Thromb Haemost 2011; 106(04): 617-623
DOI: 10.1160/TH11-04-0251
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Hypercoagulability biomarkers in Trypanosoma cruzi-infected patients

María-Jesús Pinazo
1   Barcelona Centre for International Health Research (CRESIB), Hospital Clínic / IDIBAPS, Universitat de Barcelona, CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
,
Dolors Tassies
2   Hemotherapy and Hemostasis Department. Hospital Clínic, Barcelona, Spain
,
Jose Muñoz
1   Barcelona Centre for International Health Research (CRESIB), Hospital Clínic / IDIBAPS, Universitat de Barcelona, CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
,
Roser Fisa
3   Laboratori de Parasitologia, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain
,
Elizabeth de Jesús Posada
1   Barcelona Centre for International Health Research (CRESIB), Hospital Clínic / IDIBAPS, Universitat de Barcelona, CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
,
Juan Monteagudo
2   Hemotherapy and Hemostasis Department. Hospital Clínic, Barcelona, Spain
,
Edgar Ayala
4   Health Biostatistics, Centre for International Health Research (CRESIB), Barcelona, Spain
,
Montserrat Gállego
3   Laboratori de Parasitologia, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain
,
Joan-Carles Reverter
2   Hemotherapy and Hemostasis Department. Hospital Clínic, Barcelona, Spain
,
Joaquim Gascon
1   Barcelona Centre for International Health Research (CRESIB), Hospital Clínic / IDIBAPS, Universitat de Barcelona, CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
› Author Affiliations
Further Information

Publication History

Received: 18 April 2011

Accepted after minor revision: 17 June 2011

Publication Date:
29 November 2017 (online)

Summary

There is a current controversy over the hypothesis that a number of thromboembolic events could be related to hypercoagulable state in patients with chronic Chagas disease. This study was designed to determine whether a prothrombotic state existed in chronic Trypanosoma cruzi-infected patients and, if so, to describe its evolution after treatment with Benznidazole. Twenty-five patients with chronic Chagas disease and 18 controls were evaluated. The markers used were prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin, plasminogen, protein C, total protein S, free protein S, factor VIII, D-dimer, activated factor VIIa, tissue-type plasminogen activator inhibitor-1, prothrombin fragment 1+2 (F1+2), plasmin-antiplasmin complexes, soluble P-selectin and endogenous thrombin potential (ETP). Despite statistically significant differences between cases and controls in several markers, only ETP (which quantifies the ability of plasma to generate thrombin when activated through tissue factor addition) (p<0.0001) and F1+2 (a marker of thrombin generation in vivo) (p<0.0001) showed values outside the normal levels in patients compared with controls. Similar results were obtained in these markers six months after treatment in the cohort of cases (p<0.0008 and p<0.004, respectively). These results may be relevant in clinical practice. Though current treatment for Chagas disease is still controversial, if it were considered as a thromboembolic risk factor the antiparasitic treatment strategy could be reinforced. The results also support further research on haemostasis parameters as candidates for early surrogate bio -markers of cure or progression of Chagas disease.

 
  • References

  • 1 Pan American Health Organization. Estimación cuantitativa de la enfermedad de Chagas en las Americas. Organizatión Panamericana de la Salud. Montevideo, Uruguay: 2006.
  • 2 Gascon J, Bern C, Pinazo MJ. Chagas disease in Spain, the United States and other non-endemic countries. Acta Trop 2010; 115: 22-27.
  • 3 Punukollu G, Gowda RM, Khan IA. et al. Clinical aspects of the Chagas' heart disease. Int J Cardiol 2007; 115: 279-283.
  • 4 Carod-Artal FJ, Vargas AP, Horan TA. et al. Chagasic cardiomyopathy is independently associated with ischemic stroke in Chagas disease. Stroke 2005; 36: 965-970.
  • 5 Carod-Artal FJ. Chagas cardiomyopathy and ischemic stroke. Expert Rev Cardiovasc Ther 2006; 4: 119-130.
  • 6 Andrade ZA, Sadigurski M. Trombo-embolismo command post chagásicos sem cardiac insuficiência. Gaz Med Bay 1971; 71: 50-64.
  • 7 Carod-Artal FJ. Stroke: a neglected complication of American trypanosomiasis (Chagas' disease). Trans R Soc Trop Med Hyg 2007; 101: 1075-1080.
  • 8 Lowe GD. Virchow's triad revisited: abnormal flow. Pathophysiol Haemost Thromb 2004; 33: 455-457.
  • 9 Berra HH, Piaggio E, Revelli SS. et al. Blood viscosity changes in experimentally Trypanosoma cruzi-infected rats. Clin Hemorheol Microcirc 2005; 32: 175-182.
  • 10 Salomone OA. Chagas’ Cardiomyopathy and Thrombosis: the Beginning and the End of a Dangerous Affair. Rev Esp Cardiol 2003; 56: 333-334.
  • 11 Carod-Artal FJ. Enfermedad de Chagas e Ictus. Neurología 2006; 21: 135-149.
  • 12 Schuetz P, Christ-Crain M, Morgenthaler NG. et al. Circulating precursor levels of endothelin-1 and adrenomedullin, two endothelium-derived, counteracting substances, in sepsis. Endothelium 2007; 14: 345-351.
  • 13 Schuetz P, Stolz D, Mueller B. et al. Endothelin-1 precursor peptides correlate with severity of disease and outcome in patients with community acquired pneumonia. BMC Infect Dis 2008; 28: 8-22.
  • 14 Kreutz RP, Tantry US, Bliden KP. et al. Inflammatory changes during the ‘common cold’ are associated with platelet activation and increased reactivity of platelets to agonists. Blood Coagulation and Fibrinolysis 2007; 18: 713-718.
  • 15 Herrera RN, Diaz E, Pérez R. et al. The prothrombotic state in early stages of chronic Chagas' disease. Rev Esp Cardiol 2003; 56: 377-382.
  • 16 Herrera RN, Diaz E, Perez Aguilar R. et al. Prothrombotic state in early stages of chronic Chagas' disease. Its association with thrombotic risk factors. Arch Cardiol Mex 2005; 75: 38-48.
  • 17 Carod-Artal FJ, Fernandes da Silva TV, Vilela Nunes S. et al. Thrombophilia is not a predictive factor of stroke in Chagas Disease. Neurology 2004; 62: A240-241.
  • 18 World Health Organization (WHO). Chagas disease. Thirteenth Programme Report UNDP/TDR. Geneva, Switzerland: 1997.
  • 19 Riera C, Vergés M, López-Chejade P. et al. Desarrollo y evaluación de una técnica ELISA con antígeno crudo de Trypanosoma cruzi para el diagnóstico de la enfermedad de Chagas. Enf Emerg 2009; 11: 22-29.
  • 20 Tobler LH, Contestable P, Pitina L. et al. Evaluation of a new enzyme-linked immunosorbent assay for detection of Chagas antibody in US blood donors. Transfusion 2007; 47: 90-96.
  • 21 Marcon GE, Andrade PD, de Albuquerque DM. et al. Use of a nested polymerase chain reaction (N-PCR) to detect Trypanosoma cruzi in blood samples from chronic chagasic patients and patients with doubtful serologies. Diagn Microbiol Infect Dis 2002; 43: 39-43.
  • 22 Piron M, Fisa R, Casamitjana N. et al. Development of a real-time PCR assay for Trypanosoma cruzi detection in blood samples. Acta Trop 2007; 103: 195-200.
  • 23 Stata-Corp. 2007. Stata Statistical Software: Release 10. College Station, TX: Stata-Corp LP.;
  • 24 Py M, Pedrosa R, Silveira J. et al. Neurological Manifestations in Chagas Disease without Cardiac Dysfunction: Correlation between Dysfunction of the Parasympathetic Nervous System and White Matter Lesions in the Brain. J Neuroimaging 2009; 19: 332-336.
  • 25 Tanowitz HB, Burns ER, Sinha AK. et al. Enhanced platelet adherence and aggregation in Chagas' disease: a potential pathogenic mechanism for cardiomyopathy. Am J Trop Med Hyg 1990; 43: 274-281.
  • 26 Schnittler HJ, Preissner KT. Vascular endothelium and infectious diseases: trick and treat. Thromb Haemost 2005; 94: 238-239.
  • 27 Jong E, Louw S, van Gorp EC. et al. The effect of initiating combined antirretroviral therapy on endotelial cell activation and coagulation markers in South African HIV-infected individuals. Thromb Haemost 2010; 104: 1228-1234.
  • 28 Fota-Markowska H, Modrzewska R, Krzowska-Firych J. et al. Concentration of prothrombin fragment 1 + 2 (f1 + 2) in patients with liver cirrhosis and chronic hepatitis C infection. Ann Univ Mariae Curie Sklodowska Med 2004; 59: 4-7.
  • 29 Consolazio A, Borgia MC, Ferro D. et al. Increased thrombin generation and circulating levels of tumour necrosis factor-alpha in patients with chronic Helicobacter pylori-positive gastritis. Aliment Pharmacol Ther 2004; 1: 289-294.
  • 30 Manucci PM. Mechanisms, markers and management of coagulation activation. Thrombosis 1993; 44: 851-870.
  • 31 Fuster V, Badimon L, Badimon JJ. et al. The pathogenesis of coronary artery disease and the acute coronary syndromes. N Eng J Med 1992; 326: 242-250 310-318.
  • 32 Cançado JR.. Long term evaluation of Chagas disease with Benznidazole. Rev Inst Med Trop Sao Paulo 2002; 44: 29-37.
  • 33 Urbina JA, Docampo R. Specific chemotherapy of Chagas disease: controversies and advances. Trends Parasitol 2003; 19: 495-501.
  • 34 Rodrigues Coura J, de Castro SL. A critical review on Chagas disease chemotherapy. Mem Inst Oswaldo Cruz 2002; 97: 3-24.
  • 35 Jackson Y, Chappuis F. Tolerance of Nifurtimox for the treatment of Chagas disease in adults. Enf Emerg 2009; 11: 49.
  • 36 Pinazo MJ, Muñoz J, Posada E. et al. Tolerance of benznidazole in treatment of Chagas' disease in adults. Antimicrob Agents Chemother 2011; 54: 4896-4899.
  • 37 Viotti R, Vigliano C, Lococo B. et al. Long-term cardiac outcomes of treating chronic Chagas disease with benznidazole versus no treatment: a nonrandomized trial. Ann Intern Med 2006; 144: 724-734.
  • 38 Laucella SA, Mazliah DP, Bertocchi G. et al. Changes in Trypanosoma cruzi-specific immune responses after treatment: surrogate markers of treatment efficacy. Clin Infect Dis 2009; 49: 1675-1684.