children of all ages, with an incidence of 31.9 cases (defined as a platelet count less than 150,000/mm3) per 1 million children under age 15 years per year (Cohn, 1976). Approximately 70 percent of cases occur following viral illnesses (Lightsey, 1980). In most cases, thrombocytopenia in children is mild and transient, and it is often discovered only incidentally when a complete blood count is performed. Severe thrombocytopenia associated with spontaneous bleeding, including bleeding into the skin, is called thrombocytopenic purpura.

History of Suspected Association

In 1966, Oski and Naiman reported a decrease of greater than 25,000/ mm3 in the platelet counts of 38 of 44 (86 percent) subjects immunized with live, attenuated Edmonston B measles vaccine. The lowest platelet counts were observed 1 week following immunization, and the platelet counts returned to prevaccination levels after 3 weeks in all but two patients. There were no petechiae and no purpura or bleeding problems in any of the patients. Nieminen and colleagues (1993) found acute thrombocytopenic purpura in 23 of approximately 700,000 children after they were immunized with MMR. The mean interval between immunization and purpura was 19 days. There also have been several individual case reports of thrombocytopenia following measles vaccination in the literature and VAERS. These studies are described in detail in a later section.

Evidence for Association

Biologic Plausibility

There is demonstrated biologic plausibility that measles or mumps vaccines could be associated with thrombocytopenia on the basis of experience with wild-type virus infections. Early case reports of purpura and bleeding associated with measles did not provide sufficient data to indicate the cause of bleeding. Specifically, they did not differentiate isolated thrombocytopenia from the thrombocytopenia found in disseminated intravascular coagulation. Severe hemorrhage is a well-documented, but rare, complication of infection with measles virus. It is known as the "black measles" because of hemorrhage into the skin (Hudson et al., 1956) and most likely results from disseminated intravascular coagulation. The first case of fatal purpura associated with measles was reported by Jackson in 1890. Hudson et al. (1956) reported 2 cases of thrombocytopenic purpura in patients with measles and reviewed 20 other cases reported in the literature. They found that the hemorrhagic manifestations began an average of 6 days (range, 2 to 14 days) after the onset of the measles rash. The number of circulating plate-



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