Disease Directory Paroxysmal Nocturnal Hemoglobinuria
Blood

Paroxysmal Nocturnal Hemoglobinuria

Also known as: PNH, Marchiafava-Micheli syndrome

Prevalence

1-5 per million

Onset

Young to middle-aged adults; median age of diagnosis 35-40 years

Type

Acquired somatic mutation

Gene

PIG-A

About Paroxysmal Nocturnal Hemoglobinuria

Paroxysmal nocturnal hemoglobinuria is an acquired clonal disorder of hematopoietic stem cells caused by somatic mutations in the PIGA gene, resulting in deficiency of GPI-anchored complement regulatory proteins (CD55 and CD59) on blood cell surfaces. The loss of these proteins renders red blood cells, white blood cells, and platelets vulnerable to complement-mediated destruction, leading to intravascular hemolysis, thrombosis in unusual sites, and cytopenias. PNH is closely associated with aplastic anemia and carries a significantly elevated risk of life-threatening venous thromboembolism.

Common Clinical Features

Hemoglobinuria (dark urine, especially in the morning) Chronic intravascular hemolysis with elevated LDH Venous thrombosis in unusual sites (hepatic, mesenteric, cerebral veins) Abdominal pain and dysphagia from smooth muscle dystonia Severe fatigue and anemia Pulmonary hypertension Recurrent infections from neutropenia in aplastic anemia-associated PNH Erectile dysfunction in males

Clinical Trial Eligibility Tips

What to know before applying to Paroxysmal Nocturnal Hemoglobinuria trials.

Flow cytometry quantifying the PNH clone size (percentage of GPI-deficient granulocytes and red cells) is essential for most trial eligibility criteria; a clone size greater than 10% in granulocytes is typically required.

Current use of complement inhibitors (eculizumab, ravulizumab) affects eligibility for trials of novel complement pathway agents; document your treatment history and any breakthrough hemolysis events.

LDH levels, transfusion history, thrombotic event history, and FACIT-Fatigue scores are commonly used outcome measures in PNH trials and should be documented prospectively.

Patient Resources

Patient Organization

PNH Alliance

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Natural History Registry

International PNH Registry

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Orphanet

European reference resource for rare diseases (ORPHA:447)

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NORD

National Organization for Rare Disorders

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Find recruiting Paroxysmal Nocturnal Hemoglobinuria trials

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