Introduction: COVID-19 has been associated with venous and arterial thrombotic complications. The objective of our study was to determine whether markers of coagulation and hemostatic activation (MOCHA) on admission could identify COVID-19 patients at risk for thrombotic events. Methods: COVID-19 patients admitted to a tertiary academic healthcare system from April 3, 2020 to July 31, 2020 underwent admission testing of MOCHA profile parameters (plasma d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, and fibrin monomer). For this analysis we excluded patients on outpatient anticoagulation therapy preceding admission. Prespecified endpoints monitored during hospitalization included deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke and access line thrombosis. Results: During the study period, 276 patients were included in the analysis cohort (mean age 59 ± 6.3 years, 47% female, 83% non-white race). Arterial and venous thrombotic events occurred in 43 (16%) patients (see Table). Each coagulation marker was independently associated with the composite endpoint (p<0.05). Admission MOCHA with ≥ 2 abnormalities was associated with the composite endpoint (OR 3.1, 95% CI 1.2-8.3), ICU admission (OR 3.2, 95% CI 1.8-5.5) and intubation (OR 2.8, 95% CI 1.5-5.5). Admission MOCHA with < 2 abnormalities (26% of the cohort) had sensitivity of 88% and a negative predictive value of 93% for an in-hospital endpoint. Conclusion: Admission MOCHA with ≥ 2 abnormalities identified COVID-19 patients at risk for a thrombotic event, ICU admission and intubation while < 2 abnormalities identified a subgroup of patients who were at low risk for thrombotic events. Our results suggest that an admission MOCHA profile can be useful to risk stratify COVID-19 patients. Further studies are needed to determine whether an admission MOCHA profile can guide anticoagulation therapy and improve overall clinical outcomes.
VKORC1 gene polymorphism has been implicated in the variable anticoagulation response to warfarin. Accurate dosing to maintain target INR is of critical importance in the CF-LVAD population in order to minimize bleeding and thrombotic complications. We hypothesized that VKORC1 1639G>A polymorphism predicts individual response to warfarin therapy as well as the risk of hemorrhagic complications in patients with CF-LVAD.
While venous thromboembolism (VTE) is a well recognised occurrence in clinical practice in the developed world, with event rates of at least 2-3 million per year, little attention is paid to this entity in the developing world where the burden of infectious diseases and limited access to care have not recognised VTE as a significant cause of morbidity and mortality. The opportunity for Africa to do better as the inevitable recognition of the consequence of VTE becomes more apparent is available using basic tools and therapies.
High-resolution melting curve analysis using a fluorescent DNA binding dye can detect sequence variations in a closed-tube system without labeled primers or probes. We developed and verified a melting analysis assay for common single nucleotide polymorphisms of cytochrome P-450 (CYP) 2C9 that affect warfarin metabolism. We used this method to genotype 84 patients receiving warfarin. For wild-type, *1/*1, 50% fluorescence corresponded to a mean +/- SD of 87.17 +/- 0.05 degrees C, whereas *2/*2 was 0.4 degrees C lower The *1/*2 melting curve was easily distinguished from *1/*1 and *2/*2 based on transition temperature and shape. Exon 7 showed a more complex melting curve; however, genotypes *1/*1, *1/*3, and *3/*3 were easily distinguishable. Melting curves were highly reproducible (SD of temperature for multiple fluorescence values 0.04 degrees C-0.11 degrees C; mean, 0.06 degrees C). Heterozygotes (*1/*2 or *1/*3) required significantly lower mean maintenance warfarin doses compared with wild-type (30.67 and 29.56 vs 42.81 mg/wk; P < .05). High-resolution melting analysis provides a simple and accurate method for genotyping of CYP2C9.