The Impact of Risk-Adjusted Heparin Regimens on the Outcome of Patients with COVID-19 Infection. A Prospective Cohort Study

Abstract

Background. According to recent guidelines, all hospitalized patients with COVID-19 should receive pharmacological prophylaxis for venous thromboembolism (VTE), unless there are specific contraindications. However, the optimal preventive strategy in terms of intensity of anticoagulation for these patients is not well established. Objectives. To investigate the impact of individualized regimens of enoxaparin on the development of VTE and on the risk of major bleeding complications during hospitalization in patients with COVID-19 infection. Methods. All consecutive patients admitted to the medical wards of six Italian hospitals between 15 September and 15 October 2020 with COVID-19 infection of moderate severity were administered enoxaparin in subcutaneous daily doses adjusted to the Padua Prediction Score stratification model: No heparin in patients scoring less than 4, 4000 IU daily in those scoring 4, 6000 IU in those scoring 5, and 8000 in those scoring six or more. Objective tests were performed in patients developing clinical symptoms of deep vein thrombosis and/or pulmonary embolism. Bleeding complications were defined according to the ISTH classification. Results. From the 154 eligible patients, enoxaparin was administered in all: 4000 IU in 73 patients, 6000 IU in 53, and 8000 IU in the remaining 28. During the course of hospitalization, 27 patients (17.5%) died. VTE developed in 14 of the 154 patients (9.1%; 95% CI, 4.6% to 13.6%), and was fatal in 1. Major bleeding complications developed in 35 patients (22.7%; 95% CI, 16.1% to 29.3%), and were fatal in 8. Conclusions. Despite the use of risk-adjusted doses of enoxaparin, the rate of VTE events was consistent with that reported in contemporary studies where fixed-dose low-molecular-weight heparin was used. The unexpectedly high risk of bleeding complications should induce caution in administering enoxaparin in doses higher than the conventional low ones.

Heparin therapy in COVID-19: Call for randomized controlled trials (RCTs)

“…Several studies have indicated that a therapeutic dose of heparin improves clinical outcomes in patients with mild or ordinary COVID-19 on hospital admission (10,11,17). However, use of anti-thrombotics to improve outcomes in patients with severe COVID-19 is controversial (10,11,16).…”

“…Several studies have indicated that a therapeutic dose of heparin improves clinical outcomes in patients with mild or ordinary COVID-19 on hospital admission (10,11,17). However, use of anti-thrombotics to improve outcomes in patients with severe COVID-19 is controversial (10,11,16). In the current study, the four coagulation indicators (D-D, FDP, PT, and APTT) were significantly higher in patients with severe/ critical COVID-19 than in patients with mild/ordinary COVID-19 at the same measuring point, possibly because tissue damage has already occurred.…”

Home pharmacological therapy in early COVID‐19 to prevent hospitalization and reduce mortality: Time for a suitable proposal

“…Much more caution should be paid towards the use of low molecular weight heparin (LMW‐Hep) 158 . Usually, LMW‐Hep, as well as other major anti‐coagulant therapy, is prescribed during hospitalization 158 ; the use of LMW‐Hep is not currently recommended in addressing early COVID‐19 symptoms, that is, mild and pauci‐symptomatic subjects, due to the many critical issues raised when the platelet‐coagulation system is targeted 159 …”

“…158 Usually, LMW-Hep, as well as other major anti-coagulant therapy, is prescribed during hospitalization 158 ; the use of LMW-Hep is not currently recommended in addressing early COVID-19 symptoms, that is, mild and paucisymptomatic subjects, due to the many critical issues raised when the platelet-coagulation system is targeted. 159 Such a protocol, which completely replaces acetaminophen with NSAIDs, has proven to reduce dramatically the hospitalization rate with respect to paracetamol only. Considering that hospitalization may exacerbate the clinical status even in hospital-acquired infections, 160 this should lead to a reduced mortality particularly in elderly patients with early COVID-19 symptoms.…”

Machine Learning to Calculate Heparin Dose in COVID-19 Patients with Active Cancer

“…Robin Park et al [ 14 ] in a meta-analysis of 16 retrospective and prospective studies, with 3558 patients, show an increased mortality in patients under active chemotherapy treatment, compared to not active chemotherapy. For this reason, a correct evaluation of antithrombotic therapy is essential in oncologic patients, and able to reduce mortality, especially when the appropriate dosage of low molecular weight heparin (LMWH) is administered [ 15 , 16 ]. Therefore, we employed an approach based on machine learning (ML), a branch of computer science that can be considered a close relative of artificial intelligence, to achieve, through an algorithm, the correct anticoagulant therapy to be administered in primary prevention to COVID-19 patients with active cancer.…”