COVID-19 and Pulmonary Embolism: Frequently Asked Questions
(Version 3.0; last updated September 22, 2020)
Input from Agnes Lee, Maria deSancho, Menaka Pai, Menno Huisman, Stephan Moll, Walter Ageno, and Lisa Bauman-Kreuziger
Note: Please review ASH's disclaimer regarding the use of the following information.
How do we diagnose pulmonary embolism (PE) if we cannot perform CTPA or V/Q lung scan because the patient must remain in isolation (e.g. due to risk of virus aerosolization, lack of personal protective equipment) or is too unstable?
When objective imaging is not feasible to confirm or refute a diagnosis of PE, clinicians must rely on clinical assessment based on history, physical findings and other tests. Observational data show that 7-39% of patients with COVID-19 infection who require mechanical ventilation have acute PE/DVT. Likelihood of PE is moderate to high in those with signs or symptoms of DVT, unexplained hypotension or tachycardia, unexplained worsening respiratory status, or traditional risk factors for thrombosis (e.g., history of thrombosis, cancer, hormonal therapy). If feasible, consider doing bilateral compression ultrasonography (CUS) of the legs, echocardiography or point-of-care ultrasonography (POCUS). These tests can confirm thrombosis if proximal DVT is documented on CUS or if a clot-in-transit is visualized in the main pulmonary arteries on echocardiography or POCUS, but they cannot rule out thrombosis if clot is not detected.
Does a normal D-dimer level effectively rule out PE/DVT?
Yes. The value of D-dimer testing is the ability to rule out PE/DVT when the level is normal. Although the false negative rate of D-dimer testing (i.e., PE/DVT is present but the result is normal) is unknown in this population, low rates of 1 – 2% using highly sensitive D-dimer assays have been reported in other high risk populations. Therefore, a normal D-dimer level provides reasonable confidence that PE/DVT is not present. (See ASH's FAQ document regarding COVID-19 and VTE/anticoagulation.) In addition, radiological imaging is not necessary when the D-dimer level is normal in the context of low pre-test probability. As ‘baseline’ D-dimer levels are higher in patients with COVID-19, current studies are evaluating whether a different (higher) cut-off value for D-dimer would be more useful in excluding VTE in these patients.
If D-dimer levels change from normal to abnormal, or rapidly increase on serial monitoring, is this indicative of PE/DVT?
An elevated D-dimer level does not confirm a diagnosis of PE/DVT in a patient with COVID-19 because the elevated D-dimer may result from the COVID-19 infection or other causes. If possible, CTPA and/or bilateral CUS should be performed to investigate for PE/DVT. It is important to determine if there are any new clinical findings that indicate acute PE/DVT and if there are other causes of high D-dimer levels, such as secondary infection, myocardial infarction, renal failure, or coagulopathy. (See ASH's FAQ document regarding COVID-19 and coagulopathy.) Published data have shown that the majority of patients with progressive, severe COVID-19 infection with acute lung injury/ARDS have very high D-dimer and fibrinogen levels, independent of the presence or absence of VTE. See below.
What are the risks and benefits of empiric therapeutic anticoagulation in COVID-19 patients?
COVID-19 infection is associated with high morbidity and mortality largely due to respiratory failure, with microvascular pulmonary thrombosis or PE originating from the leg veins playing an additional important pathophysiological role. Having undiagnosed or untreated PE may worsen patient outcomes. Anti-inflammatory effects of heparin/LMWH may offer benefit and anti-viral mechanisms have been demonstrated for factor Xa inhibitors in animal studies. Consequently, use of empiric therapeutic anticoagulation in certain COVID patients who do not have PE/DVT has been advocated. However, this remains controversial because the true incidence of PE/DVT in patients receiving pharmacological thromboprophylaxis remains uncertain and data to show improved outcomes with therapeutic anticoagulation are lacking. Current clinical trials addressing this question are underway. The risk of major bleeding is also heightened in those with risk factors for bleeding, such as older age, liver or renal impairment, and previous history of bleeding. Objective imaging to confirm a diagnosis of PE/DVT should, if possible, be done prior to starting therapeutic anticoagulation.
Are there any clinical scenarios in which empiric therapeutic anticoagulation would be considered in COVID-19 patients?
In cases where there are no contraindications for therapeutic anticoagulation and there is no possibility of performing imaging studies to diagnose PE or DVT, empiric anticoagulation has been proposed in the following scenarios:
- Intubated patients who develop sudden clinical and laboratory findings highly consistent with PE, such as desaturation, tachycardia, increased central venous pressure or pulmonary artery wedge pressure, or evidence of right heart strain on echocardiogram, especially when chest X-ray and/or markers of inflammation are stable or improving.
- Patients with physical findings consistent with thrombosis, such as superficial thrombophlebitis, peripheral ischemia or cyanosis, thrombosis of dialysis filters, tubing or catheters, or retiform purpura (branching lesions caused by thrombosis in the dermal and subcutaneous vasculature).
- Patients with respiratory failure, particularly when D-dimer and/or fibrinogen levels are very high, in whom PE or microvascular thrombosis is highly suspected and other causes are not identified (e.g., ARDS, fluid overload).
If a patient is empirically started on anticoagulation for suspected PE, how long should they be anticoagulated? What if later investigation shows no evidence of PE?
All patients with COVID-19 who are started on empiric therapeutic anticoagulation for presumed or documented PE should be given a minimum course of 3 months of the therapeutic regimen (provided the patient tolerates treatment without serious bleeding). Thrombus resolution can occur within a few days of effective anticoagulation, so negative results from delayed testing should not be interpreted as implying PE or DVT was not previously present. At 3 months, therapeutic anticoagulation can stop, provided the patient has recovered from COVID-19 and has no ongoing risk factors for thrombosis or other indications for anticoagulation (e.g. prolonged immobilization or atrial fibrillation).
For additional information, see:
- Moores et al Prevention, diagnosis and treatment of venous thromboembolism in patients with COVID-19: CHEST Guideline and Expert Panel Report
- Barnes et al. Thromboembolism and Anticoagulant Therapy During the COVID-19 Pandemic: Interim Clinical Guidance from the Anticoagulation Forum.
- International Society of Thrombosis and Hemostasis
- Bikdeli et al. COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-up. JACC.
- Antithrombotic therapy in patients with COVID-19