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Thromb Haemost 1998; 79(02): 296-301
DOI: 10.1055/s-0037-1614981
Letters to the Editor
Schattauer GmbH

Initiation and Propagation of Blood Coagulation at Artificial Surfaces Studied in a Capillary Flow Reactor[*]

Ron Blezer
1   From the Dept. of Biochemistry
,
George M. Willems
2   From the Cardiovascular Research Institute Maastricht, Maastricht University
,
Patrick T. Cahalan
3   From the Dept. of Biomaterials Technology, Medtronic Bakken Research Center, Maastricht, The Netherlands
,
Theo Lindhout
1   From the Dept. of Biochemistry
2   From the Cardiovascular Research Institute Maastricht, Maastricht University
› Author Affiliations
Further Information

Publication History

Received 26 May 1997

Accepted after revision 16 September 1997

Publication Date:
08 December 2017 (online)

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Summary

We have made use of a novel flow reactor to study the initiation and propagation of the ex vivo blood coagulation processes at artificial surfaces. The flow reactor consisted of a primary glass or polymer capillary that is connected to a secondary glass capillary, which inner wall was coated with a phospholipid bilayer of 25 mol% dioleoylphosphatidylserine/75 mol% dioleoylphosphatidylcholine (DOPS/DOPC). Citrated platelet free plasma and a CaCl2 solution were delivered by syringe pumps and mixed just before the entrance of the flow reactor. The outflowing plasma was assayed for factor XIa, factor IXa, factor Xa and thrombin activity. Perfusion of recalcified plasma through a bare glass capillary resulted in a transient generation of fluid phase factor XIa. In contrast, factor IXa production increased slowly to attain a stable steady-state level. We established that surface-bound factor XIa was responsible for a continuous production of factor IXa. Factor IXa-induced generation of factor Xa and thrombin was only observed when contact activated plasma was subsequently perfused through a DOPS/DOPC-coated capillary, showing that propagation of the factor IXa trigger requires a procoagulant, phosphatidylserine-containing, phospholipid membrane. The negatively charged inner surface of a heparin-coated polyurethane capillary, generated like the glass capillary significant amounts of factor XIa and factor IXa when perfused with recalcified plasma. No differences were found between unfractionated heparin and heparin devoid of anticoagulant activity. Thus, it is concluded that contact activation and factor IXa generation in flowing plasma is not inhibited by immobilised anticoagulant active heparin. Consequently, factor IXa-dependent thrombin generation at a downstream located phospholipid membrane was similar, regardless the specific anticoagulant activity of immobilised heparin.

* Supported by grant 902-26-192 from the Dutch Organization for Scientific Research (NWO)


 

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