Coma in adult cerebral venous thrombosis: The BEAST study.

BACKGROUND AND PURPOSE: Coma is an independent predictor of poor clinical outcomes in cerebral venous thrombosis (CVT). We aimed to describe the association of age, sex, and radiological characteristics of adult coma patients with CVT. METHODS: We used data from the international, multicentre prospective observational BEAST (Biorepository to Establish the Aetiology of Sinovenous Thrombosis) study. Only positively associated variables with coma with <10% missing data in univariate analysis were considered for the multivariate logistic regression model. RESULTS: Of the 596 adult patients with CVT (75.7% women), 53 (8.9%) patients suffered coma. Despite being a female-predominant disease, the prevalence of coma was higher among men than women (13.1% vs. 7.5%, p = 0.04). Transverse sinus thrombosis was least likely to be associated with coma (23.9% vs. 73.3%, p < 0.001). The prevalence of superior sagittal sinus thrombosis was higher among men than women in the coma sample (73.6% vs. 37.5%, p = 0.01). Men were significantly older than women, with a median (interquartile range) age of 51 (38.5-60) versus 40 (33-47) years in the coma (p = 0.04) and 44.5 (34-58) versus 37 (29-48) years in the non-coma sample (p < 0.001), respectively. Furthermore, an age- and superior sagittal sinus-adjusted multivariate logistic regression model found male sex (odds ratio = 1.8, 95% confidence interval [CI] = 1.0-3.4, p = 0.04) to be an independent predictor of coma in CVT, with an area under the receiver operating characteristic curve of 0.61 (95% CI = 0.52-0.68, p = 0.01). CONCLUSIONS: Although CVT is a female-predominant disease, men were older and nearly twice as likely to suffer from coma than women.

[Evaluation of a diagnostic test for heparin-induced thrombocytopenia: validation of a delayed test time]. / Évaluation d'un test d'orientation diagnostique de thrombopénie induite à l'héparine : validation d'un délai différé de réalisation du test.

Heparin-induced thrombocytopenia (HIT) is a rare, iatrogenic condition, characterized by its potential severity and diagnostic difficulties. The diagnosis is based on a set of arguments allowing the calculation of a pre-test score pointing to HIT. There are rapid diagnostic tests for suspected HIT. Among these, the STic Expert® HIT has a good sensitivity to detect HIT. However, it must be performed within 2 hours after sampling. The aim of this study was to evaluate a delayed STic Expert® HIT test at 8 hours and in frozen plasma. Thirty-six patients were prospectively included for HIT testing between April 01, 2018, and July 1, 2022, at the University Rouen Hospital. For any request for HIT testing, an analysis by STic Expert® HIT was performed within 2 hours and 8 hours post-sampling. Any positive result was confirmed by a functional test, platelet aggregation with heparin, release of 14C-serotonin assay (SRA), and immunological assay by a research for anti-platelet factor 4 IgG antibodies. Twenty-three patients had a STic Expert® HIT. Sixteen presented platelet aggregations in the presence of heparin and had a positive anti-PF4 test, 17 had a positive SRA. Six patients had no HIT. For the test performed within 2 hours of collection, the Se = 100%, Sp = 68.42%, PPV = 73.91%, and NPV = 100%. The X2 = 18.21 with p < 0.001. For the test performed at 8 hours post sampling, the Se = 100%, Sp = 68.42%, PPV = 73.91% and NPV = 100%. The X2 = 18.21 with p < 0.001. In conclusion, we have demonstrated that the STic Expert® can be used to perform an HIT diagnostic test 8 hours after sampling and on thawed plasma. However, this study needs to be confirmed on a larger number of samples.

Genome-Wide Association Study Identifies First Locus Associated with Susceptibility to Cerebral Venous Thrombosis.

OBJECTIVE: Cerebral venous thrombosis (CVT) is an uncommon form of stroke affecting mostly young individuals. Although genetic factors are thought to play a role in this cerebrovascular condition, its genetic etiology is not well understood. METHODS: A genome-wide association study was performed to identify genetic variants influencing susceptibility to CVT. A 2-stage genome-wide study was undertaken in 882 Europeans diagnosed with CVT and 1,205 ethnicity-matched control subjects divided into discovery and independent replication datasets. RESULTS: In the overall case-control cohort, we identified highly significant associations with 37 single nucleotide polymorphisms (SNPs) within the 9q34.2 region. The strongest association was with rs8176645 (combined p = 9.15 × 10-24 ; odds ratio [OR] = 2.01, 95% confidence interval [CI] = 1.76-2.31). The discovery set findings were validated across an independent European cohort. Genetic risk score for this 9q34.2 region increases CVT risk by a pooled estimate OR = 2.65 (95% CI = 2.21-3.20, p = 2.00 × 10-16 ). SNPs within this region were in strong linkage disequilibrium (LD) with coding regions of the ABO gene. The ABO blood group was determined using allele combination of SNPs rs8176746 and rs8176645. Blood groups A, B, or AB, were at 2.85 times (95% CI = 2.32-3.52, p = 2.00 × 10-16 ) increased risk of CVT compared with individuals with blood group O. INTERPRETATION: We present the first chromosomal region to robustly associate with a genetic susceptibility to CVT. This region more than doubles the likelihood of CVT, a risk greater than any previously identified thrombophilia genetic risk marker. That the identified variant is in strong LD with the coding region of the ABO gene with differences in blood group prevalence provides important new insights into the pathophysiology of CVT. ANN NEUROL 2021;90:777-788.