Coronavirus disease (COVID-19) is threatened our societies and the need for personalized
medicine and efficient drugs are compulsory. COVID-19 can lead to systemic coagulation
activation and thrombotic complications. Excessive cytokine release and activation
of coagulation are key drivers of COVID-19 pneumonia and associated mortality. Contact
activation has been linked to pathologic upregulation of both inflammatory mediators
and coagulation. Congenital factor XI (FXI) deficiency is more frequent than previously
expected, as it has been demonstrated in numerous reports and all over the world.
Although it was first described prevalent in exclusively etnias (Ashkenazy or Iraqi-Jewish),
it seems to be misdiagnosed and not so exclusive, with a potential high prevalence
at least in heterozygosis, also in Europe.[1 ] Moreover, acquired deficiency can occur with the presence of inhibitors or antibodies
such as antiphospholipid as β2-glycoprotein I.[2 ] Whether or not COVID-19 contributing to the appearance of antiphospholipid antibodies,
is still unclear and requires further studies.
FXI is a pleiotropic molecule whose role is extended from coagulation to inflammation.
The main role in the clot cascade is to amplify the thrombin activation. However,
its deficiency in humans or in animal models does not produce bleeding even under
risk situations, but importantly, it reduces the risk of thrombosis. Indeed, pharmacological
or molecular inhibition of FXI has been shown to prevent thrombosis without increasing
the bleeding risk.[3 ] Besides, FXI is also involved in the inflammatory system as part of the contact
activation pathway with FXII. Therapeutic drugs inhibiting this molecule have shown
to prevent coagulopathy, systemic inflammatory response, and also mortality in experimental
sepsis and without immune compromise ([Fig. 1 ]).
Fig. 1 Schematic representation of the potential role of FXI and FXII in the thrombotic
and inflammation complications induced by SARsS-CoV-2 infection. The antithrombotic
and anti-inflammatory capacity of the inhibition of contact pathway and FXI and FXII
deficiency could be a therapeutic option in this disease with low risk of bleeding.
Whether SARS-CoV-2 infection could produce antiphospholipid antibodies able to cause
an acquired FXI deficiency with protective role remains to be clarified. F, factor;
SARS-CoV-2, severe acute respiratory syndrome-coronavirus-2.
For that reason, the description and characterization of COVID-19 patients with congenital
or acquired FXI deficiency, as the one presented by Andreani et al in this issue,[4 ] could help to understand the disease and to identify new targets in this disease.
They can also contribute to show new evidences supporting a personalized medicine.
Indeed, if FXI deficiency is modulating the risk of thrombosis in COVID-19, we can
assume that the coagulation is some way through the action of this coagulation factor
(and probably the contact pathway), making very attractive to consider drugs targeting
FXI to prevent thrombotic complication. The potential effect of these treatments in
the respiratory distress mediated to cytokine release might also be evaluated. However,
this is only one case report and further studies of FXI-deficient patients with COVID-19
would be of great value to support this hypothesis.
