Extravascular hemolysis

The accumulation of hydrogen peroxidase affects many intracellular processes and results in hemolysis. These include the cross-linking of membrane proteins hemoglobin denaturation (manifest as Heinz body formation), which in turn affects the physical properties of the erythrocyte and lipid peroxidation, which may affect the cell membrane to cause direct hemolysis (Fig. 11-8). The resultant damage leads to a mixture of intravascular hemolysis and extravascu-lar hemolysis (by which hemolysis occurs in the reticuloendothelial system). In acute hemolytic episodes, the clinical picture is of predominantly intravascular hemolysis, while predominantly extravascular hemolysis is seen in patients with chronic hemolysis. 

Non-IgE-antibody-mediated immunological reactions Modification of erythrocyte surface components due to binding of beta-lactams or their metabolic products is thought to be the cause of the formation of antierythrocyte antibodies and the development of a positive Coombs test implicated in the development of immune hemolytic anemia (211). About 3% of patients receiving large doses of intravenous penicillin (10-20 million units/ day) will develop a positive direct Coombs test (212). However, only a small fraction of Coombs positive patients will develop frank hemolytic anemia (213). Antibody-coated erythrocytes are probably eliminated by the reticuloendothelial system (extravascular hemolysis) (214), or less often by complement-mediated intravascular erythrocyte destruction (215). Another mechanism implicates circulating immune complexes (anti-beta-lactam antibody/beta-lactam complexes), resulting in erythrocyte elimination by an innocent bystander mechanism (82). Similar mechanisms have been implicated in thrombocytopenia associated with beta-lactam antibiotics (216,217). 

Branch DR, Berkotvitz LR, Becker RL, Robinson J, Martin M, Gallagher MT, Petz LD. Extravascular hemolysis follotving the administration of cefamandole. Am J Hematol 1985 18(2) 213-19. 

The serum potassium concentration may also be falsely elevated in some conditions, and not reflect the actual in vivo potassium concentration. This is termed pseudohyperkalemia. Pseudohyperkalemia occurs most commonly in the setting of extravascular hemolysis of red blood cells. When a blood specimen is not processed promptly and cellular destruction occurs, intracellular potassium is released into the serum. Pseudohyperkalemia can also occur in conditions of thrombocytosis or leukocytosis. If severe hyperkalemia is found in a patient who is asymptomatic with an otherwise normal laboratory report, the hyperkalemia is most likely pseudohyperkalemia, and a repeat blood sample should be evaluated. Elevated potassium concentrations are normally associated with other laboratory abnormalities. 

A novel 2-fluorenonyl carbapenem antibiotic, when injected intravenously to rhesus monkeys (Macaca mulata) for 2-4 weeks induced a hemolytic anemia (extravascular hemolysis, splenomegaly, Coombs test positive for IgG, and up to 25% reduction in the erythron). After 3 weeks of recovery, the erythron had returned to normal after additional 2 months the animals were Coombs test negative. Of note, other species tested, i.e., rats, mice, and squirrel monkeys Saimiri sciureus) did not show any sensitivity to the drug, suggesting an increased sensitivity in rhesus monkeys compared to other species (Lankas et al.,1996). 

Systemic ribavirin causes dose-related anemia due to extravascular hemolysis and dose-related suppression of bone marrow. Reversible increases of serum bilirubin, serum iron, and uric acid concentrations occur during shortterm oral administration. Bolus intravenous infusion may cause rigors. In HIV-infected patients, chronic oral therapy is also associated with dose-related lymphopenia and gastrointestinal and CNS complaints, including headache, lethargy, insomnia, and mood alteration. 

Concentrated sodium chloride injection Inadvertent direct injection or absorption of concentrated sodium chloride injection may give rise to sudden hypernatremia and such complications as cardiovascular shock, CNS disorders, extensive hemolysis, cortical necrosis of the kidneys, and severe local tissue necrosis (if administered extravascularly). Do not use unless solution is clear. When administered peripherally, slowly infuse through a small bore needle placed well within the lumen... 

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