Paroxysmal nocturnal hemoglobinuria: Difference between revisions
m (Rossdonaldson1 moved page Paroxysmal Nocturnal Hemoglobinuria (PNH) to Paroxysmal nocturnal hemoglobinuria) |
No edit summary |
||
| Line 1: | Line 1: | ||
== | ==Background== | ||
*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== | |||
==Clinical | |||
*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) | ||
| Line 32: | Line 18: | ||
*Impotence/ED | *Impotence/ED | ||
==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== | ||
| Line 41: | Line 44: | ||
*Anticoagulation for thrombosis | *Anticoagulation for thrombosis | ||
==See Also== | |||
[[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