International Normalized Ratio (INR), which standardizes prothrombin time (PT) during oral anticoagulation, has been extended to standardize PT in liver diseases and is included in prognostic models such as the Model for End stage Liver Disease (MELD). However, mechanisms of PT prolongation in liver diseases differ from those involved in oral anticoagulation, and the thromboplastin reagents differ in their sensitivities to these 2 mechanisms. Our aim was to determine whether, in the calibration model for thromboplastins proposed by the World Health Organization, the use of plasmas from patients with liver diseases instead of plasmas from patients on oral anticoagulation could lead to a new INR specific for liver diseases (INR "LD"), achieving a real standardization of PT. First, 5 thromboplastins were calibrated against an international reference using 60 plasmas of patients with liver failure and, in a second step, the variation of PT reported as seconds, the ratio of patient PT to normal PT, See Editorial on Page 295 P rothrombin time (PT) is the usual test for monitoring oral anticoagulation by vitamin K antagonists 1 and is widely adopted to assess the severity of acute and chronic liver injury. 2 PT is the recalcification time of citrated plasma in the presence of a thromboplastin reagent. 3 The term thromboplastin refers to a complex mixture of tissue factor and phospholipids prepared from tissue extracts of animal or human origin. Recent thromboplastins contain recombinant tissue factor. PT is influenced by the levels of the following coagulation factors: I (fibrinogen), II, V, VII, and X, all factors being synthesized by the liver and, among them, 3 (II, VII, and X) being vitamin K dependent. Thromboplastins can vary markedly in their responsiveness to the defects induced by vitamin K antagonist therapy. As a result, the poor agreement between PT in different laboratories whatever the methods of reporting results 4 has led to important differences in oral anticoagulant dosing. 5,6 Standardization of PT reporting in patients on oral anticoagulation has been improved by the calibration model for thromboplastins proposed by the World Health Organization (WHO). 7 This system defines, for a specific thromboplastin reagent, the International Sensitivity Index (ISI) obtained by a calibration using plasmas of patients on stable oral anticoagulant doses, against a WHO international reference thromboplastin. 7 The ISI is a numerical value that reflects the responsiveness of a given thromboplastin to reduction of the vitamin K-dependent coagulation factors; the lower the ISI value, the greater the sensitivity of the reagent. The recommended scale of reporting PT results is

Background-Heart valve disease (HVD) is frequent in patients with systemic lupus erythematosus (SLE), and the role of antiphospholipid antibodies (aPL) is controversial. Thus, our objective was to estimate the risk of HVD, including Libman-Sacks endocarditis, associated with aPL in patients with SLE. Methods and Results-Studies were selected if they investigated the association between aPL and HVD in SLE patients and if aPL-negative patients were included for comparison. Data sources were MEDLINE, Embase, Cochrane Library, hand search, contact with investigators, and reference lists of studies, without language restrictions. Data on study and patient characteristics, risk estimates, and study quality were independently extracted by 2 investigators. Pooled effect estimates were obtained by using the DerSimonian-Laird method. Of 234 identified abstracts, 23 primary studies (15 cross-sectional, 7 cohort, 1 case-control) met inclusion criteria, including 1656 SLE patients and 508 cases of HVD. Compared with SLE patients without aPL (nϭ988), the overall pooled odds ratios for HVD and Libman-Sacks endocarditis in aPL-positive patients (nϭ668) were 3.13 (95% confidence interval, 2.31 to 4.24) and 3.51 (95% confidence interval, 1.93 to 6.38), respectively. The risk of HVD depending on aPL subtypes was the highest for lupus anticoagulant at 5.

SummaryOne of the frequently proposed mechanisms for pregnancy losses refers to uteroplacental thrombosis. However the contribution of classical thrombotic risk factors remains questionable and, if real, does not account for a large number of pregnancy losses. The aim of this study was to investigate the presence of circulating procoagulant microparticles, a new marker of cell activation already associated with various prothrombotic clinical settings. Microparticles were assessed by an original prothrombinase assay on platelet depleted plasma obtained from 74 women with a history of pregnancy loss without apparent cause and 50 controls. Patients were studied at least 2 months after the last obstetrical event and were classified into 2 groups: 49 women with at least 3 consecutive spontaneous abortions at or before the 10th postmenstrual week and 25 with at least one fetal death beyond the 10th postmenstrual week. Among the 74 patients, 41 had increased levels of circulating microparticles, 29 belonging to the group of early pregnancy loss (59%) and 12 to the group of late pregnancy loss (48%). The high prevalence of increased levels of procoagulant microparticles in both groups makes this new marker very promising for the understanding, follow up and therapeutical handling of pregnancy loss.

The members of the Réseau d'Etude des Microangiopathies Thrombotiques (Centre de Réfé-rence Maladies Rares) are cited in the appendix. AbstractHuman immunodeficiency virus (HIV) infection is a risk factor for thrombotic microangiopathy (TMA). We sought whether a severe deficiency in ADAMTS13, the enzyme specifically involved in the cleavage of von Willebrand factor, was associated with specific presenting features and outcome in HIV-associated TMA. In this prospective, multicentre, case-control study, 29 patients of 236 in the French Network on TMA had an HIV-associated TMA. Seventeen patients with severe ADAMTS13 deficiency (ADAMTS13 <5% HIV + group) were compared to 12 patients with a detectable ADAMTS13 activity (ADAMTS13 ‡5% HIV + group). HIV + patients were also compared to 62 patients with idiopathic TMA, either with (45 patients, ADAMTS13 <5% idiopathic group) or without (17 patients, ADAMTS13 ‡5% idiopathic group) severe ADAMTS13 deficiency. ADAMTS13 <5% HIV + patients had less AIDS-related complications than ADAMTS13 ‡5% HIV + patients (23.5% versus 91.6%, respectively, P = 0.0005) and their median CD4 + T cell count was higher (P = 0.05). TMA-associated death rate was higher in ADAMTS13 ‡5% HIV + patients than in ADAMTS13 <5% HIV + patients (50% versus 11.7%, respectively, P = 0.04). In ADAMTS13 <5% patients, TMA-associated death rate was comparable between HIV + and idiopathic patients (15.5% in idiopathic patients, P-value was non-significant). By contrast, TMA-associated death rate in ADAMTS13 ‡5% HIV + patients was higher than in idiopathic patients (11.7% in idiopathic patients, P = 0.04). In conclusion, HIV-associated TMA with severe ADAMTS13 deficiency have less AIDS-related complications and a higher CD4 + T cell count. TMA prognosis is better and comparable to this of idiopathic forms.