Coagulation Parameter Abnormalities and Their Relationship to Clinical Outcomes in Hospitalized and Severe COVID-19 Patients: A Prospective Study

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The extreme inflammatory state caused by COVID-19 results in severe disruption of hemostasis and significant alteration in coagulation parameters8.9. COVID-19 infection has been associated with altered coagulation parameters as well as a high rate of venous and arterial thrombotic complications, including unusual thrombotic eventsten.

In COVID-19 patients, coagulopathy is common11,12,13 and has been linked to poorer outcomes12,14,15. Tang and his colleagues2for example, found that in COVID-19 patients, abnormal conventional coagulation tests, particularly elevated D-dimer and fibrinogen levels after hospitalization, were linked to poor prognosis.

The aim of this study was to see how well coagulation markers predict hospitalization, disease severity and mortality in patients with COVID-19.

We found in this prospective single-center study that hospitalized patients with SARS-CoV-2 infection had a marked hypercoagulable state characterized by elevated levels of aPTT, NLR, D-dimer, and fibrinogen. plasma, with a decrease in plasma levels of PC and AT-III. Depending on the severity of the disease, the severity of coagulation abnormalities appears to be related to the severity of inflammation and the severity levels of COVID-19. Numerous studies have shown that a high NLR is significantly associated with increased risk of thrombosis, disease severity and mortality in COVID-1916.17.

The existence of lupus anticoagulant (LA) or antiphospholipid antibodies (APA) is a possible explanation for the prolongation of aPTT in some COVID-19 patients. In a series of 56 hospitalized patients with COVID-19, LA was detected in 44.6%18. We also previously observed a 20.7% prevalence of transient APA in 29 COVID-19 patients with unusual thrombotic eventsten.

In the clinic, PC and prothrombin time (PT) are commonly used to measure coagulation function as one of the most critical markers. Many studies have looked at how PC and PT change in COVID-19 patients19,20,21. Several studies21,22,23 found that severe patients had a significant decrease in PC and longer PT than non-severe patients. Additionally, non-survivors showed higher PT levels and lower CP than survivors in the COVID-19 trial2. We also found that severe COVID-19 patients and non-survivors had significantly lower admission CP than non-severe cases.

Moreover, the level of D-dimers has also been the subject of many investigations on COVID-19. According to a meta-analysis, 37.2% of COVID-19 patients had an elevated level of D-dimers24. Many researchers have suggested that D-dimers could be a useful early indicator to improve the management of patients with COVID-1924.25. They found that COVID-19 patients with D-dimer levels above 2.0 g/mL had a higher mortality rate than those with D-dimer levels below 2.0 g/mL. Additionally, elevated levels of D-dimers have been used as an excellent marker to identify groups at high risk for thromboembolism in patients with severe COVID-19 presented with patients with pneumonia.20.

Our study showed that D-dimer levels were above the upper limit of normal in severe, hospitalized patients with COVID-19, and non-survivors had significantly higher D-dimer levels than survivors. . The same results were observed for fibrinogen levels. Zou et al.26 studied the coagulation function of 303 COVID-19 patients and found a correlation between increased fibrinogen and disease severity.

Regarding AT-III, we found that the median value is lower in severe cases than in non-severe cases, with medians of 78 and 90, respectively. Anakl et al. and Arachchillage et al. discovered similar results27.28. Interestingly, in recent studies, a transient acquired AT-III deficiency has been reported10.29.

Moreover, we observed that marked coagulation abnormalities such as higher levels of aPTT, D-dimers and fibrinogen were more frequently detected in non-survivors compared to non-severe.

Blood coagulation abnormalities were found to be common in COVID-19 patients hospitalized or in intensive care units, and these coagulation abnormalities were statistically significant correlated with multi-inflammatory factors among subcategories based on the hospitalization as well as disease severity status similar to Lui et al.30 and Pujani et al.31.

A retrospective cohort study conducted in Spain showed that COVID-19 non-survivors had significantly abnormal coagulation compared to survivors32, indicating that coagulation parameters could be an effective measure to predict the prognosis of patients with SARS COV-2 and used as a guide for clinical management. Long et al. also found that coagulation dysfunction is a likely finding in critically ill and critically ill patients. D-dimers, prothrombin time and concentration have also been shown to be important indicators in predicting mortality of COVID-19 patients in many studies.11.12.

Moreover, patients with severe COVID-19 had higher amounts of inflammatory biomarkers and many reports suggest that they can be used as prognostic markers.33.34. Similarly, we found that most hospitalized patients with severe COVID-19 infection had a pronounced inflammatory state, characterized by higher level of inflammatory markers including CRP, ESR, ferritin, LDH and the NLR. Additionally, we observed lower hemoglobin levels and platelet count with lymphopenia and neutrophilia in severe cases. Lymphopenia could be explained by Covid-19, which enters human cells by attaching to the receptor for angiotensin-converting enzyme 2 (ACE2), present on many cells and tissues. Due to the presence of the angiotensin converting enzyme 2 (ACE2) receptor on the surface of lymphocytes, it has become more vulnerable to viral invasion and lysis. This conclusion could be confirmed by a considerable drop in blood lymphocytes in the week following COVID-19 infection.35.

In the present investigation, a multivariate logistic regression analysis revealed that the prediction of D-dimers, LDH and AT-III can be considered as excellent independent predictors of the risk of severity in COVID-19, with a threshold (2.0 ng/L, 500 IU/L and 75%) and AUC of (0.940, 0.848, 0.781) respectively by analysis of the ROC curve. Chen et al.36 found that D-dimer levels greater than 1 g/mL on admission were associated with an increased risk of in-hospital death. Cui et al.20 reported that increased D-dimer levels at admission were strongly related to death using multivariate logistic regression. Wu et al.14 found that D-dimers were associated with ARDS progression to mortality in bivariate Cox regression analysis. These results were in agreement with Liu et al.13 report and another COVID-19 study that found the AUCs of PT and D-dimer to predict death on admission were 0.643 and 0.742, respectively12.

Given these data, we believe that specific parameters of coagulation function at admission, such as D-dimers, AT-III, and fibrinogen, in addition to serum ferritin and LDH, may reliably predict the fate of COVID-19 patients. Although serial measurements can offer further information and guide treatment. Assessing coagulation parameters on admission has the advantage of providing physicians with critical information at the right time and helping physicians provide valuable treatments quickly in the early stages of hospital treatment.

Bottom Line: Because most COVID-19 patients have coagulopathy, coagulation systems have value. Early assessment and dynamic monitoring of coagulation system parameters can be a gold standard in controlling COVID-19 severity and mortality by adding another indication to hospitalization criteria and preventing or stopping occurrence. of thrombus or DIC in COVID-19 patients.

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