Recombinant factor VIIa (Novoseven) restores deficient coagulation: experience from an ex vivo model.
The action of recombinant factor VIIa (rFVIIa) in coagulation deficiencies with increased risk of bleeding was investigated using in vitro perfusion. Blood samples were drawn from healthy donors, a patient with hemophilia A and inhibitors, and six patients undergoing oral anticoagulant treatment. Fragmin 10 U/mL was used as anticoagulant. rFVIIa (10 microg/mL in plasma) was added to blood samples, incubated for 1 minute at 37 degrees C, and perfusion studies performed for 10 minutes at 600 x s(-1) through annular chambers containing damaged vascular segments. Subendothelial fibrin and platelets were expressed as a percentage of subendothelial surface screened. Under different conditions, rFVIIa consistently restored or improved fibrin formation on the damaged vascular subendothelium exposed to circulating blood. It restored fibrin deposition in blood from the hemophilia A patient; in patients undergoing acenocoumarol treatment, it reduced the international normalized ratio (INR) from 2.47 to 1.25 with a significant increase in fibrin deposition. Platelet deposition varied slightly between clinical conditions but was less evident in the hemophilia A patient. These data support the concept that rFVIIa facilitates fibrin formation in these clinical situations, promoting procoagulant activity at sites of vascular damage where tissue factor is exposed. This could improve hemostasis in patients with hemophilia A and inhibitors, and in patients treated with oral anticoagulants.
Galán
A M
AM
Servicio de Hemoterapia-Hemostasia, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain.
Tonda
R
R
Altisent
C
C
Maragall
S
S
Ordinas
A
A
Escolar
G
G
D000328:Adult; D000925:Anticoagulants / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects; D003029:Coagulants / Q000494:pharmacology / Q000627:therapeutic use; D017985:Dalteparin / Q000494:pharmacology; D005167:Factor VII / Q000494:pharmacology* / Q000627:therapeutic use; D015942:Factor VIIa; D005337:Fibrin / Q000378:metabolism; D006467:Hemophilia A / Q000097:blood; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D010477:Perfusion; D010974:Platelet Aggregation / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D013314:Stress, Mechanical; D013921:Thrombocytopenia / Q000188:drug therapy*
D000925:Anticoagulants; D003029:Coagulants; D011994:Recombinant Proteins; D005167:Factor VII; D005337:Fibrin; C103587:recombinant FVIIa; D015942:Factor VIIa; D017985:Dalteparin