Levels of prothrombin fragment F1+2 in patients with hyperhomocysteinemia and a history of venous thromboembolism.
Increased thrombin generation occurs in many individuals with inherited defects in the antithrombin or protein C anticoagulant pathways and is also seen in patients with thrombosis without a defined clotting abnormality. Hyperhomocysteinemia (H-HC) is an important risk factor of venous thromboembolism (VTE). We prospectively followed 48 patients with H-HC (median age 62 years, range 26-83; 18 males) and 183 patients (median age 50 years, range 18-85; 83 males) without H-HC for a period of up to one year. Prothrombin fragment F1+2 (F1+2) was determined in the patient's plasma as a measure of thrombin generation during and at several time points after discontinuation of secondary thromboprophylaxis with oral anticoagulants. While on anticoagulants, patients with H-HC had significantly higher F1+2 levels than patients without H-HC (mean 0.52 +/- 0.49 nmol/l, median 0.4, range 0.2-2.8, versus 0.36 +/- 0.2 nmol/l, median 0.3, range 0.1-2.1; p = 0.02). Three weeks and 3, 6, 9 and 12 months after discontinuation of oral anticoagulants, up to 20% of the patients with H-HC and 5 to 6% without H-HC had higher F1+2 levels than a corresponding age- and sex-matched control group. 16% of the patients with H-HC and 4% of the patients without H-HC had either F1+2 levels above the upper limit of normal controls at least at 2 occasions or (an) elevated F1+2 level(s) followed by recurrent VTE. No statistical significant difference in the F1+2 levels was seen between patients with and without H-HC. We conclude that a permanent hemostatic system activation is detectable in a proportion of patients with H-HC after discontinuation of oral anticoagulant therapy following VTE. Furthermore, secondary thromboprophylaxis with conventional doses of oral anticoagulants may not be sufficient to suppress hemostatic system activation in patients with H-HC.
Kyrle
P A
PA
Department of Internal Medicine I, University of Vienna, Austria.
Stümpflen
A
A
Hirschl
M
M
Bialonczyk
C
C
Herkner
K
K
Speiser
W
W
Weltermann
A
A
Kaider
A
A
Pabinger
I
I
Lechner
K
K
Eichinger
S
S
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage; D005260:Female; D006487:Hemostasis / Q000235:genetics; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis*; D011446:Prospective Studies; D011498:Protein Precursors / Q000032:analysis*; D011516:Prothrombin / Q000032:analysis*; D012008:Recurrence; D012307:Risk Factors; D012737:Sex Factors; D013924:Thrombophlebitis / Q000097:blood* / Q000188:drug therapy / Q000209:etiology
D000925:Anticoagulants; D010446:Peptide Fragments; D011498:Protein Precursors; D006710:Homocysteine; C029733:prothrombin fragment 1; C044183:prothrombin fragment 2; D011516:Prothrombin