Thrombocytopenia associated with gold therapy: a drug-induced autoimmune disease?

We studied 13 patients with rheumatoid arthritis (RA) and gold-induced thrombocytopenia. Platelet-specific autoantibodies of the IgG and often also of the IgM class were detected by immunofluorescence on the patient's platelets and in ether eluates from these platelets. In nine patients we also detected autoantibodies in the serum. The antibodies were unreactive with platelets from patients with Glanzmann's disease in most cases, and were not EDTA dependent. Thus, they had the serological characteristics of true autoantibodies. The reaction of the antibodies with platelets was not influenced by the addition of extra gold. By atomic absorption spectrophotometry we found that the ether eluates, which were often strongly reactive with donor platelets, were free of gold. This indicated that the autoantibodies in the thrombocytopenic patients were not dependent on gold for their reaction. The possibility is raised that gold treatment of rheumatoid arthritis patients induces or enhances the formation of platelet-specific autoantibodies, and that gold-induced thrombocytopenia is a drug-induced autoimmune disease.

The serology of febrile transfusion reactions.

Sera from 40 patients with febrile, nonhemolytic transfusion reactions were tested for the presence of alloantibodies using a number of techniques, including immuno-fluorescence tests on granulocytes, lymphocytes and platelets, a modified NIH lymphocytotoxicity test and the leukocyte agglutination test. Cells of at least 9 donors were used as target cells. Alloantibodies were detected in all sera. The frequency of the occurrence of antibodies was not much higher in sera obtained about 1 month after the transfusion reaction as in sera obtained within 4 days. Most of these antibodies were anti-HLA, but quite frequently platelet-specific antibodies were found, and sometimes these were the only antibodies detected. Granulocyte-specific antibodies were the least frequent. The nature of the antibodies was specified by their difference in reactivity with the cells of multiple donors, by applying panels of cells from typed donors and by absorption and elution experiments. It appeared that not only granulocyte-specific but also HLA- and perhaps platelet-specific antibodies may be responsible for a febrile transfusion reaction. We did not find that the occurrence of rigors, together with fever, was associated with particular serologic results.

Platelet autoantibodies in septicaemia.

Thirty-three patients, 16 of whom had a platelet count below 100 X 10(9)/l, were studied for the presence of platelet antibodies using the platelet suspension immunofluorescence test (PSIFT). In the acute phase platelet-bound immunoglobulins (PBIg) were found in 62% of the thrombocytopenic patients, but also in 65% of the patients with a normal platelet count. Fourteen patients were re-examined after successful treatment of their infection. At that time all had a normal platelet count, yet PBIg were found in 71%. In all but four patients the PBIg could be eluted with ether and were shown to bind to normal platelets but not to Glanzmann type I platelets in 11 of 12 patients tested, indicating the platelet-specific autoantibody nature of the PBIg. Platelet autoantibodies were also demonstrated in the sera: in 38% in the acute phase and in 43% after treatment. In those patients in whom this could be tested the antibodies appeared to be strictly or partially EDTA-dependent. It is postulated that the antibodies are mainly directed against cryptantigens, exposed in vivo only on platelets damaged by the septicaemia and in vitro in the presence of EDTA. This would also explain the lack of relationship between the platelet count and the serological findings.

Platelet freezing for serological purposes with and without a cryopreservative.

We compared the reactivity of fresh platelets with platelets frozen in dimethylsulfoxide (DMSO) or without a cryopreservative by testing agglutinating and non-agglutinating platelet-specific alloantibodies in titration. Frozen platelets, irrespective of the method of preservation, showed no loss of antigenicity as compared with fresh platelets. The yield of platelets frozen without a cryopreservative proved to be higher (80%) than platelets frozen in the presence of DMSO (50%). Platelets sensitized with autoantibodies from patients with autoimmune thrombocytopenia could also be stored by simple freezing in platelet-rich plasma and used for (re)testing.