Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal stem cell disorder characterized by intravascular hemolysis, hemoglobinuria, and life-threatening thrombotic episodes [1]. An increase in venous thrombotic incidence has been noted in patients with PNH. The Budd–Chiari syndrome is a serious manifestation of hepatic venous thrombosis in these patients [2]. Inherited risk factors for vascular disease include factor (F)V Leiden, factor (F)II and MTHFR point mutations [3–5]. The frequency of FII mutation in Lebanon was found to be 3% among healthy subjects and 12.5% among patients with deep venous thrombosis (DVT) [6]. In a report by Almawi et al., the prevalence of the mutated heterozygous (C/T) C677T MTHFR genotype was 39.73%[7].

Our patient is a 28-year-old man, a known case of PNH, who presented with acute abdominal pain and fever. His history dated back to 2 years ago, when he presented with anemia and recurrent episodes of abdominal pain. Since then he was maintained on steroids (15 mg p.o. daily); however, he kept having intermittent abdominal pain. Three months before admission, he sustained bilateral DVT and he was maintained on warfarin [International Normalized Ratio (INR) 2.5–3]. On admission, the patient was weak and icteric. An abdominal computed tomography scan showed hepatosplenomegaly with massive ascites consistent with the Budd–Chiari syndrome. The patient was started on i.v. heparin for 24 h and was switched to oral anticoagulation with warfarin (INR 2.5–3). Thrombophilia work-up was requested. The results revealed heterozygosity for both FII (G20210A) and MTHFR C677T mutations. No mutation of FV was present. The patient had no family history of thrombosis. Now he is doing well on warfarin.

The frequency of FII and MTHFR mutations in the Eastern Mediterranean region suggests a screening role for inherited thrombophilia in patients who are vulnerable to thrombotic vascular accidents. Our patient sustained bilateral DVT and was maintained on oral anticoagulation therapy. Despite being on oral anticoagulation, he developed hepatic vein thrombosis. The prevalence of inherited thrombophilia in PNH patients has not been studied yet. In our patient, the compound double-heterozygosity for FII and MTHFR mutations may have contributed to the increased risk of thrombosis. Our patient is the first PNH patient reported in the English literature who concomitantly had two inherited thrombophilia mutations. Whether or not patients with PNH should be screened for thrombophilia is still not known. Doing this might help identify those with a higher risk of thrombosis and also guide the physician towards anticoagulation. Studies are lacking to determine the prevalence of inherited thrombophilia and to define a prophylactic anticoagulation approach for PNH patients with underlying thrombophilic tendencies.


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  2. References
  • 1
    Rotoli B, Luzzatto L. Paroxysmal nocturnal haemoglobinuria. Baillieres Clin Haematol 1989; 2: 11338.
  • 2
    Smith LJ. Paroxysmal nocturnal hemoglobinuria. Clin Lab Sci 2004; 17: 1727.
  • 3
    Dahlback B. Resistance to activated protein C caused by the factor VR506Q mutation is a common risk factor for venous thrombosis. Thromb Haemost 1997; 78: 4838.
  • 4
    Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variation in the 30-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996; 88: 3698703.
  • 5
    Graham IM, Daly LE, Refsum HM, Robinson K, Brattstrom LE, Ueland PM, Palma-Reis RJ, Boers GH, Sheahan RG, Israelsson B, Uiterwaal CS, Meleady R, McMaster D, Verhoef P, Witteman J, Rubba P, Bellet H, Wautrecht JC, De Valk HW, Sales Luis AC, Parrot-Rouland FM, Tan KS, Higgins I, Garcon D, Andria G. Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project. JAMA 1997; 277: 177581.DOI: 10.1001/jama.277.22.1775
  • 6
    Taher A, Khalil I, Abou-Merhi R, Shamseddine A, Bazarbachi A. High prevalence of prothrombin G20210A mutation among patients with deep venous thrombosis in Lebanon. Thromb Haemost 2003; 89: 9456.
  • 7
    Almawi WY, Finan RR, Tamim H, Daccache JL, Irani-Hakime N. Differences in the frequency of the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene among the Lebanese population. Am J Hematol 2004; 76: 857.DOI: 10.1002/ajh.20047