Thrombosis: The Leading Cause of Death in PNH1-3
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 sites.1-4
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Thromboses (venous or arterial) account for approximately 40% to 67% of PNH-related deaths5
- First thrombotic event (TE) can be fatal6
- First TE increases risk for death 5- to 10-fold5
- Pulmonary embolism (PE) or deep vein thrombosis (DVT) is the most common clinical presentation7
- 15% of all thrombotic events were identified in the arterial circulation5
All PNH patients — regardless of clone size — are at risk for thrombotic events.6
- While risk of thrombosis increases with clone size, even patients with smaller clone sizes experience thrombosis6
- 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.5
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 the French Society of Haematology. Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic factors. Lancet. 1996;348:573-577.
3. Nishimura J-I, Kanakura Y, Ware RE, et al. Clinical course and flow cytometric analysis of paroxysmal nocturnal hemoglobinuria in the United States and Japan. Medicine. 2004;83:193-207.
4. 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.
5. Hillmen P, Muus P, Duhrsen U, et al. Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood. 2007;110:4123-4128.
6. Hall C, Richards S, Hillmen P. Primary prophylaxis with warfarin prevents thrombosis in paroxysmal nocturnal hemoglobinuria (PNH). Blood. 2003;102:3587-3591.
7. Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995;333:1253-1258.
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. Hill A, Richards SJ, Hillmen P. Recent developments in the understanding and management of paroxysmal nocturnal haemoglobinuria. Br J Haematol. 2007;137:181-192.