thromboplastin and Abortion--Habitual

Antiphospholipid syndrome (APS) is an autoimmune disorder defined by the presence of antiphospholipid antibodies in plasma of patients with vascular thrombosis and/or pregnancy morbidity. APS is considered the major cause of brain infarction in young adults and is a generally accepted cause of recurrent pregnancy loss. Antiphospholipid antibodies are a heterogeneous group of autoantibodies strongly related to the clinical manifestations of APS and with a widely recognized pathogenic role in thrombosis. In this article, recent clinical and pathophysiological advances in APS are discussed.

Topics: Abortion, Habitual; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Autoimmunity; Biomarkers; Female; Humans; Male; Molecular Targeted Therapy; NF-kappa B; P-Selectin; p38 Mitogen-Activated Protein Kinases; Pregnancy; Pregnancy Complications; Risk Assessment; Signal Transduction; Thromboplastin; Thrombosis

Recurrent fetal loss affects 1-5% of women of childbearing age. Immunological mechanisms may account for 40% of recurrent miscarriages, and in particular, the antiphospholipid syndrome (APS) appears to be implicated in 7-25% of the cases. Because antiphospholipid (aPL) antibodies have thrombogenic properties, fetal loss in patients with APS has been ascribed to thrombosis of placental vessels. However, we have shown that inflammation, specifically activation of complement with generation of the anaphylotoxin C5a, is an essential trigger of fetal injury. Thrombosis and inflammation are linked in many clinical conditions. Tissue factor (TF), the major cellular initiator of the coagulation protease cascade, plays important roles in both thrombosis and inflammation, and its expression is increased in patients with APS. Here we describe how TF, acting as a proinflammatory molecule, induces trophoblast injury and fetal death in a mouse model of APS. Importantly, we will discuss how TF contributes to C5a-induced oxidative burst in neutrophils leading to trophoblasts and fetal injury in APS. The finding that TF is an important effector in aPL-induced inflammation may allow the development of new therapies to abrogate the inflammatory loop caused by tissue factor and improve pregnancy outcomes in patients with aPL antibodies. Statins downregulate TF-induced inflammation and rescued the pregnancies in aPL-treated mice, suggesting they may be a good treatment for women with aPL-induced pregnancy complications.

Topics: Abortion, Habitual; Animals; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Complement Activation; Disease Models, Animal; Embryo, Mammalian; Factor VIIa; Female; Fetal Death; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mice; Neutrophil Activation; Pregnancy; Receptor, PAR-2; Thromboplastin; Thrombosis

Antiphospholipid antibodies (Abs) are associated with thrombosis and are a risk factor for recurrent pregnancy loss and obstetric complications in patients with the antiphospholipid syndrome. It is generally accepted that the major autoantigen for aPL Abs is beta (2) glycoprotein I, which mediates the binding of aPL Abs to target cells (i.e., endothelial cells, monocytes, platelets, trophoblasts, etc.) leading to thrombosis and fetal loss. This article addresses molecular events triggered by aPL Abs on endothelial cells, platelets, and monocytes and complement activation, as well as a review of the current knowledge with regard to the putative receptor(s) recognized by aPL Abs on target cells as well as novel mechanisms that involve fibrinolytic processes. A section is devoted to the description of thrombotic and inflammatory processes that lead to obstetric complications mediated by aPL Abs. Based on experimental evidence using in vitro and in vivo models, new targeted therapies for treatment and/or prevention of thrombosis and pregnancy loss in antiphospholipid syndrome are proposed.

Topics: Abortion, Habitual; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Autoantigens; beta 2-Glycoprotein I; Blood Platelets; Complement Activation; Endothelial Cells; Female; Fibrinolysis; Humans; Inflammation Mediators; Monocytes; Placenta; Pregnancy; Pregnancy Complications, Hematologic; Thrombin; Thrombophilia; Thromboplastin; Trophoblasts; Venous Thrombosis

The antiphospholipid syndrome (APS) is characterized by clinical manifestations such as venous and arterial thrombosis, thrombocytopenia and/or recurrent pregnancy loss, as well as the persistent presence of laboratory markers of antiphospholipid (aPL) antibodies detected in laboratory assays. Though it is generally accepted that aPL antibodies, such as anticardiolipin (aCL), anti-beta2 glycoprotein I (anti-beta2GPI), and lupus anticoagulants (LA) contribute to the pathogenesis of APS, precise mechanism(s) are yet to be fully described. It is probable that aPL antibodies bind to a range of cellular targets (e.g., platelets, endothelial cells, and monocytes), leading to thrombosis and obstetric complications. There is now increasing evidence that alterations to the tissue factor (TF) pathway of blood coagulation contribute toward hypercoagulability in patients with aPL antibodies. This article reviews current evidence that suggests changes and/or interference to the major pathway of blood coagulation may represent a novel mechanism that contributes to the development of APS.

Topics: Abortion, Habitual; Antibodies, Antiphospholipid; Antibody Specificity; Antiphospholipid Syndrome; Autoantibodies; beta 2-Glycoprotein I; Endothelial Cells; Female; Humans; Immunoglobulin G; Lipoproteins; Lupus Coagulation Inhibitor; Models, Biological; Pregnancy; Pregnancy Complications, Hematologic; Thrombin; Thrombophilia; Thromboplastin; Venous Thrombosis

Antiphospholipid-protein antibodies (APA) are a family of immunoglobulins which have been defined by varying laboratory test systems. Lupus anticoagulants (LA) and anticardiolipin antibodies (ACA) are the two most prominent members of this family of antibodies. LA are detected utilizing various phospholipid (PL) dependent tests of coagulation (e.g., activated partial thromboplastin time [APTT], Kaolin Clotting Time [KCT], dilute Russell Viper Venom Time [dRVVT]). Originally, LA were thought to be a laboratory nuisance since the vast majority of individuals with LA did not bleed. Paradoxically, patients with LA were found to have an increased incidence of thromboembolic events and also recurrent spontaneous abortions (RSA). Thus, the laboratory detection of LA has become part of the work up of patients with thromboembolic disorders and RSA. ACA are detected using solid phase assay systems (radioimmunoassay or ELISA). The presence of ACA has the same clinical implications as that of LA. Although originally it was suggested ACA and LA were the same antibody, it is now well accepted that they, in many instances, are different antibodies. Therefore, it is critical for laboratories to evaluate patient samples for both LA and ACA. In approximately 60% of circumstances, both antibodies will be found. In the remaining cases, there will be discordance between the two test systems. The question of whether APA are causative, coincidental, or a consequence of the clinical complications of RSA and thrombosis remains controversial. Recent evidence based on prospective clinical studies and analysis of markers of in vivo coagulation suggests APA are causative.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Abortion, Habitual; Adult; Animals; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Autoimmune Diseases; beta 2-Glycoprotein I; Cattle; Eicosanoids; Endothelium, Vascular; Female; Glycoproteins; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Pregnancy; Thromboplastin; Thrombosis

Antiphospholipid antibodies are autoantibodies that can be detected in plasma or serum with phospholipid-dependent coagulation tests or solid-phase immunoassays. The presence of these autoantibodies is strongly associated with an increased risk for arterial and venous thrombosis, recurrent fetal loss and thrombocytopenia. This paradoxical association of the in vitro prolongation of clotting assays and in vivo thrombosis has stimulated the search for the real antigen to which the autoantibodies are directed. A large number of potential pathological mechanisms have been proposed, and although disturbance of a certain metabolic pathway by the antibodies can explain a thrombotic tendency in one patient, no general pathological mechanism explaining thrombosis in the whole patient population has been found. This suggests that the antiphospholipid antibodies are a heterogeneous group of autoantibodies and is supported by the recent observations that antiphospholipid antibodies are not directed against phospholipids alone but against a combination of phospholipids and phospholipid-binding proteins. Both the phospholipid and the protein are part of the antigen. For the detection of antiphospholipids in an ELISA set-up, beta 2-glycoprotein I is the protein cofactor. In the coagulation tests, beta 2-glycoprotein, as well as prothrombin, can act as cofactor. However, the presence of these two proteins as a part of the epitope of the antiphospholipid antibodies does not explain the thrombotic tendency in the patient group. We have found that more physiologically relevant cofactors such as protein C and protein S, for which it is known that a partial deficiency is correlated with a thrombotic tendency, can also act as cofactors for the binding of antiphospholipid antibodies. It is concluded that antiphospholipid antibodies are a heterogeneous group of autoantibodies with varying affinity for different protein-phospholipid complexes and that inhibition of the biological activity of the protein part of the complex determines the pathological capacity of the antibodies.

Topics: Abortion, Habitual; Antibodies, Antiphospholipid; Antibody Specificity; Antiphospholipid Syndrome; beta 2-Glycoprotein I; Endothelium, Vascular; Epoprostenol; Female; Glycoproteins; Humans; Lupus Coagulation Inhibitor; Monocytes; Phospholipids; Platelet Aggregation; Pregnancy; Protein C; Thrombocytopenia; Thromboembolism; Thrombomodulin; Thromboplastin; von Willebrand Factor

In a controlled, prospective study of 44 consecutive women with idiopathic habitual abortion, only 5% had symptoms of rheumatic disease. Patients did not differ from control subjects in the frequency of positive results on tests for antinuclear antibody or anti-double-stranded DNA. Levels of C3 and C4 were higher in the habitual aborters. No patients had anti-Ro. The antiphospholipid antibody results were analyzed using 2 methods: the frequency of antiphospholipid antibodies was 9% by lupus anticoagulant using the Russell viper venom time (95% confidence interval 22-2.5) and 11% by anticardiolipin antibody assay (95% confidence interval 25-3.7), which was not significantly different from that in control subjects. However, the mean levels in the aborters (although within the normal range) were significantly higher than those in control subjects for anti-double-stranded DNA (P = 0.004), lupus anticoagulant (by Russell viper venom time; P = 0.05), and anticardiolipin antibody (P = 0.0007), when examined by multiple linear regression analysis corrected for age and concurrent pregnancy. Of the 3 patients with antiphospholipid antibodies and subsequent successful pregnancies, only 1 was treated with prednisone and aspirin. We conclude that, in the majority of women, subclinical lupus, anti-Ro, the lupus anticoagulant, and anticardiolipin antibodies are not associated with idiopathic habitual abortion.

Topics: Abortion, Habitual; Adult; Antibodies, Antinuclear; Autoantibodies; Blood Coagulation Factors; Cardiolipins; Clinical Trials as Topic; Female; Humans; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Pregnancy; Prospective Studies; Thromboplastin

Essentials Activated protein C (APC) resistance is a prevalent risk factor for venous thrombosis. A novel missense mutation (Ala512Val - FVBonn ) was characterized in vitro and in silico. FVBonn is a new cause of APC resistance and venous thrombosis. FVBonn expresses additionally enhanced procoagulant activity in the absence of APC.. Background Activated protein C (APC) resistance is a prevalent risk factor for venous thrombosis. This phenotype is most commonly associated with the factor V Arg506Gln mutation (FV Leiden), which impairs the APC-mediated inactivation of both activated FV (FVa) and activated FVIII (FVIIIa). Objectives Here, we report the identification and characterization of a novel FV mutation (Ala512Val, FVBonn ) in six patients with APC resistance and venous thrombosis or recurrent abortions. Methods FVBonn was expressed in a recombinant system and compared with recombinant wild-type (WT) FV and FV Leiden in several functional assays. Results FVBonn conferred APC resistance to FV-depleted plasma, both in the activated partial thromboplastin time (APTT)-based test (APC sensitivity ratio [APCsr] of 1.98 for FVBonn versus 4.31 for WT FV and 1.59 for FV Leiden) and in the thrombin generation-based test (normalized APCsr of 5.41 for FVBonn versus 1.00 for WT FV and 8.99 for FV Leiden). The APC-mediated inactivation of FVaBonn was slower than that of WT FVa (mainly because of delayed cleavage at Arg506), but was greatly stimulated by protein S. The APC cofactor activity of FVBonn in FVIIIa inactivation was ~ 24% lower than that of WT FV. In line with these findings, an in silico analysis showed that the Ala512Val mutation is located in the same loop as the Arg506 APC cleavage site and might hamper its interaction with APC. Moreover, FVBonn was more procoagulant than WT FV and FV Leiden in the absence of APC, because of an increased activation rate and, possibly, an enhanced interaction with activated FX. Conclusions FVBonn induces hypercoagulability via a combination of increased activation/procoagulant activity, decreased susceptibility to APC-mediated inactivation, and slightly reduced APC cofactor activity.

Topics: Abortion, Habitual; Activated Protein C Resistance; Adult; Aged; Blood Coagulation; Blood Coagulation Tests; Catalysis; Coagulants; Cohort Studies; Factor V; Factor Va; Factor VIIIa; Female; Humans; Male; Mutation; Mutation, Missense; Partial Thromboplastin Time; Pregnancy; Protein C; Thrombin; Thromboplastin; Venous Thrombosis; Young Adult

Bad pregnancy outcomes have been associated with increased activation of the coagulation cascade and inflammation, in particular the activation of the complement cascade. Recent studies have suggested that inflammatory processes modulate thrombogenic pathways and vice versa. We studied the cross-talk between the coagulation and the complement cascade in the pathogenesis of recurrent miscarriages and preeclampsia in mice. We identified tissue factor (TF) as a crucial mediator of fetal and placental damage in mouse models of recurrent miscarriages and preeclampsia. Increased TF expression increases the release of reactive oxygen species and antiangiogenic molecules from inflammatory cells inducing trophoblast damage and bad pregnancy outcomes. We also demonstrated that pravastatin, by downregulating TF expression, prevents miscarriages and the onset of preeclampsia in mice.

Topics: Abortion, Habitual; Animals; Anticholesteremic Agents; Blood Coagulation; Complement Activation; Complement System Proteins; Female; Humans; Inflammation; Mice; Pravastatin; Pre-Eclampsia; Pregnancy; Thromboplastin

Miscarriages in patients with antiphospholipid (aPL) antibodies have been attributed to thrombosis of placental vessels. However, we have shown that inflammation plays a crucial role in fetal injury. We identified tissue factor (TF), the major cellular activator of the coagulation cascade, as a key mediator in inflammation and fetal injury in aPL antibody-treated mice. We found that TF in maternal neutrophils was associated with fetal injury. TF expression in neutrophils contributes to the respiratory burst and subsequent trophoblast oxidative injury and pregnancy loss induced by aPL antibodies. We also analysed how TF contributes to neutrophil activation and trophoblast injury in this model. We showed that neutrophils from aPL antibody-treated mice express protease activated receptor 2 (PAR-2) and that stimulation of this receptor leads to neutrophil activation, trophoblast injury and fetal death. Mice deficient in PAR-2 and treated with aPL antibodies exhibited reduced neutrophil activation and normal pregnancies, indicating that PAR-2 plays an important role in the pathogenesis of aPL antibody-induced fetal injury. In addition, we demonstrated that the statins simvastatin and pravastatin downregulate TF and PAR-2 expression in neutrophils and thus prevent pregnancy loss. In summary, this study shows that TF signaling through PAR-2 mediates neutrophil activation and fetal death in antiphospholipid syndrome, and that statins may be an appropriate treatment for women with aPL antibody-induced pregnancy complications.

Topics: Abortion, Habitual; Animals; Antibodies, Antiphospholipid; Female; Injections, Intraperitoneal; Mice; Mice, Knockout; Mice, Transgenic; Neutrophil Activation; Neutrophils; Pravastatin; Pregnancy; Receptor, PAR-2; Simvastatin; Thromboplastin

Antiphospholipid antibodies (aPL) are closely related to the development of thrombosis, but the exact mechanism(s) leading to thrombotic events remains unknown. In this study, using proteomic techniques, we evaluated changes in protein expression of monocytes from patients with antiphospholipid syndrome (APS) related to the pathophysiology of the syndrome.. Fifty-one APS patients were included. They were divided into 2 groups: patients with previous thrombosis, and patients with recurrent spontaneous abortion. As controls, we studied patients with thrombosis but without aPL, and age- and sex-matched healthy subjects.. The proteins that were more significantly altered among monocytes from APS patients with thrombosis (annexin I, annexin II, protein disulfide isomerase, Nedd8, RhoA proteins, and Hsp60) were functionally related to the induction of a procoagulant state as well as to autoimmune-related responses. Proteins reported to be connected to recurrent spontaneous abortion (e.g., fibrinogen and hemoglobin) were also determined to be significantly deregulated in APS patients without thrombosis. In vitro treatment with IgG fractions purified from the plasma of APS patients with thrombosis changed the pattern of protein expression of normal monocytes in the same way that was observed in vivo for monocytes from APS patients with thrombosis.. For the first time, proteomic analysis has identified novel proteins that may be involved in the pathogenic mechanisms of APS, thus providing potential new targets for pathogenesis-based therapies for the disease.

Topics: Abortion, Habitual; Adolescent; Adult; Aged; Analysis of Variance; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Autoantibodies; Autoimmunity; Blotting, Western; Cells, Cultured; Electrophoresis, Gel, Two-Dimensional; Female; Flow Cytometry; Humans; Male; Middle Aged; Monocytes; Proteomics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Statistics, Nonparametric; Thromboplastin; Thrombosis

Antiphospholipid syndrome (APS), characterized by circulating antiphospholipid (aPL) antibodies, is a major cause of early pregnancy failure and placental insufficiency. In this study, we examined whether impaired endometrial differentiation before conception contributes to the high incidence of pregnancy complications in APS. Timed secretory endometrial biopsies were obtained from a cohort of women with recurrent pregnancy loss (RPL). Real-time quantitative (RTQ)-PCR was used to determine the expression levels of transcripts that encode for decidual markers, proinflammatory cytokines and complement regulatory proteins. Expression of decidual markers such as prolactin (PRL), tissue factor (TF) and signal transducer and activator of transcription 5 (Stat5), but not insulin-like growth factor-binding protein 1 (IGFBP-1), was significantly lower in samples obtained from aPL(+) patients (n = 24) when compared with aPL(-) group (n = 58) (P < 0.05). The abundance of transcripts encoding for interferon gamma (IFNgamma), tumour necrosis factor alpha (TNFalpha) or Stat1 did not differ significantly between both groups (P >/= 0.05). However, analysis of transcripts that encode for complement regulatory proteins showed a marked decrease in decay-accelerating factor (DAF/CD55) levels in aPL(+) patients (P = 0.005), which was mimicked at protein level as demonstrated by immunohistochemistry. In summary, patients with RPL have distinct endometrial gene expression profiles depending on the presence or absence of circulating aPL antibodies. In APS, impaired endometrial differentiation and lower DAF/CD55 expression before conception may compromise implantation and predispose to complement-mediated pregnancy failure.

Topics: Abortion, Habitual; Adult; Antibodies, Antiphospholipid; Antigens, Differentiation; Antiphospholipid Syndrome; Case-Control Studies; CD55 Antigens; CD59 Antigens; Complement System Proteins; Endometrium; Female; Gene Expression; Humans; Immunohistochemistry; Insulin-Like Growth Factor Binding Protein 1; Interferon-gamma; Membrane Cofactor Protein; Pregnancy; Prolactin; Reverse Transcriptase Polymerase Chain Reaction; Thromboplastin; Tumor Necrosis Factor-alpha

Topics: Abortion, Habitual; Adult; Animals; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Autoimmune Diseases; Drug Monitoring; Female; Humans; International Normalized Ratio; Intracranial Embolism; Intracranial Thrombosis; Male; Middle Aged; Pregnancy; Recombinant Proteins; Recurrence; Risk; Seizures; Thromboembolism; Thrombophilia; Thrombophlebitis; Thromboplastin; Warfarin

Trophoblasts and endothelial cells represent a potential target for antibodies in women with recurrent spontaneous abortions. These antibodies have been shown to be associated with anti-phospholipid antibodies. Are they also present in women with unexplained pregnancy losses in the absence of anti-phospholipid antibodies?. The anti-trophoblast antibodies were tested by an immunofluorescence assay on cells purified from pooled first-trimester placentae, whereas the anti-endothelial cell antibodies were measured by enzyme-linked immunoadsorbent assay (ELISA) on cells isolated from the umbilical vein and were cultured to confluence. The cytotoxicity of trophoblasts was evaluated in a homologous system. The expression of adhesion molecules on endothelial cells was quantitated by ELISA using specific monoclonal antibodies, and the expression of tissue factor was quantitated by a chromogenic assay measuring the formation of factor Xa.. Complement-fixing antibodies to trophoblast represent a better marker to discriminate patients with recurrent spontaneous abortions from controls and are cytotoxic for the target cells. Anti-endothelial antibodies are also present in these patients and exhibit pro-inflammatory and pro-coagulant activities.

Topics: Abortion, Habitual; Antibodies; Case-Control Studies; Cell Adhesion Molecules; Cytotoxicity, Immunologic; Endothelium, Vascular; Female; Humans; Immunoglobulin G; In Vitro Techniques; Pregnancy; Thromboplastin; Trophoblasts

We have previously reported the presence in normal human placentae of coagulation, macrophages and helper T lymphocytes in inflammatory foci known as villitis of unestablished etiology. In order to investigate the link between coagulation and immunity, we have studied fetal stem vessel endothelium for tissue factor, which is made available by cytokines and activates coagulation via the extrinsic pathway. We found that fetal stem vessel endothelial cells of normal chorionic villi did not react with antibody to tissue factor. Normal placentae contain small numbers of villitis areas and endothelium in these areas was reactive with antibody to tissue factor. Endothelial tissue factor reactivity was more prominent in placentae from secondary recurrent spontaneous aborters and these placentae have greatly increased numbers of villitis areas. The tissue factor availability on fetal stem vessel endothelium may result from immunologically mediated cytokine release. The net effect of these reactions is the presence of lymphocytes, macrophages, coagulation, necrosis and vasculitis in villitis.

Topics: Abortion, Habitual; Chorionic Villi; Endothelium, Vascular; Female; Fetus; Humans; Inflammation; Placenta Diseases; Pregnancy; Pregnancy Trimester, Third; Thromboplastin

Topics: Abortion, Habitual; Autoimmune Diseases; Blood Coagulation Factors; Enzyme-Linked Immunosorbent Assay; Female; Humans; Lupus Coagulation Inhibitor; Male; Partial Thromboplastin Time; Phospholipids; Pregnancy; Reagent Kits, Diagnostic; Thromboembolism; Thromboplastin

Topics: Abortion, Habitual; Animals; Autoantibodies; Blood Coagulation Factors; Blood Coagulation Tests; Cardiolipins; Cattle; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoglobulin G; Immunoglobulin M; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Male; Phospholipids; Pregnancy; Thromboplastin

The relationship between abortive disease and systemic lupus erythematosus is complex as shown by data from the literature and by our 9 patients selected for presenting with abortive disease, circulating anticoagulant and biological signs of autoimmunity. The risk of transformation into a systemic disease is real, although difficult to evaluate in the absence of prospective studies, but the major problem with these patients is the severity of the obstetrical pathology. The sombre foetal prognosis, already reported in the literature, requires close supervision and sustained treatment during pregnancy. For these reasons we suggest calling autoimmune abortive disease the disease which affects women with signs of autoimmunity who have had several, often late foetal deaths associated with the presence of circulatory anticoagulant thought to interfere with placental blood flow.

Topics: Abortion, Habitual; Adult; Antibodies, Antinuclear; Autoantibodies; Autoimmune Diseases; Blood Coagulation Factors; Female; Fetal Death; Humans; Lupus Coagulation Inhibitor; Pregnancy; Prognosis; Thromboplastin

A solid phase ELISA was developed to investigate the association between anticardiolipin antibodies and lupus anticoagulant in pregnancy. Twenty-seven pregnant women with a history of recurrent fetal losses or systemic lupus erythematosus (SLE) were tested for the presence of lupus anticoagulant, anticardiolipin antibodies, antinuclear antibodies (ANA) and anti-single-stranded DNA antibodies. Nineteen women with a total of 49 previous unsuccessful pregnancies were found to have lupus anticoagulant and anticardiolipin antibodies. Three women who had suffered four fetal deaths from six pregnancies had anticardiolipin antibodies without lupus anticoagulant. Cardiolipin antibodies were not detected in the remaining five patients. This assay for measuring anticardiolipin antibodies appears to provide a simple and inexpensive method of identifying women at risk of fetal death from the adverse effects of lupus anticoagulant.

Topics: Abortion, Habitual; Antibodies; Antigens, Surface; Autoantibodies; Blood Coagulation Factors; Cardiolipins; Enzyme-Linked Immunosorbent Assay; Female; Humans; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Pregnancy; Pregnancy Complications; Thromboplastin

The physiopathological role of antithromboplastin-type circulating anticoagulants in habitual abortion may be envisaged since the presence of antithromboplastin has been reported in most studies on women at high risk of abortion. To avoid a possible statistical bias, we conducted a prospective study in a sufficiently large group of women with habitual abortion (n = 99) compared with a control group of women with normal fecundity (n = 50). In addition, all women were investigated for lupus symptoms. The circulating antibody was detected by the diluted thromboplastin time and activated cephalin time methods. The results were considered positive when the patient/control diluted thromboplastin time ratio was 1.2 and/or when the increase in activated cephalin time was not corrected by a control plasma. In the patients' group, 10 women (10%) had an anti-thromboplastin type circulating anticoagulant, whereas no circulating anticoagulant could be detected in the control group. Three women with circulating anticoagulant had signs of systemic lupus erythematosus. None of the patients presented with Soulier-Boffa syndrome. These data have established a significant correlation between habitual abortion and circulating anticoagulant whilst avoiding statistical bias. Our results suggest that women with idiopathic habitual abortion should be subjected to systematic immunological exploration and that a small number of them should be followed attentively.

Topics: Abortion, Habitual; Antibodies, Antinuclear; Autoantibodies; Blood Coagulation Disorders; Female; Hemostasis; Humans; Immunoglobulins; Lupus Erythematosus, Systemic; Partial Thromboplastin Time; Pregnancy; Prospective Studies; Thromboplastin

We discovered a "lupus' anticoagulant in 2 out of 42 women with a history of repeated abortions, intrauterine growth retardation and intrauterine death of unknown origin. The "lupus' anticoagulant was detected by an abnormal dilute tissue thromboplastin assay(prothrombin time performed with dilute thromboplastin). The production of prostacyclin by fresh or exhausted rings of rat aorta was decreased by the plasma of one of these two patients with a "lupus' anticoagulant. In view of the increasing evidence for a physiological role of prostacyclin in pregnancy and fetal life, we suggest that an inhibition of prostacyclin production could compromise fetal outcome.

Topics: Abortion, Habitual; Adult; Animals; Aorta; Biological Assay; Blood Coagulation Factors; Epoprostenol; Female; Fetal Death; Fetal Growth Retardation; Humans; Lupus Coagulation Inhibitor; Partial Thromboplastin Time; Pregnancy; Prostaglandins; Prothrombin Time; Rats; Thromboplastin