The in vitro effect of recombinant factor VIIa on coated platelet formation and clot dynamics of stored platelet concentrates.
BACKGROUND
Storage can negatively impact the hemostatic potential of platelet concentrates (PCs) used for transfusion. At the site of vascular injury, normal platelets (PLTs) are hypothesized to change into highly procoagulant-coated PLTs upon costimulation with collagen and thrombin. We investigated whether activated recombinant factor VII (rFVIIa, NovoSeven, Novo Nordisk A/S) could improve the ability of stored PLTs to support coagulation under conditions that promote the formation of coated PLTs.


METHODS
PCs stored for 1, 4, 6, and 8 days were costimulated with thrombin and with convulxin, a collagen glycoprotein VI receptor agonist, to create coated PLTs. The effect of rFVIIa on the ability of stored PCs to form coated PLTs, generate thrombin, and impact clot dynamics was evaluated by flow cytometry, a plasma-based assay, and thrombelastography, respectively.


RESULTS
Coated PLT formation decreased significantly with increasing storage time (80% vs. 50%-55%, p < 0.05), and this was not affected by the addition of rFVIIa. rFVIIa accelerated thrombin generation (p < 0.001) and clot formation (p < 0.001) and significantly increased thrombin generation throughout the storage period (p < 0.001). Resistance to fibrinolysis was impaired at the end of storage, and this was not affected by the addition of rFVIIa.


CONCLUSIONS
rFVIIa accelerated thrombin and clot formation throughout storage, with the most pronounced effect observed in the PCs that had been stored for the shortest length of time (Day 1). Resistance to fibrinolysis was gradually impaired throughout the storage period and was not affected by the addition of rFVIIa.
Svendsen
Mette S
MS
Blood Bank, Department of Clinical Immunology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark.
Kristensen
Annemarie T
AT
Bochsen
Louise
L
Salado-Jimena
José A
JA
Johansson
Pär I
PI
D001777:Blood Coagulation / Q000187:drug effects*; D001792:Blood Platelets / Q000737:chemistry / Q000187:drug effects*; D003029:Coagulants / Q000494:pharmacology*; D003435:Crotalid Venoms / Q000737:chemistry; D015942:Factor VIIa / Q000494:pharmacology*; D005342:Fibrinolysis / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D037181:Lectins, C-Type / Q000737:chemistry; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013916:Thrombelastography; D013917:Thrombin / Q000737:chemistry
D003029:Coagulants; D003435:Crotalid Venoms; D037181:Lectins, C-Type; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; C028890:convulxin; C103587:recombinant FVIIa; D015942:Factor VIIa; D013917:Thrombin