01. What is COVID-19–associated coagulopathy (CAC), and how does it compare to DIC?

b. What is Known

There is a growing body of literature and expert opinion that patients with COVID-19 are at increased risk for thrombosis and specifically venous thromboembolism (VTE). Very early in the pandemic, studies from the initial epicenter in China cited elevated rates of VTE in hospitalized patients with COVID-19.⁵ Since that time, this predilection toward thrombosis has been reported in a wide array of clinical locations.^6-12 Currently, multiple societies acknowledge that patients with COVID-19 are at increased risk of thrombosis and specifically identify laboratory changes that are different than what is commonly seen in DIC. This etiology has been coined COVID-19–associated coagulopathy (CAC) and is typified primarily by elevated serological levels of D-dimer and fibrinogen, with relatively normal levels of prothrombin time, aPTT, and platelets.¹

Evidence is accumulating indicating that patients with COVID-19 experience higher rates of VTE than would be expected based on severity of illness, which is thought to be potentially related to an underlying coagulopathy. Patients who experience VTE have higher rates of morbidity and mortality than patients without VTE.¹³ These patients have been described as often having abnormal laboratory findings of markedly elevated D-dimers, elevated fibrinogen, but without reliable abnormalities in prothrombin time, aPTT, platelets, or evidence of microangiopathy. This differs markedly from patients who experience thrombosis secondary to DIC, as is more commonly seen in other viral illnesses.¹⁴

c. What is Not Known

Although some hypotheses exist as to the pathophysiology by which SARS-COV2 precipitates coagulopathy and thrombosis, its exact pathway is not fully understood at this time. Additionally, as CAC remains only a loosely defined etiology, much remains unknown including the most appropriate approach to its diagnosis and treatment. As discussed above, some laboratory derangements are typical, but there are no defined laboratory test ranges or clinical parameters which are validated to diagnose the entity of CAC or even to reliably identify patients with COVID-19 who are at increased risk of VTE. It is also unclear if there is utility in identifying and trending laboratory markers of coagulation/thrombosis (D-dimer, fibrinogen). Even less evidence currently exists to guide appropriate treatment or prevention of thrombosis in patients with COVID-19 at this time. While multiple randomized controlled trials are under way, no clear evidence exists for the efficacy or potential harm for any specific approach to VTE prophylaxis and anticoagulation in patients with COVID-19 with or without evidence of CAC.