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 [[hemolytic anemia|hemolysis]] caused by increased sensitivity of RBCs to hemolytic action of complement
  
 
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===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
  
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==Clinical Features==
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*[[Abdominal pain]] or [[back pain]]
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*Intravascular [[hemolytic anemia|hemolysis]]
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*[[Renal failure]] (both from intravascular hemolysis causing AKI and chronic hemolysis causing iron deposition in kidneys)
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*[[DVT]], thrombosis of hepatic/intraabdominal/cerebral veins, [[arterial thrombosis]]
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*Bone marrow failure leading to [[aplastic anemia]]
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*[[Myelodysplastic syndrome]] (MDS) or [[myeloproliferative disorders]]
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*[[Acute leukemia]]
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*Esophageal spasm
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*Crampy [[abdominal pain]]
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*Impotence/erectile dysfunction
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*May progress to [[aplastic anemia]]
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 +
==Differential Diagnosis==
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{{Hemolytic anemia DDX}}
  
==Diagnosis==
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==Evaluation==
*Anemia
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*[[Anemia]]
 
*Negative Coombs test
 
*Negative Coombs test
 
*Hemoglobinuria
 
*Hemoglobinuria
 
*Elevated LDH
 
*Elevated LDH
 
*Decreased haptoglobin
 
*Decreased haptoglobin
*Positive sucrose lysis test or Ham test (both test sensitivity of RBCs to lysis by complement)
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*Positive sucrose lysis test or Ham test (both test sensitivity of RBCs to lysis by complement). Ham's test is when the patient's cells are incubated in acidified serum, which triggers the alternative compliment pathway, resulting in lysis of PNH cells. Sucrose lysis test is when the patient's serum is mixed in sucrose, which causes hemolysis of PNH cells.
 
*Other clues: granulocytopenia/thrombocytopenia, venous thrombosis, aplastic anemia, MDS, dysphagia or abdominal pain
 
*Other clues: granulocytopenia/thrombocytopenia, venous thrombosis, aplastic anemia, MDS, dysphagia or abdominal pain
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*Flow cytometry of cell membrane proteins (CD55 and CD59) is a sensitive test for PNH
  
 
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==Management==
==Clinical Manifestations==
 
*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
 
 
 
 
 
==Treatment==
 
 
*Eculizumab (C5 antibody): stops hemolysis in PNH
 
*Eculizumab (C5 antibody): stops hemolysis in PNH
*Iron/folate supplements
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*[[iron supplementation|Iron]]/[[folate]] supplements
*RBC transfusion PRN
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*[[pRBCs|RBC transfusion]] PRN
*Prednisone may decrease RBC destruction
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*[[Prednisone]] may decrease RBC destruction
*For severe hematopoietic dysfunction w/ marked cytopenias: hematopoietic cell transplant or immunosuppression (cyclosporine or antithymocyte globulin)
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*For severe hematopoietic dysfunction with marked cytopenias: hematopoietic cell transplant or immunosuppression (cyclosporine or antithymocyte globulin)
*Anticoagulation for thrombosis
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*[[Anticoagulation]] for thrombosis
  
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==Disposition==
  
 
==See Also==
 
==See Also==
*[[DIC]], [[TTP]], [[HUS]], [[Microangiopathic Hemolytic Anemia (MAHA)]]
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*[[HELLP]], [[HIT]], [[Hereditary Sperocytosis (HS)]]
 
  
 
[[Category:Heme/Onc]]
 
[[Category:Heme/Onc]]

Latest revision as of 17:21, 1 October 2019

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

Differential Diagnosis

Microangiopathic Hemolytic Anemia (MAHA)

Evaluation

  • 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). Ham's test is when the patient's cells are incubated in acidified serum, which triggers the alternative compliment pathway, resulting in lysis of PNH cells. Sucrose lysis test is when the patient's serum is mixed in sucrose, which causes hemolysis of PNH cells.
  • Other clues: granulocytopenia/thrombocytopenia, venous thrombosis, aplastic anemia, MDS, dysphagia or abdominal pain
  • Flow cytometry of cell membrane proteins (CD55 and CD59) is a sensitive test for PNH

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

Disposition

See Also