A Prospective Study of Specialized Coagulation Parameters in Admitted COVID-19 Patients and Their Correlation With Acute Respiratory Distress Syndrome and Outcome.

ABSTRACT

Background Acute respiratory distress syndrome (ARDS) is a frequent complication of COVID-19 and is associated with a component of thrombo-inflammation and cytokine storm. COVID-19 also affects the hemostatic system causing multiple coagulation abnormalities that is a cause of concern and needs to be addressed.  Objective We aimed to assess coagulation parameters of COVID-19 patients and identify whether they could be used as potential prognostic biomarkers to predict ARDS and immediate outcomes. Methods This was a prospective study done on 68 patients at four serial time points. Patients between 18-85 years admitted to the hospital as in-patients and ICU with a confirmed diagnosis of COVID-19 by RT-PCR were included. Exclusion criteria included pregnancy, patients below and above the mentioned age, previously known coagulopathy, systemic anticoagulants or anti-platelet therapy or vitamin K antagonists and moribund patients. Patients were divided into three categories based on SOFA score at admission, presence (group 1) or absence (group 2) of ARDS and outcome (dead or alive). Routine and specialized coagulation tests were performed on patients' platelet-poor plasma at the time of study inclusion (day 0), days 3, 7 and at discharge on STAR Max®3 (Diagnostica Stago France) automated coagulation analyzer and included prothrombin time (PT), international normalized ratio (INR) (STA® -NeoPTimal), activated partial thromboplastin time (APTT) (STA® -Cephascreen), fibrinogen (STA® Liquid Fib), D-dimer (STA® LiatestD- Dimer), Protein C (STA Stachrom® Protein C), Protein S (STA® Latest Free Protein S) and Antithrombin (STA® Chrom ATIII). ELISA did testing for tissue plasminogen activator (Asserachrom® tPA) as per the manufacturer's protocol. Results Sixty-eight patients, including 43 (63%) males and 25 (37%) females, with a median age of 48 years (IQR 20-85), were recruited in this study. The incidence of ARDS was 34%, with a mortality of 13%. History of contact with a COVID-19 case was present in 71% (48/68) of the patients. Fever was the most common presenting symptom in 84% (57/68) of the patients. The most common comorbidities were hypertension and diabetes mellitus (DM) in 22% (15/68) and 21% (14/68) of the patients. DM (p=0.07) and chronic obstructive pulmonary disease (COPD) (p=0.03) were significantly associated with ARDS. DM (p=0.02), hypertension (p=0.01), and COPD (p=0.02) were also significantly associated with mortality. APTT was markedly prolonged among non-survivors at day 0 (D0) and D7 (p=0.03, p=0.02). D-Dimer was elevated in 38/68 (56%) patients at D0. D-Dimer levels were significantly higher in non-survivors (p<0.001), in ARDS patients (p=0.001) and patients with higher SOFA scores (p=0.001). ROC curve showed that D-dimer cut-off > 2.13 (AUC of 0.86) and >0.85 (AUC of 0.74) predicts mortality and ARDS, respectively. Among the natural anticoagulants, protein C was significantly associated with a high SOFA score at D0 and D3 (p=0.04).  Conclusion Diabetes mellitus, hypertension and COPD were associated with poor outcomes. D-dimer levels must be monitored in COVID patients due to their association with ARDS and mortality. We observed that the levels of natural anticoagulants fell during the illness, making them prone to coagulopathies; however, none were seen in this study. Elevated tPA levels were also found in our patients; fibrinolytic therapy may benefit COVID-19 patients suffering from ARDS.