Paroxysmal Nocturnal Hemoglobinuria (PNH)

Paroxysmal nocturnal hemoglobinuria (PNH) is an uncommon, benign clonal proliferation of hematopoietic stem cells that lack the glycosylphosphatidylinositol (GPI) anchor protein. The absence of GPI anchor protein leads to increased red blood cell sensitivity to complement destruction and an increased propensity of platelets to start clotting in an abnormal way.

Clinical manifestations:

• Hemolytic anemia with intermittent hemoglobinuria
• Venous thrombosis: mainly intraabdominal veins (portal, hepatic, mesenteric) → Budd-Chiari syndrome, congestive splenomegaly, abdominal pain
• Deficient hematopoiesis → granulocytopenia and thrombocytopenia

Diagnosis:

• Demonstrate RBC breakdown after complement activation by:

– Acid (Ham test)

-Reduction in ionic strength (sucrose lysis test)

• Flow cytometry – for analysis of GPI-linked proteins on RBCs and WBCs

Treatment:

• Transfusion with washed RBCs:

-To raise Hb

-To suppress bone marrow

• Androgens
• Glucocorticoids
• Management of thrombosis:

-thrombolytic agents for acute thrombosis

-anticoagulation

• Bone marrow transplantation