key: cord-0771592-v3nzr8sq authors: Karimzade, Sedighe; Dong, Vinh; Hassan, Osama Gamal; Raut, Akshay; Fouda, Ahmed; Parrill, Allison; Eaton, Kimberly; Huy, Nguyen Tien title: Covid-19-induced coagulopathy and observed benefits with anticoagulation date: 2020-08-03 journal: Transfus Apher Sci DOI: 10.1016/j.transci.2020.102906 sha: c55413149af44620d4bb9f1421adfab6f364126f doc_id: 771592 cord_uid: v3nzr8sq nan This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Additionally, COVID-19 is characterized by an increase in pro-inflammatory markers, such as IL-6 and IL-Iβ, and induction of cytokine storms. Such events cause alveolar thickening, hyaline membrane formation, diffuse organ damage, and microthrombi via coagulation cascade activation which contributes to low SpO2 [11] . In fact, the pulse oximeter may inaccurately identify blood oxygen saturation (SpO2) in COVID-19 patients due to sepsis-induced vasodilation, formation of arteriovenous shunts, and culmination of venous blood containing carbon dioxide (CO2) [12] . An observational study identified thrombotic event incidence in COVID-19 patients who received nadroparin 2850 IU or 5700 IU (if body weight was >100 kg) subcutaneous per day for thromboprophylaxis [13] . Venous Thromboembolism (VTE) in 27% of patients (95% Confidence Interval (CI) 17-37%) and arterial thrombotic events in 3.7% of patients (95% CI 0-8.2%) were confirmed with computed tomography pulmonary angiography (CTPA) and/or ultrasonography. Of these events, pulmonary embolism (PE) was the most common complication (n = 25, 81% of all thrombotic events) [13] . A subsequent Italian observational study reported 16.7% (95% CI 8.7 -29.6%) of a total of 48 intensive care unit (ICU) patients had at least one thrombo-embolic event, although all patients received thromboprophylaxis with weight adjusted low-molecular-weight heparin. This study also found that 6.4% of 314 ward patients ( The improvement of PaO2/FiO2 upon receiving anticoagulation suggests that micro-emboli secondary to coagulopathy may cause V/Q mismatch. This may partially explain the high mortality rate for patients on ventilation, as ventilating a lung with decreased circulation is ineffective [15] . This is supported by post-mortem assessment of Italian and American COVID-19 patient pulmonary tissue that revealed microthrombi and diffuse alveolar damage from thrombotic microangiopathy which may be a plausible mechanism of fatality [16, 17] . Additionally, if PaO2/FiO2 can be improved, the use of therapeutic anticoagulation should be explored in COVID-19 patients with acute respiratory distress syndrome. Presenting features of thrombosis in COVID-19 are not limited to microvasculature. Thrombotic events, such as large vessel occlusion (carotid and cerebral arteries), were reported in 5 patients <50 years of age [18] . A recent retrospective study of 2,773 COVID-19 hospitalized patients determined longer periods of anticoagulation treatment were correlated with reduced mortality risk with a multivariate proportional hazards model (adjusted Hazards Ratio (HR) of 0.86 per day; 95% confidence interval: 0.82 to 0.89; p < 0.001) [19] . A second study reported lower 28-day mortality rates among COVID-19 patients with sepsis-induced coagulopathy (SIC) score ≥ 4 (40.0% vs 64.2%, P = .029), or D-dimer > 6 times the normal upper limit (32.8% vs 52.4%, P = .017) in a heparin-treated group compared to a non-heparin-treated group [2] . Based on the current evidence, (2020) noted a paucity of data and did not provide recommendations, however, did state that elevated D-dimer levels are associated with a greater risk of death [22] . Therefore, for patients without contraindications to anticoagulation therapy, it may be logical to titrate heparin dosing according to D-dimer. Negri et al., (2020) completed this without any bleeding complications or fatalities within 72 hours of administration. In conclusion, more studies must be conducted to evaluate the safety and benefit of titrating low molecular weight heparin to D-dimer. Additionally, therapeutic anticoagulation in the context of ARDS should be explored, as preliminary findings show an increase in PaO2/FiO2 following anticoagulation in COVID-19 infected patients. 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