Paroxysmal nocturnal hemoglobinuria: Difference between revisions
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*RBC transfusion PRN | *RBC transfusion PRN | ||
*Prednisone may decrease RBC destruction | *Prednisone may decrease RBC destruction | ||
*For severe hematopoietic dysfunction | *For severe hematopoietic dysfunction with marked cytopenias: hematopoietic cell transplant or immunosuppression (cyclosporine or antithymocyte globulin) | ||
*Anticoagulation for thrombosis | *Anticoagulation for thrombosis | ||
Revision as of 04:52, 12 July 2016
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
Microangiopathic Hemolytic Anemia (MAHA)
- Disseminated Intravascular Coagulation (DIC)
- Thrombotic Thrombocytopenic Purpura (TTP)
- Hemolytic Uremic Syndrome (HUS)
- HELLP syndrome
- Heparin-Induced Thrombocytopenia (HIT)
- Hereditary spherocytosis
- Paroxysmal nocturnal hemoglobinuria (PNH)
- Malignant hypertension
- Scleroderma
- Antiphospholipid Syndrome (APS)
- Other medical causes: malignancy, renal allograft rejection, vasculitides like polyarteritis nodosa and Wegener's granulomatosis
- Drugs: chemotherapy; Clopidogrel (Plavix) associated with TTP
- Nonvascular causes: prosthetic valve (more common with mechanical, more common at aortic valve), LVAD, TIPS, coil embolization, patched AV shunt, AVM
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
Management
- Eculizumab (C5 antibody): stops hemolysis in PNH
- Iron/folate supplements
- RBC transfusion PRN
- Prednisone may decrease RBC destruction
- For severe hematopoietic dysfunction with marked cytopenias: hematopoietic cell transplant or immunosuppression (cyclosporine or antithymocyte globulin)
- Anticoagulation for thrombosis