COVID-19 research focused on anticoagulation, vaccine-induced thrombocytopenia

Several recent studies looked at clots: preventing them in inpatients with COVID-19 and treating those that have developed after vaccination against SARS-CoV-2.

A multicenter Brazilian trial randomized inpatients with COVID-19 and elevated D-dimer concentrations to therapeutic anticoagulation (oral rivaroxaban, 20 or 15 mg/d for 30 days, in stable patients, with initial enoxaparin or unfractionated heparin for unstable patients; n=311) or prophylactic anticoagulation (in-hospital enoxaparin or unfractionated heparin; n=304). Results published by The Lancet on June 4 showed no significant difference between groups on a composite outcome that included time to death, length of stay, and duration of supplemental oxygen. Clinically relevant bleeding occurred in 26 patients (8%) on therapeutic anticoagulation and seven (2%) on prophylactic anticoagulation (P=0.0010). The authors concluded that “therapeutic-dose rivaroxaban, and other direct oral anticoagulants, should be avoided in these patients in the absence of an evidence-based indication for oral anticoagulation.”

A cohort study assessed the use of anticoagulation by Michigan hospitals during the early months of the pandemic (March to June 2020). The study, published by JAMA Network Open on June 11, included 1,351 inpatients with COVID-19, 18 of whom had confirmed venous thromboembolism. Treatment-dose anticoagulation was provided to 219 patients (16.2%), a rate that increased over time and varied by hospital. Any dose of anticoagulation was associated with lower inpatient mortality, but only prophylactic anticoagulation was associated with a reduction in 60-day mortality, leading the authors to conclude that “prophylactic dosing strategies may be optimal for patients hospitalized with COVID-19.” An accompanying editorial comment noted that although these results support prophylactic anticoagulation, studies of anticoagulation in COVID-19 continue to have inconsistent results. “Practically, we still lack the granular data we need to help guide us in patient-by-patient decision-making—such as anticoagulation agent choice, dosage, and duration of therapy—especially as dictated by acuity of patient illness,” the commenters said.

Vaccine-induced immune thrombotic thrombocytopenia was the focus of multiple recent New England Journal of Medicine articles. An analysis of 23 cases associated with the AstraZeneca vaccine, published June 10, reported that all patients had low or normal fibrinogen levels and elevated D-dimer levels at presentation; 22 had positive antibodies to platelet factor 4. “On the basis of the pathophysiological features observed in these patients, we recommend that treatment with platelet transfusions be avoided because of the risk of progression in thrombotic symptoms and that the administration of a nonheparin anticoagulant agent and intravenous immune globulin [IVIG] be considered for the first occurrence of these symptoms,” the authors said.

A Brief Report, published June 9, reported on the response to IVIG in three patients who received the AstraZeneca vaccine and had clots. “After the initiation of IVIG, reduced antibody-induced platelet activation in serum was seen in all three patients,” it said.

An editorial published June 10 noted that these complications of vaccination appear to be very rare but “indicate the need for maintaining a high level of concern when patients present with central nervous system or abdominal symptoms after receiving any SARS-CoV-2 vaccine.”

In other COVID-19 research, a study published by CHEST on June 8 reported the feasibility of early rehabilitation for ICU patients with COVID-19, and a case series published by Annals of Internal Medicine on June 15 found that a third dose of vaccine increased SARS-CoV-2 antibody levels in recipients of solid organ transplants.