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At a glance

A rare, acquired hemolytic stem cell disorder characterized by hemolytic anemia, bone marrow aplasia, and frequent thrombosis.

Synonyms

Immune Hemolytic Anemia; Marchiafava-Micheli Syndrome.

Incidence

Approximately 1:500,000. PNH is an uncommon disorder of unknown frequency both in the United States and worldwide. It is estimated that it is observed 5 to 10 times less than with aplastic anemia. It may be more frequent in Southeast Asia and the Far East.

Genetic inheritance

Acquired hemolytic anemia.

Pathophysiology

Expansion of hematopoietic stem cells harboring a mutation in the PIGA gene, which encodes a protein required for the biosynthesis of glycosylphosphatidylinositol (GPI). This deficiency on erythrocytes leads to intravascular hemolysis. The red blood cells (RBCs) have increased sensitivity to complement-mediated hemolysis as a result of deficient decay-accelerated factor. The hemolysis might be triggered by acidosis during sleep. Platelets, too, are more sensitive to complement activation.

Diagnosis

Laboratory diagnosis is based on the Ham test, which mixes affected RBCs with slightly acidified, but otherwise normal, serum. This leads to complement-mediated hemolysis.

Clinical aspects

The disease process is insidious and has a chronic course, with a median survival of about 10 years. The morbidity is influenced by the importance of the hemolysis, bone marrow failure, and thrombophilia. Men and women are affected equally and the onset begins in childhood (<2 years of age) to adulthood (as old as 85 years of age). Other complications include infections and thrombosis. Characterized by chronic hemolysis, anemia, pancytopenia, potentially life-threatening thrombosis secondary to platelet activation, low serum haptoglobin, elevated lactate dehydrogenase, hemosiderinuria, intermittent hemoglobinuria, especially when urine is concentrated, and normal peripheral smear. Eculizumab is the only drug approved for the treatment of PNH and has become the current standard for therapy but not for all.

Precautions before anesthesia

Check hematocrit, anticipate need for transfusion. Check prothrombin time if the administration of anticoagulant is considered against thrombosis.

Anesthetic considerations

Maintain oxygen-carrying capacity. Avoid regional anesthesia if the patient is anticoagulated or if thrombocytopenia is present.

Pharmacological implications

Steroid supplementation is highly recommended.

References

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Kelly  RJ, Höchsmann  B, Szer  J, Kulasekararaj  A,  et al: Eculizumab in pregnant patients with paroxysmal nocturnal hemoglobinuria. N Engl J Med 373:1032, 2015.  [PubMed: 26352814]
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Kjaer  K, Comerford  M, Godalla  F: General anesthesia for cesarean delivery in a patient with paroxysmal nocturnal hemoglobinuria and thrombocytopenia. Anesth Analog 98:1471, 2004.
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Parker  C: Eculizumab for paroxysmal nocturnal haemoglobinuria. Lancet 373(9665):759, 2009.  [PubMed: 19144399]
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Tabbara  IA: Hemolytic anemias diagnosis and management. Med Clin North Am 76:649, 1992.  [PubMed: 1578962]

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