Study of Coagulation Profile and Role of Heparin Like Effect in Patients With COVID-19
Study of Coagulation Profile and Role of Heparin Like Effect in Patients With COVID-19
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is a pandemic, which
 has affected approximately 4 lakhs individuals and claimed 16,362 deaths till now. SARS-CoV-2
 has been associated with myocarditis and renal dysfunction. Patients hospitalized for
 Covid-19 severe infection are more prone to excessive coagulation activation leading to
 thrombotic events both in the venous and arterial circulations, due to excessive
 inflammation, platelet activation, endothelial dysfunction, and stasis. Nearly 20% of
 COVID-19 patients present severe coagulation abnormalities, which may occur in almost all of
 the severe and critical ill COVID-19 cases. Concomitant venous thromboembolism (VTE), a
 potential cause of unexplained deaths, has been frequently reported in COVID-19 cases, but
 its management is still challenging due to the complexity between antithrombotic therapy and
 coagulation disorders. The importance of high D-dimer and Fibrin degradation product level to
 determine the patient prognostic and the risk of thrombosis is known. In a French study, it
 was found that a high rate of thromboembolic events in COVID-19 patients treated with
 therapeutic anticoagulation, with 56% of VTE and 6 pulmonary embolisms. Preliminary reports
 on COVID-19 patients' clinical and laboratory findings include thrombocytopenia, elevated
 D-dimer, prolonged prothrombin time, and disseminated intravascular coagulation. COVID-19
 patients with acute respiratory failure present a severe hypercoagulability rather than
 consumptive coagulopathy.

 Another study highlights this common finding in most COVID-19 patients with high D-dimer
 levels which are associated with a worse prognosis. Cases showed significantly higher
 fibrinogen and D-dimer plasma levels versus healthy controls (p < 0.0001). Markedly
 hypercoagulable thromboelastometry profiles were observed in COVID-19 patients, as reflected
 by shorter Clot Formation Time (CFT) in INTEM (p = 0.0002) and EXTEM (p = 0.01) and higher
 Maximum Clot Firmness (MCF). Fibrin formation and polymerization may predispose to thrombosis
 and correlate with a worse outcome.

 Global VE tests provide a more physiologic assessment of coagulation and should be considered
 to guide blood transfusion requirements in liver transplantation and other major surgery. Its
 application in patients with Covid19 or in a critical care setting requires more data.
 Viscoelastic tests, which include TEG, ROTEM, and Sonoclot, offer a means of assessing the
 activity of pro-and anticoagulant pathways, hyperfibrinolysis, and excessive clot lysis.
 Assessment of clot formation can be performed in 10 to 20 minutes as a point of care (POC)
 test; however, assessment of clot lysis takes 30 to 60 minutes. SIRS and sepsis trigger the
 release of endogenous heparinoids, or a heparin-like effect (HLE), due to small
 endothelium/mast cell-derived glycosaminoglycan's, which can be detected on
 heparinase-treated viscoelastic assays.

 Viscoelastic testing of global coagulation such as thromboelastometry and Sonoclot has been
 proposed as a superior tool to rapidly diagnose and help guide resuscitation with blood
 products and anticoagulation. it is deemed necessary to determine the influence of Covid 19
 on coagulation parameters using point of care coagulation using sonoclot and conventional
 coagulation tests. In this prospective trial, the investigators aim to evaluate coagulation
 abnormalities via traditional tests and whole blood Sonclot profiles in a group of 50
 consecutive patients with critically ill COVID-19 patients admitted to the Covid ICU OF Nehru
 Hospital extension, Postgraduate Institute of Medical Education and Research, Chandigarh.
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.
Inclusion Criteria:

 -  Inclusion Criteria:

 -  Age 18-80 years

 -  Confirmed Covid19 patient with positive RT PCR

 -  Exclusion Criteria:

 -  Current therapy: Recent blood or blood component transfusion in the last 2 weeks.

 -  HIV positive/ AIDS patients

 -  Pregnancy

 -  Active malignancy within the last 5 years

 -  Not willing to participate in the study