Thirteen cases of posttransfusion purpura (PTP) which were diagnosed in Germany and Austria from 1977-1985 are described. All patients were women with a mean age of 58.6 years (range, 36-77 years). All but one had been pregnant and received blood transfusions 2 to 12 days prior to the onset of PTP. The thrombocytopenic purpura was always severe with a nadir of platelet counts below 10 X 10(9)/l and lasted between 3 and 60 days. All patients recovered from PTP. Optimal therapy consisted of administration of high-dose IgG. Twelve of the 13 patients had developed platelet-specific Zwa antibodies (eight of them together with HLA antibodies), in one Zwa positive individual only HLA antibodies were detectable. Five of six HLA-DR typed patients carried DR3 which is considered an immunogenetic risk factor in PTP. Clinical awareness of this rare, but serious iatrogenic transfusion complication is prerequisite for prompt diagnosis and improved therapy.

Adult↗

PubMed1986

[Hemolytic anemia and renal failure caused by nomifensine].

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Acute Kidney Injury↗

PubMed1986

Effect of IgG anti-Rho(D) in adult patients with chronic autoimmune thrombocytopenia.

Seventeen adult patients with chronic (15 cases) or acute (two cases) autoimmune thrombocytopenia (ITP) were given intravenous and/or intramuscular injections of 0.75-4.5 mg of IgG anti-Rho(D) over a period of 1-5 days. Significant elevations of the platelet count (increments greater than 50 X 10(9)/liter) resulted in 13 of 15 Rh-positive patients but not in either of two Rh-negative patients. Heat-aggregated human albumin given to one of the Rh-negative patients also did not lead to a significant increase of the platelet count. The elevation of the platelet counts in Rh-positive patients after IgG anti-Rho(D) administration was often transient (less than 4 weeks), but long-term benefit (greater than 5 months) was achieved in five cases. The IgG concentration on RBC from five Rh-positive patients studied increased from a usually undetectable value before to approximately 700-1,700 IgG molecules/per RBC after anti-Rho(D) administration resulting in a strongly positive direct antiglobulin test. Nevertheless, an overt clinical hemolysis was seen in only one patient. The clearance of autologous 51Cr-labeled RBC was determined in four patients and was slightly enhanced in three and normal in one splenectomized patient. We conclude that the Fc receptor blockade involved in platelet sequestration was not associated with the induction of significant RBC clearance and that a reversible interaction of sensitized RBC with phagocytic cells and/or a low-grade destruction of these cells might be sufficient for the elevation of circulating platelets in the majority of patients with ITP.

Adult↗

PubMed1986

Platelet-associated immunoglobulins IgG, IgM, IgA and complement C3 in immune and nonimmune thrombocytopenic disorders.

A two-stage radioactive antiglobulin test--using unlabelled antisera specific for IgG, IgA, IgM and C3 followed by binding of 125I-staphylococcal protein A--was applied to determine platelet-associated immunoglobulins (PAIg) and complement (PAC3) in thrombocytopenias of various etiologies. One hundred and one patients with immune thrombocytopenia (chronic autoimmune, 48; acute autoimmune, 37; Evans syndrome, nine; connective tissue diseases, seven) and 20 patients with presumed nonimmune thrombocytopenia (bone marrow aplasia or malignancy, six; septicemia, five; hypersplenism, five; cirrhosis of liver, three; others, one) were studied. Increased levels of PAIg/C3 were found in 76% of patients with immune thrombocytopenia. PAIgG was raised in 66%, PAIgM in 57%, PAIgA in 44%, and PAC3 in 29%. Isolated elevation of PAIgG and of PAIgM was found in four and three cases, respectively; PAIgA and PAC3 were elevated in one case each. PAIgG was associated with PAIgM in 56%, with PAIgA in 34%, and with PAC3 in 27%. Both patients with Evans' syndrome and patients with connective tissue diseases had significantly higher PAIgM levels than the other patients with immune thrombocytopenia. In patients with nonimmune thrombocytopenia, increased rates of PAIg/C3 were also encountered. Positive test results were found in 88% (PAIgG 88%, PAIgM 47%, PAIgA 35%, and PAC3 24%). In immune-mediated thrombocytopenia, we observed a significant inverse correlation between platelet counts and PAIgG, PAIgA, and PAC3, but not with PAIgM. In contrast, no such correlation was found in patients with nonimmune thrombocytopenia. Our data indicate that the evaluation of neither parameter alone nor the combination of PAIg/C3 will discriminate between immune and nonimmune thrombocytopenia. Preferential coating with certain immunoglobulins, however, may be present in some subgroups of immune thrombocytopenias.

Blood Platelets↗

PubMed1986

Immune phagocytosis inhibition by commercial immunoglobulins.

Sixteen commercially available immunoglobulins (Ig) and 5 anti-Rho (D) hyperimmune globulins were investigated for immune phagocytosis inhibition (IPI) factors as well as for T, B lymphocytotoxic and monocytotoxic antibodies. All Ig contained IPI factors with lowest inhibitory IgG concentrations ranging from 0.08 to 50 mg/ml. Pepsin-digested Ig was noninhibitory. IPI factors in anti-D preparations were uniformly high (inhibitory IgG concentrations 0.6-2.5 mg/ml). Cytotoxic antibodies against T, B lymphocytes and monocytes were found in 2,2 and 7 products, respectively. Since we have recently shown that IPI is caused by antibodies against major histocompatibility complex antigens, most likely HLA, the hypothesis is put forward that IPI factors in Ig are HLA-related, cytotoxic as well as noncytotoxic antibodies which act via Fc receptor blockade of human monocytes.

B-Lymphocytes↗

PubMed1986

Treatment of childhood idiopathic thrombocytopenic purpura with Rhesus antibodies (anti-D).

We have recently reported that a rise of platelet numbers in ITP can be induced by blockade of the RES with antibody-coated red blood cells. We now present a collaborative study in which 15 Rhesus-positive children with ITP (nine boys and six girls aged 1-15 years) were treated with low-dose anti-D. Ten patients had chronic ITP (duration 6-47 months), five had acute ITP. Doses of 28-50 micrograms anti-D/kg bodyweight per course were given intravenously. In all patients clinical signs of bleeding ceased and platelet counts were elevated. An excellent, good or fair response with platelet increments of greater than 100, 50-100, or 20-50 X 10(9)/l, respectively, was observed in 19, 7, and 12 out of 45 courses in chronic ITP, and in 4, 1, and 2 out of 8 courses in acute ITP. The platelet increase (greater than 40 X 10(9)/l) persisted for 10 to over 360 days in chronic ITP. There were no untoward side reactions. Haemoglobin values remained stable in all patients but laboratory signs of mild, compensated haemolysis ensued. The direct antiglobulin test became positive in all cases due to anti-D IgG. Previous therapy of patients with chronic ITP included high-dose immunoglobulins and prednisone. These regimens were both effective but remissions were short. We conclude that anti-D therapy is an effective and safe form of treatment in childhood ITP.

Adolescent↗

PubMed1986

Post-transfusion purpura.

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Female↗

PubMed1986

Two types of nomifensine-induced immune haemolytic anaemias: drug-dependent sensitization and/or autoimmunization.

Thirty-one patients who developed immune haemolytic anaemia while receiving nomifensine were studied. We provide evidence that nomifensine can cause two forms of immune haemolytic anaemia: one that is associated with an abrupt haemolytic episode due to drug-dependent antibodies, and a less acute form associated with IgG autoantibodies. The majority of patients' serum samples (23 cases) contained IgG and/or IgM antibodies reacting to a highly variable extent with red blood cells (RBC) only in the presence of the drug and/or its metabolites. Sera of six patients contained IgG autoantibodies which reacted, like those in warm autoimmune haemolytic anaemia, with RBC in the absence of drugs. Three patients had developed both types of antibodies. From a diagnostic viewpoint, nine of the drug-dependent antibodies could not be identified by using the drug itself, but by its known (three cases) or unknown urine-born metabolites (ex vivo antigens). We conclude that nomifensine can induce in vivo the production of RBC drug- and/or metabolite-dependent antibodies, autoantibodies, or both in the same patient.

Adult↗

PubMed1986

Immune thrombocytopenic purpura: autoimmune or immune complex disease?

To assess the pathogenic role of circulating immune complexes (CIC) in idiopathic thrombocytopenic purpura (ITP), 39 patients with ITP were compared to 17 patients with other forms of thrombocytopenia (hypersplenism (N = 12), impaired thrombopoiesis (3), thrombocytopenia of unknown origin (2)) and six nonthrombocytopenic subjects. In all patients, platelet mean life span (MLS), platelet associated IgG (PAIgG), as well as circulating anti-platelet antibodies and C1q binding activities were determined. In most cases, immune complex solubilization capacity (ICSC) and immune complex precipitation inhibition capacity (ICPIC) of sera were also assessed. All patients with ITP had a reduced platelet MLS, but PAIgG was elevated in only 16 out of 24 patients with chronic ITP, in six out of 10 patients with acute ITP and in four out of five patients with secondary ITP. In the group of patients with thrombocytopenia due to splenomegaly, seven out of 12 patients had elevated PAIgG while the platelet MLS was only slightly reduced. Of the 39 patients with ITP only one with secondary ITP had C1q binding material in his serum, as opposed to six out of 12 thrombocytopenic patients with splenomegaly. Whereas only three patients with ITP had abnormal immune-complex modulating capacities, such deviations were found in seven out of 12 patients with thrombocytopenia due to splenomegaly. We conclude that our data render the role of CIC in the pathogenesis of ITP very questionable.

Adolescent↗

PubMed1986

HLA and narcolepsy in a German population.

In this paper the first MHC data including HLA-A, B, C, DR, DQ and complement BF, C4A, C4B determinants in German narcoleptics are presented together with the first family studies in European Caucasoids. 57 out of 58 unrelated patients (98.3%) were positive for DR2 and DQw1, respectively. In contrast to all other reports, one patient with typical signs of narcolepsy was found to be DR2/DQw1 negative. Data showing significant increase in the frequency of B7, and normal frequencies of B35 were discordant with data from Japanese patients. Definition of the extended DR2 linked haplotypes, deduced from 6 families, revealed that 5 out of 12 were DQw1, DR2, BFS, C4B1, C4A3, B7 (Cw7), while 11/12 had DR2, DQw1, BFS, C4A3, C4B1 in common. In one multiple case family two genotypically different DR2 haplotypes were identified in affected siblings. Results from the family study were concordant with a dominant mode of inheritance with incomplete penetrance of a hypothetical disease susceptibility gene.

Complement C4↗

PubMed1986

Inhibition of immune phagocytosis by human sera with HLA A, B, C and DR but not with DQ or EM type reactivity.

613 sera from pregnant women were investigated for inhibition of immune phagocytosis (IPI) by monocytes exposed to anti-D (Rh)-sensitized human red blood cells. IPI was detected in 42 (26%) of 165 and in 78 (17%) of 448 sera assessed against monocytes from 15 or 5 panel donors, respectively. All IPI-positive sera reacted in an allotypic pattern. Eight IPI-positive sera tested with autologous monocytes were found to be nonreactive. Upon comparative analysis of 448 sera, a significant correlation was found between the specific patterns of IPI and lymphocytotoxicity by HLA antibodies. In addition, 13 sera (4%) were positive for IPI, but not for lymphocytotoxicity. Twenty IPI-positive sera were tested by indirect immunofluorescence against platelets and T lymphocytes and revealed IgG antibodies in 16 and 11 sera, respectively. IPI activity could be removed from 8 out of 10 positive sera by platelet pool absorption. While virtually all sera exhibiting HLA, A, B or C-like activity (cytotoxicity with all cells) or HLA DR-like activity (exclusive cytotoxicity with B lymphocytes and monocytes) were IPI-positive, IPI was infrequently observed with sera containing HLA DQ-like activity (cytotoxicity with B lymphocytes only). IPI was also rarely seen with sera cytotoxic only to monocytes and not at all with sera containing antibodies against endothelial/monocyte antigens. We conclude that IPI is caused by cytotoxic as well as noncytotoxic HLA A, B, C, DR-specific antibodies. This effect may bear significance for the maternal immune response against fetal antigens and may be useful for pretransplant histocompatibility testing.

Adult↗

PubMed1986

HLA antigens on platelet membranes. In vitro and in vivo studies.

In order to determine whether HLA-A,B antigens of platelets are integral membrane constituents or rather represent adsorbed plasma proteins, their presence in plasma and their adsorbability onto platelet membranes was studied by in vitro and in vivo experiments. The amount of HLA antigens was quantitated by inhibition of lymphocytotoxicity (LCT) and by enzyme-linked immunosorbent assay (ELISA) using operationally monospecific polyclonal HLA antibodies or murine HLA-specific monoclonal antibodies, respectively. We found that in 11 out of 13 HLA-A2 and in 9 out of 10 HLA-B13 experiments, platelets from antigen-negative donors pretreated with plasma from the same number of antigen-positive donors inhibited LCT to the same extent as platelets from antigen-positive donors. Nevertheless, the in vitro adsorbed HLA antigens onto antigen-negative platelets were, unlike those on antigen-positive platelets or in plasma, not reactive with monoclonal antibodies as quantitated by ELISA. Similarly, infusion of HLA-A2-negative platelets from single donors into 3 HLA-A2-positive, thrombocytopenic patients with bone marrow failure led to a good platelet increment, but did not convert the HLA type of donor platelets, neither at 2 h nor at 18 h posttransfusion. On the basis of these results, we conclude that soluble HLA antigens can be taken up by human platelets from plasma in small amounts. However, the major portion of HLA antigens appears to be integral membrane constituents.

Adsorption↗