Anticoagulation for COVID-19: More Harm than Good?

Andrew N. Wilner, MD


October 01, 2020

A 68-year-old African American woman with a medical history of diabetes, hypertension, gout, and obesity presented with 2 days of shortness of breath and cough. Vital signs were temperature 37.1 °C, heart rate 73 beats/min, respiratory rate 50 breaths/min, and blood pressure 161/99 mm Hg. She was alert and oriented with bilateral wheezing. CT of the chest was negative for pulmonary embolus but had multifocal ground-glass opacities. COVID-19 nasal swab was positive.

In the intensive care unit, she received heparin anticoagulation for thrombosis prophylaxis in the setting of COVID-19 and elevated D-dimer levels. Two weeks later, she had an abrupt mental status alteration. CT revealed a massive intracranial hemorrhage (Figure 1). Other than anticoagulation, no other cause of cerebral hemorrhage could be identified. The patient was declared brain dead the following day.

Figure 1. Axial brain CT scan with massive intraparenchymal hemorrhage with intraventricular extension and extensive mass effect with left to right subfalcine. herniation, and left uncal herniation. There is also subtle loss of differentiation of the gray-white matter consistent with global hypoxic encephalopathy.


Thrombotic events affect approximately 16% of hospitalized patients with COVID-19. A retrospective study demonstrated that mechanically ventilated patients (n = 395) had lower in-hospital mortality (29.1%) when anticoagulated vs those who did not receive anticoagulation (62.7%). Postmortem examination of pulmonary vessels has demonstrated thrombosis with microangiopathy. These and other observations have led to recommendations of anticoagulation for patients with COVID-19 to prevent venous and arterial thromboembolic events. For example, a new treatment protocol, MATH+, endorsed by the Front Line COVID-19 Critical Care Alliance for all hospitalized patients with COVID-19 who develop respiratory distress, includes heparin to treat hypercoagulability.

Elevated D-dimer levels indicate an underlying hypercoagulable state associated with mortality. In a review of 1835 patients with COVID-19 from Mount Sinai Hospital and seven other New York City hospitals, postanticoagulant D-dimer levels were a high and independent predictor value for in-hospital mortality. Patients with high mean postanticoagulant D-dimer values also tended to be older and had more comorbidities, lower oxygen saturation, worse renal function, and higher inflammatory markers than those with low mean postanticoagulant D-dimer values. Of note, baseline D-dimer levels failed to predict mortality.

Although anticoagulation protects against thrombosis, a recent study revealed that 33 of 755 patients with COVID-19 developed intracranial hemorrhage. Most of these cases represented hemorrhagic transformation of ischemic stroke. Eighteen of the patients had received prophylactic anticoagulation for an elevated D-dimer level and concern for prothrombotic state.

I have cared for at least two patients with COVID-19 who had catastrophic intracranial hemorrhage associated with prophylactic anticoagulation, including the patient detailed above. Whether these patients would have died secondary to their COVID-19 infection without anticoagulation is unknown.


The observation that COVID-19 infection may cause a hypercoagulable state has led to anticoagulant treatment protocols, such as MATH+, without the benefit of supportive data balancing the risks and benefits from prospective, randomized trials. Although preventing thrombotic events, such as pulmonary embolism and ischemic strokes, is important, the risk for fatal hemorrhagic stroke emphasizes the need for further study before prophylactic therapeutic anticoagulation of all patients with COVID-19 with severe respiratory compromise becomes routine practice.

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