Conventional and near-patient testsof coagulation
Andy NG Curry MA MB BChir FRCA JM Tom Pierce MRCP FRCA
Preoperative anticoagulation or perioperativecoagulopathy secondary to trauma, massivetransfusion, sepsis, cardiopulmonary bypass(CPB) or hypothermia may impair haemostasis.Under such circumstances, reducing the turnaround time (TAT) between sampling and theresult of coagulation tests could reduce inap-propriate blood product administration bycorrect targeting of speciﬁc coagulationdeﬁciencies.
In this article, we shall describesome of the devices currently available for near-patient testing (NPT) of coagulation that havethe potential to reduce coagulation result TAT.Before considering NPT of coagulation, it isnecessary to consider standard laboratory tests of coagulation and their relationship to our currentunderstanding of the coagulation process. Byconvention, we will describe coagulation factors(F) by their Roman numerals and activatedfactors as ‘a’.
Haemostasis and thecell-based modelof coagulation
Under normal circumstances, coagulation isinitiated within seconds of a breach in the vas-culature, with platelets forming a plug at thesite of injury; this is termed primary haemo-stasis. Secondary haemostasis involves acomplex interaction between plasma coagu-lation factors, resulting in the formation of ﬁbrin strands to strengthen the platelet plug.This provides a mechanism of ampliﬁcation togenerate the necessary quantities of ﬁbrin. Inorder to clot, 100 ml of blood requires 0.2 mgof FVIII, 2 mg FX, 15 mg of prothrombin (FII)and 250 mg of ﬁbrinogen (FI). Propagation of haemostasis throughout the vasculature is pre-vented by inhibitors, of which tissue-factorpathway inhibitor (TFPI), protein C and antith-rombin are the most important.
Secondary haemostasis was classicallydescribed in terms of intrinsic and extrinsicpathways uniting at a ﬁnal common pathway.This model is useful to understand the actions of therapeutic anticoagulants and the derivation of the prothrombin time (PT) and activated partialthromboplastin time (APTT). In reality, this
model disregards the interaction betweenprimary and secondary haemostasis and does notcorrelate well with the
process. The minorrole that the contact factor pathway (extrinsicpathway) plays in initiation of clot formation
is illustrated by patients with severedeﬁciencies of high molecular weight kininogen(HMWK), prekallikrein and FXII; all have aprolonged APTT but no bleeding disorder.The currently accepted model of coagulationhas been updated, more closely reﬂecting
activity. This cell-based model placestissue factor-VIIa complex as pivotal ininitiation and highlights the importance of platelet activity and recognises the key role of thrombin in both promoting and inhibitingcoagulation. Rather than covering in detail thecurrently accepted view of haemostasis, wedirect the reader to consult the article byBombeli and Spahn
or the chapter by Laffan.
The process involves ﬁve steps (Fig. 1):initiation, ampliﬁcation, propagation, stabilis-ation, and inhibition of further coagulation.
: Tissue factor (TF) binds to circu-lating FVIIa and, in the presence of FV, con-verts FIX to FIXa, and FX to FXa. FXa bindsto prothrombin to generate a small amount of thrombin. In health, only 1% of total circulat-ing FVII is present as FVIIa and available forthe ﬁrst step of initiation.
: The small amount of throm-bin generated by initiation is insufﬁcient toconvert ﬁbrinogen to ﬁbrin. Thrombin-triggeredfeedback mechanisms occur principally on theactivated platelet surface, as follows:1. TF, thrombin, FIXa, FXa complex activatesmore FVII.
Laboratory methods useplatelet poor plasma; near-patient testing (NPT) useswhole blood.NPT should be thought of asexpressing the effects of theprothrombin time orinternational normalized ratioand activated partialthromboplastin time oractivated thromboplastin ratiorather than measuring them.The complexity of thecoagulation system is unlikelyto be adequately expressed bythe relatively crude teststypically used.The thromboelastogram is oneof the few tests to representﬁbrinolysis.NPT has the potential toreduce inappropriate bloodproduct administration.
Andy NG Curry MA MB BChir FRCA
Specialist Registrar in AnaesthesiaShackleton Department of AnaesthesiaSouthampton General HospitalTremona RoadSouthampton SO16 6YDUK
JM Tom Pierce MRCP FRCA
Consultant Cardiac AnaesthetistShackleton Department of AnaesthesiaSouthampton General HospitalTremona RoadSouthampton SO16 6YDUK Tel: 023 8079 6135Fax: 023 8079 4348E-mail: email@example.com (for correspondence)
doi:10.1093/bjaceaccp/mkm002Continuing Education in Anaesthesia, Critical Care & Pain | Volume 7 Number 2 2007
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