Study of Coagulation Profile and Role of Heparin Like Effect in Patients With COVID-19

Several Consensus statements have been published in the literature in the last 2 months emphasizing the need for data in Covid 19 to assess the risk of both bleeding i.e. disseminated intravascular coagulation (DIC) and thromboses (stoke, myocardial infarction, dialysis catheter blocks).

Early reports showed that very high D-dimer levels are common in COVID-19 pneumonia and correlate with a worse prognosis. To better characterize COVID-19-related coagulation changes, many studies are showing some initial data regarding the role of procoagulant micro thrombotic changes rather than DIC. Coagulation profiles observed in studies published in the last one month reflect a severe hypercoagulability rather than a consumptive coagulopathy (e.g., disseminated intravascular coagulation). Such a laboratory pattern and association can be linked to both markedly increased levels of fibrinogen and an excessive fibrin polymerization due to the infection. SARS-CoV-2 is likely to promote massive fibrin formation and deposition which can also account for the extremely high D-dimer levels found in these patients. Fibrin deposition in alveolar and interstitial lung spaces, in addition to microcirculation thrombosis, may contribute to worsening respiratory failure resulting in prolonged mechanical ventilation, poor prognosis, and death. Furthermore, other major venous thromboembolic events and arterial complications (e.g., acute myocardial infarction) have been reported and are likely to be largely underestimated. In this regard, anticoagulant therapy may improve the prognosis in COVID19 patients as reported by various studies. In light of the severe hypercoagulable state observed in these patients, effective anticoagulant prophylaxis should be considered to reduce the risk of thrombotic complications. This will be the first prospective study to assess the impact of adequate dosages of anticoagulants on clotting parameters in an Indian scenario.

There are several ways in which the COVID-19 pandemic may affect the prevention and management of the thrombotic and thromboembolic disease.

• First, the direct effects of COVID-19 or the indirect effects of infection, such as through severe illness and hypoxia, may predispose patients to thrombotic events. Preliminary reports suggest that hemostatic abnormalities, including disseminated intravascular coagulation (DIC), occur in patients affected by COVID-19.
• Additionally, the severe inflammatory response, critical illness, and underlying traditional risk factors may all predispose to thrombotic events, similar to prior virulent zoonotic coronavirus outbreaks.
• Investigational therapies for treating COVID-19 may have adverse drug-drug interactions with antiplatelet agents and anticoagulants.
• Lastly the pandemic, because of resource allocations or social distancing recommendations, may adversely affect the care of patients without COVID-19 but who present with thrombotic events. For example, (mis)perception that antithrombotic agents confer increased risk for contracting COVID-19, may lead to untoward interruption of anticoagulation by some patients

Further, a few of these investigational agents being used for Covid19 have been associated with excess risk (or, in other cases, reduced risk) for thrombotic events, or for thrombocytopenia in prior studies of non-COVID-19 populations. For example, bevacizumab, a monoclonal antibody that binds to vascular endothelial growth factor (VEGF), and is under investigational use for COVID-19, is associated with increased risk for adverse cardiovascular events, including MI, cerebrovascular accidents, and venous thromboembolism (VTE). Alternatively, fingolimod, an immunomodulating agent being tried for COVID-19, may reduce reperfusion injury and improve outcomes in patients suffering from acute ischemic stroke. Hydroxychorloquine, recently receiving Emergency Use Authorization from the U.S. Food and Drug Administration for treatment of COVID-19, may potentially exert antithrombotic properties, especially against anti-phospholipid antibodies.

There is no data available on the subject of India. However preliminary data from our institute suggest the following which is in concordance with published data elsewhere

• The most consistent hemostatic abnormalities with COVID-19 include mild thrombocytopenia and increased D-dimer levels, which are associated with a higher risk of requiring mechanical ventilation, intensive care unit [ICU] admission, or death.
• Disease severity is variably associated with prolongation of the prothrombin time (PT) and international normalized ratio (INR) and variably by a trend toward shortened activated partial thromboplastin time (aPTT).

Hospitalized patients with COVID-19 who have respiratory failure or co-morbidities (e.g., active cancer, or heart failure), patients who are bedridden, and those requiring intensive care should receive pharmacological VTE prophylaxis, unless there are contraindications. The choice of agents and dosing should be based on available guideline recommendations. The World Health Organization interim guidance statement recommends prophylactic daily low-molecular weight heparins (LMWHs), or twice daily subcutaneous unfractionated heparin (UFH). If pharmacological prophylaxis is contraindicated, mechanical VTE prophylaxis (intermittent pneumatic compression) should be considered in immobilized patients. In this regard, the once-daily dosing regimen of LMWHs may be advantageous over UFH to reduce personal protective equipment (PPE) use and exposure of healthcare workers.

POC test services as quality assured pathology services using analytical devices (including test kits and analysers), provided near to the patient rather than in the traditional environment of a clinical laboratory.

These POC tests can be classified as Viscoelastic POC (vPOC) tests which include Thromboelastography (TEG), rotation thromboelastometry (ROTEM), and Sonoclot; and Platelet function tests which are Platelet function analyser, etc. TEG, ROTEM, and Sonoclot analysis are point-of-care coagulation monitoring devices which assess the viscoelastic properties of whole blood. They measure the entire clotting process, at the bedside and in a sample of whole blood. Coagulation factors present in plasma interact with platelets and red cells displaying results in a pictorial manner starting with fibrin formation and continue through clot retraction and fibrinolysis.

The role of SCTS for coagulation correction in patients with Covid19 is unclear and using POC tests in ICUs will be of great help in tailoring treatment

Investigators will also try to determine the influence of sepsis on coagulation disorders in COVID - 19 patients, to correctly identify the type and optimal quantity of blood product requirement in at-risk patients.