Multisite thrombosis in a patient with paroxysmal nocturnal hemoglobinuria

Introduction Paroxysmal nocturnal hemoglobinuria (PNH) is an extremely rare bone marrow disorder [1]. In addition to complement-mediated hemolysis and cytopenia, venous and arterial thromboses at multiple and/or unusual sites are a common complication [1] [2]. Here, we describe the case of a 58-year-old woman with catastrophic PNH-associated thrombosis.

Method Coagulation and flow cytometric analyses and imaging studies were carried out as part of the patient’s routine diagnostic workup.

Results The patient was admitted to our emergency department with a 2-day history of rapidly progressive muscle weakness of all extremities and altered behavior. The patient reported severe headache and abdominal pain for about a week. In addition, she had dark-colored urine for about 2 years. Imaging diagnostics revealed extensive thromboses of cerebral sinus and bridging veins with congestive brain infarctions and hemorrhages. In addition, multilocular hepatic vein thrombosis and splenic infarction were identified. Blood count showed mild anemia (Hb 12.1 g/dL) and thrombocytopenia (71 Mrd/L). Bilirubin, LDH and schistocytes were not available at admission. While global coagulation tests were normal, plasma D-dimers were markedly elevated (12.5 mg/L). Deficiencies in antithrombin, protein C or protein S, activated protein C resistance, dysfibrinogenemia, antiphospholipid syndrome, and JAK2^V617F mutation were excluded. Flow cytometric analysis of peripheral blood revealed glycosylphosphatidylinositol anchor protein deficiency in up to 65% of leukocytes and erythrocytes, confirming diagnosis of PNH. Despite immediate initiation of anticoagulation with unfractionated heparin and endovascular mechanical thrombectomy, the patient died few days later. At the time of PNH diagnosis, initiation of complement inhibitory therapy was waived due to the patient’s unfavorable clinical prognosis.

Conclusion Although PNH is an orphan disease, it has promising treatment options. PNH should be considered in patients with newly diagnosed thromboses, especially if located at multiple and/or unusual sites.

Publikationsverlauf

Artikel online veröffentlicht:
26. Februar 2024

• References

• 1 Panse J.. Paroxysmal nocturnal hemoglobinuria: Where we stand. Am J Hematol 2023; 98 (Suppl. 04) S20-S32
• 2 Hill A, Kelly RJ, Hillmen P.. Thrombosis in paroxysmal nocturnal hemoglobinuria. Blood 2013; 121 (25) 4985-96 Available from: URL: https://www.sciencedirect.com/science/article/pii/S0006497120572492