Paroxysmal nocturnal hemoglobinuria
Revision as of 12:38, 29 June 2015 by Rossdonaldson1 (talk | contribs)
Background
- Intravascular hemolysis caused by increased sensitivity of RBCs to hemolytic action of complement
Pathophysiology
- Abnormal PIG-A gene > defect in GPI-linked anchor > partial/complete absence of GPI-linked proteins (mainly CD55 and CD59) > increased sensitivity of RBCs to hemolytic action of complement
- Hemolysis precipitated by stresses that activate complement (eg infection)
- Nocturnal hemolysis attributed to intestinal absorption of lipopolysaccharide (strong activator of complement) at night
Clinical Features
- Intravascular hemolysis
- Renal failure (both from intravascular hemolysis causing AKI and chronic hemolysis causing iron deposition in kidneys)
- DVT, thrombosis of hepatic/intraabdominal/cerebral veins, arterial thrombosis
- Bone marrow failure leading to aplastic anemia
- Myelodysplastic (MDS) or myeloproliferative disorders
- Acute leukemia
- Esophageal spasm
- Crampy abdominal pain
- Impotence/ED
Differential Diagnosis
Diagnosis
- Anemia
- Negative Coombs test
- Hemoglobinuria
- Elevated LDH
- Decreased haptoglobin
- Positive sucrose lysis test or Ham test (both test sensitivity of RBCs to lysis by complement)
- Other clues: granulocytopenia/thrombocytopenia, venous thrombosis, aplastic anemia, MDS, dysphagia or abdominal pain
Treatment
- Eculizumab (C5 antibody): stops hemolysis in PNH
- Iron/folate supplements
- RBC transfusion PRN
- Prednisone may decrease RBC destruction
- For severe hematopoietic dysfunction w/ marked cytopenias: hematopoietic cell transplant or immunosuppression (cyclosporine or antithymocyte globulin)
- Anticoagulation for thrombosis