Thrombin generation in severe haemophilia A and B: the endogenous thrombin potential in platelet-rich plasma

Thromb Haemost. 2003 Nov;90(5):781-6. doi: 10.1160/TH03-01-0027.

Abstract

Thrombin generation was investigated in platelet-rich plasma (PRP) from 11 healthy controls, 17 patients with severe haemophilia A and 7 patients with severe haemophilia B. Mean endogenous thrombin potential (ETP) in arbitrary fluorescence units (FU) was 226.9 +/- 44.6, 186.4 +/- 22.5, 154.2 +/- 41.3 in controls, haemophilia A and B, respectively, all at a platelet count of 200 x 10(9)/l (p = 0.004 for controls vs. haemophilia A, p = 0.003 for controls vs. haemophilia B, no significant difference between haemophilia A and B). The contribution of FVIII to thrombin generation in haemophilia A was 1.31 +/- 0.16 FU/% of FVIII:C activity, while for FIX in haemophilia B this was 0.80 +/- 0.21 FU/% of FIX activity. There was an almost linear relationship between increasing platelet count and thrombin generation up to a mean platelet count of 100 x 10(9)/l. Further increase in platelet count has only a marginal influence on thrombin generation. Platelets increase ETP in haemophilia A by 0.184 +/- 0.022 FU/10(9) platelets/l and in haemophilia B by 0.319 +/- 0.085 FU/10(9) platelets/l, and this was significantly different between the two groups (p = 0.0002). This influence of plate-lets diminishes with increasing concentration of either FVIII or FIX. In conclusion, there is a difference in thrombin generation between haemophilia A and B, and this may be attributed to the role of platelets in the assembly of the tenase complex on their surface.

MeSH terms

  • Adult
  • Blood Coagulation
  • Blood Platelets / physiology*
  • Case-Control Studies
  • Factor IX / physiology
  • Factor VIII / physiology
  • Hemophilia A / blood*
  • Hemophilia B / blood*
  • Humans
  • Kinetics
  • Middle Aged
  • Models, Theoretical
  • Spectrometry, Fluorescence
  • Thrombin / analysis*
  • Thrombin / biosynthesis
  • Thrombin / physiology

Substances

  • Factor VIII
  • Factor IX
  • Thrombin