COVID-19 Associated Haemostasis Abnormalities (CAHA)

There is increasing recognition of hemostatic abnormalities in COVID 19. While raised D-dimer levels were noted in most early reports, these changes were attributed to disseminated intravascular coagulation (DIC) or sepsis-induced coagulopathy (SIC), based on existing scoring systems. However, on closer scrutiny, these abnormalities neither included thrombocytopenia, hypofibrinogenemia or overtly deranged clotting times which are hallmarks of DIC/SIC nor was bleeding a significant clinical feature in most cohorts. The high incidence of elevated D-dimer level in admitted patients with COVID-19 illness, early in the course of the illness in the absence of any distal thrombosis, was confusing in the beginning but soon suggested a lung rather than distal or disseminated source of thrombosis, possibly implicating the micro vasculature.

Of note, in a study done on 184 ICU patients, cumulative incidence of thrombotic events was found to be 31%; most being pulmonary sites. This increased incidence of pulmonary thrombotic complications has been shown in multiple cohorts subsequently.

Corroborating this, multiple autopsy based reports have shown unprecedented pulmonary microvascular thrombosis and endothelial damage which is most probably related to direct viral cytopathic on the endothelial cells due to shared receptors with the alveolar cells. Other possible etio-pathogenic mechanisms include immune/cytokine mediated dysregulation of pro-coagulant& anti-fibrinolytic pathways.

There is now fairly broad-based consensus, including ISTH interim guidelines, that all COVID-19 pneumonia admissions receive prophylactic anticoagulation. As the severity of these COVID-19 Associated Haemostasis Abnormalities [CAHA] has been shown to directly correlate with respiratory outcomes, these parameters may be used to broadly stratify patients and direct therapy. Below is a figure with proposed CAHA stages and some of the relevant research questions/management advice.

In summary, we as healthcare providers need to be vigilant of CAHA as an entity and keep a high index of suspicion for it so as to initiate anticoagulation early; even prophylaxis should be considered for those at higher risk. As data from randomized control trials/meta-analyses are unlikely to be available in the near future, this approach should provide guidance in the management of COVID-19, where pulmonary thrombosis appears to be a clear and present danger.

References

  1. Thachil J, Srivastava A. SARS-2 Coronavirus–Associated Hemostatic Lung Abnormality in COVID-19: Is It Pulmonary Thrombosis or Pulmonary Embolism? Semin Thromb Hemost. 2020 May 12
  2. Wichmann D, Sperhake J-P, Lütgehetmann M, Steurer S, Edler C, Heinemann A, et al. Autopsy Findings and Venous Thromboembolism in Patients With COVID-19. Ann Intern Med 2020 May 6
  3. Thachil J, Tang N, Gando S, Falanga A, Cattaneo M, Levi M, et al. ISTH interim guidance on recognition and management of coagulopathy in COVID‐19. J Thromb Haemost. 2020 May;18(5):1023-1026
  4. Thachil J, Cushman M, Srivastava A. A Proposal for Staging COVID‐19 Coagulopathy. Res Pract Thromb Haemost. 2020 May 11;rth2.12372