PNH Overview

Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired disease, characterised by intravascular haemolysis, thrombosis and is associated with bone marrow failure. PNH occurs due to a clonal expansion of abnormal haematopoietic cells that are exquisitely sensitive to the uncontrolled activity of terminal complement. In its most severe form PNH leads to severe anaemia with patients frequently being transfusion dependent for many years (if not indefinitely). In addition to the anaemia, patients suffer from the direct effects of intravascular haemolysis that results in the absorption of nitric oxide, a key molecule in homeostasis, leading to smooth muscle dysfunction, platelet activation and other consequences. This often results in severe disabling abdominal pain, dysphagia, profound lethargy and, in men, erectile dysfunction. It can also contribute to many of the complications seen in PNH such as thromboses, renal impairment and raised pulmonary pressures.

Approximately half of patients suffer from thrombosis, often in major vessels, and historically a third of patients die as a direct result of thrombotic complications. In addition, the haemolysis in PNH results in renal impairment in over half of patients and approximately half of patients develop raised pulmonary pressures.

PNH can occur at any age and in most patients will persist for the remainder of the patient’s life. Approximately half of patients with PNH die as a direct result of their disease, many others are transfusion-dependent for decades and for most patients with haemolytic PNH the disease has a major impact on the patient’s quality of life. Pregnancy is extremely high risk in PNH with reported maternal mortalities of up to 20%, predominantly resulting from thrombotic complications, and reports of a high incidence of foetal loss.

Most of the observed symptoms and complications are due to the uncontrolled activity of complement on the abnormal PNH cells. Eculizumab is a monoclonal antibody that blocks the activation of terminal complement and was approved for the treatment of PNH in 2007. Eculizumab stops intravascular haemolysis in PNH rendering most patients transfusion independent whilst causing a dramatic improvement in quality of life. In addition, eculizumab stabilises or improves renal function, prevents the occurrence of thrombotic complications and reduces the risk of pulmonary hypertension. Recent data demonstrates that eculizumab both prevents most of the complications of PNH and significantly improves survival.

For more information visit the PNH National Service website