Thrombin generation in severe haemophilia A and B: the endogenous thrombin potential in platelet-rich plasma.
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.
Siegemund
Thomas
T
Clinical Haemostaseology, Medical Clinic I, University of Leipzig, Leipzig, Germany.
Petros
Sirak
S
Siegemund
Annelie
A
Scholz
Ute
U
Engelmann
Lothar
L
D000328:Adult; D001777:Blood Coagulation; D001792:Blood Platelets / Q000502:physiology*; D016022:Case-Control Studies; D005164:Factor IX / Q000502:physiology; D005169:Factor VIII / Q000502:physiology; D006467:Hemophilia A / Q000097:blood*; D002836:Hemophilia B / Q000097:blood*; D006801:Humans; D007700:Kinetics; D008875:Middle Aged; D008962:Models, Theoretical; D013050:Spectrometry, Fluorescence; D013917:Thrombin / Q000032:analysis* / Q000096:biosynthesis / Q000502:physiology
D005169:Factor VIII; D005164:Factor IX; D013917:Thrombin