T N Bongers

Publications (5)19.51 Total impact

• Article: Reduced ADAMTS13 in children with severe meningococcal sepsis is associated with severity and outcome.

  Tamara N Bongers, Marieke Emonts, Moniek P M de Maat, Ronald de Groot, Ton Lisman, Jan A Hazelzet, Frank W G Leebeek
  [show abstract] [hide abstract]
  ABSTRACT: Multiple organ failure is a common feature of pediatric meningococcal sepsis and is associated with an imbalance of coagulation and fibrinolysis. This is partly due to an increased secretion of prothrombotic ultra-large von Willebrand factor (VWF) as the result of vascular endothelial damage. Another factor that may contribute is ADAMTS13, which converts VWF into smaller, less active, VWF multimers and thus influences VWF activity in plasma. We investigated the role of ADAMTS13 and VWF in the severity and outcome of sepsis. In 58 children with severe meningococcal sepsis we measured ADAMTS13 activity and antigen, VWF collagen binding activity (VWF:CB) and antigen levels (VWF:Ag), VWF propeptide and factor VIII at different time points during their stay in the paediatric intensive care unit. In the acute phase, both ADAMTS13 activity and antigen were decreased (median 23.4% and 33.7% of normal, respectively) and VWF:CB and VWF:Ag levels were strongly increased (325% and 348%, respectively.) ADAMTS13 antigen (23.9% vs. 34.6%; p=0.06) and VWF:CB (240% and 340% p<0.001) were lower in non-survivors than in survivors. ADAMTS13 activity and VWF:CB were both correlated with the severity of the disease, as indicated by the Pediatric Risk of Mortality score (R(s)= -0.38 and R(s)= -0.50, p=0.01, respectively, p<0.001). In the acute phase of severe sepsis decreased levels of ADAMTS13 and increased levels of VWF are observed, and the changes are related to severity of disease and outcome. This may contribute to the formation of microthrombi and the severity of thrombotic sequelae of sepsis.
  Thrombosis and Haemostasis 04/2010; 103(6):1181-7. · 5.04 Impact Factor
• Article: Lower levels of ADAMTS13 are associated with cardiovascular disease in young patients.

  T N Bongers, E L E de Bruijne, D W J Dippel, A J de Jong, J W Deckers, D Poldermans, M P M de Maat, F W G Leebeek
  [show abstract] [hide abstract]
  ABSTRACT: ADAMTS13 may play a role in arterial thrombosis by cleaving the highly active and thrombogenic ultralarge Von Willebrand Factor (VWF) multimers into less active VWF multimers. The aim was to investigate the relationship between plasma levels of ADAMTS13, VWF and genetic variation in the ADAMTS13 gene with cardiovascular disease. We performed a case-control study in 374 patients with a first-ever arterial thrombosis before the age of 45 years in males and 55 years in women. We included 218 patients with coronary heart disease (CHD), 109 patients with ischemic stroke (IS) and 47 patients with peripheral arterial disease (PAD) and 332 healthy population-based controls. ADAMTS13 and VWF levels were measured 1-3 months after the event. ADAMTS13 levels were associated with cardiovascular disease (OR antigen 5.1 (95% CI 3.1-8.5, p<0.001) and OR activity 4.4 (95% CI 2.5-7.5, p<0.001), in the lowest quartiles). VWF levels were associated with cardiovascular disease (OR antigen 2.1 (95% CI 1.3-3.3, p=0.001) and OR activity 2.0 (95% CI 1.3-3.1, p=0.003), in the highest quartile). Patients with combined low ADAMTS13 levels and high VWF levels had an odds ratio of 7.7 (95% CI 3.3-17.7) (p for trend <0.0001). No association was found between genetic variation in the ADAMTS13 gene with levels of ADAMTS13 or with risk of cardiovascular disease. In conclusion, levels of ADAMTS13 and VWF are strongly associated with the risk of cardiovascular disease.
  Atherosclerosis 04/2009; 207(1):250-4. · 3.79 Impact Factor
• Article: Frequency of the von Willebrand factor Tyr1584Cys polymorphism in arterial thrombosis.

  T N Bongers, M P M de Maat, J W Deckers, D W J Dippel, F W G Leebeek
  British Journal of Haematology 04/2008; 140(5):578-9. · 4.94 Impact Factor
• Article: Absence of Pro475Ser polymorphism in ADAMTS-13 in Caucasians.

  T N Bongers, M P M De Maat, D W J Dippel, A G Uitterlinden, F W G Leebeek
  Journal of Thrombosis and Haemostasis 05/2005; 3(4):805. · 5.73 Impact Factor
• Article: Elevated levels of von Willebrand Factor in cirrhois support platelet adhesion despite reduced functional capacity

  J.A. Lisman, T N Bongers, J. Adelmeijer, H.L. Janssen, M.P. de Maat, Ph.G. de Groot, F W G Leebeek