Plasma levels of factor XII, prekallikrein and high molecular weight kininogen in normal blood donors and patients having suffered venous thrombosis.
BACKGROUND
The contact system proteins factor XII (FXII), prekallikrein (PK) and high molecular weight kininogen (HK) have roles in coagulation, fibrinolysis, thrombin-induced platelet activation, cell adhesion and angeogenisis. It has been suggested that inherited or acquired deficiencies of these proteins may be risk factors for thrombosis. Studies on the levels of FXII in plasma from normal and thrombotic patient populations have been reported, to our knowledge however, no systematic study on plasma levels of PK and HK in large populations of normal blood donors and patients having had venous thrombotic events has been performed.


METHODS
Chromogenic substrate assays were used to measure plasma levels of FXII, PK and HK in 300 normal blood donors (ND) and 300 patients attending our anticoagulant clinic who had a history of venous thrombosis (deep vein thrombosis or pulmonary embolism [VT]). All subjects were Caucasian, antiphospholipid antibody negative and had normal liver function.


RESULTS
Mean values +/- SD were: FXII: ND 99.4 +/- 26.7%: VT 91.0 +/- 27.2%: PKK: ND 99.7 +/- 19.8%: VT 99.1 +/- 21.2%: HK: ND 101.0 +/- 20.5%: VT 110.7 +/- 32.3%. Statistical analysis of the data revealed significantly lower (p< or =0.001) mean values for FXII and significantly higher (p< or =0.001) mean values for HK in the VT group. Calculated lower limits of normal for each parameter were: FXII: 49.1%, PKK: 66.8%, HK: 63.4%. The prevalence of values below the lower limit of normal were FXII-ND 2.3%: FXII-VT 8.0%, PKK-ND 3.0%: PKK-VT 4.7%, HK-ND 2.3%: HK-VT 5.0%. No homozygous deficiency patients were found for any parameter. One VT patient had combined FXII and HK deficiency and one ND and two VT patients had combined PK and HK deficiency.


CONCLUSIONS
FXII levels were lower and HK levels and the prevalence of FXII, PK and HK deficiency higher in a population of patients with a history of VT than in a population of healthy blood donors.
Kent Haemophilia Centre, Kent and Canterbury Hospital, Ethelbert Road, Canterbury, Kent CT1 3NG, UK. mikejgallimore@aol.com
Michael J
MJ
Gallimore
Simon L
SL
Harris
David W
DW
Jones
Mark
M
Winter
D015415:Biomarkers / Q000097:blood; D001782:Blood Donors / Q000706:statistics & numerical data*; D004198:Disease Susceptibility / Q000097:blood / Q000453:epidemiology; D005174:Factor XII / Q000032:analysis*; D005260:Female; D006801:Humans; D015994:Incidence; D019679:Kininogen, High-Molecular-Weight / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D011288:Prekallikrein / Q000032:analysis*; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D017678:Sex Distribution; D006113:United Kingdom / Q000453:epidemiology; D020246:Venous Thrombosis / Q000097:blood* / Q000453:epidemiology*
D015415:Biomarkers; D019679:Kininogen, High-Molecular-Weight; D005174:Factor XII; D011288:Prekallikrein