CASE HISTORY • Part 1
A 54-year-old woman presents with a 2–3 month history of increasing fatigue, dyspnea on exertion, and ankle edema. She denies any recent illness and her review of systems is basically negative, including any prior history of anemia. Examination reveals an anxious middle-aged woman with pale conjunctiva and slightly jaundiced sclera. Vital signs: BP - 150/60 mm Hg, P - 110 bpm, R - 20 bpm T - normal. Signs of congestive heart failure include inspiratory rales heard over both lung bases, cardiomegaly, a systolic murmur at the apex, and 2+ pitting edema in both ankles. There is no hepatosplenomegaly or lymphadenopathy.
CBC: Hematocrit/hemoglobin - 18%/5 g/dL
MCV - 100 fL MCHC - 36 pg MCH - 33 g/dL
RDW-CV - 14% RDW-SD - 53 fL
Reticulocyte count/index - 22%/>3
White blood cell count - 11,000/μL
Platelet count - 220,000/μL
The distinguishing feature of all hemolytic anemias is the increased rate of adult red blood cell destruction. Clinical presentation will vary according to the disease process. Some hemolytic anemias present as acute, self-limited episodes of red blood cell destruction, and others as chronic, well-compensated hemolytic states. Signs and symptoms of hemolysis will also differ according to the mechanism of red blood cell destruction. Sudden intravascular hemolysis results in hemoglobinemia and hemoglobinuria, whereas destruction limited to the extravascular monocyte-macrophage system may only be apparent from a fall in hemoglobin level and a rise in the serum bilirubin and lactic dehydrogenase (LDH) levels. Chronic, well-compensated hemolytic anemias are easily detected from the red blood cell production response (ie, increase in the reticulocyte index).
Red blood cell hemolysis can result because of environmental factors or an inherent defect in red blood cell structure or function. Even normal red blood cells can fall victim to environmental challenges such as mechanical trauma, infection, or autoimmune attack. Patients who inherit defects in membrane structure, hemoglobin stability, or metabolic function demonstrate both spontaneous shortening of red blood cell lifespan and a greater sensitivity to environmental factors.
NORMAL RED BLOOD CELL TURNOVER
Red blood cells are extremely pliable, resilient cells that survive for 100 or more days in circulation. Their capacity to survive is a tribute to the strength of the membrane and the metabolic pathways that supply the high-energy phosphate needed to maintain the membrane and keep hemoglobin in a soluble, reduced state (see Chapter 1). As red blood cells become older, however, metabolic pathways decay, oxidized hemoglobin accumulates, and oxidized phospholipids, especially phosphatidylserine, appear on the surface of the cell. A concomitant loss of flexibility interferes with the cell's ability to move through the microvasculature and initiates the process of removal by the monocyte-macrophage system via the CD36 receptor.