A. H. Waters

HIGH-DOSE INTRAVENOUS IgG IN ADULTS WITH AUTOIMMUNE THROMBOCYTOPENIA

A study of the effect of high-dose intravenous IgG in 25 adults with autoimmune thrombocytopenia confirmed the predictable rise in the platelet count seen during the infusion and previously reported in children. Unlike the data based on children, there was no sustained response unless the IgG infusion was closely associated with splenectomy. There was no correlation between the presence of platelet autoantibodies or the Ig class of the autoantibody and the pattern of response to the infusion. The initial platelet response appears to be the result of transient blockade of the reticuloendothelial system, including the macrophage Fc receptor mechanism. The long-term response in some patients requires another explanation and may be due to a more specific immunosuppressive effect of the high-dose IgG infusion. Splenectomy may have an additive effect by removing a major site of platelet autoantibody production.

Use of leucocyte-poor blood components and HLA-matched-platelet donors to prevent HLA alloimmunization

Summary. Recent studies have shown that the incidence of alloimmunization due to repeated platelet transfusions from random donors may be reduced by the use of leucocyte‐poor blood components. These results were confirmed by this study, where 16% of patients with acute leukaemia undergoing initial chemotherapy and receiving leucocyte‐poor blood components developed lymphocytotoxic antibodies, compared with 48% of patients in a control group receiving standard (non‐leucocyte‐depleted) blood components. In a third group, who received leucocyte‐poor blood components and HLA‐matched platelets, none of the patients developed lymphocytotoxic antibodies. There was a low incidence of platelet‐specific antibodies (8%) but no difference between the three groups. Improved methods of removing leucocytes from blood components appear to offer the best approach for minimizing HLA alloimmunization, as the provision of HLA‐matched platelet donors for prophylactic platelet support of all patients is not feasible.

Incidence and mechanism of neutropenia and thrombocytopenia in patients with human immunodeficiency virus infection

The incidence of lymphopenia, thrombocytopenia and neutropenia was studied in 105 homosexual men with HIV infection. Lymphopenia was common in patients with AIDS (75%), but its incidence in PGL (24%) was not significantly different from that in asymptomatic anti‐HIV positive (15%) homosexual men. Neutropenia and thrombocytopenia were found in patients with AIDS or PGL. but not in asymptomatic anti‐HIV positive homosexuals. The study suggests that the neutropenia and thombocytopenia in these patients were due to autoimmune destruction of neutrophils and platelets.

Relative Importance of Immune and Non-Immune Causes of Platelet Refractoriness

In this prospective study, 26 consecutive patients being treated for haematological malignancies receiving standard (i.e. non‐leucocyte‐depleted) blood components were observed for the development of refractoriness to platelet transfusions. One hundred and sixteen of the 266 (44%) platelet transfusions failed to produce a satisfactory response. In 102/116 (88%), the poor response was in the presence of non‐immune factors known to be associated with platelet refractoriness. Non‐immune factors were present alone in 78/116 (67%), and in combination with immune factors in a further 24/116 (21%). Immune factors (HLA and platelet‐specific antibodies) were present during 29/116 (25%) of unsuccessful platelet transfusions. Statistical analysis confirmed that platelet refractoriness was significantly associated with the presence of nonimmune factors. The non‐immune factors associated with refractoriness were often multiple, most frequently a combination of fever, infection and antibiotic therapy. This study provides evidence that immune mechanisms were not the predominant cause of platelet refractoriness in the patient population studied. It also suggests that measures for the prevention of HLA alloimmunisation, such as leucocyte depletion, may have a limited impact in reducing the incidence of refractoriness to platelet transfusions.

Guidelines for platelet transfusions

SUMMARY. Recommendations for the optimal transfusion support of patients likely to receive repeated platelet transfusions

Antenatal management of fetomaternal alloimmune thrombocytopenia—report of 15 affected pregnancies

SUMMARY. The recognition that spontaneous intracranial haemorrhage (ICH) may occur in utero in fetomaternal alloimmune thrombocytopenia (FMAIT) led us to attempt to prevent this in 15 pregnancies of 11 women who had previously affected infants with FMAIT due to anti‐HPA‐la. The antenatal management included fetal platelet transfusions and maternal steroids and/or high‐dose intravenous immunoglobulin (IVIgG).

Demonstration of an immune‐mediated mechanism of penicillin‐induced neutropenia and thrombocytopenia

Severe neutropenia may be a more common complication of high‐dose penicillin therapy than previously recognized. This report describes five such patients, one of whom also had thrombocytopenia. The neutrophil and platelet counts rapidly increased on stopping penicillin, and the bone‐marrow, which was hypocellular in some cases, became normal. Further studies on one of these patients, using a fluorescent antiglobulin technique with paraformaldehyde‐fixed cells, demonstrated a complement‐fixing IgG penicillin antibody reacting with the patients granulocytes and platelets in the presence of the drug. This suggested an immune mechanism similar to the well‐recognized penicillin‐induced immune haemolytic anaemia. The associated bone‐marrow hypoplasia may also be due to antibody‐mediated suppression of penicillin‐coated precursor cells.

HPA‐1 typing by PCR amplification with sequence‐specific primers (PCR‐SSP): a rapid and simple technique

Summary. A DNA‐based method was developed to genotype donors for the human platelet antigens HPA‐la and ‐1b. Sequence‐specific primers (SSP) were used in the polymerase chain reaction (PCR) which allowed the HPA‐la/la. ‐lb/lb and ‐la/lb genotypes to be determined by PCR alone, no second analytical stage was required. 10 donors were tested by PCR‐SSP and the results were concordant with serological phenotyping and independent DNA analysis.

IMMUNOLOGICAL ASPECTS OF PLATELET TRANSFUSIONS

Platelet transfusions are standard treatment for bleeding thrombocytopenic patients. The more recent acceptance of the prophylactic use of platelet transfusions for severe thrombocytopenia (platelet counts below 20 x 10y/l) due to bone-marrow failure has meant that patients with acute leukaemia, aplastic anaemia and those undergoing bone marrow transplantation often receive repeated platelet transfusions. One of the major problems associated with multiple platelet transfusions from random donors is poor survival of the transfused platelets because of alloimmunization (Stefanini et al, 1952; Aster et al, 1964; Shulman, 1966; Grumet & Yankee, 1970; Howard & Perkins, 1978). and this may become a severe complication in the management of these patients.

AUTOIMMUNE THROMBOCYTOPENIA ACQUIRED FROM AN ALLOGENEIC BONE-MARROW GRAFT

Severe thrombocytopenia developed after an allogeneic bone-marrow graft in a 40-year-old woman in first remission from acute myeloblastic leukaemia. The thrombocytopenia had an autoimmune basis and was acquired from the bone-marrow donor who had an identical platelet autoantibody. The patient responded to high-dose intravenous IgG, and she has a normal platelet count 10 months after the graft. This study suggests that the immune defect in autoimmune thrombocytopenia can be transferred in cells capable of proliferating in a bone-marrow graft.