Venous thromboembolism in critically ill COVID-19 patients receiving prophylactic or therapeutic anticoagulation: a systematic review and meta-analysis

Abstract

Many aspects of care such as management of hypercoagulable state in COVID-19 patients, especially those admitted to intensive care units is challenging in the rapidly evolving pandemic of novel coronavirus disease 2019 (COVID-19). We seek to systematically review the available evidence regarding the anticoagulation approach to prevent venous thromboembolism (VTE) among COVID-19 patients admitted to intensive care units. Electronic databases were searched for studies reporting venous thromboembolic events in patients admitted to the intensive care unit receiving any type of anticoagulation (prophylactic or therapeutic). The pooled prevalence (and 95% confidence interval [CI]) of VTE among patients receiving anticoagulant were calculated using the random-effects model. Subgroup pooled analyses were performed with studies reported prophylactic anticoagulation alone and with studies reported mixed prophylactic and therapeutic anticoagulation. We included twelve studies (8 Europe; 2 UK; 1 each from the US and China) in our systematic review and meta-analysis. All studies utilized LMWH or unfractionated heparin as their pharmacologic thromboprophylaxis, either prophylactic doses or therapeutic doses. Seven studies reported on the proportion of patients with the previous history of VTE (range 0–10%). The pooled prevalence of VTE among ICU patients receiving prophylactic or therapeutic anticoagulation across all studies was 31% (95% CI 20–43%). Subgroup pooled analysis limited to studies reported prophylactic anticoagulation alone and mixed (therapeutic and prophylactic anticoagulation) reported pooled prevalences of VTE of 38% (95% CI 10–70%) and 27% (95% CI 17–40%) respectively. With a high prevalence of thromboprophylaxis failure among COVID-19 patients admitted to intensive care units, individualised rather than protocolised VTE thromboprophylaxis would appear prudent at interim.

Acute pulmonary embolism in acutely ill COVID-19 patients admitted to internal medicine wards.

“…From the 1 st to 30 th April 2020, 41 acutely ill patients admitted to internal medicine department wards underwent a CTPA because respiratory deterioration after admission, and represent the study population. The median (IRQ) age of the cohort was 71.7 (63-76) years, 30 (73%) were females, the median days (IRQ) since onset of symptoms to hospitalization was 8 (4-12) and the median days (IRQ) since onset of symptoms to CTPA was 11 (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). By the end of May 2020 in-hospital mortality of the cohort was 4.88%, with 2 patients still hospitalized and 90% already discharged.…”

“…Although emerging data suggest that acutely ill patients with COVID-19 have an increased risk for APE, the actual prevalence of APE in this clinical setting is not well known. Most information on the thrombotic complications of COVID-19 derives from studies including critical ill patients admitted to ICUs [8,[10][11][12][13][14][15], and data on severe -not critical -acutely ill subjects are lacking.…”

“…This nding is even more noticeable when considering that most patients were receiving heparin at anticoagulant doses. As mentioned, most data on prevalence of APE and thrombotic events in general, are from COVID-19 ICU critical patients [8,[10][11][12][13][14][15]. COVID-19 patients admitted to the ICUs of 3 Dutch hospitals, Klok and colleagues found a cumulative incidence of the composite thromboembolic outcome of 31% (CI95%: 20-41%) with APE representing 81% of all these thrombotic complication (n = 25) [10].…”

“…Therefore, data on the value of D-dimer and other clinical and biochemical markers for the diagnosis of VTE in subjects hospitalized for COVID-19 may improve the diagnostic and therapeutic approach to this disease. In addition, most of the few published studies evaluating thrombotic complications of COVID-19 included intensive care unit (ICU) critical ill patients [8,[10][11][12][13][14][15], and less is known on acutely ill severe -not critical -subjects admitted to internal medicine department general wards.…”

Pharmacological treatment of COVID-19: an update

“…A meta-analysis of COVID-19 patients admitted in the intensive care unit who were given heparin (unfractionated and low molecular weight heparin) for thromboprophylaxis showed a high failure rate. 93 Argatroban, a direct thrombin inhibitor has been shown to improve thrombotic complications in COVID-19 patients who fail heparin therapy. 94 The role of other anticoagulants such as warfarin, dabigatran, bivalirudin, need to be investigated.…”