What Is COVID-19?
COVID-19 is an infectious disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or coronavirus. Few individuals infected with the virus show mild to moderate respiratory illness and recover without special treatment. However, some individuals become seriously ill and thus require medical attention. Older individuals and those with underlying comorbid conditions such as chronic respiratory disease, cardiovascular disease, cancer, or diabetes can develop serious complications. Individuals who get seriously ill with COVID-19 may die at any point of the disease, irrespective of age.
What Is Thromboprophylaxis?
Thrombosis is the formation of blood clots within the body's blood vessels. The medical treatment for the prevention of the formation of thrombus in individuals who are at risk of developing thrombosis is known as thromboprophylaxis. Specific individuals are at a greater risk for the development of blood clots, such as those suffering from cancer, or dengue, those undergoing a surgical procedure, or being infected with COVID-19. The prophylactic measures usually begin after surgery as immobility might increase a person's risk. Blood thinners are medicines that are used to prevent blood clots; these blood thinners differ in their effectiveness and safety profiles.
Individuals hospitalized with COVID-19 often have microvascular and macrovascular thrombosis and inflammation, which are associated with poor prognosis. One such drug used in thromboprophylaxis is Heparin. Heparins have antithrombotic, anti-inflammatory, and antiviral properties. Anticoagulation achieved with the help of Heparin administered at higher than routinely used doses for venous thromboprophylaxis might improve the results. Several studies have determined the use of various antithrombotic agents for hospitalized COVID-19 individuals.
How Does Venous Thromboembolism Develop in COVID-19 Individuals?
VTE, or venous thromboembolism, is one of the complications for patients hospitalized with COVID-19. Venous thromboembolism is a condition in which a blood clot forms within a vein. Venous thromboembolism includes deep vein thrombosis and pulmonary embolism. Earlier increased rates of venous thromboembolism have been found to occur in patients hospitalized with acute illness and critical illness related to COVID-19 in spite of pharmacological thromboprophylaxis. Additionally, arterial thrombotic complications such as strokes have been found to occur. Microvascular thrombosis, involving the vasculature of the lungs and other organs, has been reported in autopsies. Therefore, the correct thromboprophylaxis strategy for individuals hospitalized with COVID-19-related illness remains unclear. Several laboratory parameters predicting venous thromboembolism in hospitalized individuals with COVID-19, such as increased d-dimer, C-reactive protein, erythrocyte sedimentation rate, and platelet count, have been confirmed.
Additionally, clinical risk factors for venous thromboembolism in COVID-19 have been identified, such as the development of acute respiratory distress syndrome and older age. However, it is uncertain whether such parameters should be used to classify people for risk of thrombotic complications or thromboprophylaxis. Although COVID-19–associated coagulopathy is caused primarily by thrombotic complications, such individuals might develop bleeding complications while on anticoagulation therapy, which can impact the safety of the thromboprophylaxis regimens.
How Is Thromboprophylaxis Carried Out for COVID-19 Individuals?
COVID-19 individuals with an increase in the level of small fragments of protein that is made once the blood clot dissolves in the body (d-dimer) have been associated with vascular thrombosis and poor clinical prognosis. Thus, the assessment of d-dimer levels guides the anticoagulant administration of anticoagulants.
The American Society of Hematology has laid down certain guidelines for the use of anticoagulants for thromboprophylaxis in individuals with COVID-19.
For COVID-19 Individuals With Chronic Illness:
The American Society of Hematology (ASH) suggests using prophylactic-intensity over therapeutic-intensity anticoagulation for COVID-19 individuals with associated critical illness and does not have suspected or confirmed venous thromboembolism (VTE) -
An individualized evaluation of the individual's risk of thrombosis and bleeding is essential when deciding on anticoagulation therapy. Higher-intensity anticoagulation might be applicable for individuals with high thrombotic and low bleeding risks. Currently, there is no high-certainty evidence comparing different anticoagulants. The selection of a particular agent, such as low-molecular-weight Heparin, unfractionated Heparin, etc., is based on the availability, requirement of resources, familiarity, and the aim of reducing the use of personal protective equipment (PPE) or exposure of the health care personnel to COVID-19 infected individuals, and patient-specific factors such as renal function, history of Heparin-induced thrombocytopenia, gastrointestinal tract absorption, etc.
For COVID-19 Individuals With Active Illness:
The American Society of Hematology guideline suggests using prophylactic-intensity over therapeutic-intensity anticoagulation for COVID-19 patients with acute illness and do not have suspected or confirmed venous thromboembolism.
COVID-19-infected individuals with acute illness are defined as those with clinical features that result in the admission of the person to a medicine inpatient ward without the need for advanced clinical support. Examples of such individuals include people with dyspnea or mild to moderate hypoxia. An individualized evaluation of the individuals. Currently, there is no certainty on the evidence comparing different anticoagulants. The selection of a certain anticoagulant, such as low-molecular-weight Heparin, unfractionated Heparin, etc., is based on the availability, resources required, familiarity, and the aim of minimizing the use of personal protective equipment or exposure of the staff to COVID-19 infected patients.
In non-critical hospitalized COVID-19 individuals, the anticoagulation carried out with low molecular weight Heparin administered with the therapeutic dosage increased the survival rate until discharge from the hospital with a reduction in the organ support at 21 days compared to the regular thromboprophylaxis. Anticoagulation carried out with therapeutic-dose Heparin has been found to be favorable irrespective of the individual's d-dimer level.
For Patients Requiring ICU:
Critically ill individuals should receive the standard prophylactic doses of anticoagulants since increased doses of Heparin do not prevent the progression of COVID-19 or death.
All hospitalized individuals with COVID-19 should receive thromboprophylaxis unless the risk of bleeding outweighs the risk of thrombosis. Low molecular weight heparin is preferred over unfractionated Heparin (UFH). Fondaparinux is recommended in case of heparin-induced thrombocytopenia. In individuals with contraindicated or unavailable anticoagulants, mechanical thromboprophylaxis, such as pneumatic compression devices, can be used for thromboprophylaxis. Combined use of mechanical and pharmacological prophylaxis is not recommended.
Conclusion:
Prothrombotic coagulopathy in individuals infected with COVID-19 has led to a recommendation for thromboprophylaxis in all hospitalized patients. However, there are significant differences in the dosage regimens among hospitals, and their outcomes remain uncertain. People infected with COVID-19, caused by the novel severe acute respiratory distress syndrome coronavirus 2, might develop hemostatic abnormalities in the long run. Specific reports showed high rates of venous thromboembolism for critically ill or hospitalized individuals with COVID-19, including those receiving critical care. The strategy for thromboprophylaxis in these patients remains unclear.
