Paroxysmal nocturnal hemoglobinuria

Last revised by Rohit Sharma on 6 May 2024

Paroxysmal nocturnal hemoglobinuria (PNH), also known as Marchiafava-Micheli syndrome or Strübing-Marchiafava anemia, is an acquired hematopoietic stem cell disorder whereby some of the red blood cells produced are defective and are susceptible to premature destruction by the immune system, leading to complement-mediated hemolysis and hemoglobinuria.

The term comes from a mistaken 19th century belief that the hemolysis and subsequent hemoglobinuria occurred only intermittently (paroxysmally) and with greater frequency during the night (nocturnal). Hemoglobinuria is most prominent in the morning after the urine has concentrated overnight during sleep but hemolysis in paroxysmal nocturnal hemoglobinuria is actually a constant process.

Prevalence is low, at 1-10 per 1,000,000. No difference in prevalence between the sexes has been found, M:F = 1:1. Median age at diagnosis is in the fourth decade 2.

Paroxysmal nocturnal hemoglobinuria is caused by a defect in surface proteins of red blood cells, typically due to an acquired mutation in the PIGA gene on the X chromosome in a hematopoietic stem cell 1,7. These surface proteins usually protect red blood cells and other immune cells from destruction via the complement system, thus a defect in these proteins increases their destruction, leading to the aforementioned clinical presentation 1.

In addition to the anemia from hemolysis, patients suffer from the direct effects of intravascular hemolysis that results in the absorption of nitric oxide, a key molecule in homeostasis, leading to smooth muscle dysfunction and platelet activation, markedly raising the risk of thrombosis 1.

Ultrasound, CTA and MRI/MRA may show features of thrombosis of major vessels, particularly in the abdomen. Rarely thrombosis of smaller vessels may cause osteonecrosis of the femoral head.

MRI of the abdomen shows renal hemosiderosis.

Management options include:

  • blood transfusions

  • anticoagulation

  • haematopoetic stem cell transplant 1

  • eculizumab 1

    • has been shown to prevent most of the complications and significantly improves survival 2,5,6

Without therapy approximately 50% of patients die as a direct result of the disease. Many others are transfusion dependent for decades 3. Pregnancy results in extremely high risk for maternal and fetal mortality, predominantly resulting from thrombotic complications 4.

The condition was first described by German physician Paul Strübing in 1882, with further descriptions made by Italian physicians Ettore Marchiafava (1847-1935) and Ferdinando Micheli (1872-1936) 8.

ADVERTISEMENT: Supporters see fewer/no ads