Paroxysmal nocturnal hemoglobinuria

Last updated: September 11, 2023

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Summarytoggle arrow icon

Paroxysmal nocturnal hemoglobinuria (PNH) is a hemolytic anemia caused by an acquired defect of the phosphatidylinositol glycan anchor (PIGA) gene, which leads to dysfunction of a red cell membrane protein (glycosylphosphatidylinositol) that is normally responsible for protecting RBCs from complement-mediated destruction. PNH can present with clinical features of hemolysis (particularly signs of anemia and episodic hemoglobinuria), systemic vasoconstriction, venous thromboemboli, and pancytopenia. It can also occur in patients with aplastic anemia or myelodysplastic syndrome. Diagnostics typically reveal laboratory signs of hemolysis with a negative direct Coombs test (DAT), and PNH can be confirmed using flow cytometry of peripheral blood. Management ranges from watchful waiting and supportive care to targeted anti-C5 antibody therapy (e.g., eculizumab, ravulizumab) for patients with significant clinical manifestations. Notable complications include Budd-Chiari syndrome, infections, and acute leukemia.

Definitiontoggle arrow icon

An acquired genetic defect of the hematopoietic stem cell characterized by a triad of hemolytic anemia, pancytopenia, and thrombosis [2]

Epidemiologytoggle arrow icon

  • Median age of onset: approx. 35–40 years.
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Epidemiological data refers to the US, unless otherwise specified.

Pathophysiologytoggle arrow icon

Clinical featurestoggle arrow icon

Diagnosticstoggle arrow icon

CATCH PNH by testing patients with any of the following: Cytopenias, Aplastic anemia/MDS, Thrombosis, Coombs-negative hemolysis, and/or Hemoglobinuria. [11]

Typical biochemical findings in hemolysis include haptoglobin, LDH concentration, indirect bilirubin concentration, peripheral blood smear abnormalities (e.g., reticulocytes, schistocytes, spherocytes, polychromasia), and urinalysis abnormalities (e.g., hemoglobinuria, hemosiderinuria, and urobilinogen).

References: [10][12]

Treatmenttoggle arrow icon

Approach [5][10][11]

  • Patients with mild or no clinical manifestations: watchful waiting with close surveillance
  • Patients with significant clinical manifestations: Start targeted therapy.
  • Provide supportive care for all patients.

Targeted therapy [5][10][11]

Supportive care [5][9][10][11]

Consider eculizumab in patients with PNH and thromboembolism, as it is thought to prevent thrombus propagation and protect patients from further thromboembolic events. [10]

Complicationstoggle arrow icon

References: [10]

We list the most important complications. The selection is not exhaustive.

Referencestoggle arrow icon

  1. Ram R, Adiraju KP, Gudithi S, Dakshinamurty KV. Renal Manifestations in Paroxysmal Nocturnal Hemoglobinuria. Indian J Nephrol. 2017; 27 (4): p.289–293.doi: 10.4103/0971-4065.205201 . | Open in Read by QxMD
  2. Schrezenmeier H, Muus P, Socie G, et al. Baseline characteristics and disease burden in patients in the International Paroxysmal Nocturnal Hemoglobinuria Registry. Haematologica. 2014; 99 (5): p.922-929.doi: 10.3324/haematol.2013.093161 . | Open in Read by QxMD
  3. Risitano A. Paroxysmal nocturnal hemoglobinuria: pathophysiology, natural history and treatment options in the era of biological agents. Biologics: Targets & Therapy. 2008: p.205.doi: 10.2147/btt.s1420 . | Open in Read by QxMD
  4. Brodsky RA. Paroxysmal nocturnal hemoglobinuria. Blood. 2014; 124 (18): p.2804-2811.doi: 10.1182/blood-2014-02-522128 . | Open in Read by QxMD
  5. Kinoshita T, Inoue N. Relationship between aplastic anemia and paroxysmal nocturnal hemoglobinuria. Int J Hematol. 2002; 75 (2): p.117-22.
  6. Young NS, Maciejewski JP, Sloand E, et al. The relationship of aplastic anemia and PNH. Int J Hematol. 2002; 76 Suppl 2: p.168-72.
  7. Young NS. Paroxysmal nocturnal hemoglobinuria and myelodysplastic sydromes: clonal expansion of PIG-A-mutant hematopoietic cells in bone marrow failure. Haematologica. 2009; 94 (1): p.3-7.doi: 10.3324/haematol.2008.001297 . | Open in Read by QxMD
  8. Mohammed AA, EL-Tanni H, Atiah TA-M, Atiah AA-M, Atiah MA-M, Rasmy AA. Paroxysmal Nocturnal Hemoglobinuria: From Bench to Bed. Indian Journal of Hematology and Blood Transfusion. 2016; 32 (4): p.383-391.doi: 10.1007/s12288-016-0654-2 . | Open in Read by QxMD
  9. Hill A, DeZern AE, Kinoshita T, Brodsky RA. Paroxysmal nocturnal haemoglobinuria. Nature Reviews Disease Primers. 2017; 3 (1).doi: 10.1038/nrdp.2017.28 . | Open in Read by QxMD
  10. Patriquin CJ, Kiss T, Caplan S, et al. How we treat paroxysmal nocturnal hemoglobinuria: A consensus statement of the Canadian PNH Network and review of the national registry. Eur J Haematol. 2018; 102 (1): p.36-52.doi: 10.1111/ejh.13176 . | Open in Read by QxMD
  11. Dezern AE, Borowitz MJ. ICCS/ESCCA Consensus Guidelines to detect GPI-deficient cells in Paroxysmal Nocturnal Hemoglobinuria (PNH) and related Disorders Part 1 - Clinical Utility. Cytometry Part B: Clinical Cytometry. 2018; 94 (1): p.16-22.doi: 10.1002/cyto.b.21608 . | Open in Read by QxMD
  12. $Contributor Disclosures - Paroxysmal nocturnal hemoglobinuria. None of the individuals in control of the content for this article reported relevant financial relationships with ineligible companies. For details, please review our full conflict of interest (COI) policy:.
  13. Hoekstra J, Leebeek FW, Plessier A, Raffa S, Darwish Murad S, Heller J, Hadengue A, Chagneau C, Elias E, Primignani M, Garcia-Pagan JC, Valla DC, Janssen HL; European Network for Vascular Disorders of the Liver.. Paroxysmal nocturnal hemoglobinuria in Budd-Chiari syndrome: findings from a cohort study.. Journal of Hepatology. 2009.

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