Thrombosis and paroxysmal nocturnal haemoglobinuria

Thrombosis is the most common, most feared complication of paroxysmal nocturnal haemoglobinuria (PNH), a striking example of the effect of uncontrolled complement activation and haemolysis on vascular biology and haemostasis. Uncontrolled complement activation and haemolysis may occur at any site and there is a higher incidence of thrombosis at atypical sites. The mechanisms are highly multifactorial and still not fully understood. Eculizumab (a complement C5 inhibitor) has been observed to reduce the number of thrombotic events and, consequently, it is thought that the signalling pathways that depend on the activation of complement C5 may be involved. Complement inhibition, initially using eculizumab together with anticoagulation, is thus the key to treating and preventing thrombosis. New proximal complement inhibitors targeting complement C3 have also shown promising results with further improvements in the clinical prognosis and quality of life of patients. Screening for PNH in patients with unexplained thrombosis must be systematically considered in well characterized cases.