Paroxysmal nocturnal haemoglobinuria (PNH) is a disease caused by a defect in the bone marrow stem cells causing a red cell membrane abnormality. It is characterised by red cell haemolyisis (breakdown) resulting in the release of haemoglobin into the urine imparting a dark colour to it. The disease may present as a haemolytic anaemia, thrombotic episodes in large veins or bone marrow suppression causing pancytopaenia (i.e. anaemia, decrease in white cells [leukopaenia] and reduced platelets [thrombocytopaenia]). The condition is insidious and follows a chronic course with morbidity depending on the degree of haemolyisis, thrombophilia and bone marrow failure.
Being a defect of the marrow stem cell, the ideal curative treatment would be a stem cell transplant but in reality this is not done due to lack of a histocompatible donor and the significant morbidity and mortality associated with the procedure. BMT is reserved for patients with severe aplastic anaemia or those in leukaemia transformation. Instead antithymocyte globulin (ATG) has been used to treat aplastic anaemia.
The current therapy is symptomatic. Anaemia is treated by folic acid & iron supplements along with leukocyte-depleted packed cell transfusions. High dose glucocorticoids have been used too but these have serious long-term complications. Red cell production (erythropoiesis) can be stimulated using the hormone erythropoietin, which has largely replaced the use of androgens. Thrombosis is treated conventionally by heparin and oral anticoagulants. A new drug, eculizumab, has recently been shown to be highly effective in reducing intravascular haemolyisis and clinical trials are on.
Prognosis is variable, depending on the severity of symptoms and presence of complications. An aplastic phase is a serious prognostic factor, because the resulting pancytopaenia and thrombosis of hepatic, abdominal, and cerebral veins can lead to life-threatening consequences. In many patients, the abnormal clone eventually may disappear. This usually takes at least 5 years and often as long as 15-20 years. Reactivation of PNH in these patients has been observed with acute infections. Patients with chronic anaemia alone, without thrombotic complications, can live relatively normal lives for many years.