Factor XIII improves platelet adhesion to fibrinogen by protein disulfide isomerase-mediated activity

BACKGROUND Factor XIII (FXIII), a plasma pro-transglutaminase, consists of two A subunits and two B subunits (FXIIIA2B2). Following activation by thrombin, it cross-links fibrin chains at the final step of coagulation. We previously reported that FXIII subunit A (FXIIIA) serves as a protein disulfide isomerase (PDI), and that PDI promotes platelet adhesion and aggregation. OBJECTIVE This study sought to examine possible mechanistic effect of FXIII on platelet adhesion to fibrinogen; specifically, the role of its PDI activity. METHODS Ex vivo experiments: Blood platelets derived from five patients with hereditary FXIIIA deficiency before and after treatment with Fibrogammin-P (FXIIIA2B2 concentrate) were washed and incubated on immobilized fibrinogen. Bound platelets were stained and counted by microscopy. In vitro experiments: Platelets derived from patients before treatment and five healthy controls were washed and analyzed for adhesion in the presence or absence of Fibrogammin-P or recombinant FXIII (FXIIIA2 concentrate). RESULTS In ex vivo experiments, one hour after Fibrogammin-P treatment, mean (±SEM) platelet adhesion to fibrinogen increased by 27±2.32% (p<0.001). In in vitro experiments, treatment with Fibrogammin-P or recombinant FXIII (10IU/mL each) enhanced platelet adhesion to fibrinogen (in patients, by 29.95±6.7% and 29.05±5.3%, respectively; in controls, by 26.06±3.24% and 26.91±4.72, respectively; p<0.04 for all). Iodoacetamide-treated FXIII (I-FXIII), where transglutaminase activity is blocked, showed similar enhanced adhesion as untreated FXIII. By contrast, addition of an antibody that specifically blocks FXIIIA-PDI activity inhibited FXIII-mediated platelet adhesion to fibrinogen by 65%. CONCLUSION These findings indicate that FXIII-induced enhancement of platelet adhesion is mediated by FXIII-PDI activity

EMERGENCY CESAREAN SECTION WITH REDO MITRAL VALVE REPLACEMENT FOR ACUTE PROSTHETIC VALVE DYSFUNCTION: A CASE REPORT

Objective: Cardiovascular diseases emerge as one of the leading causes of maternal morbidity and mortality in developed countries. These risks are even higher in women with prosthetic cardiac valves. The core of the care for these women and the fetus during the hypercoagulable state of the pregnancy and postpartum period is the achievement of coagulation control using adjusted anticoagulation therapy protocols. A multidisciplinary team that includes obstetricians, cardiologists, hematologists, and anesthesiologists in a referral center is essential for an optimal maternal-fetal outcome. In particular, these measures are directed at preventing one of the most serious complications associated with mechanical valve dysfunction. The dysfunctional valve in the mitral position increases maternal and fetal mortality by 30%, especially in the presence of heart failure symptoms. Here we present a case of a 32-week pregnant woman diagnosed with dysfunction of the mechanical mitral valve (MV) and an emergency multidisciplinary approach to her treatment

Predictors of Hypoxemia and Related Adverse Outcomes in Patients Hospitalized with COVID-19: A Double-Center Retrospective Study

Hypoxemia is a hallmark of coronavirus disease 2019 (COVID-19) severity. We sought to determine predictors of hypoxemia and related adverse outcomes among patients hospitalized with COVID-19 in the two largest hospitals in Jerusalem, Israel, from 9 March through 16 July 2020. Patients were categorized as those who developed reduced (&lt;94%) vs. preserved (≥94%) arterial oxygen saturation (SpO2) within the first 48 h after arrival to the emergency department. Overall, 492 hospitalized patients with COVID-19 were retrospectively analyzed. Patients with reduced SpO2 were significantly older, had more comorbidities, higher body surface area (BSA) and body mass index (BMI), lower lymphocyte counts, impaired renal function, and elevated liver enzymes, c-reactive protein (CRP), and D-dimer levels as compared to those with preserved SpO2. In the multivariable regression analysis, older age (odds ratio (OR) 1.02 per year, p &lt; 0.001), higher BSA (OR 1.16 per 0.10 m2, p = 0.003) or BMI (OR 1.05 per 1 kg/m2, p = 0.011), lower lymphocyte counts (OR 1.72 per 1 × 103/μL decrease, p = 0.002), and elevated CRP (1.11 per 1 mg/dL increase, p &lt; 0.001) were found to be independent predictors of low SpO2. Severe hypoxemia requiring ventilatory support, older age, and pre-existing comorbidities, including underlying renal dysfunction and heart failure, were found to be significantly associated with in-hospital mortality. These findings suggest that assessment of predictors of hypoxemia early at the time of hospitalization with COVID-19 may be helpful in risk stratification and management