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.
Clinical Haemostaseology, Medical Clinic I, University of Leipzig, Leipzig, Germany.
Thomas
T
Siegemund
Sirak
S
Petros
Annelie
A
Siegemund
Ute
U
Scholz
Lothar
L
Engelmann
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