Immune thrombocytopenic purpura--from agony to agonist.

In the summer of 1950, two hematology fellows working at the Barnes Hospital in St. Louis — William J. Harrington and James W. Hollings­ worth — hatched a plan to test their idea that the cause of the idiopathic thrombocytopenic pur­ pura (ITP) in a woman under their care was a factor in the blood that destroyed platelets. They decided that of the two fellows, the one whose blood type matched the patient’s would receive 500 ml of her blood. In a flip of the genetic coin, Harrington matched. Within a few hours after receiving the wom­ an’s blood, Harrington’s platelet count dropped precipitously, and he had a major seizure. For 4 days, his platelet count hovered at dangerously low levels, and bruises and petechiae were evi­ dent. Reprieve occurred on the fifth day, when the platelet count began to return to normal. Ex­ amination of Harrington’s bone marrow, obtained by means of sternal puncture before and after the transfusion, showed no visible changes in megakaryocytes, indicating an effect not on the marrow but on the circulating platelets. Subse­ quently, all suitable members of the Hematology Division of the Barnes Hospital, including its head, Dr. Carl V. Moore, received plasma from a patient with ITP, and in each recipient the platelet count plunged within 3 hours (Fig. 1).1 This experiment, one of the most important ever to be performed in the field of hematology, established that ITP is caused by a circulating factor. The thrombocytopenic factor has since been definitively identified as a cluster of IgG antibodies with specificity for one or more plate­ let glycoproteins.2 The Harrington–Hollingsworth experiment changed the meaning of the “I” in ITP from idio­ pathic to immune, but “immune” in this case means “autoimmune,” because the antibodies bind to and cause the destruction of the patient’s own platelets. Molecular studies of the antiplate­ let antibodies in patients with ITP indicate that