Coagulopathy and thrombosis in COVID-19 patients: parameters to be checked to assess disease severity

As the clinical evidence keeps on accumulating, we can clearly state that coronavirus disease 2019 (COVID-19) very often shows features of a coagulation disease/disorder.¹ This association poses important consequences in the management of both patients suffering from COVID-19, and of patients who were affected by thrombotic and thromboembolic disease before the onset of the pandemic.

The major clinical outcomes observed in severely ill COVID-19 patients related to hemostasis disorders are venous thromboembolism, myocardial infarction and disseminated intravascular coagulation (Figure 1)².

How does COVID-19 affect the onset of thrombotic/thromboembolic disease? The exact mechanism by which the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus induces thrombotic events is yet to be fully understood and the concomitant intervention of indirect factors may play a role.

Some of the consequences of the SARS-CoV-2 infection that predispose to thrombotic complications are:

• Severe illness and hypoxia
• Severe inflammatory response
• Experimental therapies that may cause adverse drug–drug interactions with antiplatelet agents and anticoagulants
• Unbalanced allocation of resources, which may result in neglecting the care of patients without COVID-19 but with thrombotic events

In particular, the dysregulated inflammatory response, which has been described in COVID-19 acute cases (often referred as “cytokine storm”), could activate coagulation pathways, and this results in a double effect³:

• Inducing thrombi formation
• Amplifying the inflammatory signals, in a self-generating loop, which will keep fueling adverse events

How can a high-risk thrombotic situation be promptly identified? Which are the most common parameters that must be assessed with priority?

Even if it is not clear whether these changes in marker levels are a specific effect of SARS-CoV-2 or just a consequence of the cytokine storm, healthcare professionals need some specific points to focus on to guide their intervention.

Despite the general worldwide decrease in the hospitalization burden, the need of an unequivocal way to assess patients at risk is still urgent as the pandemic is far to be a mere memory.

The thrombosis and hemostasis parameters identified to be associated with poor COVID-19 outcome that should be checked at hospital admission are:

• D-dimer levels, that are often increased⁴
• Thrombocytopenia⁵
• Lymphopenia⁶
• Prolongation of the prothrombin time⁷
• Thrombin time⁸
• Activated partial thromboplastin time⁹
• Troponin levels as a marker for myocardial injury¹⁰

A guidance on recognition and management of coagulopathy in COVID-19 was also proposed earlier in the pandemic by the International Society of Thrombosis and Haemostasis (ISTH).¹¹

In addition to markers for coagulation disorders, common laboratory abnormalities found in patients with COVID-19 that would need special attention (also in relation to the tight relation between coagulation and inflammation) are:

• Lactate dehydrogenase⁷
• Inflammatory markers (C reactive protein, ferritin and interleukin-6)⁷

To summarize the association between markers of thrombosis and hemostasis and clinical outcomes in patients with COVID-19, see Table 1 (adapted from²).

While there is a general agreement for some of the parameters, for others there are still some contradictory issues (such as for activated partial thromboplastin time). Nevertheless, it is important not to ignore any marker a priori, and to see the complete picture of the situation.

Data are rapidly accumulating from clinical evidence and combined with the analysis of the follow-up time, it will be feasible to soon adjust these general indications.

References

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