Microfluidic assay of hemophilic blood clotting: distinct deficits in platelet and fibrin deposition at low factor levels.
J Thromb Haemost
; 12(2): 147-58, 2014 Feb.
Article
em En
| MEDLINE
| ID: mdl-24261634
ABSTRACT
BACKGROUND:
Coagulation factor deficiencies create a range of bleeding phenotypes. Microfluidic devices offer controlled hemodynamics and defined procoagulant triggers for measurement of clotting under flow.OBJECTIVES:
We 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.METHODS:
Whole blood (WB) treated with low level corn trypsin inhibitor (4 µg mL⻹) 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 = 100 s⻹.RESULTS:
Using healthy WB, platelets deposited within 30 s, while fibrin appeared within 6 min. 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 > 40 s). Full occlusion of the 60-µm 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.CONCLUSION:
Spontaneous 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 ~40-60 s), a level that does not necessarily rescue fibrin formation under flow.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Coagulação Sanguínea
/
Plaquetas
/
Fibrina
/
Microfluídica
/
Hemofilia A
Limite:
Humans
Idioma:
En
Revista:
J Thromb Haemost
Assunto da revista:
HEMATOLOGIA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos