Pragmatic Recommendations for the Management of Anticoagulation and Venous Thrombotic Disease for Hospitalized Patients with COVID-19 in Low- and Middle-Income Countries

Abstract

New studies of COVID–19 are constantly updating best practices in clinical care. Often, it is impractical to apply recommendations based on high-income country investigations to resource limited settings in low- and middle-income countries (LMICs). We present a set of pragmatic recommendations for the management of anticoagulation and thrombotic disease for hospitalized patients with COVID-19 in LMICs. In the absence of contraindications, we recommend prophylactic anticoagulation with either low molecular weight heparin (LMWH) or unfractionated heparin (UFH) for all hospitalized COVID-19 patients in LMICs. If available, we recommend LMWH over UFH for venous thromboembolism (VTE) prophylaxis to minimize risk to healthcare workers. We recommend against the use of aspirin for VTE prophylaxis in hospitalized COVID-19 and non–COVID-19 patients in LMICs. Because of limited evidence, we suggest against the use of “enhanced” or “intermediate” prophylaxis in COVID-19 patients in LMICs. Based on current available evidence, we recommend against the initiation of empiric therapeutic anticoagulation without clinical suspicion for VTE. If contraindications exist to chemical prophylaxis, we recommend mechanical prophylaxis with intermittent pneumatic compression (IPC) devices or graduated compression stockings (GCS) for hospitalized COVID-19 patients in LMICs. In LMICs, we recommend initiating therapeutic anticoagulation for hospitalized COVID-19 patients, in accordance with local clinical practice guidelines, if there is high clinical suspicion for VTE, even in the absence of testing. If available, we recommend LMWH over UFH or Direct oral anticoagulants for treatment of VTE in LMICs to minimize risk to healthcare workers. In LMIC settings where continuous intravenous UFH or LMWH are unavailable or not feasible to use, we recommend fixed dose heparin, adjusted to body weight, in hospitalized COVID-19 patients with high clinical suspicion of VTE. We suggest D -dimer measurement, if available and affordable, at the time of admission for risk stratification, or when clinical suspicion for VTE is high. For hospitalized COVID-19 patients in LMICs, based on current available evidence, we make no recommendation on the use of serial D -dimer monitoring for the initiation of therapeutic anticoagulation. For hospitalized COVID-19 patients in LMICs receiving intravenous therapeutic UFH, we recommend serial monitoring of partial thromboplastin time or anti-factor Xa level, based on local laboratory capabilities. For hospitalized COVID-19 patients in LMICs receiving LMWH, we suggest against serial monitoring of anti-factor Xa level. We suggest serial monitoring of platelet counts in patients receiving therapeutic anticoagulation for VTE, to assess risk of bleeding or development of heparin induced thrombocytopenia.

The Effect of Anti-coagulation Dosage on the Outcome of Hospitalized COVID-19 Patients in Ethiopia: A multi-center retrospective cohort study

“…The study compared 28-day mortality in severe COVID-19 patients who received prophylactic anticoagulation against those who did not receive any anticoagulant, and they found that the 28-day mortality was signi cantly lower in heparin-users as compared to non-users, particularly in patients with markedly elevated D-dimer and those with a higher sepsis-induced coagulopathy (SIC) score (10). This nding was further supported by other studies (11,12), and as a result standard dose thromboprophylaxis was adopted as part of routine clinical care for COVID-19 patients who require inpatient care (7,13). Despite the use of low-dose anticoagulation however, in some studies ( 14), a high proportion of patients were still developing life-threatening thrombotic complications.…”

“…All this evidence and recommendations however are from studies done in high-income nations and require patient strati cation based on laboratory tests like D-dimer, which are typically unavailable in most low-and middleincome settings. A pragmatic recommendation for hospitalized COVID-19 patients in low-and middle-income countries (LMICs) indicated administration of prophylactic anticoagulation with either Low Molecular Weight Heparin (LMWH) or unfractionated heparin (UFH) for all hospitalized COVID-19 patients in LMICs if there are no contraindications (7). Furthermore, the review recommended against the initiation of empiric therapeutic anticoagulation without clinical suspicion for venous thromboembolism (VTE).…”

The Effect of Anti-coagulation Dosage on the Outcome of Hospitalized COVID-19 Patients in Ethiopia: A multi-center retrospective cohort study

“…The study compared 28-day mortality in severe COVID-19 patients who received prophylactic anticoagulation against those who did not receive any anticoagulant, and they found that the 28-day mortality was signi cantly lower in heparin-users as compared to non-users, particularly in patients with markedly elevated D-dimer and those with a higher sepsis-induced coagulopathy (SIC) score (10). This nding was further supported by other studies (11,12), and as a result standard dose thromboprophylaxis was adopted as part of routine clinical care for COVID-19 patients who require inpatient care (7,13). Despite the use of low-dose anticoagulation however, in some studies (14), a high proportion of patients were still developing life-threatening thrombotic complications.…”

“…All this evidence and recommendations however are from studies done in high-income nations and require patient strati cation based on laboratory tests like D-dimer, which are typically unavailable in most low-and middle-income settings. A pragmatic recommendation for hospitalized COVID-19 patients in low-and middleincome countries (LMICs) indicated administration of prophylactic anticoagulation with either Low Molecular Weight Heparin (LMWH) or unfractionated heparin (UFH) for all hospitalized COVID-19 patients in LMICs if there are no contraindications (7). Furthermore, the review recommended against the initiation of empiric therapeutic anticoagulation without clinical suspicion for venous thromboembolism (VTE).…”

“…Furthermore, the review recommended against the initiation of empiric therapeutic anticoagulation without clinical suspicion for venous thromboembolism (VTE). In LMICs, it was recommended to initiate therapeutic anticoagulation for hospitalized COVID-19 patients, in accordance with local clinical practice guidelines, if there is high clinical suspicion for VTE, even in the absence of testing (7).…”