Reference Work Entry

Rheumatology and Immunology Therapy

pp 688 -688

Paroxysmal nocturnal hemoglobulinuria

Definition

PNH is a clonal disorder of hematopoietic stem cells with faulty glycolipid anchors leading to membrane protein dysfunction. In particular without the anchor proteins can not migrate out of the intracellular Golgi apparatus. Approximately 15 proteins have been found to date affected by said mutation they include: complement defense proteins, immunologic proteins, enzymes, receptors, and granulocyte proteins of unknown function. Both normal and abnormal erythrocytes, granulocytes, monocytes, and platelets can be found at any one time. The faulty gene expression has been localized to the X chromosome. Clinical presentation includes haemolytic anemia, relative and absolute bone marrow failure, thrombophilia (particularly Budd-Chiari syndrome), dysphagia, impotence, severe low back pain, and fatigue. Diagnosis is best with flow cytometric analysis for membrane protein deficiencies especially CD59 and CD55 are recommended. A less sensitive laboratory test include complement sensitivity of the red blood cells.

Therapy

Pharmacological

First line anemia treatment is prednisone. Danazol if unresponsive and transfusions as indicated. Allogenic bone marrow transplant is suggested when possible in resitant cases and or potential marrow stimulators as needed. Thrombolytic agents with subsequent heparin and coumadin is strongly suggested.

Prognosis

Prognosis is variable but usually mean life spans after diagnosis are 8–15 years. Most mortality is due to thrombotic events or complications of bone marrow hypoproliferation, particularly infections and bleeding. Some cases have described a dying off of those clonal cell lines if patient survival is long enough, unfortunately 3–5% develop acute leukemia.

Copyright information

© Springer-Verlag 2004
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