Antiphospholipid and antiprotein syndromes in non-thrombotic, non-autoimmune women with unexplained recurrent primary early foetal loss. The Nîmes Obstetricians and Haematologists Study--NOHA.

Various antiphospholipid and/or antiprotein antibodies have been suspected to be associated with recurrent early foetal loss in absence of any habitual aetiology. We conducted a hospital-based case control study on women with no antecedent of thromboembolic or autoimmune disease. We studied 3 groups of 518 women: patients with unexplained primary recurrent early foetal loss, patients with explained episodes and mothers with no previous obstetrical accident. Matching the 3 groups was carried out on the basis of age, number or pregnancies and time elapsed since the end of the last pregnancy. Significant biological markers were then prospectively tested. The various antibodies were shown to be dependent on parity and on the presence of previous foetal loss: cut-off values were thus calculated using data obtained from the group of explained accidents, and adjusted for parity. Only anti-phosphatidylethanolamine IgM [odds ratio: 6.0, 95% confidence interval (2.3-15.7), p = 0.0003], anti-beta2-glycoprotein I IgG [4.4, (1.6-11.7), p = 0.0035] anti-annexin V IgG antibodies [3.2 (1.2-8.1), p = 0.015] and lupus anticoagulant [3.0, (1.3-6.8), p = 0.009], were found to be independent retrospective risk factors for unexplained early foetal loss. These four markers were subsequently found to be, during the following pregnancy, associated with a significant risk of foetal loss despite a low-dose aspirin treatment. In non-thrombotic, non-auto-immune women with unexplained primary recurrent early foetal loss, subgroups of patients with positive anti-phosphatidylethanolamine IgM antibodies, or positive anti-beta2-glycoprotein-I IgG antibodies, or positive anti-annexin V IgG antibodies or lupus anticoagulant must be particularised. This should allow therapeutic trials to be carried in well-defined patients.

Evaluation of incidence, clinical significance, and prognostic value of circulating cardiac troponin I and T elevation in hemodynamically stable patients with suspected myocardial contusion after blunt chest trauma.

BACKGROUND: The frequency and prognostic influence of myocardial injury in patients with blunt chest trauma is controversial. We investigated the value of cardiac troponin I (cTn-I) and cardiac troponin T (cTn-T), highly specific markers of myocardial injury, to determine whether their measurement would improve the ability to detect myocardial contusion in stable patients with blunt chest trauma in comparison with conventional markers and whether they were associated with significantly worse late clinical outcome. METHODS AND RESULTS: Over an 18-month period, myocardial contusion was diagnosed in 26 of 94 patients (27.6%) with acute blunt chest trauma (motor vehicle crash; 81%), because of echocardiographic abnormalities (n = 12), electrocardiographic abnormalities (n = 29), or both. Patients with myocardial contusion had a significantly higher Injury Severity Score at the time of admission (p = 0.001) and a significantly longer hospital stay (p = 0.0008). All patients survived admission to hospital and were hemodynamically stable. None of the patients died or had severe in-hospital cardiac complications. The percentage of patients with elevated CK, (CK-MB/total CK) ratio, or CK-MB mass concentration was not significantly different between patients with or without myocardial contusion. However, there were significant differences between the two groups when we applied the commonly used threshold levels of CK-MB activity and myoglobin. The percentage of patients with elevated circulating cTn-I and cTn-T (> or = 0.1 microg/L) was significantly higher in patients with myocardial contusion (23% vs. 3%; p = 0.01 and 12% vs. 0%; p = 0.03, respectively). Complete changes in cTn-I and cTn-T correlated well (r = 0.91, p = 0.0001). Sensitivity, specificity, and negative and positive predictive values of cTn-I and cTn-T in predicting a myocardial contusion in blunt trauma patients were 23%, 97%, and 77%, 75%, and 12%, 100%, and 74%, 100%, respectively. Clinical follow-up was available in 83 patients (88%) (mean, 16 +/- 7.5 months). There were no deaths in either group directly attributed to cardiac complications. None of the patients had any long-term cardiac complications or myocardial failure related to blunt chest trauma. CONCLUSION: Although improved specificity of cTn-I and cTn-T compared with conventional markers, it should be emphasized that the main problem with cTn-I and cTn-T is low sensitivity as well as low predictive values in diagnosing myocardial contusion. cTn-I and cTn-T measurement is currently not an improved method in diagnosing blunt cardiac injury in hemodynamically stable patients. Moreover, there was no association of postmyocardial contusion cell injury and late outcome in these patients when cTn-I and cTn-T and other conventional markers were considered.

Case-control study of the frequency of thrombophilic disorders in couples with late foetal loss and no thrombotic antecedent--the Nîmes Obstetricians and Haematologists Study5 (NOHA5).

BACKGROUND: Women with familial thrombophilia have an increased risk of still birth. We postulated that the presence of asymptomatic risk factors for venous thrombosis might be a risk factor for late foetal loss. METHODS: We performed a case-control study on the prevalence of heritable thrombophilic defects, of antiphospholipid-related markers and of the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with at least one episode of late unexplained foetal loss and in control women with successful pregnancies. Partners of cases and controls were also studied. Written conclusions of the pathological examination of the placentas, when available, were also reviewed. RESULTS: We found at least one positive biological risk factor for venous thrombosis in 21.1% of the patients and in 3.9% of the controls (p < 10(-4)). In women, the crude odds ratio for still birth associated with any positive biological risk factor for venous thrombosis was 5.5, 95% confidence interval (95%CI) [3.4-9.0]. No difference was found between partners of cases and controls (5.2% and 4.7%). Using conditional logistic regression analysis, 4 adjusted risk factors for still birth remained: protein S deficiency, positive anti beta2 glycoprotein I IgG antibodies, positive anticardiolipin IgG antibodies and the factor V Leiden mutation. The C677T mutation in the MTHFR gene was not an individual risk factor but an homozygous genotype was strongly associated with the former 4 risk factors (16.8% of patients vs. 0.9% of controls). In women with such associations, still births always occurred in absence of folic acid supplementation during pregnancy. Available conclusions of pathological analysis of placentas were found to have a very high proportion of "maternal vascular disease of the placenta" in patients with at least one positive risk marker for thromboembolism, specially in case of association with the C677T MTHFR homozygous genotype, compared to patients with negative markers (p <10(-4)). CONCLUSIONS: Late foetal loss, through placenta thrombosis, may sometimes be the consequence of a maternal multifactorial prothrombotic state associating traditional heritable or acquired thrombosis risk factors to conditions predisposing to an acute mild hyperhomocysteinaemia (coexistence of a genetic predisposition with late pregnancy-related increased folate needs).