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PubMed2002

Effects of a synthetic factor Xa inhibitor (JTV-803) on various laboratory tests.

Synthetic direct inhibitors of factor Xa are capable of prolonging the global anticoagulant assay times in a concentration-dependent fashion. The relative degree of thrombin generation inhibition at an equivalent prolongation is not similar to the results observed with heparins and oral anticoagulant drugs. In addition, the direct factor Xa inhibitors prolong the Russell's viper venom test (RWT) and Heptest clotting times. Ecarin clotting time (ECT) and thrombin time (TT) remain unaffected. The kinetics of factor Xa inhibition are markedly different than those observed with pentasaccharide and heparins. Therefore, the methods developed for heparins and pentasaccharides may not be applicable for the monitoring of factor Xa inhibitors. To test the feasibility of using the prothrombin time (PT), International Normalized Ratio (INR), activated partial thromboplastin time (aPTT), Heptest, thrombin time, RVVT, ECT, and a modified anti-Xa amidolytic assay, to monitor a synthetic factor Xa inhibitor, normal human pool plasma samples were spiked with a synthetic factor Xa inhibitor in the concentration range of 0 to 1 microg/mL and 0 to 25 microg/mL. Different laboratory tests were performed and INR and other ratios were calculated. The anticoagulant effects on whole blood were measured using the activated clotting time (ACT). Further studies on the effect of factor Xa inhibitor on platelet aggregation; factor II, VII, and X functional levels; and fibrinopeptide A (FPA) generation were carried out at equivalent INR levels in comparison to oral anticoagulant and antithrombin agents. FPA generation at equivalent anticoagulant level in comparison to heparin (twice the baseline) was also carried out. Factor Xa inhibitor produced a concentration-dependent prolongation of the ACT. ACT was doubled at a concentration of 4 to 5 microg/mL. There was a marked difference in the prolongation of the PT by a synthetic factor Xa inhibitor dependent on the ISI of the PT reagent used. When the results were calculated to determine INR, marked variations were noted between the recombinant thromboplastin and rabbit brain thromboplastin. The rabbit brain thromboplastin reagent gave markedly high INR values. Similar results were observed when different aPTT reagents were studied. In the anti-Xa assay, modification of the incubation time was employed to extend the proper sensitivity range. These studies warrant further investigation to understand the mechanism of action of factor Xa inhibitors.

Anticoagulants↗

PubMed1999

Effects of aprosulate, a novel synthetic glycosaminoglycan, on coagulation and platelet function parameters: a prospective, randomized phase I study.

In a phase I clinical trial the effect of the highly sulfated polyanion "Aprosulate" was studied in healthy volunteers using different coagulation and platelet function parameters. Eighteen healthy volunteers aged 21 to 30 years received two single subcutaneous doses of aprosulate (0.5 mg/kg body weight; 1.0 mg/kg body weight), or unfractionated heparin (Calciparin 7,500 IU). The washout period between the different drugs/doses was at least 7 days. Coagulation and platelet function parameters (activated partial thromboplastin time, Heptest, fibrinogen, von Willebrand factor, ristocetin cofactor, platelet adhesion to siliconized glass, and platelet-induced thrombin generation time [a new method for measuring thrombin generation in platelet-rich plasma in the presence of platelets]) were assessed during 24 hours after each injection. Aprosulate led to a significant and dose-dependent prolongation of activated partial thromboplastin time and Heptest. This effect lasted for 4 hours (activated partial thromboplastin time) to 8 hours (Heptest). Activated partial thromboplastin time was not prolonged after the injection of unfractionated heparin (7,500 IU). Fibrinogen, von Willebrand factor, and ristocetin cofactor remained unchanged with both drugs. Platelet induced thrombin generation time was slightly prolonged and platelet adhesion was slightly diminished up to 2 hours using 0.5 mg/kg aprosulate, and up to 4 hours using 1.0 mg/kg aprosulate while the platelet induced thrombin generation time system was not influenced by the subcutaneous injection (7,500 IU) of unfractionated heparin. Both drugs and doses were well tolerated. Plasma transaminase concentrations alanin aminotransferase and aspartate aminotransferase serum values were slightly increased in some volunteers but returned to normal during or after the study (< 4 weeks). Further clinical trials will have to establish whether aprosulate is an effective drug for the prophylaxis of deep venous thrombosis.

Adolescent↗

PubMed2006

Interference of blood cell lysis on routine coagulation testing.

CONTEXT: Preanalytical factors influencing the reliability of laboratory testing are commonplace. It is traditionally accepted that hemolytic samples are unsuitable for coagulation assays because of the release of hemoglobin, intracellular components, and thromboplastic substances from damaged blood cells. OBJECTIVE: To evaluate the influence of blood cell lysis on routine coagulation testing. DESIGN: Twelve aliquots prepared by serial dilutions of homologous lysated samples collected from 10 different subjects, and displaying a final percentage of lysis ranging from 0% to 9.1%, were tested for prothrombin time, activated partial thromboplastin time, fibrinogen, and dimerized plasmin fragment D. Lysis was achieved by subjecting citrated whole blood to a freeze-thaw cycle. OUTCOME MEASURES: Interference from blood cell lysis on routine coagulation testing. RESULTS: Statistically significant increases in prothrombin time and dimerized plasmin fragment D were observed in samples containing final lysate concentrations of 0.5% and 2.7% respectively, whereas significant decreases were observed in activated partial thromboplastin time and fibrinogen in samples containing a final lysate concentration of 0.9%. The current analytical quality specifications for desirable bias are +/-2.0% for prothrombin time, +/-2.3% for activated partial thromboplastin time, and +/-4.8% for fibrinogen. Percent variations from the baseline values exceeding the current analytical quality specifications for desirable bias were achieved for lysate concentrations of 0.9% (prothrombin time and activated partial thromboplastin time) and 1.8% (fibrinogen), corresponding to average free plasma hemoglobin concentrations of 1.7 and 3.4 g/L, respectively. CONCLUSION: Our results confirm that, although slightly hemolyzed specimens might still be analyzable, a moderate blood cell lysis, as low as 0.9%, influences the reliability of routine coagulation testing. Because the interference in coagulation assays has a wide interindividual bias, we do not recommend lysis correction and we suggest that the most appropriate corrective measure should be free hemoglobin quantification and sample recollection.

Artifacts↗

PubMed2004

[International normalized ratio in the prothrombin test: clinical significance and use].

The safety and efficiency of therapy by peroral anticoagulants (PA) depend on a laboratory monitoring based on the prothrombin test (PT). The test is distinguished through its variability conditioned by different means of results' presentation as well as through the sensitivity of thromboplastin and a type of a device used in coagulation detection. WHO recommended, 1983, to standardize the thromboplastin preparations through adjusting their sensitivity (the so-called International Sensitivity Index--ISI) to blood coagulation defects induced by PA versus the primary international reference thromboplastin. Thromboplastin ISI as well as the mean normal prothrombin time (MNPT) of blood plasma are used to calculate the international normalized ratio (INR). The presentation of PT results as INR is justified exclusively for the PA-therapy stabilized patients. The INR system makes it possible to optimize the PA therapy only if the laboratory expert and clinician can clearly understand the PT standardization essence and observe the key WHO recommendations, i.e. definition of a coagulometer-specific ISI by manufacturing companies, estimation of MNPT by laboratories and use of the correct anticoagulant concentration.

Humans↗

PubMed1990

Clinical significance of various ELISA assays for detecting antiphospholipid antibodies.

We have compared the prevalence of antiphospholipid antibodies (APA) measured by enzyme-linked immunosorbent assay (ELISA), in 119 selected patients using five different antigens: bovine cardiolipin, phosphatidylserine, phosphatidylinositol, bovine partial thromboplastin and human brain partial thromboplastin. All the plasmas have been evaluated for the presence of lupus anticoagulant (LA) activity by clotting techniques. We found a significant association between the incidence of LA and APA (p less than 0.001), only moderate agreement between the prolongation of the activated partial thromboplastin time (APTT) and ELISAs (r around 0.50) and a good agreement between the ELISAs (r around 0.80). The combination of antibodies against cardiolipin (ACA) and human brain partial thromboplastin (AHPTA) allowed the detection of antibodies in most of the LA positive cases. ACA, AHPTA and antiphosphatidylinositol antibodies detected all the positive samples. Six patients (5%) had a single APA detected. The clinical associations of APA according to phospholipid specificity, immunoglobulin isotype and titer are shown.

Autoantibodies↗

PubMed1989

[Circulating anticoagulants in immunodeficiency virus infection. Results of a prospective study of 157 seropositive patients].

One hundred and fifty-seven HIV seropositive patients were included in a prospective study of coagulation parameters. Activated partial thromboplastin time, prothrombin time, thrombin time and specific factor assays of the intrinsic pathway were performed using standard techniques. The tissue thromboplastin inhibition test and antiphospholipid antibodies were used to establish the presence of circulating lupus anticoagulant. Among the 46 patients with a prolonged activated partial thromboplastin time, an anti-prothrombinase was present in 33. Of the 111 patients with a normal activated partial thromboplastin time, anti-prothrombinase was present in 51. Circulating lupus anticoagulant seems to be common in HIV seropositive patients, since it was found in 84 patients (53.5%). Our findings confirm that the presence of circulating anticoagulants is not particularly associated with opportunistic infections or the development of the disease. It is possible that these inhibitors could be mediated by anti-phospholipid antibodies. In HIV seropositive patients, defective T cell regulation of B cells leads to polyclonal hypergammaglobulinemia. These antibodies may be directed against endogenous or exogenous phospholipids.

Acquired Immunodeficiency Syndrome↗

PubMed1995

[Factitious disease caused by secret administration of the oral anticoagulant phenprocoumon: study of 16 personal cases].

BACKGROUND: It is frequently difficult to disclose covert ingestion of cumarins being the underlying cause of a bleeding disorder. PATIENTS AND METHODS: We report on 16 cases (15 patients) of phenprocoumon (Marcumar) abuse. All patients (9 females, 6 males) were admitted to the hospital because of bleeding and/or prolonged thromboplastin times. Analysis of phenprocoumon in the blood was performed by HPLC. RESULTS AND CONCLUSIONS: The clinical presentation of the bleeding was highly variable. Thromboplastin times ranged from < 5 to 58%. With the exception of two patients with hepatic dysfunctions factor V activity was normal. All but one patient denied the ingestion of Marcumar. One patient died from hemorrhage. Two types of patients emerge from our series: Type I is the young nurse (8 cases), type II the usually male patient formerly treated with phenprocoumon (5 cases). Type I patients had long medical histories and showed autoaggressive behavior including the artificial manipulation of disorders other than hemorrhage. Thromboplastin times however were within or close to the therapeutic range (10 to 25%). Type II patients did not simulate other diseases in addition to hemorrhage. Thromboplastin times were longer than in type I patients. In all instances discrimination between non suicidal and suicidal behaviour was difficult. Psychiatric consultance is indicated.

Administration, Oral↗

PubMed1994

[Methodological aspects for the determination of the coagulative activity of coagulation factors II, V, VII and X from dog plasma].

For optimization of single factor II, V, VII and X activity measurements in dogs, dilution series of dog pool plasma were prepared using different commercially available calcium thromboplastins and deficient plasmas. Measured by use of a canine reference curve, the single factor activity in humans was 89% (factor II), 13% (factor V), 27% (factor VII) and 84% (factor X). Because the factor V and VII activity in dogs is much higher than in humans, in measurements using human-deficient plasma, a high sample predilution of at least 1:40 seems to be of advantage. Otherwise extreme variations of the factor V and VII activity may also influence the results of the other single factors. For determination of factor II, V and X activity, therefore, a non-standardized human placenta thromboplastin was especially suitable. With this reagent, the results were also reproducible at high sample dilutions (1:80, factor II and X; 1:160, factor V). Because of the low sensitivity of non-standardized human placenta thromboplastin to factor VII, measurements of this factor at a sample dilution of 1:40 required a standardized human placenta, or rabbit brain thromboplastin had to be used. For factor II measurements, the selection of a suitable deficient plasma is particularly important. Here, the reference curve showed a clear dependence on the commercial preparation chosen.

Animals↗

PubMed1994

[Optimized methods for measuring coagulation factors II, IV, VII and X in cats].

Since the single factor activity of the cat differed in part distinctly from humans (factor II: 94%, factor V: 500%, factor VII: 125%, factor X: 62%) the method had to be optimized, above all to exclude an influence of a reactive increased factor V-activity on the results of the other coagulation factors. Dilution series of cat pool plasma (CPP) (n = 50 cats) showed, that a commercial human placenta thromboplastin was more suitable as activating reagent than rabbit brain thromboplastin. Using the required sample predilution (1:40), measurements with the latter reagent were more precise when measured on the relation between the imprecision and the time interval between different CPP-dilution steps. Reference curves were prepared for CPP using the optimized method and human placenta thromboplastin (50 microliters 1:40 prediluted sample and 50 microliters deficient plasma were incubated at 37 degrees C for 1 minute, addition of 200 microliters Ca-thromboplastin) and reference ranges were calculated using the values of 57 cats (factor II: 74-126%, factor V: 42-184%, factor VII 56-150%, factor X: 65-143%).

Animals↗

PubMed1994

Acute pulmonary embolism.

Prevention of deep venous thrombosis is fundamental in the prevention of pulmonary embolism. Deep venous thrombosis is common after all surgical procedures, but the frequency differs, as does the effectiveness of various methods of prevention. Low-dose heparin, low molecular weight heparin, graduated compression elastic stockings, intermittent pneumatic compression, and oral anticoagulants have a role in the prevention of deep venous thrombosis, depending on the risks of deep venous thrombosis and their demonstrated effectiveness (or lack of effectiveness) in the particular circumstance. The optimal method of prophylaxis is specific to the predisposing condition. Heparin continues to be a mainstay of anticoagulant therapy. Major bleeding is rare in patients treated with low doses of heparin to prevent deep venous thrombosis. With therapeutic doses, however, major bleeding occurs in about 5% of patients. The optimal dose of warfarin and the method of evaluating the anticoagulant effect of warfarin have undergone modifications in recent years. It is now recognized that the prothrombin time ratio depends on the activity of the thromboplastin used for measuring the prothrombin time. An International Normalized Ratio, which relates to a standardized thromboplastin, has been developed, thus avoiding differences of the prothrombin time ratio that occur from batch to batch of thromboplastin reagent from the same manufacturer and that occur with different thromboplastin reagents from different animal sources and different manufacturers. The bedside diagnosis of pulmonary embolism is useful in helping a physician determine the extent to which diagnostic tests should be pursued. A sound bedside impression also contributes strongly to the formulation of a noninvasive diagnosis of pulmonary embolism. The clinical manifestations of pulmonary embolism form a recognizable constellation of findings that often lead to a correct diagnosis or exclusion of pulmonary embolism. Important clues to the diagnosis of pulmonary embolism relate to the initial syndrome. The presentation of pulmonary embolism is most often in the form of the pulmonary hemorrhage-pulmonary infarction syndrome. The next most common presentation is unexplained dyspnea, unaccompanied by pulmonary hemorrhage or infarction. Least common, but most severe, is the syndrome of circulatory collapse. Immobilization, usually caused by surgery, is the most frequent predisposing factor. Most patients with clinically recognizable pulmonary embolism have dyspnea or tachypnea. Dyspnea or tachypnea or pleuritic pain occurs in nearly all patients who have clinically apparent pulmonary embolism (97%). Ordinary tests such as the electrocardiogram and chest radiograph are helpful if the physician is attentive to nonspecific abnormalities.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗

PubMed1993

Are capillary whole blood coagulation monitors suitable for the control of oral anticoagulant treatment by the international normalized ratio?

The 512 Coagulation Monitor is a portable coagulation photometer that uses disposable cartridges containing a lyophilized rabbit brain thromboplastin to measure the PT for capillary whole blood. It has been proposed as a suitable system for patient self monitoring at home, but its performance has never been thoroughly assessed for results expressed as International Normalized Ratio (INR). In particular, there is no available information about the adequacy of the WHO calibration model with the Monitor. The aims of the study were to determine the International Sensitivity Index (ISI) against the secondary International Reference Preparation for rabbit thromboplastin and to assess the precision of the INR. The study demonstrates that the Monitor can be calibrated with the WHO model, because log-transformed PTs for patients stabilized on oral anticoagulants and normal individuals are linearly related and because the same orthogonal regression line describes patient and normal data points adequately. However, the ISI calculated in this study (2.715) is higher than that adopted by the manufacturer (2.036). The between-assay reproducibility of the Monitor is acceptable (CV = 9.7%) with results expressed in seconds, but become unacceptably poor when the results are converted into INR (CV = 18.8%) because of the high ISI value of the thromboplastin used. We think that the Monitor might be suitable for monitoring oral anticoagulant therapy if the manufacturer would provide a more sensitive thromboplastin in the cartridges.

Administration, Oral↗

PubMed1976

[Quality control of coagulation tests (author's transl)].

The results of quality control of coagulation tests from intralaboratory control programmes are reported and compared with interlaboratory surveys. The test programme includes the following assays: the thromboplastin time (Quick), the partial thromboplastin time and the thrombotest. It can be seen from the results of the thromboplastin time that reliable figures were obtained from intralaboratory quality control examinations only (CV=7% to 13%). In comparison to these results great differences were found in interlaboratory surveys (CV=15% to 30%). The result of interlaboratory surveys of the thrombotest demonstrated a CV of 15% to 20%. The intralaboratory quality control of the partial thromboplastin time showed satisfactory reliability (CV=7.4%). Satisfactory conformity of results was obtained between different laboratories only by using common reagents (CV=8.7%). Possible factors responsible for deviations in laboratory examinations are discussed and proposals for improvement in the realibility of coagulation tests are made.

Blood Coagulation Tests↗

PubMed1994

African-American factor VII-deficient variants in Georgia (FVII variants).

We studied African-American Factor (FVII)-deficient variants and carriers in Georgia by measuring their levels of FVII antigen (FVIIAG) and FVII procoagulant (FVIIC). Factor VIIAG was determined using enzyme-linked immunoassay (ELISA), whereas FVIIC was measured in two ways: 1) by fibrin clotting methods that employed human recombinant (HRFVIIC), human placental (HPFVIIC), rabbit brain (RBFVIIC), and bovine brain (BBFVIIC) thromboplastins; and 2) by an amidolytic method (AMFVIIC). Prothrombin time tests (PT) were also performed by standard methods. These 4 FVII-deficient patients and 3 carriers demonstrated the following results: PT: 18.2 +/- 6.5 sec; FVIIAG: 73.0 +/- 14.9%; HRFVIIC: 30.6 +/- 20.3%; HPFVIIC: 30.5 +/- 21.4%; RBFVIIC: 25.3 +/- 21.4%; BBFVIIC: 30.6 +/- 17.5%; AMFVIIC: 44.1 +/- 18.3%. We conclude that a group of clinically mild African-American FVII-deficient variants exists in Georgia. This group is characterized by the presence of FVIIAG and decreased FVIIC, using a variety of thromboplastins; and excellent correlation was noted for both human thromboplastins.

Antibodies↗

PubMed1983

Thrombin generation in normal plasma enriched with purified coagulation factors.

During the intrinsic coagulation of normal platelet-rich plasma only 11% of the prothrombin is converted to thrombin. Complete conversion of prothrombin to thrombin occurs only via the extrinsic pathway (1). Addition of purified prothrombin to normal plasma to double or triple its concentration, doubled or tripled the amount of the generated thrombin as determined by the thrombin elution assay (1), so that the percentage of the proenzyme which was converted to thrombin remained the same. At the same time the activated partial thromboplastin time (APTT) was prolonged. Proportionality of the amount of the generated thrombin to the amount of prothrombin added and a delay in the appearance of thrombin activity was also observed with the thrombin generation test. Normalization of the APTT was observed when factor IX was added together with prothrombin. Addition of factor IX or X to normal plasma shortened the APTT but did not increase the amount of prothrombin which was converted to thrombin as determined by both the thrombin elution assay and the thrombin generation test. Further experiments indicated that (a) more factor X is activated per mg tissue factor than per mg of activated partial thromboplastin and (b) more thrombin is generated per unit of factor Xa in the presence of tissue factor than in the presence of activated partial thromboplastin. Thus, the two pathways differ not only by the mechanism of factor X activation but also by the extent to which prothrombin is activated by factor Xa.

Blood Coagulation↗

PubMed1991

Inhibition of extrinsic pathway inhibitor shortens the coagulation time of normal plasma and of hemophilia plasma.

An increasing amount of evidence suggests that coagulation factors VIII and IX play a role not only in the intrinsic but also in the extrinsic pathway of coagulation. In this context the influence of the Extrinsic Pathway Inhibitor (EPI) on the coagulation time of hemophilia plasma lacking FVIII or FIX has been investigated. The coagulation time was measured in a dilute thromboplastin assay. Addition of recombinant EPI (rEPI) prolonged the coagulation time of normal plasma while the addition of an inhibitory antibody against EPI shortened the coagulation time. At low concentrations of thromboplastin the coagulation time of hemophilia plasma was prolonged and at all dilutions of thromboplastin, addition of anti-EPI IgG normalized the coagulation time of a hemophilia plasma. Analysis of 10 individual donor plasma samples and 8 individual hemophilia samples showed that addition of anti-EPI IgG shortened the coagulation time more in hemophilia plasma than in normal plasma. This illustrates the importance of a powerful extrinsic FVII dependent pathway to achieve hemostasis in the case of FVIII or FIX deficiency (hemophilia A and B).

Antibody Specificity↗

PubMed1990

Factor VIIa-catalyzed activation of factor X independent of tissue factor: its possible significance for control of hemophilic bleeding by infused factor VIIa.

Infusing factor VIIa (FVIIa) has been reported to control bleeding in hemophilic patients with factor VIII (FVIII) inhibitors. This is difficult to attribute to an enhanced FVIIa/tissue factor (TF) activation of factor X, since in vitro studies suggest that infusion of FVIIa should neither increase substantially the rate of formation of FVIIa/TF complexes during hemostasis (Proc Natl Acad Sci USA 85:6687, 1988) nor bypass the dampening of TF-dependent coagulation by the extrinsic pathway inhibitor (EPI) (Blood 73:359, 1989). Partial thromboplastin times have also been reported to shorten after infusion of FVIIa. The experiments reported herein establish that shortening of partial thromboplastin times after adding FVIIa to hemophilic plasma in vitro stems from an FVIIa-catalyzed activation of factor X independent of possible trace contamination of reagents with TF. Experiments in purified systems confirmed that FVIIa can slowly activate factor X in a reaction mixture containing Ca2+ and phospholipid but no source of TF. The rate of activation was sufficient to account for the shortening of partial thromboplastin times observed. EPI, which turned off continuing FVIIa/TF activation of factor X, was unable to prevent continuing FVIIa/phospholipid activation of factor X. Because circulating plasma contains only a trace, if any, free FVIIa, such a reaction could never occur physiologically. However, infusing FVIIa creates a nonphysiologic circumstance in which a continuing slow FVIIa/phospholipid catalyzed activation of factor X could conceivably proceed in vivo unimpeded by EPI. Such a mechanism of factor X activation might compensate for an impaired factor IXa/FVIIIa/phospholipid activation of factor X during hemostatis, and therefore control bleeding in a hemophilic patient.

Blood Coagulation↗

PubMed1989

Sphingosine inhibits monocyte tissue factor-initiated coagulation by altering factor VII binding.

Tissue factor is a lipoprotein, expressed on the surface of cells, which binds coagulation Factor VII or VIIa, leading to activation of Factors X and IX with subsequent fibrin generation. Cellular tissue factor activity is important in pathophysiologic processes such as inflammation and disseminated intravascular coagulation. In this study, the long-chain base sphingosine inhibited coagulation initiated by lipopolysaccharide-stimulated intact human monocytes. Sphingosine (5-100 microM) also profoundly inhibited thromboplastin-initiated coagulation (greater than 90% decrease in thromboplastin activity). This inhibition was dose- and time-dependent. Sphingosine inhibited neither the intrinsic pathway of coagulation nor thrombin generation of fibrin. The sphingosine analogues sphingomyelin, ceramide, or N-acetylsphingosine did not affect thromboplastin activity, suggesting that the polar head of sphingosine was necessary for interaction of the molecule with the coagulation system. Investigation of the biochemical mechanism revealed that sphingosine (5-50 microM), but neither sphingomyelin nor ceramide, inhibited specific binding of radiolabeled Factor VII to lipopolysaccharide-stimulated intact monocytes. The results suggest that sphingosine may regulate monocyte tissue factor-initiated coagulation by modulating Factor VII binding to tissue factor. Sphingosine may represent a new class of inhibitors of hemostasis.

Blood Coagulation↗

PubMed1986

[Immunological disorders of coagulation in habitual abortion. Prospective study].

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.

Abortion, Habitual↗

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