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[Haemophilia] Recombinant factor VIIa addition to haemophilic blood perfused over collagen/tissue factor can sufficiently bypass the factor IXa/VIIIa defect to rescue fibrin generation

May 9, 2017





Factor VIII (FVIII) or factor IX (FIX)-deficient haemophilic patients display deficits in platelet and fibrin deposition under flow detectable in microfluidics. Compared to fibrin generation, decreased platelet deposition in haemophilic blood flow is more easily rescued with recombinant factor VIIa (rFVIIa), whereas rFVIIa requires FXIIa participation to generate fibrin when tissue factor (TF) is absent.



Perfusion of haemophilic whole blood (WB) over collagen/TF surfaces was used to determine whether rFVIIa/TF was sufficient to bypass poor FIXa/FVIIIa function in blood from patients with haemophilia A and B.



Whole blood treated with high-dose corn trypsin inhibitor (40 μg mL−1) from seven healthy donors and 10 patients was perfused over fibrillar collagen presenting low or high TF (TFlow or TFhigh) at wall shear rate of 100 s−1.



With WB from healthy controls, platelet deposition and fibrin accumulation increased as TF increased. Factor-deficient WB (1–3% of normal) displayed striking deficits in platelet deposition and fibrin formation at either TFlow or TFhigh. In contrast, mildly factor-deficient WB (14–32%) supported fibrin formation under flow on TFhigh/collagen. With either TFlow or TFhigh, exogenously added rFVIIa (20 nm) increased platelet deposition and fibrin accumulation in WB from factor-deficient patients (1–3% of normal) to levels commensurate with untreated healthy WB.



The absence of FIXa/FVIIIa in patients with severe haemophilia results in deficits in fibrin formation that cannot be rescued by wall-derived TF ex vivo. The effects of rFVIIa on platelet adhesion and rFVIIa/TF can act together to reinforce thrombin generation, platelet deposition and fibrin formation under flow.


R. Li,, K. A. Panckeri,, P. F. Fogarty,, A. Cuker,, S. L. Diamond
First published: 5 May 2017
DOI: 10.1111/hae.13259


Link: http://onlinelibrary.wiley.com/doi/10.1111/hae.13259/abstract



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