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Intensive-Dose Tinzaparin in Hospitalized COVID-19 Patients: The INTERACT Study
Karolina Akinosoglou1, Christos Savopoulos2, Abraham Pouliakis3
1Internal Medicine Department, University General Hospital of Patras, 265 04 Rio, Greece.
Insights
Higher doses of tinzaparin anticoagulation effectively prevented venous thromboembolism (VTE) in hospitalized COVID-19 patients. This study supports using intermediate to full therapeutic doses for VTE prophylaxis in non-critical COVID-19 cases.
Area of Science:
- Cardiology
- Hematology
- Infectious Diseases
Background:
- Coronavirus disease-2019 (COVID-19) is pro-inflammatory, activating coagulation and increasing hypercoagulability.
- COVID-19-induced hypercoagulability is linked to adverse outcomes and mortality.
- Pharmacological prophylaxis against venous thromboembolism (VTE) is recommended for hospitalized COVID-19 patients.
Purpose of the Study:
- To evaluate the clinical effectiveness and safety of higher prophylactic doses of tinzaparin for VTE prevention.
- To assess tinzaparin's efficacy in non-critically ill COVID-19 patients with moderate disease severity.
Main Methods:
- Retrospective, phase IV, observational cohort study (INTERACT).
- Involved 705 patients from 13 Greek hospitals (April 2020 - November 2021).
- Patients received intermediate (63.9%) or full therapeutic (36.3%) doses of tinzaparin for VTE prophylaxis.
Main Results:
- Low rates of thrombotic events (2.0%, 14 cases) and bleeding events (0.6%, 4 cases) were observed.
- In-hospital mortality was 1.7% (12 patients).
- Thrombosis correlated with older age and elevated D-dimer levels; clinical improvement seen with decreasing D-dimer and CRP.
Conclusions:
- Prophylactic anticoagulation with intermediate to full therapeutic doses of tinzaparin is favored.
- Findings support tinzaparin's use in non-critically ill, hospitalized COVID-19 patients.
- The study demonstrates favorable effectiveness and safety of higher tinzaparin doses for VTE prevention.
Abstract:
(1) Background: It is well-established that coronavirus disease-2019 (COVID-19) is highly pro-inflammatory, leading to activation of the coagulation cascade. COVID-19-induced hypercoagulability is associated with adverse outcomes and mortality. Current guidelines recommend that hospitalized COVID-19 patients should receive pharmacological prophylaxis against venous thromboembolism (VTE). (2) INTERACT is a retrospective, phase IV, observational cohort study aiming to evaluate the overall clinical effectiveness and safety of a higher than conventionally used prophylactic dose of anticoagulation with tinzaparin administered for VTE prevention in non-critically ill COVID-19 patients with moderate disease severity. (3) Results: A total of 705 patients from 13 hospitals in Greece participated in the study (55% men, median age 62 years). Anticoagulation with tinzaparin was initiated immediately after admission. A full therapeutic dose was received by 36.3% of the participants (mean ± SD 166 ± 33 IU/Kgr/day) and the remaining patients (63.9%) received an intermediate dose (mean ± SD 114 ± 22 IU/Kgr/day). The median treatment duration was 13 days (Q1−Q3: 8−20 days). During the study (April 2020 to November 2021), 14 thrombotic events (2.0%) were diagnosed (i.e., three cases of pulmonary embolism (PE) and 11 cases of deep venous thrombosis, DVT). Four bleeding events were recorded (0.6%). In-hospital death occurred in 12 patients (1.7%). Thrombosis was associated with increasing age (median: 74.5 years, Q1−Q3: 62−79, for patients with thrombosis vs. 61.9 years, Q1−Q3: 49−72, p = 0.0149), increased D-dimer levels for all three evaluation time points (at admission: 2490, Q1−Q3: 1580−6480 vs. 700, Q1−Q3: 400−1475, p < 0.0001), one week ± two days after admission (3510, Q1−Q3: 1458−9500 vs. 619, Q1−Q3: 352−1054.5, p < 0.0001), as well as upon discharge (1618.5, Q1−Q3: 1010−2255 vs. 500, Q1−Q3: 294−918, p < 0.0001). Clinical and laboratory improvement was affirmed by decreasing D-dimer and CRP levels, increasing platelet numbers and oxygen saturation measurements, and a drop in the World Health Organization (WHO) progression scale. (4) Conclusions: The findings of our study are in favor of prophylactic anticoagulation with an intermediate to full therapeutic dose of tinzaparin among non-critically ill patients hospitalized with COVID-19.
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