Dr Mohini Bhargava
Principal Consultant & Head Biochemistry
Max Hospital, Ghaziabad

D-dimer’s role in the management and prognosis of Covid-19

December 2019 brought with it the novel corona virus disease (COVID-19), with the initial cases reported from Wuhan, China. In March of 2020, the World Health Organization (WHO) officially declared it as a pandemic. Evolving clinical resources confirm a convoluted role of coagulopathy in COVID-19 that at times manifests in the form of both micro-thrombosis and venous thromboembolism (VTE). Clinically, D-dimer is a coagulation marker that aids in the diagnosis of venous thromboembolism by being an early sensitive marker for thrombotic disorders, such as deep vein thrombosis (DVT), pulmonary embolism (PE), disseminated intravascular coagulation (DIC), and for coronary artery diseases.

Emerging evidence shows that coagulopathy can complicate severe COVID-19. In the most severe cases, it manifests as DIC, which is a pro-thrombotic condition with a high risk of VTE. One of the most significant poor prognostic features in those patients is the development of coagulopathy.

Confirmation of DIC in COVID-19 positive patients was a compelling conjecturer of mortality. A retrospective review conducted by Tang et al. at a single institution, consisting of 183 consecutive patients with COVID-19, indicated 71.4 percent of non-survivors and 0.6 percent of survivors showed evidence of explicit DIC (in accordance with the DIC score). Clinical research exhibited that a sizable number of patients with COVID-19 had highly atypical D-dimer levels, particularly toward the increasing trends, thus having a prognostic reputation too. The prevalence of VTE in COVID-19 patients is though not well defined, but early reports suggest it may be higher than in non-COVID hospitalized patients with similar degrees of illness, even in the presence of prophylactic anticoagulation.

Early signs in a COVID-19 pneumonia diagnosis. Yao et al., in a study published on March 15, 2020, suggested formation of hyaline membrane in some alveoli that were subverted by macrophages and monocytes (immune cells) along with giant cells, lymphocytes, eosinophils, and neutrophils. The infiltrated lymphocytes were CD4-positive T cells. Alveolar septum blood vessels were clogged with unassertive permeation of monocytes and lymphocytes.

A cytokine storm/macrophage/endothelial activation due to a lung injury results in a profound inflammatory state along with an increase in IL-1, IL-6, IL-8, TNF-alpha, ferritin, CRP, D-dimer, and fibrinogen.

Increased D-dimer level and prognostic importance in COVID-19. Presumably, fibrinolytic activation in COVID-19 is a product of thrombin generation, i.e., due to secondary fibrinolysis thrombin stimulates t-PA (tissue plasminogen activator) release from the endothelium. This results in plasminogen to change to plasmin, which now acts as an activator for fibrin degradation, resulting in formation of various fibrin-degradation products, including D-dimer.

The first hypothesis suggestive of the increase in D-dimer levels and the role it plays in prognostics of COVID-19 is that the hallmark of acute lung injury is intra-alveolar fibrin deposition and later remodeling of fibrin resulting in lung fibrosis. Urokinase-type plasminogen activator (uPA), produced locally, regulates extravascular proteolysis, inhibited by PAI-1. The pathways are not yet clearly understood though.

The second hypothesis attributes the increase in D-dimer levels to the activated macrophages. COVID-19 pneumonia lung histology is characterized by many macrophages that generate plasmin and metalloproteinase (MMPs). Fibrin degradation also occurs by an alternative pathway –fibrin/fibrinogen binding to CD11b/CD18 I internalized into the lysosome where cathepsin D degrades it.

Criteria for prophylaxis. If the patient is above 75 years of age, has a past history of cancer/VTE or falls in the extra risk factor category of VTE, the patient should be considered for prophylaxis along with further clinical correlation. The extra risk factors include D-dimers ≥2 upper limit of normal range or greater than 1 microgram per liter, intensive care unit stay, or two other factors, such as past history of superficial VT, obesity, varicose veins, chronic venous insufficiency, lower-extremity paresis, hormone therapy, thrombophilia, concomitant use of erythropoiesis-stimulating agents.

Share this:
Stay Updated on Medical Equipment and Devices industry.
Receive our Daily Newsletter.