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Thromb Haemost 2005; 93(01): 88-91
DOI: 10.1160/TH04-06-0391
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

High incidence of thrombosis in African-American and Latin-American patients with Paroxysmal Nocturnal Haemoglobinuria

David J. Araten
1   Memorial Sloan-Kettering Cancer Center, New York, New York, USA
,
Howard T. Thaler
1   Memorial Sloan-Kettering Cancer Center, New York, New York, USA
,
Lucio Luzzatto
1   Memorial Sloan-Kettering Cancer Center, New York, New York, USA
2   Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
› Author Affiliations
Grant support: This work was supported by the Doris Duke Charitable Foundation Clinical Scientist Development Award, and by NIH grant R01 HL56778–06. This work was also supported in part by grants from Ministero della Sanità, FIRB and Compagnia di San Paolo, Italy
Further Information

Correspondence to:

David J. Araten
Division of Hematology
Memorial Sloan-Kettering Cancer Center
1275 York Avenue, New York
NY 10021, USA
Phone: + 1 212–639–2972   
Fax: + 1 646–422–2125   

Publication History

Received 23 June 2004

Accepted after revision 04 October 2004

Publication Date:
14 December 2017 (online)

Also available at
 
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Summary

Paroxysmal Nocturnal Haemoglobinuria (PNH) results in a marked thrombophilic state by unknown mechanisms. Geographic differences in thrombosis incidence in PNH have been observed. We have reviewed 64 patients with “Classic PNH” from a single institution in order to determine the rate of thrombosis in different ethnic groups.When we compared African- Americans (n=11) and Latin-Americans (n=8) with other patients (n= 45), we found that African-American and Latin-American patients are at increased risk [Hazard ratio 3.66 (p=0.005) and 3.52, (p= 0.035) respectively by Cox regression]. Our data also suggest that this difference in the rate of thrombosis has an impact on length of survival.These findings demonstrate that ethnicity is a risk factor for thrombosis in PNH and have implications for decision-making regarding the management of these patients,including the prevention of thrombosis.


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Keywords

Paroxysmal Nocturnal Hemoglobinuria (PNH) - ethnicity - thrombosis - hypercoagulable states - deep venous thrombosis

 


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  • References

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    CrossrefPubMedSearch in Google Scholar
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    CrossrefPubMedSearch in Google Scholar
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    PubMedSearch in Google Scholar
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    PubMedSearch in Google Scholar
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    PubMedSearch in Google Scholar
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    CrossrefPubMedSearch in Google Scholar
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    PubMedSearch in Google Scholar
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    PubMedSearch in Google Scholar
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    PubMedSearch in Google Scholar
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    CrossrefPubMedSearch in Google Scholar
  • 25 McMullin MF, Hillmen P, Jackson J. et al Tissue plasminogen activator for hepatic vein thrombosis in paroxysmal nocturnal hemoglobinuria. J Intern Med 1994; 235: 85-9.
    CrossrefPubMedSearch in Google Scholar
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    CrossrefPubMedSearch in Google Scholar
  • 27 Stein PD, Kayali F, Olson RE. et al Pulmonary thromboembolism in Asians/Pacific islanders in the United States: Analysis of data from the National Hospital Discharge Survey and the United States Bureau of the Census. Am J Med 2004; 116: 435-42.
    CrossrefPubMedSearch in Google Scholar

Correspondence to:

David J. Araten
Division of Hematology
Memorial Sloan-Kettering Cancer Center
1275 York Avenue, New York
NY 10021, USA
Phone: + 1 212–639–2972   
Fax: + 1 646–422–2125   

  • References

  • 1 Rotoli B, Luzzato L. Paroxysmal Nocturnal Hemoglobinuria. Bailliere's Clin Hematol 1989; 2: 118-38.
    PubMedSearch in Google Scholar
  • 2 Socie G, Mary JY, de Gramont A et al. Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic factors. Lancet. 1996; 348: 573-7.
    CrossrefPubMedSearch in Google Scholar
  • 3 Hillmen P, Lewis SM, Bessler M. et al Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med 1995; 333: 1253-8.
    CrossrefPubMedSearch in Google Scholar
  • 4 Ronne E, Pappot H, Grondahl-Hansen J. et al The receptor for urokinase plasminogen activator is present in plasma from healthy donors and elevated in patients with paroxysmal nocturnal haemoglobinuria. Br J Haematol 1995; 89: 576-81.
    CrossrefPubMedSearch in Google Scholar
  • 5 Nicholson-Weller A, Spicer DB, Austen KF. Deficiency of the complement regulatory protein, „decayaccelerating facor" on membranes of granulocytes, monocytes, and platelets in paroxysmal nocturnal hemoglobinura. N Engl J Med 1985; 1091-7.
    PubMedSearch in Google Scholar
  • 6 Jin JY, Tooze JA, Marsh JCW. et al Glycosylphosphatidyl- inositol (GPI)-linked protein deficiency on the platelets of patients with aplastic anaemia and paoxysmal nocturnal haemoglobinuria: two distinct patterns correlating with expression on neutrophils. Br J Haematol 1997; 96: 493-6.
    CrossrefPubMedSearch in Google Scholar
  • 7 Polley MJ, Nachman RL. Human complement in thrombin-mediated platelet function. J Exp Med 1979; 150: 633-45.
    CrossrefPubMedSearch in Google Scholar
  • 8 Zimmerman TS, Kolb WP. Human platelet-initiated formation and uptake of the C5–9 complex of human complement. J Clin Invest 1976; 57: 203-11.
    CrossrefPubMedSearch in Google Scholar
  • 9 Dixon RH, Rosse WF, Thorpe AM. Mechanism of complement-mediated activation of human blood platelets in vitro. J Clin Invest 1977; 59: 360-8.
    CrossrefPubMedSearch in Google Scholar
  • 10 Devine DV, Siegel RSRWF. Interactions of the platelets in paroxysmal noctunral hemoglobinuria with complement J Clin Invest 1987; 79: 131-7.
    CrossrefPubMedSearch in Google Scholar
  • 11 Wiedmer J, Hall SE, Ortel TL. et al Complement- Induced Vesiculation and Exposure of Membrane Prothrombinase Sites in Platelets of Paroxysmal Nocturnal Hemoglobinuria. Blood 1993; 82: 1192-6.
    CrossrefPubMedSearch in Google Scholar
  • 12 Hugel B, Socie G, Vu T. et al Elevated levels of circulating procoagulant microparticles in patients with paroxysmal nocturnal hemoglobinuria and aplastic anemia. Blood 1999; 93: 3451-6.
    CrossrefPubMedSearch in Google Scholar
  • 13 Sims PJ, Faioni EM, Wiedmer T. et al Complement proteins C5b-9 cause release of membrane vesicles from the platelet surface that are enriched in the membrane receptor for coagulation factor Va and express prothrombinase activity. J Biol Chem 1988; 263: 18205-12.
    PubMedSearch in Google Scholar
  • 14 Ott I, Miyagi Y, Miyazaki K. et al Reversible regulation of tissue factor-induced coagulation by glycosyl phosphatidylinositol-anchored tissue factor pathway inhibitor. Arterioscler Thromb Vascular Biol 2000; 20: 874-82.
    CrossrefPubMedSearch in Google Scholar
  • 15 Ware RE, Hall SE, Rosse WF. Paroxysmal nocturnal hemoglobinuria New Engl J Med. 1991; 325: 991-6.
    PubMedSearch in Google Scholar
  • 16 Tudela M, Jarque I, Perez-Sirvent ML. et al Clinical profile and course of paroxysmal nocturnal hemoglobinuria. Sangre 1993; 38: 301-7.
    PubMedSearch in Google Scholar
  • 17 Koduri PR, Gowrishnakar S. Paroxysmal nocturnal haemoglobinuria in Indians. Acta Haemtologica 1992; 88: 126-8.
    PubMedSearch in Google Scholar
  • 18 Xio-feng L, Tian-ying Y, Xue-yon Y. Characteristics of paroxysmal nocturnal hemoglobinuria in China. Chin Med J 1990; 103: 885-9.
    PubMedSearch in Google Scholar
  • 19 Gongora-Biachi RA, Gonzalez-Martinez P, Sosa-Munoz J. et al Natural history of paroxysmal nocturnal hemoglobinuria in adolescents, adults, and children: the Mexican experience. Sangre 1997; 42: 171-7.
    PubMedSearch in Google Scholar
  • 20 Krutrachue M, Wasi P, Na-Nakorn S. Paroxysmal Nocturnal Haemoglobinuria in Thailand with special reference to an association with aplastic anaemia. Br J Haematol 1978; 39: 267-76.
    CrossrefPubMedSearch in Google Scholar
  • 21 Fujioka S, Asai T. Prognostic features of paroxysmal nocturnal hemoglobinuria in Japan. Acta Haematologica Japonica 1989; 52: 1386-94.
    PubMedSearch in Google Scholar
  • 22 Araten DJ, Bessler M, McKenzie S. et al Dynamics of hematopoiesis in paroxysmal nocturnal hemoglobinuria (PNH): no evidence for intrinsic growth advantage of PNH clones. Leukemia 2002; 2243-8.
    PubMedSearch in Google Scholar
  • 23 Antin JH, Ginsburg D, Smith BR. et al Bone marrow transplantation for paroxysmal nocturnal hemoglobinuria. Blood 1985; 66: 1247-50.
    PubMedSearch in Google Scholar
  • 24 Hall C, Richards S, Hillmen P. Primary prophylaxis with warfarin prevents thrombosis in paroxysmal nocturnal hemoglobinuria (PNH). Blood 2003; 102: 3587-91.
    CrossrefPubMedSearch in Google Scholar
  • 25 McMullin MF, Hillmen P, Jackson J. et al Tissue plasminogen activator for hepatic vein thrombosis in paroxysmal nocturnal hemoglobinuria. J Intern Med 1994; 235: 85-9.
    CrossrefPubMedSearch in Google Scholar
  • 26 Stein PD, Kayali F, Olson RE. Regional differences in rates of diagnosis and mortality of pulmonary thromboembolism. Am J Cardiol 2004; 93: 1194-7.
    CrossrefPubMedSearch in Google Scholar
  • 27 Stein PD, Kayali F, Olson RE. et al Pulmonary thromboembolism in Asians/Pacific islanders in the United States: Analysis of data from the National Hospital Discharge Survey and the United States Bureau of the Census. Am J Med 2004; 116: 435-42.
    CrossrefPubMedSearch in Google Scholar

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