Clinical outcome with different doses of low-molecular-weight heparin in patients hospitalized for COVID-19

Abstract

A pro-thrombotic milieu and a higher risk of thrombotic events were observed in patients with CoronaVirus disease-19 (COVID-19). Accordingly, recent data suggested a beneficial role of low molecular weight heparin (LMWH), but the optimal dosage of this treatment is unknown. We evaluated the association between prophylactic vs. intermediate-to-fully anticoagulant doses of enoxaparin and in-hospital adverse events in patients with COVID-19. We retrospectively included 436 consecutive patients admitted in three Italian hospitals. Outcome according to the use of prophylactic (4000 IU) vs. higher (> 4000 IU) daily dosage of enoxaparin was evaluated. The primary end-point was in-hospital death. Secondary outcome measures were in-hospital cardiovascular death, venous thromboembolism, new-onset acute respiratory distress syndrome (ARDS) and mechanical ventilation. A total of 287 patients (65.8%) were treated with the prophylactic enoxaparin regimen and 149 (34.2%) with a higher dosing regimen. The use of prophylactic enoxaparin dose was associated with a similar incidence of all-cause mortality (25.4% vs. 26.9% with the higher dose; OR at multivariable analysis, including the propensity score: 0.847, 95% CI 0.400–0.1.792; p = 0.664). In the prophylactic dose group, a significantly lower incidence of cardiovascular death (OR 0.165), venous thromboembolism (OR 0.067), new-onset ARDS (OR 0.454) and mechanical intubation (OR 0.150) was observed. In patients hospitalized for COVID-19, the use of a prophylactic dosage of enoxaparin appears to be associated with similar in-hospital overall mortality compared to higher doses. These findings require confirmation in a randomized, controlled study.

The Role of Alveolar Edema in COVID-19

“…[42,43] Intravascular coagulation and microthrombi formation Lead to increased wasted ventilation and less efficient carbon dioxide removal. [44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62] Diffuse alveolar damage (DAD) Lead to hypoxia at the edematous alveoli.…”

“…Aspirin administration had an association with less mechanical ventilation and reduced ICU cases, but showed no apparent association with the fatality rate (Table 2) [51]. The therapeutic effects of low molecular weight heparin have also been investigated comprehensively [52][53][54][55][56][57][58]. Heparin may reduce the risk of in-hospital mortality and decrease the occurrence of severe cases.…”

“…Heparin may reduce the risk of in-hospital mortality and decrease the occurrence of severe cases. However, critically-ill COVID-19 patients still had high incidences of venous thromboembolism and worse outcomes, despite the heparin administration at the prophylactic dosage [52][53][54][55][56][57][58]. Moreover, besides its anticoagulation effect, heparin relieves the symptoms through complex mechanisms.…”

“…In summary, initial anticoagulant treatments with low-molecular-weight heparin or aspirin may reduce mortality and achieve a significant improvement in P a O 2 :F i O 2 in some patients but however could not completely prevent occurrence of severe cases [49][50][51][52][53][54][55][56][57][58].…”

Lower Blood pH as a High Predisposing Factor for a Fatal Outcome in Critically Ill COVID-19 Patients at Intensive Care Unit: a Multivariable Analysis

“…Mesas et al identi ed Interleucin 6 (IL-6) together with preexisting diseases as predictors of a lethal course in patients under the age of 60 and elevated bilirubin and liver enzymes together with decreased albumin in patients older than 60 years (12). Mennuni et al found that the dosage of low molecular weight heparin hardly affected outcome (13).…”