Pregnancy may be complicated by a rare but life-threatening disease called thrombotic thrombocytopenic purpura (TTP). Most cases of TTP are due to an acquired autoimmune or hereditary (Upshaw-Schulman syndrome [USS]) severe deficiency of a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13 (ADAMTS13). In the present study, we performed a cross-sectional analysis of the national registry of the French Reference Center for Thrombotic Microangiopathies from 2000-2010 to identify all women who were pregnant at their initial TTP presentation. Among 592 adulthood-onset TTP patients with a severe ADAMTS13 deficiency, 42 patients with a pregnancy-onset TTP were included. Surprisingly, the proportion of USS patients (n = 10 of 42 patients [24%]; confidence interval, 13%-39%) with pregnancy-onset TTP was much higher than that in adulthood-onset TTP in general (less than 5%) and was mostly related to a cluster of ADAMTS13 variants. In the present study, subsequent pregnancies in USS patients not given prophylaxis were associated with very high TTP relapse and abortion rates, whereas prophylactic plasmatherapy was beneficial for both the mother and the baby. Pregnancy-onset TTP defines a specific subgroup of patients with a strong genetic background. This study was registered at www.clinicaltrials.gov as number NCT00426686 and at the Health Authority, French Ministry of Health, as number P051064.

In ambulatory patients with solid cancer, routine thromboprophylaxis to prevent venous thromboembolism is not recommended. Several risk prediction scores to identify cancer patients at high risk of venous thromboembolism have been proposed, but their clinical usefulness remains a matter of debate. We evaluated and directly compared the performance of the Khorana, Vienna, PROTECHT, and CONKO scores in a multinational, prospective cohort study. Patients with advanced cancer were eligible if they were planned for chemotherapy or had started chemotherapy in the previous 3 months. The primary outcome was objectively confirmed symptomatic or incidental deep vein thrombosis or pulmonary embolism during a 6-month follow-up period. A total of 876 patients were enrolled, of whom 260 (30%) had not yet received chemotherapy. Fifty-three patients (6.1%) developed venous thromboembolism. The c-statistics of the scores ranged from 0.50 to 0.57. At the conventional positivity threshold of 3 points, the scores classified 13% to 34% of patients as high risk; the 6-month venous thromboembolism incidence in these patients ranged from 6.5% (95% CI, 2.8-12) for the Khorana score to 9.6% (95% CI, 6.6-13) for the PROTECHT score. High risk patients had a significantly increased risk of venous thromboembolism when using the Vienna (subhazard ratio 1.7; 95% CI 1.0-3.1) or PROTECHT scores (subhazard ratio 2.1; 95% CI 1.2-3.6). In conclusion, the prediction scores performed poorly in predicting venous thromboembolism in cancer patients. The Vienna CATS and PROTECHT scores appear to discriminate better between low and high risk patients, but further improvements are needed prior to considering introduction in clinical practice.

Objective: The pathogenesis of idiopathic sudden sensorineural hearing loss (ISSHL) remains unknown, but vascular involvement is one of the main hypotheses. The main objective of this study was to investigate the association between ISSHL and cardiovascular and thromboembolic risk factors. Study Design: Multicentric case-control study. Methods: Ninety-six Caucasian patients with ISSHL and 179 sex- and age-matched controls were included. Patients were evaluated on the day of the inclusion and 1 week, 3 weeks and 3 months later. Clinical information concerning personal and familial cardiovascular and thromboembolic risk factors and concerning the ISSHL was collected. Blood samples were collected for genetic analysis of factor V Leiden and G20210A polymorphism in the factor II gene. The severity of the hearing loss was classified as mild (21–40 dB), moderate (41–70 dB), severe (71–90 dB) and profound or total (>90 dB). Hearing improvement was calculated as a relative improvement of hearing thresholds using the contralateral ear as baseline. Results: Systolic blood pressure was higher in patients (130 ± 1.7 mm Hg) than in controls (124 ± 1.1 mm Hg, p = 0.003). The personal/familial history of cardiovascular events was also more prevalent in patients (p = 0.023 and p = 0.014, respectively), whereas no difference was found in the prevalence of personal cardiovascular risk factors (hypertension, diabetes mellitus, hyperlipidemia, smoking habits). There was no correlation between the audiogram type, the hearing outcome and the presence of cardiovascular risk factors. No significant difference was observed in the personal/familial history or in the presence of thromboembolic risk factors. The prothrombin and factor V mutations were uncommon in both patients and controls. The final hearing threshold was only correlated with the severity of the initial hearing loss (p < 0.001), but not influenced by the presence of vertigo, audiogram type, time elapsed from onset of ISSHL to hospitalization or failure of a previous oral therapy. Hearing stabilization was obtained at 21 days in 92% of patients. Conclusion: These results support the theory of vascular involvement as the etiology of some cases of ISSHL. The sole predictive factor of poor final hearing is the severity of the initial hearing loss.

Objective To clarify the relationships between circulating microparticles (MPs), leukocyte–platelet aggregates (LPAs), obesity, and metabolic abnormalities and evaluate the effect of losing weight on these parameters. Design and Methods In 151 severely obese women and 60 lean controls, total MPs (annexin-V positive), platelet (annexin V/CD41+) and endothelial (CD31+/CD41−) MPs, and LPAs using flow cytometry, and the presence of metabolic syndrome (MS) were assessed. The effect of weight loss was studied in 32 subjects after a 1 year follow-up. Results Total microparticle count, platelet MPs (PMPs) and endothelial MPs (EMPs), and neutrophil–platelet aggregates were significantly increased in obese subjects versus lean controls, independently of the MS. Within obese subjects, there was no significant difference between those having and those not having MS. MPs and LPA counts did not vary significantly in subjects who lost 25% of their excess weight. Conclusions PMPs and EMPs, and LPAs are associated with obesity independently of metabolic abnormalities, but do not significantly change after massive weight loss. Further studies are needed to evaluate the prognostic significance of these observations, as beneficial effects of MPs are currently reported in addition to their initially described deleterious effects.

Objective—The goal of this study was to search for an association between a desintegrin-like and metalloprotease thrombospondin type 1 motif, member 13 (ADAMTS13) levels and the occurrence of preeclampsia, its characteristics (time-onset and severity), and its consequences (occurrence of fetal growth restriction or preterm delivery). Methods and Results—We studied 140 pairs of women in a case-control study with 3 matching criteria: maternal age, gestational age, and ethnic origin. We measured ADAMTS13 activity using a fluorescence resonance energy transfer assay with the fluorescence resonance energy transfer-VWF73 peptide. ELISA was used to assess protein antigen levels: ADAMTS13, von Willebrand Factor (VWF), interleukin-6, C-reactive protein, P-selectin, and thrombospondin-1. The lowest levels of ADAMTS13 (activity ≤70% or antigen ≤592 ng/mL) were significantly associated with preeclampsia (odds ratios [OR] [95% confidence interval] of 4.2 [1.1 to 15] and 14.3 [1.7 to 123], respectively). This association was independent of VWF levels and preeclampsia risk factors but dependent on interleukin-6 and C-reactive protein levels for ADAMTS13 activity. Levels of ADAMTS13 activity (≤57%) were significantly associated with early-onset preeclampsia (OR=2.5 [1.1 to 5.8]). Severe preeclampsia was associated with the highest levels of P-selectin (>57 ng/mL) (OR=3.4 [1.2 to 9.7]). Conclusion—Preeclampsia is associated with decreased levels of ADAMTS13, independently of VWF. This decrease is quantitative, occurs early, and seems to be dependent on inflammation. Our results suggest that ADAMTS13 could participate in the pathophysiology of preeclampsia.