Should a COVID-19 (Coronavirus Disease 2019) positive patient with a positive D-dimer (D-dimer test) be started on heparin (unfractionated heparin)?

Management of COVID-19 Positive Patient with Elevated D-dimer

For a COVID-19 positive patient with elevated D-dimer, initiate prophylactic-dose low molecular weight heparin (LMWH) unless contraindicated. 1

Initial Assessment and Risk Stratification

• Evaluate the severity of COVID-19 infection and determine if the patient is critically ill (requiring ICU-level care) or acutely ill (hospitalized but not requiring critical care) 1
• Assess for contraindications to anticoagulation: active bleeding, platelet count <25 × 10^9/L, or high bleeding risk 1
• Obtain baseline coagulation parameters: D-dimer, platelet count, PT/INR, and fibrinogen if available 1
• Consider the presence of objectively confirmed venous thromboembolism (VTE) such as DVT or PE, which would warrant therapeutic anticoagulation 1

Anticoagulation Recommendations Based on Clinical Status

For Non-Critically Ill Hospitalized Patients:

• Initiate prophylactic-dose LMWH (preferred) or fondaparinux over unfractionated heparin (UFH) 1
• For patients with markedly elevated D-dimer (>6 times upper limit of normal), consider therapeutic-dose anticoagulation with LMWH 1, 2
• Recent evidence shows therapeutic-dose anticoagulation in non-critically ill COVID-19 patients increases probability of survival and reduces need for organ support compared to prophylactic dosing 2

For Critically Ill Patients:

• Administer standard prophylactic-dose anticoagulation with LMWH (preferred) or UFH 1, 3
• Therapeutic-dose anticoagulation has not shown benefit in critically ill COVID-19 patients and may increase bleeding risk 4
• UFH might be preferred over LMWH in patients with severe renal failure or those with imminent hemodynamic decompensation 1

Laboratory Monitoring

• Monitor D-dimer, platelet count, PT/INR, and fibrinogen every 24-48 hours during the first 7-10 days of hospitalization 1
• Worsening of these parameters may indicate disease progression requiring more aggressive care 1
• If using UFH, monitor with anti-Xa assay rather than aPTT, especially in critically ill patients with hyperinflammatory state 1
• For therapeutic UFH, target anti-Xa level of 0.5-0.7 IU/mL 1

Special Considerations

• Do not use antiplatelet agents for VTE prevention in COVID-19 patients 1
• Do not administer systemic thrombolytic therapy unless the patient has confirmed PE with hypotension or signs of obstructive shock 1
• For patients with recurrent VTE despite prophylactic LMWH, consider increasing the dose by 25-30% 1
• Abnormal PT or aPTT is not a contraindication to thromboprophylaxis 1

Duration of Anticoagulation

• For patients with confirmed VTE (DVT or PE), continue anticoagulation for a minimum of three months 1
• For hospitalized patients without confirmed VTE, continue prophylactic anticoagulation throughout the hospital stay 1
• Extended post-discharge thromboprophylaxis is not routinely recommended but may be considered in patients at high risk for VTE and low risk for bleeding 1

Monitoring Response to Treatment

• Recent evidence shows that enoxaparin treatment in COVID-19 patients with elevated D-dimer leads to significant reduction in D-dimer levels 3
• Improvement in coagulation parameters along with clinical improvement may guide step-down of care 1
• If bleeding occurs (uncommon in COVID-19), follow standard protocols for management including blood product transfusion as needed 1

Remember that COVID-19 coagulopathy differs from classic DIC and has a strong component of pulmonary intravascular coagulopathy with thrombo-inflammation 5. Prompt initiation of appropriate anticoagulation is essential to reduce morbidity and mortality in these patients.