Prevention of platelet refractoriness due to HLA antibodies by administration of leukocyte-poor blood components.

From January 1972 to July 1974, 28 patients with bone marrow depression due to aplastic anemia or cytostatic treatment, were transfused with packed cells and platelet concentrates, both containing 10-20% of the amount of leukocytes present in whole blood. Of these patients, 26 (93%) became refractory to random platelets. Since July 1974, 68 patients have been given red cells filtered through cotton-wool, a procedure which removes over 97% of the leukocytes, and leukocyte-poor platelet suspensions obtained by an additional centrifugation step. Of this latter group, 16 patients (24%) became refractory. Fifty-two recipients were non-refractory to random platelet transfusions after an exposure time of at least 6 weeks and maximally 32 weeks. A possible explanation is that platelets are less immunogenic than leukocytes; on the other hand platelets may not be immunogenic at all with regard to induction of HLA antibodies, and the occurrence of the immunization is purely the result of the contamination with leukocytes in the red cell and platelet preparations.

Alloimmunization against the MHC antigens after platelet transfusions is due to contaminating leukocytes in the platelet suspension.

Repeated platelet transfusion to thrombocytopenic patients frequently induce anti HLA antibodies, which are responsible for transfusion refractoriness. As the transfused platelet suspensions usually contain 15-30% of the leukocytes originally present in the blood, it is not known whether these antibodies are raised by the platelets or by the contaminating leukocytes in the platelet suspensions. In the mouse, pure platelet suspensions are not able to induce a primary antibody response, as measured by the NIH test and the indirect immunofluorescence test on platelets and leukocytes, despite repeated injections. However, when the platelet suspensions are contaminated with leukocytes (10(3) or more/injection) an antibody response is induced. This response is higher than the response indiced by an equal amount of leukocytes alone. As in man the use of leukocyte poor platelets postpones the development of refractoriness to random platelets it is concluded that transfusions with leukocyte free platelets will probably prevent immunization against the HLA antigens.

Recovery of hematopoiesis after blood-group-incompatible bone marrow transplantation with red-blood-cell-depleted grafts.

Severe hemolytic transfusion reactions may complicate major blood-group-incompatible bone marrow transplantations (BMT). Probably the most appropriate way to avoid this complication is removal of the incompatible red blood cells (RBC) from the bone marrow graft. In this report we describe a method to eliminate incompatible RBCs that is based on repeated dilution of the graft with donor-and-recipient--compatible third-party erythrocytes. Four patients with ABO incompatibility and one patient with Rh-C incompatibility were transplanted using this technique. After the procedure 86 +/- 8% (mean +/- SD) of the nucleated cells, 95 +/- 14% of CFU-GM, 88 +/- 14% of BFU-e, and 103 +/- 30% of CFU-e were recovered, but only +/- 1% of the incompatible RBCs was left in the transfusate (1-3 ml). No signs of hemolysis were observed. All patients engrafted promptly. The patients with low titers of antibody had normal reticulocyte recoveries. Maturation of erythropoiesis was suppressed only when high titers of antibody were present. However, despite high antibody titers, erythroid progenitor cells (CFU-GEMM, BFU-e, and CFU-e) could be cultured from the bone marrow of the recipient after BMT. Thus, anti-A and anti-Rh-C antibodies give little, if any, inhibition of stem-cell proliferation. The method described to remove incompatible RBCs appears to be simple, safe, and--in most cases--sufficient.

Severe leukocytoclastic vasculitis of the skin in a patient with essential mixed cryoglobulinemia treated with high-dose gamma-globulin intravenously.

We describe a patient with long-standing severe leukocytoclastic vasculitis of the skin and essential mixed cryoglobulinemia type II, who showed a limited reaction to immunosuppressive drugs, plasmapheresis, and colchicine. Therapy with high-dose gamma-globulin intravenously (IV) for five days resulted in disappearance of vasculitis lesions within three weeks. After gamma-globulin IV treatment there was a decrease in cryoglobulin, circulating immune complexes, and IgM, paraprotein, and a rise in complement levels. No serious side effects were noted during or after gamma-globulin IV treatment. The patient has been in remission for 16 months.

Twenty-two years of intra-uterine intraperitoneal transfusions.

Over a period of 22 years, 154 fetuses were treated with 270 intra-uterine intraperitoneal transfusions. The patients were divided into three groups, according to the period they were treated. The overall percentage of surviving infants increased from 33% during the first period to 58% in the last period. In the group of infants that were not hydropic at the time of the first transfusion, the survival rate increased from 35 to 83%. In the group of children that were hydropic during the first transfusion, the survival rate during the first and last period was 24 and 42%, respectively. The percentage of fetuses that needed their first transfusion before the 26th week of pregnancy increased from 15 to 32% during the study period. Only 13% of these children survived. Lately, the intravascular approach has been introduced. Intravascular transfusions seem to be very effective, especially in early pregnancies and in hydropic fetuses. Application of the two techniques each in the most appropriate situation might offer optimal results for the near future.

Beneficial effect of intravenous gammaglobulin in a patient with complement-mediated autoimmune thrombocytopenia due to IgM-anti-platelet antibodies.

Intravenous gammaglobulin (IV-IgG) was administered to a patient with chronic idiopathic thrombocytopenic purpura due to an unusual IgM platelet autoantibody causing in vitro complement-dependent thrombocytoxicity and in vivo intravascular platelet destruction. After IV-IgG infusion the peripheral platelet count temporarily increased to normal values, the mean platelet survival time increased and the platelet sequestration pattern changed from intravascular to predominantly hepatic destruction. In vivo and in vitro observations in this patient illustrate a transient beneficial effect of gammaglobulin infusion due to interference with the complement-fixing autoantibodies against platelets.