Paroxysmal Nocturnal Hemoglobinuria: An Underestimated Cause of Pediatric Thromboembolism
14 September 2019
13 January 2020
20 February 2020 (online)
Paroxysmal nocturnal hemoglobinuria (PNH) is a chronic disease caused by complement-mediated hemolysis. Clinical symptoms include intravascular hemolysis, nocturnal hemoglobinuria, thromboses, cytopenia, fatigue, abdominal pain, and a strong tendency toward bone marrow failure. It is a rare disease, especially in children, with high mortality rates without appropriate treatment.
We here present the case of a 17-year-old girl with unprovoked muscle vein thrombosis. Flow cytometric analysis showed deficiency of glycosyl-phosphatidylinositol-anchored membrane proteins on all three hematopoietic cell lines and confirmed the diagnosis of PNH. Treatment with the monoclonal antibody eculizumab achieved long-term remission.
As flow cytometry is normally not part of the routine diagnostics for pediatric thrombosis, awareness is crucial and PNH is important to consider in all children with thrombosis at atypical sites and abnormalities in blood counts with regard to hemolysis and cytopenia.
- 1 Blanchette VS, Brandão LR, Breakey VR, Revel-Vilk S. SickKids Handbook of Pediatric Thrombosis and Hemostasis. 2. Auflage. Basel: Kager; 2017
- 2 Ware RE, Hall SE, Rosse WF. Paroxysmal nocturnal hemoglobinuria with onset in childhood and adolescence. N Engl J Med 1991; 325 (14) 991-996
- 3 Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med 1995; 333 (19) 1253-1258
- 4 Parker C, Omine M, Richards S. , et al; International PNH Interest Group. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood 2005; 106 (12) 3699-3709
- 5 Wiedmer T, Hall SE, Ortel TL, Kane WH, Rosse WF, Sims PJ. Complement-induced vesiculation and exposure of membrane prothrombinase sites in platelets of paroxysmal nocturnal hemoglobinuria. Blood 1993; 82 (04) 1192-1196
- 6 Rosse WF, Hillmen P, Schreiber AD. Immune-mediated hemolytic anemia. Hematology Am Soc Hematol Educ Program 2004; 2004 (01) 48-62
- 7 Rother RP, Bell L, Hillmen P, Gladwin MT. The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: a novel mechanism of human disease. JAMA 2005; 293 (13) 1653-1662
- 8 Röth A, Dührsen U. Paroxysmale nächtliche Hämoglobinurie. Dtsch Arztebl Int 2007; 104 (04) 192-197
- 9 Hill A, Kelly RJ, Hillmen P. Thrombosis in paroxysmal nocturnal hemoglobinuria. Blood 2013; 121 (25) 4985-4996 , quiz 5105
- 10 van den Heuvel-Eibrink MM. Paroxysmal nocturnal hemoglobinuria in children. Paediatr Drugs 2007; 9 (01) 11-16
- 11 Hillmen P, Muus P, Dührsen U. , et al. Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood 2007; 110 (12) 4123-4128
- 12 Reiss UM, Schwartz J, Sakamoto KM. , et al. Efficacy and safety of eculizumab in children and adolescents with paroxysmal nocturnal hemoglobinuria. Pediatr Blood Cancer 2014; 61 (09) 1544-1550
- 13 Curran KJ, Kernan NA, Prockop SE. , et al. Paroxysmal nocturnal hemoglobinuria in pediatric patients. Pediatr Blood Cancer 2012; 59 (03) 525-529
- 14 Socié G, Mary JY, de Gramont A. , et al; French Society of Haematology. Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic factors. Lancet 1996; 348 (9027): 573-577
- 15 Rosse WF. Variations in the red cells in paroxysmal nocturnal haemoglobinuria. Br J Haematol 1973; 24 (03) 327-342
- 16 Ge M, Shi J, Li X. , et al. Clinical features and survival of Asian pediatric patients with paroxysmal nocturnal hemoglobinuria: results from a single center in China. Acta Haematol 2015; 134 (01) 1-6
- 17 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 2019; 102 (01) 36-52