Effects on thrombin generation of single injections of Hirulog in patients with calf vein thrombosis.
OBJECTIVE
To determine whether single injections of Hirulog, a direct thrombin inhibitor, can inhibit thrombin generation in patients with calf vein thrombosis and, if so, if the inhibition is sustained.


METHODS
Phase II open label cohort study.


METHODS
Tertiary-care referral centres, university affiliated hospitals.


METHODS
10 patients with venographically-demonstrated calf vein thrombosis.


METHODS
Patients received a single injection of Hirulog, either 1.0 mg/kg subcutaneously or 0.6 mg/kg as a 15 min intravenous infusion. Prothrombin fragment (F1++2) levels, as an index of thrombin generation, were measured before as well as 6 h post- and 24 h post-Hirulog administration. Patients were followed with non-invasive tests to detect thrombus extension into the proximal veins.


RESULTS
There was a significant reduction in the levels of F1+2 with both regimens, 6 h after Hirulog. The F1+2 levels 24 h post-Hirulog showed a significant increase relative to the 6 h post-Hirulog results. One patient developed thrombus extension into the popliteal vein and was treated with conventional anticoagulants.


CONCLUSIONS
The single injections of Hirulog used in the study produced incomplete and temporary suppression of F1+2. Complete and permanent inhibition of thrombin generation with Hirulog in patients with calf vein thrombosis may require higher doses, multiple subcutaneous injections and/or prolonged intravenous infusion.
Ginsberg
J S
JS
Department of Medicine, McMaster University, Hamilton, Canada.
Nurmohamed
M T
MT
Gent
M
M
MacKinnon
B
B
Stevens
P
P
Weitz
J
J
Maraganore
J
J
Hirsh
J
J
D000368:Aged; D015331:Cohort Studies; D005260:Female; D024764:Hirudin Therapy; D006629:Hirudins / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D010446:Peptide Fragments / Q000008:administration & dosage / Q000032:analysis / Q000627:therapeutic use*; D011516:Prothrombin / Q000032:analysis; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D013924:Thrombophlebitis / Q000097:blood / Q000188:drug therapy*; D017211:Treatment Failure
D006629:Hirudins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C045879:prothrombin fragment 1.2; D011516:Prothrombin; D013917:Thrombin; C074619:bivalirudin