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

December 14, 2020 updated by: KAMAL KAJAL, Postgraduate Institute of Medical Education and Research

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Observational

Enrollment (Anticipated)

50

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

All patients with COVID-19 admitted in ICU/ HDU, admitted under the department of medicine and anaesthesia.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
COVID-19 positive patient with ARDS
All patients with COVID-19 diagnosed with RT-PCR.
Diagnostic test: Sonoclot
Sonoclot machine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation of of conventional coagulation tests with point of care coagulation test using sonoclot in COVID-19 patients.
Time Frame: 1 month
To correlate conventional coagulation tests with point of care coagulation test using sonoclot
1 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Evidence of thrombosis
Time Frame: 1 month
Coagulation Related Thromboembolic events
1 month
Coagulation-related Bleeding Event
Time Frame: 28 days
Coagulation-related Bleeding Event
28 days
Presence of Endogenous Heparinoids as demonstrated on POC test [ Time Frame 0, 3 days]
Time Frame: [ Time Frame 0, 3 days
Presence of Endogenous Heparinoids as demonstrated on POC test [ Time Frame 0, 3 days]
[ Time Frame 0, 3 days
Intensive care admission duration
Time Frame: 28 days
Intensive care admission duration
28 days
28 day mortality
Time Frame: 28 days
28 day mortality
28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Postgraduate Institute of Medical Education and Research

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 24, 2020

Primary Completion (Anticipated)

January 1, 2021

Study Completion (Anticipated)

February 1, 2021

Study Registration Dates

First Submitted

December 10, 2020

First Submitted That Met QC Criteria

December 14, 2020

First Posted (Actual)

December 16, 2020

Study Record Updates

Last Update Posted (Actual)

December 16, 2020

Last Update Submitted That Met QC Criteria

December 14, 2020

Last Verified

December 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IEC-04/2020-1641

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Covid19

Clinical Trials on Sonoclot

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Türkiye

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe