The Hemolytic Process

Red cell senescence or death is a natural process for red cells at the end of their 120-day life span. As a natural byproduct, the contents of the red cell are released and returned to various parts of the circulation to be recycled in the process of red cell regeneration. When red cell death occurs in an orderly fashion, the hematologi-cal balance is maintained. Hemoglobin is kept at normal levels, and the bone marrow maintains a steady production of red cells. If premature red cell death or hemolysis occurs, a series of events begin to cascade, which provide laboratory evidence that red cells are dying faster than their normal 120-day life cycle (Table 4.2). When this happens, the body's peripheral circulation begins its intervention process. There is evidence

Table 4.1 O Abnormal Hemoglobins

Sulfhemoglobin

Carboxyhemoglobin

Methemoglobin

Table 4.2

Clinical Events

Relationship of Hemolysis and Clinical Events

Physical Symptoms

T Bilirubin

Hemoglobinemia

Hemoglobinuria

Symptoms of anemia: pallor, fatigue, tachycardia

Jaundice

Blood-tinged plasma Blood-tinged urine for hemolysis in the bone marrow, in the peripheral circulation, and in the blood plasma. The bone marrow will show erythroid hyperplasia, meaning an increase in red blood cell precursors and premature release of reticulocytes and young red cells. The normal M:E ratio of 3 to 4:1 will be shifted toward the red blood cell, giving a ratio of perhaps 1:2. The peripheral smear will provide visual clues of hemolysis by showing an increase in polychromasia and the presence of nucleated red cells and possibly spherocytes. Spherocytes may appear in the peripheral circulation if red cells become coated with antibody. As antibody-coated red cells travel through the spleen, the spleen subsequently shears off the antibody as the red cell percolates through this organ.7 None of these visual indicators are likely to be observed in the normal peripheral smear. They are seen in the peripheral smear in response to a hemolytic event. Plasma changes are discussed later in the chapter.

Types of Hemolysis

Hemolysis can be an extravascular or an intravascular process. Ninety percent of all hemolysis is extravascular and occurs in the spleen, liver, lymph nodes, and the bone marrow, the organs of the reticuloendothelial system. Red cells are destroyed and their contents are phagocytized with hemoglobin released into the macrophages. Extravascular hemolysis is a well-established pathway in which red cell breakdown leads to the release of the internal products of hemoglobin, primarily heme and globin (Fig. 4.4). The amino acids of the globin chains are recycled into the amino acid pool, while the products of heme are taken through different pathways. Iron is transported via transferrin; the transport protein to the bone marrow or storage sites to be used in erythropoiesis, while the rest of the hemoglobin molecule reacts with hemoxygenase, yielding a byproduct biliverdin, which is reduced to unconjugated biliru-bin. This bilirubin product attaches to albumin and is then transported to the liver.

56 Part I • Basic Hematology Principles

Hemoglobin a - ß dimers

RBC I

Hemoglobin tetramers

Hemoglobin a - ß dimers

Hemoglobin-haploglobin

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