Paroxysmal Nocturnal Hemoglobinuria

  • Paroxysmal Nocturnal Hemoglobinuria (PNH) is the result of an acquired somatic mutation in a gene required for membrane anchoring of certain proteins, including those that comprise the "Decay Activating Factor" that inhibits the alternative complement pathway (see page). Because these cells can not inhibit the alternative complement pathway, activated C3 convertase deposits on the cellular membrane, resulting in complement-mediated lysis. Remarkably, this somatic mutation is thought to occur in a single hematopoietic stem cell which can proliferate to occupy a proportion of a patient's bone marrow.
Clinical Consequences
  • The clinical consequences of the disease likely reflect to what extent the patient's bone marrow is replaced by this mutated clone of stem cells. With mild replacement, patients may simply display repeated episodes of intravascular hemolysis with consequent signs and symptoms of anemia (see page). When replacement is more extensive, pancytopenia may arise due to aplastic anemia. For unclear reasons, patients are often hypercoagulable and thus display a propensity to develop thromboses.