Blood transfusions are regarded as hazardous in patients with warm-type autoimmune haemolytic anaemia (AIHA) because of potential intensification of haemolysis and a presumed high incidence of alloimmunisation. We have retrospectively analysed data of 79 multitransfused patients (74 adults, 5 children) with detectable warm autoantibodies and transitory or persisting haemolytic anaemia. All patients had received blood transfusions on at least two occasions. Patients were reexamined at least twice within the first 6 months of transfusion (duration of follow-up 6 months-12 years). 53 patients had received blood transfusions because of decompensated AIHA, all of whom presented with detectable autoantibodies against red blood cells. None of these patients had transfusion-related alloimmunisation or a definite increase in haemolysis, even when the transfused red cells were serologically incompatible because of free serum autoantibodies. The other 26 patients had no signs of AIHA at presentation (negative direct and indirect antiglobulin test), but received blood transfusions for anaemia due to various other causes. 23 of these 26 patients went on to develop alloantibodies as well as autoantibodies upon transfusion, and 3 patients developed autoantibodies alone. Our findings do not support the generally accepted notion that transfusion therapy should be avoided in AIHA patients. Rather, they indicate that the incidence of alloimmunisation as well as adverse haemolytic transfusion reactions are less common in AIHA patients than in other multitransfused patients.

Adolescent↗

PubMedDate not supplied

Delayed hemolytic transfusion reactions. Evidence for complement activation involving allogeneic and autologous red cells.

Twenty-six patients with delayed hemolytic transfusion reactions ( DHTR ) were investigated. The reaction of hemolysis often was concealed by other disorders that were usually associated with signs of hemolysis or blood loss. Coating of red cells was analyzed with regard to IgG and/or complement bound in vivo. Although many of the alloantibodies involved (K [8]; E [5]; Fya [2]; Fyb [2]; D [1]; c [1]; multiple [7]) are usually thought to be incapable of complement activation, a strongly positive direct antiglobulin test (DAT) due to C3d was found in all cases. On first examination after transfusion, C3d was present on circulating red cells in large amounts and remained discernible for weeks and even months. IgG on red cells was detected by the DAT in only 10 out of 26 cases. By means of a sensitive radioimmunoassay, IgG was demonstrated in 16 out of 17 cases, but usually in small quantities. Despite the low IgG concentrations, the causative alloantibodies could be eluted in 25 of 26 cases, and, as shown by sequential investigations, in six cases were recoverable from circulating red cells for over 100 days posttransfusion. Since the antiglobulin reactions due to anti-complement were usually strong, not of the "mixed-field" type, and in some cases remained detectable on circulating red cells for months, we conclude that complement is regularly activated in DHTR and binds not only to donated but probably also to autologous red cells.

Adult↗

PubMedDate not supplied

The clinical significance of HLA antigens on red cells. Survival studies in HLA-sensitized individuals.

To investigate the clinical significance of HLA determinants expressed on red cells (RBCs), 51Cr survival studies were carried out in six women (four healthy individuals, two patients with solid carcinoma) immunized against HLA antigens by pregnancy or blood transfusions, respectively. Donors were selected who were compatible in typical RBC antigen systems assayed by conventional techniques but were mismatched for the HLA antigens in question. Crossmatches also were performed with RBC, as well as with lymphocytes, by means of a radioimmune anti-IgG test (RIAT). We found that RBC survival was shortened in all cases. The mean life-span of RBCs depended on antigen specificity rather than on the antibody strength. HLA incompatibility of RBCs could be monitored by the RIAT in all donor/recipient pairs. We conclude that a shortened mean life-span of RBC is to be expected by HLA antibodies, especially when HLA-B7 is involved, but the severity of an in vivo immune reaction in HLA incompatible transfusions cannot be predicted from the in vitro tests used.

Adult↗

PubMedDate not supplied

Binding of fluid phase C3b to nonsensitized bystander human red cells. A model for in vivo effects of complement activation on blood cells.

There is evidence that activated complement fragments (C3b) can bind to human red cells (RBCs) serving as adsorbing surfaces, but not as antigens. This evidence prompted the present in vitro experiments. Using the standard antiglobulin test (AGT), the radioimmune antiglobulin test (RIAT), and the immune adherence test, we found that C3 can indeed be attached to "bystander" human RBCs if complement is activated either through the classical pathway (anti-A hemolysins plus blood group A1 RBCs) or the alternative pathway (activator surfaces, i.e., Escherichia coli bacteria, rabbit RBCs, or inulin). On Scatchard plot analysis, between 24,000 and 44,000 radiolabeled anti-C3d molecules were bound per one adjacent "bystander" RBC, while untreated control RBCs, or RBCs preincubated with fresh compatible serum, bound only 200 to 300, and 600 to 800 molecules, respectively. Despite strong coating with C3 fragments, only "bystander" paroxysmal nocturnal hemoglobinuria, but not normal, RBCs were hemolyzed by complement activation, i.e., through E. coli at pH 8.0. RBCs were not coated with C3 when complement was activated in the fluid phase by heat-aggregated IgG or a staphylococcal "decomplementation antigen." We conclude that the findings of our in vitro experiments accurately mimic some old, but as yet insufficiently understood, in vivo effects of complement activation on circulating blood cells.

Binding Sites, Antibody↗

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Immune thrombocytopenia in severe hemophilia A treated with high-dose intravenous immunoglobulin.

Five patients with severe hemophilia A receiving long-term treatment with commercial factor VIII concentrates developed severe immune thrombocytopenia (ITP, platelet counts less than 20 X 10(9)/l). Concomitantly, they presented with a marked elevation of serum IgG concentrations (mean, 2364 mg/dl;range, 1712-2954 mg/dl). In four patients, the T helper to suppressor cell ratio was below 1. Treatment with high-dose intravenous immunoglobulin (IgG, 7s) at doses of 0.2g (n = 2) or 0.4g (n = 3) per kg of body weight on 5 consecutive days was effective immediately. The bleeding tendency ceased and platelet counts rose transiently. In three cases, treatment was repeatedly effective and patients underwent uneventful splenectomies. Thus, high-dose IgG therapy may serve as a life-saving agent in patients with severe hemophilia complicated by ITP.

Adolescent↗

PubMedDate not supplied

Evidence suggesting the occurrence of C3-independent intravascular immune hemolysis. Reactive hemolysis in vivo.

The authors present circumstantial evidence for the involvement of reactive hemolysis, i.e., C3-independent binding of the cytolytic C5b-9 complement complex to bystander red cells (RBC), in a case of intravascular immune hemolysis. Fresh serum obtained from a 6-year-old patient during the hemolytic episode, but not obtained thereafter, induced C5b-9-dependent hemolysis of human RBCs but the indirect C3 antiglobulin test remained negative. Particles (presumably RBC ghosts) isolated from the patient's plasma anticoagulated with EDTA at the peak of hemolysis were coated with C5b-9 complexes, whereas the direct antiglobulin test was strongly positive for IgA, only weakly positive for IgG, and negative for C3. Moreover, neither the autoantibodies isolated by elution (IgG plus IgA), nor free serum autoantibodies (IgA alone) activated complement in vitro. Additionally, serum samples collected later during the 12-month period of observation contained normal levels of C3, C4, C8, and C9, but markedly reduced levels of C7. These serums all produced strong reactive lysis in agarose plates, but not in test tubes. These results appear compatible with the working hypothesis that the intravascular hemolytic episode in this patient might have arisen through a local initiation of complement activation with subsequent C3-independent binding of C5b-9 to and hemolysis of bystander RBCs.

Anemia, Hemolytic, Autoimmune↗

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Nomifensine-induced immune hemolytic anemia and posttransfusion purpura in the same patient.

A 53-year-old white woman had severe hemolytic anemia while taking nomifensine. A drop of hemoglobin to 61 g per I prompted the transfusion of two units of packed red cells. Nine days later, severe thrombocytopenia with multiple petechiae ensued. Both hemolysis and thrombocytopenia resolved promptly upon withdrawal of the drug and short-term prednisolone treatment. Serologic studies showed nomifensine-dependent, metabolite-specific red cell antibodies as the cause of immune-mediated hemolysis and, in serum samples obtained after purpura, strong platelet-specific PlA1 and weak HLA antibodies suggested a diagnosis of posttransfusion purpura.

Anemia, Hemolytic↗

PubMedDate not supplied

Metabolite-specific (IgG) and drug-specific antibodies (IgG, IgM) in two cases of trimethoprim-sulfamethoxazole-induced immune thrombocytopenia.

Two cases of trimethoprim-sulfamethoxazole (TMP-SMX)-induced immune thrombocytopenia are reported in which unusual drug-dependent platelet antibodies were demonstrated by immunofluorescence and enzyme-linked immunosorbent assay. Whereas two distinct sulfamethoxazole-dependent antibodies of the IgG and IgM class were detectable in the serum of one patient, the serum of the other patient contained a platelet antibody exclusively reactive with N-4-acetyl-sulfamethoxazole, a metabolite of sulfamethoxazole. Urine from a healthy volunteer collected after administration of therapeutic doses of TMP-SMX proved to be an appropriate source of ex vivo metabolites for antibody testing. The results of this study stress the role of metabolite-specific antibodies in drug-dependent immune thrombocytopenia and underscore the necessity of including metabolite preparations of drugs in serologic analyses.

Aged↗

PubMedDate not supplied

'Immune complex' mediated intravascular hemolysis due to IgM cephalosporin-dependent antibody.

Immune hemolytic anemia (IHA) related to cephalosporins is rare and generally considered to be the result of a drug-adsorption mechanism. In previously reported cases, the hemolysis was usually extravascular and the causative antibodies were IgG, incapable of activating complement, and demonstrable by the direct or indirect antiglobulin test using red cells (RBCs) pretreated in vitro with cephalosporin. The authors report a patient in whom acute intravascular hemolysis developed while she was receiving cefotaxime (a cephalosporin as yet not reported to cause IHA). The patient's RBCs were coated only with complement fragments (C3d), even at the peak of the hemolytic episode. Her serum and eluates repeatedly yielded negative results when tested against normal or cephalosporin-coated RBCs. However, strong hemagglutination and C5b-9-mediated hemolysis were observed if the patient's serum was tested against RBCs in the presence of the drug, its ex vivo antigen and, to a lesser degree, cephalothin and ceftriaxon, but not in the presence of penicillin and other related cephalosporins. The positive reactions were not changed by preincubating the serum with different amounts of the drugs. All of these findings reflect the typical picture of drug-induced IHA by the so-called "immune complex" mechanism and not by the drug-adsorption mechanism. The authors conclude that cephalosporin can cause immune hemolysis in two ways: the drug-adsorption mechanism and, as described here, the "immune complex" mechanism.

Aged↗

PubMedDate not supplied

Frequency of platelet-specific antigens PlA1, Baka, Yuka, Yukb, and Bra in South American (Mapuches) Indians.

One hundred twelve unrelated Mapuches Indians from the area of Temuco, Chile were studied for the prevalence of five platelet-specific antigens. The prevalences found were: PlA1 (Zwa), greater than 99 percent; Baka, 89.3 percent; Yuka (Penb), 0.9 percent; Yukb (Pena), greater than 99 percent; and Bra, 4.9 percent.

Alleles↗

PubMedDate not supplied

Platelet transfusion refractoriness associated with two rare platelet-specific alloantibodies (anti-Baka and anti-PlA2) and multiple HLA antibodies.

A 65-year-old patient with pancytopenia resulting from osteomyelosclerosis became refractory to platelet transfusions during long-time transfusion support. He developed two rare, platelet-specific antibodies (anti-PlA2 and -Baka) disguised by strong, multispecific HLA antibodies. The specificity of the platelet-specific antibodies was detected by a newly designed enzyme-linked immunosorbent assay using glycoprotein-specific monoclonal antibodies for immobilization of platelet antigens.

Aged↗

PubMedDate not supplied

Autoimmune hemolytic anemia caused by a cold agglutinin with a new specificity (anti-Ju).

A cold autoantibody detected in the serum of a patient with chronic idiopathic cold agglutinin disease and hemolytic anemia is described. The antibody reacted with adult as well as with cord red cells, and its reactivity was strongly diminished by treatment of the cells with neuraminidase and to a lesser degree by treatment with protease. Thus, the specificity of the antibody is distinct from those of all cold antibodies yet described.

Agglutinins↗