Tranexamic acid combined with recombinant factor VIII increases clot resistance to accelerated fibrinolysis in severe hemophilia A.
BACKGROUND
Most patients with severe hemophilia A suffer from a profoundly compromised hemostatic response. In addition to both the delayed and slow development of a clot, previous studies have documented that severe hemophilia A is also associated with reduced clot stability.


OBJECTIVE
We examined whether the clot stability in hemophiliacs could be improved by treatment with tranexamic acid (TXA) in combination with recombinant factor VIII (rFVIII).


METHODS
Baseline blood samples were obtained from eight males with severe hemophilia A. Thereafter, a bolus injection of rFVIII was administered to increase the functional level of FVIII to approximately 50%. After 10 min, blood was collected followed by an intravenous injection of TXA. A third blood sample was obtained after a further 10 min. Whole blood clotting profiles were determined by thrombelastography using minimal tissue factor activation. Clot formation was assessed by both clot initiation and clot propagation. At clot termination, the maximum clot firmness and area under the elasticity curve were used to illustrate clot stability. Tissue-plasminogen activator was included in those experiments designed to assess clot stability.


RESULTS
As expected, rFVIII increased clot formation, whereas TXA had no effect upon this parameter. Assays including tissue-plasminogen activator revealed that rFVIII increased the maximum clot firmness 3-fold; whereas the presence of TXA induced an additional 4-fold increase. The area under the elasticity curve increased 5-fold after rFVIII and 24-fold after addition of TXA.


CONCLUSIONS
The study demonstrates that simultaneous treatment with TXA and rFVIII significantly improves the clot stability in patients with hemophilia A.
Center for Hemophilia and Thrombosis, Department of Clinical Biochemistry, Aarhus University Hospital, Skejby, Brendstrupgaardsvej 100, Aarhus N, Denmark. am.hvas@dadlnet.dk
A-M
AM
Hvas
H T
HT
Sørensen
L
L
Norengaard
K
K
Christiansen
J
J
Ingerslev
B
B
Sørensen
D000328:Adult; D000933:Antifibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects*; D004359:Drug Therapy, Combination; D005169:Factor VIII / Q000494:pharmacology / Q000627:therapeutic use*; D005342:Fibrinolysis / Q000187:drug effects*; D006467:Hemophilia A / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008297:Male; D011994:Recombinant Proteins / Q000627:therapeutic use; D012720:Severity of Illness Index; D013916:Thrombelastography; D013925:Thromboplastin / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014148:Tranexamic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014914:Whole Blood Coagulation Time
D000933:Antifibrinolytic Agents; D011994:Recombinant Proteins; D014148:Tranexamic Acid; C078147:F8 protein, human; D005169:Factor VIII; D013925:Thromboplastin; D010959:Tissue Plasminogen Activator