Unusual pattern of thrombotic events in young adult non‐critically ill patients with COVID‐19 may result from an undiagnosed inherited and acquired form of thrombophilia

Abstract

In 145 previously healthy non-critically ill young adults, coronavirus disease 2019 (COVID-19)-related symptoms, risk factors for thrombosis, coagulation and inflammatory parameters were compared, with 29 patients reporting unusual thrombotic events (UTEs) and 116 not having thrombotic events. The inflammatory indices, coagulation and prothrombotic platelet phenotype (PTPP) were significantly higher in patients with UTEs versus those without. Patients with UTEs were categorised according to detection of thrombophilic genes (TGs), coagulation and inflammatory markers to the non-TG and TG subcohort. A total of 38 UTEs were identified, which included splanchnic vein thrombosis (SVT; 11), stroke (six), cerebral vein thrombosis (five), thrombotic microangiopathy (four), limb ischaemia and inferior vena cava thrombosis (three each), ST-segment elevation myocardial infarction (two), superior vena cava thrombosis (two), upper limb deep venous thrombosis and retinal vein thrombosis, one each. We found a 55% prevalence of TGs mainly heterozygous coagulation factor II, thrombin (FII)-G20210A, Janus kinase 2 (JAK2)-V617F, protein-S, and antithrombin III deficiency with a high (76Á9%) prevalence of venous UTEs, multiple vessels thrombosis, and recurrence rate among the TG versus non-TG subcohort. The presence of JAK2-V617F, and FII-G20210A mutations was linked with SVT. Thrombosis in the non-TG subcohort was associated with more haemorrhagic problems, thrombosis progression and a significantly higher level of inflammatory markers, PTPP, mean platelet volume, von Willebrand factor, and factor VIII, which remained high for up to 6 months, as well as elevated D-dimer. Acquired and inherited thrombophilia with endotheliopathy appeared to be a relevant mechanism to explain the occurrence of UTEs that are not correlated to COVID-19 severity.

Inferior Vena Cava Thrombosis in a Young Patient With COVID-19 Infection

“…Stasis may occur due to immobilization in hospitalized patients, while increased coagulation may be seen due to elevated prothrombotic factors, such as fibrinogen, D-dimers, factor VIII, and von Willebrand factor (vWF) [ 6 ]. It has also been proposed that COVID-19 infection may establish an inflammatory and prothrombotic microenvironment leading to more severe thrombotic events in asymptomatic factor V Leiden heterozygotes, as was likely the case with our patient [ 7 ].…”

“…IVCT has also been reported in a few patients with COVID-19 infection. For example, in a recently published study that evaluated 145 previously healthy, non-critically ill, young adults with COVID-19, 38 thrombotic events were identified, which included three cases of IVCT [ 7 ].…”

Coagulation parameters abnormalities and their relation to clinical outcomes in hospitalized and severe COVID-19 patients: prospective study

“…The extreme inflammatory condition caused by COVID-19 causes hemostasis to be severely disrupted and coagulation parameters to be significantly altered 8 , 9 . COVID-19 infection has been linked to impairment of coagulation parameters as well as a high rate of venous and arterial thrombotic complications, including unusual thrombotic events 10 .…”

Platelet Activation and Thrombosis in COVID-19

“…Early in the pandemic, COVID-19 patients were noted to present with unusual arterial thrombi. 1 2 3 4 5 6 A Swedish matched cohort study including over 86,000 COVID-19 patients demonstrated the incidence rate ratios for acute myocardial infarction and ischemic stroke compared with a matched cohort as 2.89 (95% CI: 1.51–5.55) and 2.97 (1.71–5.15), respectively, in the first week following COVID-19 infection. 13 Compared with bacterial sepsis, the incidence of arterial thrombosis seems to be higher in COVID-19.…”

“…Early in the pandemic, COVID-19 patients were noted to present with unusual arterial thrombi. [1][2][3][4][5][6] A Swedish Fig. 1 The predominant role of platelets in COVID-19-associated coagulopathy.…”