Brief Overview of the Coagulation Cascade
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Brief Overview of the Coagulation Cascade Vandita Johari, MD, and Chandravathi Loke, MD Introduction The increasing number of indications for anticoagulation, as well as an increase in the number of therapeutic anticoagulants being made avail- able, makes it imperative for the modern-day practitioner to understand currently available coagulation testing and drug monitoring. Clinical testing includes a combination of clotting, immunologic, and chromo- genic assays, which screen for disorders of coagulation, whether they be genetic in origin or acquired because of either disease or anticoagulant therapy. A brief review of the pathways of coagulation and clot lysis, and the factors regulating them, will help in the understanding of how anticoagulant drugs work and how they can be monitored or, if necessary, their action reversed when toxicity is suspected. Brief Overview of Coagulation Thrombosis may be defined as the formation and propagation of a blood clot within the vasculature. Clinical thrombosis involves the following: 1. Blood flow and the blood vessels 2. Platelet–vessel interactions related to disruption of the endothelium 3. The coagulation system, in particular, the natural anticoagulants and the fibrinolytic system. 1 Thrombin is the final enzyme of the coagulation cascade and therefore the target of most of the anticoagulants. Generation of thrombin following vascular injury occurs in 2 waves of differing magnitude. During the initiation phase, small amounts of thrombin are generated, which prepares the coagulation cascade for the second larger thrombin burst. 1,2 Coagulation Cascade Two pathways of anticoagulation have been described— extrinsic/tissue factor pathway and the intrinsic/contact activation pathway (Fig 1). These Dis Mon 2012;58:421-423 0011-5029/2012 $36.00 0 http://dx.doi.org/10.1016/j.disamonth.2012.04.004 DM, August 2012 421
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Transcript of Brief Overview of the Coagulation Cascade
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Brief Overview of the CoagulationCascade
Vandita Johari, MD, and Chandravathi Loke, MD
ntroductionhe increasing number of indications for anticoagulation, as well as an
ncrease in the number of therapeutic anticoagulants being made avail-ble, makes it imperative for the modern-day practitioner to understandurrently available coagulation testing and drug monitoring. Clinicalesting includes a combination of clotting, immunologic, and chromo-enic assays, which screen for disorders of coagulation, whether they beenetic in origin or acquired because of either disease or anticoagulantherapy. A brief review of the pathways of coagulation and clot lysis, andhe factors regulating them, will help in the understanding of hownticoagulant drugs work and how they can be monitored or, if necessary,heir action reversed when toxicity is suspected.
rief Overview of CoagulationThrombosis may be defined as the formation and propagation of a blood
lot within the vasculature. Clinical thrombosis involves the following:
. Blood flow and the blood vessels
. Platelet–vessel interactions related to disruption of the endothelium
. The coagulation system, in particular, the natural anticoagulants andthe fibrinolytic system.1
Thrombin is the final enzyme of the coagulation cascade and thereforehe target of most of the anticoagulants. Generation of thrombin followingascular injury occurs in 2 waves of differing magnitude. During thenitiation phase, small amounts of thrombin are generated, which prepareshe coagulation cascade for the second larger thrombin burst.1,2
oagulation CascadeTwo pathways of anticoagulation have been described—extrinsic/tissue
actor pathway and the intrinsic/contact activation pathway (Fig 1). These
is Mon 2012;58:421-423011-5029/2012 $36.00 � 0
ttp://dx.doi.org/10.1016/j.disamonth.2012.04.004M, August 2012 421
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pathways converge, forming the common pathway, which results in thectivation of factor X to Xa.Coagulation is initiated by the interaction, in the extrinsic pathway, of
issue factor (TF) exposed by vascular injury with plasma factor VIIa,hich, in turn, activates IX and X, which results in the formation of small
mounts of thrombin. Thrombin, in turn, primes the intrinsic pathway,esulting in explosive generation of thrombin, which acts on fibrinogen toorm the fibrin clot. These reactions take place on phospholipid surfaces,sually the activated platelet surface.1,2
ntithrombotic MechanismsSeveral physiological antithrombotic mechanisms act in concert to keep
hrombosis in check under normal circumstances (Fig 1).Antithrombin III (AT-III) is the plasma protease inhibitor that neutral-
zes thrombin and other coagulation factors, such as XIa, IXa, and XaT-III, which is potentiated by heparin.Protein C is a plasma glycoprotein that is activated by thrombin that in
urn inactivates factors Va and VIIIa. This reaction is accelerated byrotein S.Tissue factor pathway inhibitor is a protease inhibitor that regulates
he extrinsic pathway by inhibiting TF/FVIIa initiation of coagula-
IG 1. Physiological downregulation of coagulation. (Color version of figure is availablenline.)
ion.1,2
22 DM, August 2012
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he Fibrinolytic SystemAny thrombin that escapes the inhibitory effects of the natural antico-
gulants described above converts soluble fibrinogen to insoluble fibrinnd activates factor XIII that stabilizes fibrin clot (Fig 2).The endogenous fibrinolytic system is then activated to clear fibrin toaintain patency of circulation. Plasmin is the major protease enzyme
hat is activated to digest fibrin-to-fibrin degradation products. Physio-ogical regulation of fibrinolysis occurs primarily via plasminogen acti-ator inhibitors and antiplasmin that inhibits plasmin.1,2
REFERENCES. Hoffbrand AV, Pettit JE. Essential Hematology. 3rd edn. Oxford, UK: Blackwell
Scientific Publications, 1993.. Goodnight SH Jr, Hathaway WE. Disorders of Hemostasis and Thrombosis, A
Clinical Guide. 2nd edn. New York, NY: McGraw-Hill, 2001.
IG 2. The fibrinolytic system. (Color version of figure is available online.)
M, August 2012 423
