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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.

Nonvascular neurological manifestations of antiphospholipid antibodies (aPLAbs) are emerging and, among these, several neuropsychiatric shymptoms. Psychiatric diseases are gradually being considered as organic illnesses of the brain. The role of blood-brain barrier regulation is under scrutiny, and increased permeability is thought to play a precipitating role. Neuropsychiatric manifestations in women with antiphospholipid syndrome (APS) are suspected of being secondary to direct binding and the effect of aPLAbs on neurons and glial cells once the permeability of the blood-brain barrier has been altered. Placental diseases, sometimes mediated by aPLAbs, are risk factors for schizophrenia in the offspring, and babies born from women with aPLAbs can develop learning disabilities and autism spectrum disorders. Women with APS more often develop mood disorders as time goes by, and diffusion tensor imaging has evidenced subtle changes in their white matter. More data are urgently needed and the therapeutic management remains to be properly planned.