Platelet full length TFPI-α in healthy volunteers is not affected by sex or hormonal use.
BACKGROUND
Only 10% of plasma TFPIα (TFPI) exists in the full length form, the rest circulates as a C-terminally truncated form. However, blood platelets exclusively contain full length TFPI, which is released at the site of injury upon platelet activation, and which could play an important local regulatory role in thrombin generation and prevention of thrombosis.


METHODS
The anticoagulant activities of full length and truncated TFPI were investigated using thrombin generation assays. Blood samples were obtained from 30 healthy volunteers (10 male subjects, 10 female subjects, and 10 females using oral contraceptives). Platelet TFPI was released in platelet rich plasma and in platelet isolates using convulxin or thrombin, and measured by free TFPI ELISA and thrombin generation assays.


RESULTS
Full length TFPI and platelet TFPI were much more potent inhibitors of thrombin generation than truncated TFPI, which was virtually inactive. Although mean plasma TFPI antigen levels decreased from men (0.30 nM) to women (0.20 nM) to women using oral contraceptives (0.11 nM), no relevant differences were found in platelet TFPI among those subgroups.


CONCLUSIONS
Platelets release similar amounts of TFPI regardless of plasma TFPI concentrations and is unaffected by sex or oral contraceptive use. We speculate that platelet TFPI is important to prevent systemic coagulation and thrombosis and restrict thrombus formation to the site of the growing platelet plug. The stable contribution of platelet TFPI to the anticoagulant potential in plasma is likely to become particularly relevant under conditions of low plasma TFPI levels in combination of oral contraceptives use.
Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands.|Department of Internal Medicine, CARIM, Maastricht University Medical Centre, Maastricht, the Netherlands.
Kristien
K
Winckers
Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands.
Stella
S
Thomassen
Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands.|Department of Internal Medicine, CARIM, Maastricht University Medical Centre, Maastricht, the Netherlands.
Hugo
H
Ten Cate
Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands.
Tilman M
TM
Hackeng
D000293:Adolescent; D000328:Adult; D001777:Blood Coagulation / Q000502:physiology; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008074:Lipoproteins / Q000097:blood* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000502:physiology; D012737:Sex Factors; D013917:Thrombin / Q000378:metabolism; D055815:Young Adult
D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D013917:Thrombin