Haemostatic differences between SARS-CoV- 2 PCR-positive and -negative patients at the time of hospital admission

Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) is associated with a prothrombotic phenotype with an increased risk for thrombosis. Aim(s): To investigate whether COVID-19 is associated with changes in coagulation parameters upon presentation at the emergency department and whether these changes are associated with the development of thrombotic complications in patients with SARS-CoV- 2 infection. Method(s): A single centre, cross-sectional cohort study: The MArkers in COVID-19 And Relations to Outcomes in the Netherlands (MACARON) study was conducted. All patients suspected of SARS-CoV- 2 infection referred to the emergency department of the Meander Medical Center between March-May 2020 were included. 519 patients (26% PCR positive, median age 66 (range 19-97 years), 52.2% male) were included from whom an oro-and nasopharyngeal swab was obtained for detection of SARS-CoV- 2 by polymerase chain reaction (PCR). Blood samples for laboratory analysis were obtained from all patients. Thrombosis was defined as a clinical diagnosis of venous thromboembolism or atherothrombotic event based upon radiology and laboratory results. Result(s): SARS-CoV- 2 PCR positive patients had increased fibrinogen levels (5.41 g/L vs. 4.21 g/L, p < 0.001) and decreased levels of protein C (85.1% vs. 96.1%, p < 0.001) and alpha2-macroglobulin (4.41 muM vs. 5.11 muM, p < 0.001) compared to the PCR negative patients. In addition, we found more acquired activated protein C resistance in PCR positive patients. Furthermore, we found that elevated levels of factor VIII (208% vs. 162%, p = 0.028) and von Willebrand Factor (208% vs. 186%, p = 0.038) and decreased ADAMTS-13 levels (597 ng/ml vs. 691 ng/ml, p < 0.001) were associated with increased occurrence of thrombosis in PCR positive patients (thrombosis vs. non-thrombosis). Conclusion(s): We found that PCR positive patients had a more pronounced prothrombotic phenotype with endothelial activation upon hospital admission showing that coagulation tests may be considered useful to discriminate severe cases of COVID-19 at risk for thrombosis.

Hyperresponsive platelets and a reduced platelet granule release capacity is associated with severity of COVID-19 symptoms and with increased mortality

Background: COVID-19 is often associated with mild thrombocytopenia and increased platelet reactivity. The aim of the current study was to investigate if platelets of COVID-19 patients were primed to hyper-reactive platelets and if the circulating platelets become exhausted during COVID-19 disease. Aim(s): To investigate if platelets of COVID-19 patients were primed to hyper-reactive platelets and if the circulating platelets become exhausted during COVID-19 disease. Method(s): Time dependent platelet activation is studied in whole blood by monitoring the ATP release kinetics from platelets upon stimulation with PAR1 receptor agonist in 41 critical ill COVID-19 patients, 47 COVID-19 patients who were hospitalized but were not critically ill and 30 healthy controls. Result(s): Our study demonstrated that platelets of critical ill COVID-19 patients were hyper-responsive and had a reduced platelet granule release capacity, probably due to exhaustion. The platelet reactivity time of COVID-19 patients admitted to the critical care unit was 2-fold reduced if compared with the response time of healthy controls and 1.6-fold reduced if compared with non-critical COVID-19 patients. Platelet responsiveness was also associated (spearman r;p-value) with D-dimer (0.5;<001), CRP (0.57;<001) and neutrophil-lymphocyte ratio (0.54;<001). Moreover, an increased platelet responsiveness and reduced platelet granule release capacity were associated with an increased mortality (OR;95% CI: 18.8;6.1-57.9 and 4.9;1.5-16.3, respectively). These relationships remained significant after adjustment for age, sex, D-dimer, CRP and neutrophil-lymphocyte ratio. Conclusion(s): Our findings show that platelet hyper-reactivity and reduced platelet granule release capacity were associated with increased critical illness and increased mortality of COVID-19 patients.

Haemostatic differences between SARS-CoV-2 PCR-positive and negative patients at the time of hospital admission.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with thrombosis. We conducted a cohort study of consecutive patients, suspected of SARS-CoV-2 infection presented to the emergency department. We investigated haemostatic differences between SARS-CoV-2 PCR positive and negative patients, with dedicated coagulation analysis. The 519 included patients had a median age of 66 years, and 52.5% of the patients were male. Twenty-six percent of the patients were PCR-positive for SARS-CoV-2.PCR positive patients had increased levels of fibrinogen and (active) von Willebrand Factor (VWF) and decreased levels of protein C and α2-macroglobulin compared to the PCR negative patients. In addition, we found acquired activated protein C resistance in PCR positive patients. Furthermore, we found that elevated levels of factor VIII and VWF and decreased levels of ADAMTS-13 were associated with an increased incidence of thrombosis in PCR positive patients. In conclusion, we found that PCR positive patients had a pronounced prothrombotic phenotype, mainly due to an increase of endothelial activation upon admission to the hospital. These findings show that coagulation tests may be considered useful to discriminate severe cases of COVID-19 at risk for thrombosis.