Thrombosis: The Leading Cause of Death in PNH1-5

During chronic hemolysis, excess free hemoglobin depletes plasma nitric oxide, leading to platelet activation and impaired fibrinolysis, thereby increasing the risk of thrombosis in both venous and arterial sites3

  • Thromboses (venous or arterial) account for approximately 40% to 67% of PNH-related deaths4
    • First thrombotic event (TE) can be fatal4,6
    • First TE increases risk for death 5- to 10-fold4
    • Pulmonary embolism (PE) or deep vein thrombosis (DVT) is the most common clinical presentation1,4
    • 15% of all thrombotic events were identified in the arterial circulation4

Pulmonary embolism (PE) is one of the most common clinical presentations.1,4

PNH patients are at risk for thrombotic events.7

  • While risk of thrombosis increases with clone size, even patients with smaller clone sizes experience thrombosis7
  • 60% of patients with PNH have evidence of undiagnosed thrombosis8

Clinical thrombosis has been identified in PNH patients with minimal hemolysis, no transfusion history, and less severe anemia. 4,9

*The majority of patients (63%) received concomitant anticoagulant therapy10,11 The effect of anticoagulant withdrawal during Soliris treatment has not been studied.10




IMPORTANT SAFETY INFORMATION

WARNING: SERIOUS MENINGOCOCCAL INFECTIONS

Soliris increases the risk of meningococcal infections. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early

  • Vaccinate patients with a meningococcal vaccine at least 2 weeks prior to receiving the first dose of Soliris; revaccinate according to current medical guidelines for vaccine use
  • Monitor patients for early signs of meningococcal infections, evaluate immediately if infection is suspected, and treat with antibiotics if necessary

The effect of withdrawal of anticoagulant therapy during Soliris treatment has not been established. Therefore, treatment with Soliris should not alter anticoagulant management.

The most frequent adverse events observed in clinical studies were headache, nasopharyngitis, back pain, nausea, and fatigue.

SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING INCLUDING WARNINGS, PRECAUTIONS, AND ADVERSE REACTIONS.


References: 1. Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995;333:1253-1258. 2. Socié G, Mary J-Y, de Gramont A, et al; for French Society of Haematology. Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic factors. Lancet. 1996;348:573-577. 3. 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;293:1653-1662. 4. Hillmen P, Muus P, Dührsen U, et al. Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood. 2007;110:4123-4128. 5. Brodsky RA. Advances in the diagnosis and therapy of paroxysmal nocturnal hemoglobinuria. Blood Rev. 2008;22:65-74. 6. Audebert HJ, Planck J, Eisenburg M, Schrezenmeier H, Haberl RL. Cerebral ischemic infarction in paroxysmal nocturnal hemoglobinuria: report of 2 cases and updated review of 7 previously published patients. J Neurol. 2005;252:1379-1386. 7. Hall C, Richards S, Hillmen P. Primary prophylaxis with warfarin prevents thrombosis in paroxysmal nocturnal hemoglobinuria (PNH). Blood. 2003;102:3587-3591. 8. Hill A, Reid SA, Rother RP, et al. High definition contrast-enhanced MR imaging in paroxysmal nocturnal hemoglobinuria (PNH) suggests a high frequency of subclinical thrombosis [ASH abstract]. Blood. 2006;108: Abstract 979. 9. Bessler M, Schrezenmeier H, Maciejewski JP, et al. Significant disease burden in paroxysmal nocturnal hemoglobinuria patients with lower levels of hemolysis, mild anemia and minimal transfusion: clinical improvement with eculizumab therapy [ASH abstract]. Blood. 2007;110: Abstract 840. 10. Soliris® [package insert]. Cheshire, CT: Alexion Pharmaceuticals Inc; 2009. 11. Brodsky RA, Young NS, Antonioli E, et al. Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Blood. 2008;111:1840-1847. 12. Rother RP, Rollins SA, Mojcik CF, Brodsky RA, Bell L. Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat Biotechnol. 2007;25:1256-1264.