Microfluidic assay of hemophilic blood clotting: distinct deficits in platelet and fibrin deposition at low factor levels

作者：Colace T V; Fogarty P F; Panckeri K A; Li R; Diamond S L^*

来源：Journal of Thrombosis and Haemostasis, 2014, 12(2): 147-158.

DOI：10.1111/jth.12457

• blood coagulation
• hemophilia
• hemostasis
• microfluidics
• platelets

BackgroundCoagulation factor deficiencies create a range of bleeding phenotypes. Microfluidic devices offer controlled hemodynamics and defined procoagulant triggers for measurement of clotting under flow.
ObjectivesWe tested a flow assay of contact pathway-triggered clotting to quantify platelet and fibrin deposition distal of dysfunctional thrombin production. Microfluidic metrics were then compared with PTT or % factor activity assays.
MethodsWhole blood (WB) treated with low level corn trypsin inhibitor (4gmL(-1)) from nine healthy donors and 27 patients (deficient in factor [F] VIII, 19 patients; FIX, one patient; FXI, one patient; VWF, six patients) was perfused over fibrillar collagen at wall shear rate=100s(-1).
ResultsUsing healthy WB, platelets deposited within 30s, while fibrin appeared within 6min. Compared with healthy controls, WB from patients displayed a 50% reduction in platelet deposition only at <1% factor activity. In contrast, striking defects in fibrin deposition occurred for patients with <13% factor activity (or PTT >40s). Full occlusion of the 60-m high channel was completely absent over the 15-min test in patients with <1% factor activity, while an intermediate defect was present in patients with >1% factor.
ConclusionSpontaneous bleeding in patients with <1% factor activity may be linked to deficits in both platelet and fibrin deposition, a risk known to be mitigated when factor levels are raised to >1% activity (PTT of similar to 40-60s), a level that does not necessarily rescue fibrin formation under flow.

• 出版日期2014-2
• 单位河北医科大学