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ISTH interim guidance on recognition and management of coagulopathy in COVID-19

The COVID-19 outbreak has now spread worldwide, and the number of severe cases is increasing exponentially. Besides the well-described respiratory insufficiency,¹ one of the reported poor prognostic features in patients with systemic disease and multiple organ dysfunction is the development of coagulopathy,² which may aggravate the prognosis of patients.³

The International Society of Thrombosis and Haemostasis (ISTH), thanks to its long-term expertise in dealing with coagulopathy in different settings, has promptly proposed an algorithm for the specific management of COVID-19 coagulopathy, which is useful in both the well-resourced and less-resourced settings.⁴

This is a “work-in-progress” statement, as the authors realize that, given the current dynamic situation, there will be a necessity of constant updates, in agreement with the progression of the knowledge of COVID-19.

Nevertheless, it is mandatory to define and share the algorithm in the current time of emergency.

Figure 1. Algorithm for the management of coagulopathy in COVID-19. *The list of markers is given in the decreasing order of importance. **Although fibrinogen assays may not be performed in many laboratories, it could be helpful after patient admission. ***Although a specific cut-off cannot be defined, a three- to four-fold increase in D-dimer values may be considered significant. Anyone of the values in this table may be considered significant.

This guidance document provides a schematic, fast-risk stratification at admission for a COVID-19 patient on the basis on easily available laboratory parameters, assuring the best assistance (Figure 1).

Coagulation markers suggested to be checked at admission are:

D-dimer, which was not only found to be increased in COVID-19 patients,³ but also associated with the most severe cases;²
Prothrombin time, shown to be mildly prolonged in patients who need critical care support;⁵
Serum fibrinogen as an indicator of disseminated intravascular coagulation, which was shown to develop in patients who did not survive the diseases.³

The recommendation for the management of coagulopathy in COVID-19-positive patients is the prophylactic dose of low-molecular-weight heparin (LMWH), which should be considered in ALL patients (including the non-critically ill).

The only exception is for patients with contraindications as follows:

Active bleeding and platelet count <25 × 10⁹/l;
Severe renal impairment.

It has to be noted that abnormal prothrombin time is not a contraindication.

Extensive clinical evidence supporting the use of LMWH in the COVID-19 setting is currently being generated. Its use protects against venous thromboembolism and in light of its anti-inflammatory properties, may counteract the cytokine burst characteristic of COVID-19.^2,5

References

Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020. pii: S2213-2600(20)30076-X. doi: 10.1016/S2213-2600(20)30076-X. [Epub ahead of print].
Guan WJ, Ni ZY, Hu Y, et al.; China Medical Treatment Expert Group for Covid-19. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020 Feb 28. doi: 10.1056/NEJMoa2002032. [Epub ahead of print].
Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost 2020;18(4):844-847. doi: 10.1111/jth.14768.
Thachil J, Tang N, Gando S, et al. ISTH interim guidance on recognition and management of coagulopathy in COVID‐19. J Thromb Haemost 2020. doi: 10.1111/jth.14810. [Epub ahead of print].
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497-506.