulting in improper activity.

Type 3 von Willebrand disease is very rare and is the most severe form. In this type of disease, individuals usually do not produce von Willebrand factor and have very low levels of factor VIII. Symptoms of type 3 von Willebrand disease might include any of the symptoms of types 1 and 2 and also include severe bleeding episodes for no reason, which can be life threatening if not treated immediately. Bleeding into soft tissues or joints causing severe pain and swelling is another symptom.

Many people with von Willebrand disease do not require treatment to manage the disease. However, if treatment is necessary, it may include a range of different interventions depending on the severity. These involve medicine to increase the level of von Willebrand factor in the blood, medicine to prevent the breakdown of clots, medicine to control heavy menstrual bleeding in women, or injection of clotting factor concentrates.


Hemophilia is a disease where there is a low levels of, or none, of a blood protein important for clotting, causing an inability to produce blood clots. There are two types of hemophilia: Type A, which is a deficiency in factor VIII, and Type B, also known as Christmas disease, which is a deficiency in factor IX. Since people with hemophilia do not have the ability to make blood clots, even a small cut can result in severe bleeding, or the smallest bump or jar to the body could cause severe bruising that does not heal for months. Hemophilia is a recessive, sex-linked inheritable disorder, which is more common in men than women. Treatment typically involves replacement of the missing blood factors through blood transfusions.

This is a diagram of how hemophilia is passed from parents to children. An unaffected father and carrier mother can have an unaffected son, an unaffected daughter, a carrier daughter, and/or an affected son.

Inheritance of X-linked Recessive Traits: Hemophilia is an x-linked recessive inheritable disorder.

Since the 1980s, the primary leading cause of death of people with severe hemophilia has shifted from hemorrhage to HIV/AIDS acquired through treatment with contaminated blood products. The second leading cause of death related to severe hemophilia complications is intracranial hemorrhage, which today accounts for one-third of all deaths of patients with hemophilia.

Factor V Leiden Thrombophilia

The opposite of hemophilia, is Factor V Leiden thrombophilia, a disorder of human factor V blood protein that causes a hypercoagulability disorder, or, overactive clotting, resulting in dangerous blood clots. In this disorder, the Leiden variant of factor V cannot be inactivated by activated protein C, as it would be in a person with normal factor V, resulting in excess clotting. Factor V Leiden is the most common hereditary hypercoagulability disorder among Eurasians. Those that have it are at a slightly higher risk of developing blood clots than those without. Those that test positive for factor V should avoid oral contraceptives, obesity, smoking, and high blood pressure to reduce their risk of developing blood clots.


Blood clot diagram.: Blood clot diagram.


Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood resulting in tissue hypoxia.

Learning Objectives

Distinguish among the types of anemia

Key Takeaways

Key Points

  • The three main classes of anemia include anemia due to hemorrhage (excessive blood loss), hemolysis (blood cell destruction), or ineffective hematapoiesis (deficient red blood cell production).
  • Symptoms of anemia include fatigue, malaise, heart enlargement, and impaired concentration.
  • Anemia may be diagnosed using a complete blood count (CBC) and/or reticulocyte counts.
  • A “kinetic” approach analyzes decreased RBC production vs. increased RBC destruction or loss.
  • Iron deficiency anemia is the most common type of anemia and is particularly common in infants, toddlers, and pregnant women who have above-average needs for iron. It is treated with iron supplements.
  • Severe anemia with blood loss may be treated with transfusions, but these come with their own adverse outcomes.

Key Terms

  • hematopoiesis: The process by which blood cells are produced; hematogenesis.
  • reticulocyte: An immature red blood cell, having a reticular network of RNA.
  • complete blood count (CBC): A test panel requested by a doctor or other medical professional that gives information about the cells in a patient’s blood.


At the beginning of the 20th century, hookworm infection was a major and severe problem in the southern United States. Hookworms mature in the small intestine where they bite into the villi of the small intestine and drink blood causing severe anemia. Individuals suffering from hookworm are lethargic, have trouble focusing, and do not appear to be very intelligent. Many negative stereotypes of the South are based on individuals suffering from hookworm. When the Rockefeller Foundation provided funding to purge the worms from these individuals and to build outhouses so that they would not be re-infected, these Southerners became bright, energetic, and able to focus on school and work.

Anemia is a decrease in number of red blood cells (RBCs), or less than the normal quantity of hemoglobin in the blood. It can include the decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin deficiencies.

Because hemoglobin (found inside RBCs) normally carries oxygen from the lungs to the tissues, anemia leads to hypoxia (lack of oxygen) in organs. Since all human cells depend on oxygen for survival, varying degrees of anemia can have a wide range of clinical consequences.

Types of Anemia

Anemia is the most common disorder of the blood. There are several kinds, produced by a variety of underlying causes. It can be classified in a variety of ways, based on the morphology of RBCs, underlying etiologic mechanisms, and discernible clinical spectra, to mention a few.

The three main classes of anemia include excessive blood loss (acutely, such as a hemorrhage or chronically, through low-volume loss), excessive blood cell destruction (hemolysis), or deficient red blood cell production (ineffective hematopoiesis).

Signs and Symptoms

Anemia goes undiagnosed in many people, as symptoms can be minor or vague. The signs and symptoms can be related to the anemia itself, or the underlying cause. Most commonly, people report non-specific symptoms of a feeling of weakness, or fatigue, general malaise, and, sometimes, poor concentration. They may also report dyspnea (shortness of breath) on exertion.

In very severe anemia, the body may compensate for the lack of oxygen-carrying capability of the blood by increasing cardiac output. This would result in symptoms such as palpitations, angina (if preexisting heart disease is present), intermittent claudication of the legs, and symptoms of heart failure.

This image displays different parts of the body along with the symptoms of anemia in that part of the body. For example, the symptoms of anemia in the skin are yellowing, coldness, and paleness.

Symptoms of Anemia: Image displays the common symptoms of anemia.


Anemia is typically diagnosed on a complete blood count. Apart from reporting the number of red blood cells and the hemoglobin level, the automatic counters also measure the size of the red blood cells by flow cytometry, which is an important tool in distinguishing between the causes of anemia.

Examination of a stained blood smear using a microscope can also be helpful and is sometimes a necessity in regions of the world where automated analysis is less accessible. Reticulocyte counts, and the “kinetic” approach to anemia, have become more common than in the past in the large medical centers of the United States and some other wealthy nations; in part, because some automatic counters now have the capacity to include reticulocyte counts. This is a quantitative measure of the bone marrow ‘s production of new red blood cells. The reticulocyte production index is a calculation of the ratio between the level of anemia and the extent to which the reticulocyte count has risen in response.

If the degree of anemia is significant, even a “normal” reticulocyte count actually may reflect an inadequate response.

In the morphological approach, anemia is classified by the size of red blood cells. This either done automatically or on microscopic examination of a peripheral blood smear. The size is reflected in the mean corpuscular volume (MCV). This scheme quickly exposes some of the most common causes of anemia. For instance, a microcytic anemia (smaller than usual red blood cells) is often the result of iron deficiency.

In clinical workup, the MCV will be one of the first pieces of information available; so even among clinicians who consider the “kinetic” approach more useful philosophically, morphology will remain an important element of classification and diagnosis.

Iron Deficiency Anemia

This is the most common type of anemia overall and it has many causes. Iron is an essential part of hemoglobin, and low iron levels result in decreased incorporation of hemoglobin into red blood cells. It is due to insufficient dietary intake or absorption of iron to meet the body’s needs. Infants, toddlers, and pregnant women have higher-than-average needs. Increased iron intake is also needed to offset blood losses due to digestive tract issues, frequent blood donations, or heavy menstrual periods.

In the United States, the most common cause of iron deficiency is bleeding or blood loss, usually from the gastrointestinal tract. Fecal occult blood testing, upper endoscopy, and lower endoscopy should be performed to identify bleeding lesions. In older men and women, the chances are higher that bleeding from the gastrointestinal tract could be due to colon polyp or colorectal cancer.

Worldwide, the most common cause of iron deficiency anemia is parasitic infestation (hookworm, amebiasis, schistosomiasis, and whipworm).

Sickle-Cell Disease

Sickle-cell disease is an autosomal recessive genetic blood disorder in which red blood cells assume a rigid sickle shape.

Learning Objectives

List the ways in which sickle-cell disease can present in affected individuals

Key Takeaways

Key Points

  • Sickle-cell disease is common in tropical and sub-tropical regions because being a carrier, carrying a single sickle-cell mutation (sickle cell trait), affords some resistance to malaria.
  • Sickle cell crisis, an acute condition occurring in patients with sickle-cell disease, include: vaso-occlusive crisis, splenic sequestration crisis, aplastic crisis, and hemolytic crisis.
  • Complications from sickle-cell disease include stoke and silent stroke, decreased immunity due to hypersplenism, avascular necrosis of joints, chronic renal failure, and pulmonary hypertension.
  • Sickle-cell disease is often diagnosed with hemoglobin levels from a complete blood count and detection of sickling of the red blood cells.

Key Terms

  • fitness: A central idea in evolutionary biology; describes the ability to both survive and reproduce.
  • tachycardia: A rapid resting heart rate, especially one above 100 beats per minute.


In the United States, sickle cell trait is most common among African Americans. However, anyone with ancestors from malarial zones should undergo genetic screening for sickle cell trait prior to pregnancy. This includes Southerners of European ancestry both because some of their ancestors may have come from circum-Mediterranean malarial zones, but also because recent DNA analysis has shown that a significant percentage have African ancestry. This is not surprising since those of African descent formed the largest population segment in the South for 200 or 300 years.

Sickle-cell disease (SCD), or sickle-cell anemia, is an autosomal recessive genetic blood disorder with overdominance characterized by red blood cells that assume an abnormal, rigid, and sickle shape. Sickling decreases the cells’ flexibility and results in a risk of various complications, including shortened life expectancy. It is caused by a change in hemoglobin’s primary structure.


Sickle cell anemia is caused by a change in hemoglobin’s primary structure: This scanning electron micrograph shows red blood cells. Some exhibit the normal donut-shaped morphology while others exhibit the sickle shape characteristic of those with sickle-cell trait or sickle-cell disease.

Disease Presentation

Sickle-cell disease, usually presenting in childhood, occurs more commonly in people (or their descendants) from parts of tropical and sub-tropical regions where malaria is or was common. One-third of all indigenous inhabitants of Sub-Saharan Africa carry the gene because, in areas where malaria is common, there is a fitness benefit in carrying only a single sickle-cell gene (sickle cell trait). Those with only one of the two alleles of the sickle-cell disease, while not totally resistant, are more tolerant to malarial infection and show less severe symptoms when infected. The prevalence of the disease in the United States is approximately 1 in 5,000, mostly affecting Americans of Sub-Saharan African descent, according to the National Institutes of Health. In the United States, about 1 out of 500 African-American children born will have sickle-cell anemia.

The term “sickle cell crisis” is used to describe several independent acute conditions occurring in patients with sickle cell disease. Sickle cell disease results in anemia and several types of crises. Most episodes of sickle cell crises last between five and seven days. The vaso-occlusive crisis is caused by sickle-shaped red blood cells that obstruct capillaries and restrict blood flow to an organ, resulting in ischaemia, pain, necrosis, and often organ damage. The frequency, severity, and duration of these crises vary considerably. Because of its narrow vessels and function in clearing defective red blood cells, the spleen is frequently affected in splenic sequestration crisis. This autosplenectomy increases the risk of infection from encapsulated organisms. Preventative antibiotics and vaccinations are recommended for those with such asplenia. Aplastic crises are acute worsenings of the patient’s baseline anemia producing pallor, tachycardia, and fatigue. This crisis is triggered by parvovirus B19, which directly affects erythropoiesis (production of red blood cells) by invading the red cell precursors and multiplying in them and destroying them. Parvovirus infection nearly completely prevents red blood cell production for two to three days. In normal individuals, this is of little consequence, but the shortened red cell life of sickle-cell patients results in an abrupt, life-threatening situation. Hemolytic crises are acute accelerated drops in hemoglobin level. The red blood cells break down at a faster rate. This is particularly common in patients with co-existent G6PD deficiency. Management is supportive, sometimes with blood transfusions.

Diagnosis and Prevention

Sickle cell can be diagnosed by a blood test. In HbSS, the full blood count reveals hemoglobin levels in the range of 6–8 g/dL with a high reticulocyte count (as the bone marrow compensates for the destruction of sickle cells by producing more red blood cells). In other forms of sickle-cell disease, Hb levels tend to be higher. Abnormal hemoglobin forms can also be detected on hemoglobin electrophoresis, a form of gel electrophoresis on which the various types of hemoglobin move at varying speeds.

People who are known carriers of the disease often undergo genetic counseling before they have a child. A test to see if an unborn child has the disease takes either a blood sample from the fetus or a sample of amniotic fluid. Since taking a blood sample from a fetus has greater risks, the latter test is usually used. Children born with sickle-cell disease will undergo close observation by the pediatrician and will require management by a hematologist to assure they remain healthy. These patients will take a 1 mg dose of folic acid daily for life. From birth to five years of age, they will also have to take penicillin daily due to the immature immune system that makes them more prone to early childhood illnesses.


Sickle-cell disease: This image shows normal red blood cells flowing freely in a blood vessel. The inset image shows a cross-section of a normal red blood cell with normal hemoglobin. Figure B shows abnormal, sickled red blood cells blocking blood flow in a blood vessel. The inset image shows a cross-section of a sickle cell with abnormal (sickle) hemoglobin forming abnormal strands.


Leukemia is a term covering a spectrum of cancers of the blood or bone marrow characterized by an increase in immature white blood cells.

Learning Objectives

Describe the diagnosis and treatment of leukemia

Key Takeaways

Key Points

  • Acute leukemia is a rapid increase in immature white blood cells, which requires immediate treatment and is the most common form of leukemia in children.
  • Chronic leukemia is a much slower process with a buildup of more mature but abnormal white blood cells and occurs more often in older patients.
  • Myeloid or myelogenous leukemias describe a cancerous change in bone marrow cells that typically mature into red blood cells, some types of white blood cells, and platelets.
  • Leukemia results from DNA mutations that activate oncogenes or deactivate tumor suppressor genes.
  • The symptoms of leukemia may all be explained by other disease; therefore, leukemia must always be diagnosed by a complete blood count or bone marrow examination.
  • Leukemia is typically treated with multi-drug chemotherapy regimens, radiation, or in some cases bone marrow transplant.

Key Terms

  • leukemia: Any specific form or type of cancer of the blood-forming tissues
  • bone marrow: The fatty vascular tissue that fills the cavities of bones; the place where new blood cells are produced.
  • complete blood count: A measure of the number, concentration, and size of white blood cells, platelets, and red blood cells in one’s blood.


Children with acute leukemia may be candidates for bone marrow transplants. Generally, the best match is another family member. However, in one famous case, no one in the family was a match, so the parents conceived another baby, hoping the baby would provide a match. The baby was born in 1990, and did, indeed, turn out to be a match. She later provided bone marrow for a transplant for her older sister. The transplant was a success. The younger sister, now in her 20s, is happy that she was able to save the life of her older sister, who was dying in 1990, but has now had two decades and counting of a healthy life thanks to her “baby” sister.

Leukemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase in the number of immature white blood cells called “blasts.” Leukemia is a broad term covering a spectrum of diseases. It is part of a broader group of diseases affecting the blood, bone marrow, and lymphoid system, which are all known as hematological neoplasms. In 2000, approximately 256,000 children and adults around the world developed some form of leukemia, and 209,000 died from it. About 90% of all leukemias are diagnosed in adults.


Clinically and pathologically, leukemia is subdivided into a variety of large groups. The first division is between its acute and chronic forms. Acute leukemia is characterized by a rapid increase in the number of immature blood cells. Crowding due to such cells makes the bone marrow unable to produce healthy blood cells. Immediate treatment is required in acute leukemia due to the rapid progression and accumulation of the malignant cells, which then spill over into the bloodstream and spread to other organs of the body. Acute forms of leukemia are the most common forms of leukemia in children. Chronic leukemia is characterized by the excessive build up of relatively mature, but still abnormal, white blood cells. Typically taking months or years to mature, the cells are produced at a much higher rate than normal, resulting in many abnormal white blood cells. Whereas acute leukemia must be treated immediately, chronic forms are sometimes monitored for some time before treatment in order to ensure maximum effectiveness of therapy. Chronic leukemia is common in older people, but it can theoretically occur in any age group.

Additionally, the disease is subdivided according to which kind of blood cell is affected. Along these lines, it is divided into lymphoblastic or lymphocytic leukemia, and myeloid or myelogenous leukemia. In lymphoblastic or lymphocytic leukemia, the cancerous change takes place in a type of marrow cell that normally forms lymphocytes, which are infection -fighting immune system cells. In myeloid or myelogenous leukemia, the cancerous change takes place in a type of marrow cell that normally goes on to form red blood cells, some other types of white cells, and platelets.


Leukemia, like other cancers, results from mutations in the DNA. Certain mutations can trigger leukemia by activating oncogenes or deactivating tumor suppressor genes, thereby disrupting the regulation of cell death, differentiation or division. These mutations may occur spontaneously or as a result of exposure to radiation or carcinogenic substances. Some people have a genetic predisposition towards developing leukemia. In addition to these genetic issues, people with chromosomal abnormalities or certain other genetic conditions have a greater risk of leukemia. For example, people with Down syndrome have a significantly increased risk of developing forms of acute leukemia (especially acute myeloid leukemia), and Fanconi anemia is a risk factor for developing acute myeloid leukemia.

Diagnosis and Treatment

People with leukemia may easily become bruised, bleed excessively, or develop pinprick bleeds (petechiae). White blood cells, which are involved in fighting pathogens, may be suppressed or dysfunctional. This could cause the patient’s immune system to be unable to fight off a simple infection or to start attacking other body cells. Because leukemia prevents the immune system from working normally, some patients experience frequent infection, ranging from infected tonsils, sores in the mouth, or diarrhea, to life-threatening pneumonia or opportunistic infections. Finally, the red blood cell deficiency leads to anemia, which may cause dyspnea and pallor. All the symptoms associated with leukemia can be attributed to other diseases. Consequently, leukemia is always diagnosed through medical tests.


Symptoms of Leukemia: Image illustrates the common symptoms of acute or chronic leukemia are shown. Because these can often be attributed to other conditions, a complete blood count and/or bone marrow aspirate are required to successfully diagnose leukemia.

Diagnosis is usually based on repeated complete blood counts and a bone marrow examination following observation of the symptoms. However, in rare cases, blood tests may not show if a patient has leukemia; usually, this may be because the leukemia is in the early stages or has entered remission. A lymph node biopsy can also be performed to diagnose certain types of leukemia in certain situations. Following diagnosis, blood chemistry tests can be used to determine the degree of liver and kidney damage or the effects of chemotherapy on the patient. Many people have not been diagnosed because many of the symptoms remain vague, unspecific, and may refer to other diseases. As a result, the American Cancer Society predicts that at least one-fifth of the population living with leukemia have not yet been diagnosed.

Most forms of leukemia are treated with pharmaceutical medication, typically combined into a multi-drug chemotherapy regimen. Some are also treated with radiation therapy. In some cases, a bone marrow transplant is useful. Treatment using gene therapy is currently being pursued. One such approach turns T cells into cancer-targeting attackers. As of August 2011, a year after treatment, two of the three patients are cancer-free.


Bone Marrow Aspirate Smear: A Wright’s stained bone marrow aspirate smear of patient with precursor B-cell acute lymphoblastic leukemia.


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