Difference between revisions of "Paroxysmal nocturnal hemoglobinuria"

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==Introduction==
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==Background==
PNH = Intravascular hemolysis caused by increased sensitivity of RBCs to hemolytic action of complement
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*Intravascular hemolysis caused by increased sensitivity of RBCs to hemolytic action of complement
  
 
+
===Pathophysiology===
==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
 
*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)
 
*Hemolysis precipitated by stresses that activate complement (eg infection)
 
**Nocturnal hemolysis attributed to intestinal absorption of lipopolysaccharide (strong activator of complement) at night
 
**Nocturnal hemolysis attributed to intestinal absorption of lipopolysaccharide (strong activator of complement) at night
  
 
+
==Clinical Features==
==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
 
 
 
 
 
==Clinical Manifestations==
 
 
*Intravascular hemolysis
 
*Intravascular hemolysis
 
*Renal failure (both from intravascular hemolysis causing AKI and chronic hemolysis causing iron deposition in kidneys)
 
*Renal failure (both from intravascular hemolysis causing AKI and chronic hemolysis causing iron deposition in kidneys)
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*Impotence/ED
 
*Impotence/ED
  
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==Differential Diagnosis==
 +
*[[DIC]]
 +
*[[TTP]]
 +
*[[HUS]]
 +
*[[Microangiopathic Hemolytic Anemia (MAHA)]]
 +
*[[HELLP]]
 +
*[[HIT]]
 +
*[[Hereditary Sperocytosis (HS)]]
 +
 +
==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==
 
==Treatment==
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*Anticoagulation for thrombosis
 
*Anticoagulation for thrombosis
  
 +
==See Also==
  
==See Also==
 
*[[DIC]], [[TTP]], [[HUS]], [[Microangiopathic Hemolytic Anemia (MAHA)]]
 
*[[HELLP]], [[HIT]], [[Hereditary Sperocytosis (HS)]]
 
  
 
[[Category:Heme/Onc]]
 
[[Category:Heme/Onc]]

Revision as of 12:38, 29 June 2015

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

See Also