Not only neurovascular thrombosis but also thrombosis at other organs are possible in COVID-19 patients/COVID-19 vaccine recipients. Additionally, some patients might have multiorgan thrombosis . Therefore, it can confirm that the basic underlying pathophysiology should primarily involve the thrombohemostatic system. This is added to the well-established ideas that hyperinflammation and disruption of ACE2 system is the main cause of thrombosis . That possible pathophysiology might explain problem in COVID-19 patient but might not in COVID-19 vaccine recipient. A Common pathophysiology for thrombosis based on abnormality of coagulation/thrombohemostatic system might give a good explanation. A basic pathophysiological process for thrombotic disorder is applied for neurovascular thrombosis due to COVID-19/COVID-19 vaccination.
Thrombosis in venous system
Virchow triad is a basic principle that helps explain pathophysiology of COVID-19/COVID-19 vaccine induced neurovascular venous thrombosis. The three main components of the triad are hypercoagulability, endothelial injury and stasis . Basic components that are associated with neurovascular thrombotic disorder in COVID-19/COVID-19 vaccination are abnormality of coagulation system, platelet and endothelium (Table 1). Both COVID-19 and COVID-19 vaccination can affect coagulation system and endothelium. In addition, the abnormality of platelet is a possible clinical problem resulted from COVID-19 or COVID-19 vaccination.
In COVID-19, hypercoagulability is a possible problem. Thrombocytosis is seen in COVID-19 [17, 18]. Coagulation cascade disturbance might be induced . Various coagulopathies can occur. In COVID-19, activation of the coagulation cascade via tissue factor expression, and decreasing of fibrinolysis occur .
Disseminated intravascular coagulation (DIC), sepsis-induced coagulopathy (SIC) and local microthrombi formation can further result in venous thrombotic disorder .
Focusing on endothelial problem, the hyperinflammation occurs in COVID-19.
A host immune response can significantly contribute to vascular endothelial cell injury . Finally, stasis also occurs in COVID-19. Infection can result in an increased blood viscosity and it can result in a stasis. According to a recent report, the higher increased blood viscosity occurs in case with COVID-19 reinfection .
For COVID-19 vaccination, the similar pathobiological process is possible. Vaccine might induce abnormal immune response and further cause problem. Vaccine related platelet disorder is sporadically reported [14, 15]. Additionally, the vaccination can result in an excessive blood viscosity . A stasis can occur and result in thrombotic complication . According to a recent report, the problem of hyperviscosity is higher after the second dose than the first dose of vaccine , hence, most neurovascular thrombotic event following COVID-19 vaccination usually follow the second dose of vaccination.
Thrombosis in arterial system
In general, the neurovascular thrombosis usually occurs in a case with underlying vascular problem. A patient might have an underlying neurological disorder, such as cerebrovascular microinfarction, which could lead to a more complex clinical course when the patient gets COVID-19 illness . Hence, a neurovascular arterial thrombosis is less common than venous thrombosis in COVID-19 . As earlier mentioned, alteration of Virchow triad component occurs in COVID-19 and it might stimulate cerebral thrombotic stroke and infarction. In addition, another concurrent medical disorder, such as coinfection, can trigger neurovascular thrombotic disorders in patients with COVID-19 . Nevertheless, the investigation for thrombosis should be performed for any COVID-19 case regardless history of underlying neurovascular problem .
Regarding COVID-19 vaccine related neurovascular thrombosis, the similar pathobiological process is possible. Vaccine might induce abnormal immune response and further cause problem [14, 15]. The underlying plays important role in determining occurrence of thrombotic event. As already noted, hyperviscosity and stasis might occur after COVID-19 vaccination. A patient with underlying neurological problem usually has a high blood viscosity, hence, that patient might have an increased risk of COVID-19 vaccination related neurovascular thrombosis. According to a recent study, the safety interval for thrombosis development is narrower in a vaccine recipient with underlying neurological disease . It is recommended for a closed monitoring of possible thrombosis in a COVID-19 vaccine recipient who has an underlying neurological disease .
The authors hereby propose that the neurovascular thrombosis in COVID-19/COVID-19 vaccination is associated with disruption on basic hemostatic system (Fig. 1). Hyperviscosity is a main clinical problem that can cause thrombosis in COVID-19/COVID-19 vaccination. The change of blood viscosity occurs in COVID-19 and the pathogenesis might be due to the inflammation process and disruption of ACE2 system [7, 20]. For COVID-19 vaccination, the change of blood viscosity is not uncommon and the underlying pathogenesis is associated with hyperstimulation of immune response by COVID-19 vaccine that further cause an abrupt increased blood viscosity . However, a remained problem for conclusion ion exact pathology is the confounding effect of underlying illness. Some patients might already have an underlying illness that can cause thrombosis regardless of COVID-19 or COVID-19 vaccination . Some recent Arabic reports showed that the incidence of thrombocytopenia and peculiar thrombotic events might be more common in viral vector technology based COVID-19 vaccine [25, 26]. According to the recent management recommendation, mass COVID-19 vaccination should continue but with special caution .