An overview of prophylaxis and treatment indications for COVID-19-related thrombotic complications

In 2020, a coronavirus-related disease (COVID-19) became a pandemic. The disease was recognized as a viral respiratory illness caused by SARS-CoV-2. Histologic analysis of pulmonary vessels in severely affected patients revealed a microangio-pathic thrombosis. It was rapidly recognized that the disease could behave as a thrombotic disease, both in the venous and arterial circulations and affecting multiple organs. Anticoa-gulant treatments were immediately considered to prevent or control the underlying coagulopathy. The emergency of the situation and the limited knowledge in the early months accounted for variable success of the anticoagulation regi-mens. The benefit/bleeding risk ratio of anticoagulant treat-ments depended on the severity and evolution of the disease in different subgroups of patients. This review aims to provide a synthesized guide on how anticoagulant protocols indicated for the prophylaxis and treatment of COVID-19-related hyper -coagulable state have evolved and have been successfully adapted to specific scenarios throughout the pandemic.

Dysfunctional hemostasis in patients under extracorporeal life support. A rapid diagnostic approach with therapeutical guidance intentions

Background: Short-term cardiopulmonary extracorporeal life supports (ECLS) are invasive devices whose use has increased exponentially during the COVID-19 pandemic. Major bleeding is a main cause of morbi-mortality in ECLS patients and acquired von Willebrand disease (aVWD) could justify this complication. Aim(s): We aim at investigating the primary hemostasis alterations profile in ECLS patients, and to propose a potential treatment if bleeding. Method(s): Patients in ECLS at our center since June 2021 were included (n = 25). Primary hemostasis was evaluated by: Von Willebrand Factor antigen (VWF:Ag) and activity (VWF:GPIbM) measurement (immunoturbidimetry), VWF multimeric analysis (agarose-gels and immunoblotting), platelet function analysis (PFA-200), and platelet activation (CD62P and CD63 expression by flow cytometry). Studies were performed 24 h after implant, each 7 days, and in the first week after ECLS extraction. T-TAS was used for hemostasis analysis in samples from bleeding patients, before and after in vitro addition of purified VWF. This study was approved by the Hospital Clinic's Ethics Committee (HCB/2021/0200). Result(s): After 24 h of ECLS implant, increased VWF:Ag levels and prolonged PFA occlusion times. In 60% of patients, altered VWF:GPIbM/VWF:Ag ratio ( < 0.7) and loss of VWF high molecular weight multimers (HMWM) were observed. CD62P expression was slightly higher in ECLS patients platelets than in controls (MFI+/-SD of 4.34 +/- 2.2 vs. 3.27 +/- 0.6, respectively;p = 0.3). Early after ECLS extraction, there was normalization of the VWF multimeric profile and PFA values. Interestingly, in samples from bleeding patients, addition of purified VWF reduced significantly the T-TAS occlusion times (776 s+/-207 s vs. 1161 s+/-251 s, Mean+/-SD, post vs. pre, respectively;p = 0.033). Conclusion(s): ECLS caused primary hemostasis alterations, leading to aVWD and platelet activation, solved early after support removal. Hemostatic efficiency in ECLS bleeding patients, with lack of HMWM, was corrected in vitro by providing functional purified VWF. (Figure Presented).

Vascular endothelial damage in the pathogenesis of preeclampsia and SARS-CoV-2 infection in pregnancy

Background: Endothelial dysfunction is crucial in moderate to severe SARS-CoV-2 infection. Preeclampsia is an endothelial pregnancyrelated syndrome that shares some clinical and analytical features with COVID19. COVID19 signs in pregnant women might be misdiagnosed as preeclampsia leading to an iatrogenic preterm delivery. Aims: To address whether endothelial damage, microvascular thrombosis and dysregulated immune response exhibit different patterns in preeclampsia and COVID19 in pregnancy. Methods: Plasma samples were obtained from pregnant women with COVID19 pneumonia classified into moderate ( n = 10) or severe disease ( n = 9). Endothelial damage and immune response markers were assessed, including VCAM-1, TNF-receptor I (TNFRI), angiotensin II (ANGII), heparan sulfate (HS), PAI-1, dsDNA for neutrophil extracellular traps (NETs), C5b9, thrombomodulin (TM) and ADAMTS-13 activity. Results were compared to those in SARS-CoV-2 negative including healthy pregnant women as controls (C, n = 10), and patients with preeclampsia (PE, n = 13). Results: All endotheliopathy markers were significantly increased in severe COVID19 and PE patients compared to healthy pregnants ( p <0,05, Table 1), except TM and ADAMTS-13 activity. Patients with moderate COVID19 presented a biomarker profile similar to the observed in control patients. Severe COVID19 and PE profiles were distinctive among them regarding four markers: VCAM-1, TNFRI and ANGII, clearly higher in PE, and HS, significantly lower in PE. The principal component analysis (PCA) in Figure 1, demonstrated the separation between severe COVID19 and PE from moderate COVID19 or uncomplicated pregnancies. The first and second components explained 29.1% and 18.4% of the variance between groups. (Figure Presented) Conclusions: Severe COVID19 exhibits signs of endothelial damage and immune dysregulation and some of them are shared with preeclampsia. However, there are specific markers with the potential to discriminate between both conditions. Investigation in this direction could help to develop new strategies for the prevention and treatment of both entities. Grants: Fundació Clínic (HCB/2020/0401), JazzPharmaceuticals (IST-16-10355), Fundació La Marató de TV3 (202026-10).