Blood performs several vital functions through its special components: the liquid portion (plasma) and the formed constituents (erythrocytes, leukocytes, and thrombocytes) that are suspended in it. Erythrocytes (red blood cells [RBCs]) carry oxygen to the tissues and remove carbon dioxide from them. Leukocytes (white blood cells [WBCs]) act in inflammatory and immune responses. Plasma (a clear, straw-colored fluid) carries antibodies and nutrients to tissues and carries waste away; plasma coagulation factors and thrombocytes (platelets) control clotting. (See Coagulation factors, page 456.)

Typically, the average person has 5 to 6 L of circulating blood, which constitute 5% to 7% of body weight (as much as 10% in premature neonates). Blood is three to five times more viscous than water, with an alkaline pH of 7.35 to 7.45, and is either bright red (arterial blood) or dark red (venous blood), depending on the degree of oxygen saturation and the hemoglobin (Hb) level.

Hematopoiesis, the process of blood formation, occurs primarily in the bone marrow of the femur, sternum, and vertebrae, where primitive blood cells (stem cells) produce the precursors of erythrocytes (normoblasts), leukocytes, and thrombocytes. During embryonic development, blood cells are derived from mesenchyma and form in the yolk sac. As the fetus matures, blood cells are produced in the liver, the spleen, and the thymus; by the fifth month of gestation, blood cells also begin to form in bone marrow. After birth, blood cells are usually produced only in the marrow.

The most important function of blood is to transport oxygen (bound to RBCs inside Hb) from the lungs to the body tissues and to return carbon dioxide from these tissues to the lungs. Blood also performs the following functions:

Blood’s other functions include control of hemostasis by platelets, plasma, and coagulation factors that repair tissue injuries and prevent or halt bleeding; acid-base and fluid balance; regulation of body temperature by carrying off excess heat generated by the internal organs for dissipation through the skin; and transportation of nutrients and regulatory hormones to body tissues and of metabolic wastes to the organs of excretion (kidneys, lungs, and skin).

Because of the rapid reproduction of bone marrow cells and the short life span and minimal storage in the bone marrow of circulating cells, bone marrow cells and their precursors are particularly vulnerable to physiologic changes that can affect cell production, or hematopoiesis. Resulting blood disorders may be primary or secondary, quantitative or qualitative, or both; they may involve some or all blood components. Quantitative blood disorders result from increased or decreased cell production or cell destruction; qualitative blood disorders stem from intrinsic cell abnormalities or plasma component dysfunction. Specific causes of blood disorders include trauma, chronic disease, surgery, malnutrition, drugs, exposure to toxins and radiation, and genetic and congenital defects that disrupt production and function. For example, depressed bone marrow production or mechanical destruction of mature blood cells can reduce the number of RBCs, platelets, and granulocytes, resulting in pancytopenia (anemia, thrombocytopenia, and granulocytopenia). Increased production of multiple bone marrow components can follow myeloproliferative disorders.

The tissues’ demand for oxygen and the blood cells’ ability to deliver it regulate RBC production, or erythropoiesis. Consequently, hypoxia (or tissue anoxia) stimulates RBC production by triggering the formation and release of erythropoietin, a hormone (produced by the kidneys) that activates bone marrow to produce RBCs. Erythropoiesis may also be stimulated by androgens (which accounts for the higher RBC counts in men). RBCs have a life span of approximately 120 days.

The actual formation of an erythrocyte begins with an uncommitted stem cell that may eventually develop into an RBC or a WBC. Such formation requires certain vitamins—B₁₂ and folic acid—and minerals, such as copper, cobalt, and especially iron, which is vital to hemoglobin’s oxygen-carrying capacity. Iron is obtained from various foods and is absorbed in the duodenum and upper jejunum, leaving the excess for temporary storage in reticuloendothelial cells, especially those in the liver. Iron excess is stored as ferritin and hemosiderin until it’s released for use in the bone marrow to form new RBCs.

RBC disorders include quantitative and qualitative abnormalities. Deficiency of RBCs (anemia) can follow any condition that destroys or inhibits the formation of these cells. Common factors leading to this deficiency include:

Comparatively few conditions lead to excessive numbers of RBCs:

WBCs, or leukocytes, protect the body against harmful bacteria and infection and are classified as granular leukocytes (basophils, neutrophils, and eosinophils) or nongranular leukocytes (lymphocytes, monocytes, and plasma cells). (See Two types of leukocytes.) Usually, WBCs are produced in bone marrow; lymphocytes and plasma cells are produced in lymphoid tissue as well. Neutrophils have a circulating half-life of less than 6 hours; some lymphocytes may survive for weeks or months. Normally, WBCs number between 5,000 and 10,000/µl.

There are six types of WBCs:

A temporary increase in production and release of mature WBCs (leukemic reaction) is a normal response to infection. However, an excessive number of immature WBC precursors and their accumulation in bone marrow or lymphoid tissue is characteristic of leukemia. These nonfunctioning WBCs (blasts) provide no protection against infection; crowd out RBCs, platelets, and mature WBCs; and spill into the bloodstream, sometimes infiltrating organs and impairing function.

WBC deficiencies may reflect inadequate cell production, drug reactions, ionizing radiation, infiltrated bone marrow (cancer), congenital defects, aplastic anemia, folic acid deficiency, or hypersplenism. The major WBC deficiencies are granulocytopenia, lymphocytopenia, and monocytopenia.

Platelets are small (2 to 4 microns in diameter), colorless, disk-shaped cytoplasmic fragments split from cells in bone marrow called megakaryocytes. The normal platelet concentration is 150,000 to 400,000/µl. These fragments, which have a life span of approximately 10 days, perform three vital functions:

Plasma consists mainly of proteins (chiefly albumin, globulin, and fibrinogen) held in aqueous suspension. Other components of plasma include glucose, lipids, amino acids, electrolytes, pigments, hormones, respiratory gases (oxygen and carbon dioxide), and products of metabolism, such as urea, uric acid, creatinine, and lactic acid. Its fluid characteristics— including osmotic pressure, viscosity, and suspension qualities—depend on its protein content. Plasma components regulate acid-base balance and immune responses and mediate coagulation and nutrition.

In a complex process called hemostasis, platelets, plasma, and coagulation factors interact to control bleeding.

Hemostasis is the complex process by which the body controls bleeding. When a blood vessel ruptures, local vasoconstriction and platelet clumping (aggregation) at the injury site initially help prevent hemorrhage. This activation of the coagulation system, called extrinsic cascade, requires release of tissue thromboplastin from the damaged cells. However, formation of a more stable clot requires initiation of the complex clotting mechanism known as the intrinsic cascade system. When endothelial vessel injury or a foreign body in the bloodstream activates this system, activating factor XII triggers clotting. In the final common pathway, prothrombin is converted to thrombin. Thrombin acts on fibrinogen to form fibrin, the basis of a clot.

Because of improved methods of collection, component separation, and storage, blood transfusions are being used more effectively than ever. Separating blood into components permits a single unit of blood to benefit several patients with different hematologic abnormalities. Component therapy allows replacement of a specific blood component without risking reactions from other components.

Blood typing, crossmatching, and human leukocyte antigen (HLA) typing are compatibility tests used to ensure safe, effective replacement therapy and minimize the risk of transfusion reactions. Blood typing determines the antigens present in the patient’s RBCs by reaction with standardized sera. (Critical antigen groups are those of ABO and Rh factor.) Crossmatching the patient’s blood with transfusion blood provides some assurance that the patient doesn’t have antibodies against donor red cells. HLA typing may be helpful for the patient who needs long-term transfusion therapy or frequent platelet transfusions, but usually, only family members can provide an appropriate match because antigenic properties are genetically determined.

Bone marrow transplantation is used to treat acute leukemia, aplastic anemia, severe combined immunodeficiency disease, Nezelof syndrome, and Wiskott-Aldrich syndrome. In this procedure, marrow from a twin or another HLAidentical donor (usually a sibling) is transfused in an attempt to repopulate the recipient’s bone marrow with normal cells.

A hematologic disorder can affect nearly every aspect of the patient’s life, perhaps resulting in life-threatening emergencies that require prompt medical treatment. This is particularly true of patients with such diseases as hemophilia and thalassemia major, diseases for which no cure is available. Astute, sensitive care founded on a firm understanding of hematologic basics can help the patient survive such illnesses. In situations with poor prognoses, the patient may need to make many adjustments to maintain an optimal quality of life.

Pernicious anemia, also known as vitamin B,₁₂ deficiency, is a type of megaloblastic anemia characterized by decreased gastric production
of hydrochloric acid and deficiency of intrinsic factor (IF), a substance normally secreted by the parietal cells of the gastric mucosa that’s essential for vitamin B₁₂ absorption in the ileum. The resulting deficiency of vitamin B₁₂ causes serious neurologic, gastric, and intestinal abnormalities. Untreated pernicious anemia may lead to permanent neurologic disability and death. (See Peripheral blood smear in pernicious anemia.)

Folic acid is a water-soluble vitamin that is rapidly excreted; body stores are limited to a few weeks. It is therefore relatively easy to develop a folic acid deficiency.

Folic acid deficiency anemia is a common, slowly progressive, megaloblastic anemia. It usually occurs in infants, adolescents, pregnant and lactating females, alcoholics, elderly people, and people with malignant or intestinal diseases.

Aplastic, or hypoplastic, anemias result from injury to or destruction of stem cells in bone marrow or the bone marrow matrix, causing pancytopenia (anemia, granulocytopenia, and thrombocytopenia) and bone marrow hypoplasia. (See Peripheral blood smear in aplastic anemia.) Although commonly used interchangeably with other terms for bone marrow failure, aplastic anemia properly refers to pancytopenia resulting from the decreased functional capacity of a hypoplastic, fatty bone marrow. These disorders generally produce fatal bleeding or infection, particularly when they’re idiopathic or stem from chloramphenicol or from infectious hepatitis. Mortality for aplastic anemias with severe pancytopenia is 80% to 90%.

Sideroblastic anemias are a group of heterogenous disorders with a common defect; they fail to use iron in hemoglobin (Hb) synthesis, despite the availability of adequate iron stores. These anemias may be hereditary or acquired; the acquired form, in turn, can be primary or secondary. Hereditary sideroblastic anemia may respond to treatment with pyridoxine. Correction of the secondary acquired form depends on the causative disorder; the primary acquired (idiopathic) form, however, resists treatment and usually proves fatal within 10 years after onset of complications or a concomitant disease.