There are no studies in experimental animals or human subjects to suggest a possible mechanism by which Hib polysaccharide or its protein conjugates might produce thrombocytopenia. Natural infections with live viruses may induce thrombocytopenia by damage to megakaryocytes, destruction of circulating platelets, or induction of vital antigen-antibody complexes that sensitize platelets to increased destruction or sequestration (Kaplan et al., 1992; Lee et al., 1993). In patients with severe bacterial infections, including Hib infections, thrombocytopenia frequently occurs as a manifestation of disseminated intravascular coagulation (DIC). Thrombocytopenia also has been reported in adult patients with gram-negative and gram-positive septicemia but without evidence of DIC (Keltow et al., 1979). The thrombocytopenia in these patients was thought to result from the interaction of platelets with immune complexes.
Thrombocytopenia without evidence of DIC also has been observed in children with bacterial septicemia, including systemic Hib infections (Corrigan, 1974: Thomas and O'Brien, 1986). The mechanism by which the decreased platelet count occurs in these children is unknown, but it should be noted that intact Hib organisms contain many components not present in Hib vaccines. Some of these components, such as lipooligosaccharide, can induce an inflammatory response, including activation of platelet-activating factor and the coagulation cascade. These events can induce platelet aggregation and thus decrease the intravascular platelet count. There is no evidence that the capsular polysaccharide of Hib causes a similar inflammatory response (Quagliarello and Scheld, 1992; Saez-Llorens et al., 1990; Syrogiannopoulos et al., 1988). No published data from studies in animals were found, but Lepow et al. (1984b) referred to hematologic studies in rats, including serial bone marrow evaluations, that failed to demonstrate any effect of PRP-D vaccine on platelet counts.
Five cases of thrombocytopenia following immunization for Hib were reported through VAERS between November 1990 and July 1992, a period during which approximately 29.5 million doses of Hib vaccine were distributed in the United States (a rough estimate based on 1991 data provided by the Centers for Disease Control). In one case, the thrombocytopenia occurred 7 days after receipt of DPT, OPV, and HbOC vaccine and was associated with high fever, diarrhea, weight loss, seizures, and renal failure, a symptom complex resembling hemolytic-uremic syndrome. The report stated