Cases reported "Abortion, Habitual"

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1/7. Neonatal thrombocytopenia induced by maternal anti-HLA antibodies: a potential side effect of allogenic leukocyte immunization for unexplained recurrent aborters.

    Allogenic leukocyte immunization is one of several treatments tried for unexplained recurrent aborters, and is reported to have few maternal and neonatal side effects after the immunotherapy having been reported to date. In the present study, we report a rare case of neonatal thrombocytopenia (41000 cells/microl) observed in a female infant delivered by an unexplained habitual aborter. The mother was immunized with her husband's leukocytes once before pregnancy and twice at the 5th and 6th week of her successful pregnancy. Serological studies using mixed passive hemagglutination assays (MPHA) showed that maternal serum did not contain any antibodies which were reactive to 11 platelet-specific antigens, or to granulocyte antigens extracted from 9 persons. Lymphocyte cytotoxicity tests, however, showed that maternal serum but not infant serum had anti-HLA antibodies against both paternal and infant lymphocytes. Moreover, the maternal serum was found to have anti-HLA IgGs against platelet antigens extracted from the father and the infant. It is highly likely that this case of neonatal thrombocytopenia was caused by transplacental perfusion of maternal anti-HLA antibodies whose production was induced or enhanced by the allogenic leukocytes immunizations.
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2/7. Impairment of the protein c anticoagulant pathway in a patient with systemic lupus erythematosus, anticardiolipin antibodies and thrombosis.

    We have identified an inhibitor of the protein c anticoagulant pathway in the plasma of a patient with systemic lupus erythematosus and a history of recurrent deep vein thrombosis, fetal wastage, and seizures. The patient's plasma contained anticardiolipin antibodies as well as a weak lupus anticoagulant. Examination of this patient's plasma revealed normal levels of protein c and protein s antigen, normal levels of functional protein c, as well as essentially normal levels of every blood coagulation factor. In a modified prothrombin time assay, the activated protein c-mediated prolongation of the clotting time observed in normal plasma was not observed in this patient's plasma. Gel permeation chromatography of the patient's plasma revealed that the inhibitory material was a high molecular weight protein that coeluted with the IgM peak. The inhibitor did not appear to circulate as a complex with protein c, since the inhibitor could easily be separated from protein c during fractionation procedures, and did not interfere with the activation of protein c in plasma as assessed by a functional amidolytic assay. Our findings suggest that the recurrent thrombotic episodes observed in this patient may have occurred as a result of the patient's antiphospholipid antibody neutralizing specific phospholipids essential for the full expression of the anticoagulant activity of activated protein c.
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3/7. Hereditary heparin cofactor ii deficiency and thrombosis: report of six patients belonging to two separate kindreds.

    We describe six patients belonging to two families with congenital heparin cofactor ii deficiency (HC II). The affected members had low levels of HC II antigen and activity, and no abnormalities in HC II electrophoretic mobility were detected in the presence of heparin or dermatan sulphate during the first migration of crossed immunoelectrophoresis. These data suggested that patients had a type I (true) HC II deficiency. The association of thrombotic manifestations with congenital HC II deficiency has not been completely clarified. In these two families, thrombotic events occurred in two out of six affected members. In addition, there was a high incidence of spontaneous abortion in the affected females. Finally, the association of congenital HC II deficiency with angiomatosis was also observed in one patient.
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4/7. Maternal-paternal histocompatibility: lack of association with habitual abortions.

    Class I human leukocyte antigens (HLA-A, -B) and class II (HLA-DR) antigens were determined in 60 and 30 carefully selected couples with multiple abortions, respectively. The study group was compared with fertile couples with no history of abortion and with a control group consisting of randomly matched women and men from our laboratory cell panel. No significant deviation from the calculated control mating frequencies was observed in the group with habitual abortions. When the study and control couples were grouped by ethnic origin into Ashkenazim and non-Ashkenazim, the frequencies of shared HLA-A, -B, and -DR antigens were similar in both groups. These results do not confirm the observations of greater HLA compatibility between partners of aborting couples reported by other laboratories. Moreover, the results of an informative family in which the woman, after three consecutive spontaneous abortions, conceived and bore a healthy male infant genotypically HLA-identical to his mother are presented. Taken together, these results challenge the concept that compatibility in determinants of the major histocompatibility complex have a major role in habitual abortions.
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5/7. A new therapeutic antibody removal method using antigen-positive red cells. II. Application to a P-incompatible pregnant woman.

    Therapeutic antibody removal using antigen-positive red cells was applied to a pregnant woman who has high titered IgG anti-P and had lost all of 4 previous fetuses in P-incompatible pregnancy. The treatment was commenced at the 6th week of gestation and was intensively performed 93 times up to the 35th week. The volume of plasma treated was 2.3 1 per procedure on the average and totalled 215 1. The antibody titer was kept at a low level. At the end of the 35th week of gestation a female infant was delivered by cesarean section. The baby did not require an exchange transfusion and encountered no complications.
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6/7. Removal of maternal antibodies from a woman with repeated fetal loss due to P blood group incompatibility.

    BACKGROUND: plasmapheresis is intended to lower plasma antibody levels in women with blood group incompatible pregnancies. CASE REPORT: Therapeutic specific antibody removal by using antigen-positive red cells was applied to a blood group p pregnant women who had a high titer (128) of IgG anti-PP1Pk and had lost all six previous fetuses in blood group P-incompatible pregnancies. Plasma was taken from the patient with an intermittent-flow cell separator, mixed with a volume of washed and packed P-positive red cells equivalent to one-fifth of the volume of plasma, and incubated for 10 minutes in an ice water bath. The PP1Pk antibodies were removed, and the autologous plasma was transfused. Treatment by specific antibody removal was started in the seventh week of gestation, and performed one to three times a week for a total of 56 times up to the 34th week. The volume of plasma treated was 2.4 L per procedure on average and totaled 135 L. After each treatment, the antibody titer in the patient's plasma usually decreased by 1 log2, and no deleterious effect on the women was noted. The titers of IgG anti-P and anti-Pk were kept between 4 and 16 after the ninth week of gestation. At the end of the 34th week of gestation, a male infant was delivered by cesarean section. The infant did not require an exchange transfusion and is now a healthy 2-year-old boy. CONCLUSION: This therapeutic method is very useful in the management of fetomaternal P-incompatibility.
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7/7. Primary antiphospholipid syndrome emerging following thymectomy for myasthenia gravis: additional evidence for the kaleidoscope of autoimmunity.

    The etiology of autoimmune diseases is multifactorial. In many of them the stimulation by a specific autoantigen is claimed to be responsible for the initiation of the disease. Alternatively, an autoimmune state may be induced by a pure dysregulation of the immune system. Such is the case in which severe systemic lupus erythematosus (SLE) is induced in young patients with myasthenia gravis following thymectomy. We have referred to this set of events as the 'kaleidoscope of autoimmunity'. Herewith, we would like to present another example of the kaleidoscope phenomenon, namely: the emergence of a full blown clinical presentation of the primary antiphospholipid syndrome (APS-recurrent thromboembolic phenomena, repeated fetal loss with high titers of anti-cardiolipid antibodies) in a 32 y old female with myasthenia gravis, two years following thymectomy. thymectomy in myasthenic patients may be associated with the emergence of new autoimmune conditions such as SLE and APS, pointing to the importance of immune dysregulation in the induction of these autoimmune diseases.
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