Review Article Overview of the coagulation system Address for correspondence: Sanjeev Palta, Richa Saroa, Anshu Palta1 Dr. Sanjeev Palta, Departments of Anaesthesiology and Intensive Care and 1Pathology, Government Medical College and Department of Anaesthesiology Hospital, Chandigarh, India and Intensive Care, Government Medical College and Hospital, Chandigarh, India. ABSTRACT E-mail: sanjeev_palta@yahoo. com Coagulation is a dynamic process and the understanding of the blood coagulation system has evolved over the recent years in anaesthetic practice. Although the traditional classification of the coagulation system into extrinsic and intrinsic pathway is still valid, the newer insights into coagulation provide more authentic description of the same. Normal coagulation pathway represents a balance between the pro coagulant pathway that is responsible for clot formation and the Access this article online mechanisms that inhibit the same beyond the injury site. Imbalance of the coagulation system may Website: www.ijaweb.org occur in the perioperative period or during critical illness, which may be secondary to numerous factors leading to a tendency of either thrombosis or bleeding. A systematic search of literature on DOI: 10.4103/0019-5049.144643 PubMed with MeSH terms ‘coagulation system, haemostasis and anaesthesia revealed twenty Quick response code eight related clinical trials and review articles in last 10 years. Since the balance of the coagulation system may tilt towards bleeding and thrombosis in many situations, it is mandatory for the clinicians to understand physiologic basis of haemostasis in order to diagnose and manage the abnormalities of the coagulation process and to interpret the diagnostic tests done for the same. Key words: Anaesthesia, Coagulation system, haemostasis INTRODUCTION It is important for a perioperative physician to understand the intricacies of two systems (more so in The concept of blood coagulation dates back to 1960’s a preexisting haematological disorder) that go side by when Davie, Ratnoff and Macfarlane described the side in maintaining the circulating blood in a fluidic “waterfall” and “cascade” theories outlining the state. fundamental principle of cascade of proenzymes leading to activation of downstream enzymes.[1] Pathological situations requiring surgery or anaesthesia Haemostasis, defined as arrest of bleeding, comes from or any other invasive procedure trigger the haemostatic Greek, haeme meaning blood and stasis meaning system. This balance is also disturbed by trauma, to stop.[2] This thrombohaemmorhagic balance is cytokines or infectious agents. Thus, the perioperative maintained in the body by complicated interactions period is at high risk for both prohaemorrhagic and between coagulation and the fibrinolytic system as prothrombotic abnormalities. Hypoxia, hypothermia, well as platelets and vessel wall. metabolic acidosis and extracorporeal circulation may also further aggravate the situation.[4] Usually, the coagulation process is under the inhibitory control of several inhibitors that limit the clot Coagulopathy, may also be encountered by the formation, thus avoiding the thrombus propagation. intensivist due to physiological disturbances, This delicate balance is interrupted whenever the disturbances in the primary haemostasis, abnormalities procoagulant activity of the coagulation factors is of blood, plasma or due to disseminated intravascular increased, or the activity of naturally occurring coagulation (DIC).[5] inhibitors is decreased.[3] Some of the thrombogenic and antithrombogenic components are listed in This review aims to simplify the understanding of Table 1. the coagulation system as a whole as well as discuss How to cite this article: Palta S, Saroa R, Palta A. Overview of the coagulation system. Indian J Anaesth 2014;58:515-23. Indian Journal of Anaesthesia | Vol. 58 | Issue 5 | Sep-Oct 2014 515 Palta, et al.: Overview: Coagulation system Table 1: Thrombogenic and antithrombogenic Normally platelets do not adhere to intact vascular components in the body endothelium. Subsequent to the vascular injury, Site Thrombogenic Antithrombogenic platelets adhere to collagen and vWF in the Vessel wall Exposed endothelium Heparin subendothelial tissue and undergo a morphological TF Thrombomodulin change by assuming irregular surface, forming Collagen Tissue plasminogen activator Circulating Platelets Antithrombin numerous pseudopods thus drastically increasing [10] elements Platelet activating factor Protein C and S their surface area. The formation of the platelet plug Clotting factor Plasminogen involves a series of steps: Prothrombin Fibrinogen Platelet adhesion vWF After vascular injury vWf acts as a bridge between vWF – Von Willebrand factor; TF – Tissue factor endothelial collagen and platelet surface receptors GpIb and promotes platelet adhesion.[9] The platelet various abnormalities of the same, which may have an glycoprotein complex I (GP-Ib) is the principal receptor impact in the perioperative period and ICU.They can be for vWF. classified as those that affect the primary haemostasis, the coagulation pathways and the fibrinolytic system. Platelet secretion After adhesion, degranulation from both types of PRIMARY HAEMOSTASIS granules takes place with the release of various factors. Release of calcium occurs here. Calcium binds to the Primary haemostasis results from complex interactions phospholipids that appear secondary to the platelet between platelets, vessel wall and adhesive proteins activation and provides a surface for assembly of leading to the formation of initial ‘platelet plug’. The various coagulation factors. endothelial cells lining the vascular wall exhibit the antithrombotic properties due to multiple factors viz: Platelet aggregation negatively charged heparin-like glycosaaminoglycans, Thromboxane A2 produced by activated platelets neutral phospholipids, synthesis and secretion provide stimulus for further platelet aggregation. of platelet inhibitors, coagulation inhibitors and TxA2 along with ADP enlarge this platelet aggregate fibrinolysis activators. In contrast, subendothelial leading to the formation of the platelet plug, which layer is highly thrombogenic and contains collagen, seals off vascular injury temporarily. ADP binding also Von Willebrand factor (vWF) and other proteins like causes a conformational change in GpIIb/IIIa receptors laminin, thrombospondin and vitronectin that are presents on the platelet surface causing deposition of involved in platelet adhesion. Any vascular insult fibrinogen. Thrombin generation also catalyses the results in arteriolar vasospasm, mediated by reflex conversion of this fibrinogen to fibrin which adds to neurogenic mechanisms and release of local mediators the stability of the platelet plug and is now known as like endothelin and platelet-derived thromboxane secondary haemostasis.[9] A2 (TxA2).[6-8] Prostacyclin inhibits platelet aggregation (platelet anti Platelets are disc shaped, anucleate cellular fragments aggregating effect) and the balance between TxA2 and derived from megakaryocytes. They have a pivotal role prostacyclin leads to localized platelet aggregation thus in haemostasis by forming the initial haemostatic plug preventing extension of the clot thereby maintaining that provides a surface for the assembly of activated the vessel lumen patency.[6,11] coagulation factors leading to the formation of fibrin stabilized platelet aggregates and subsequent clot COAGULATION DISORDERS INVOLVING PRIMARY retraction. Platelets have two types of granules: HEMOSTASIS • α granules-contain P-selectin, fibrinogen, fibronectin, factor V, factor VIII, platelet factor Defects of primary haemostasis may be due to IV, platelet-derived growth factor and tumour abnormalities of the vessel wall or qualitative/ growth factor-α (TGF-α)[9] quantitative defects of platelets that may cause • δ granules or Dense granules-contain adenosine bleeding in varying severity. triphosphate (ATP), adenosine diphosphate (ADP), calcium (Ca), serotonin, histamine and Thrombocytopenia may be observed secondary to epinephrine.[9] numerous causes listed in Table 2. The inherited platelet 516 Indian Journal of Anaesthesia | Vol. 58 | Issue 5 | Sep-Oct 2014 Palta, et al.: Overview: Coagulation system Table 2: Disorders of primary haemostasis COAGULATION PATHWAYS Bleeding disorders due to vessel wall abnormalities Septicaemia The coagulation proteins are the core components of Drug reactions the coagulation system that lead to a complex interplay Scurvy and the Ehlers-Danlos syndrome of reactions resulting in the conversion of soluble Henoch-Schönlein purpura fibrinogen to insoluble fibrin strands. Perivascular amyloidosis Bleeding disorders due to reduced platelet number (thrombocytopenia) CLOTTING FACTORS (COAGULATION PROTEINS) Leading to decreased production Vitamin B12 deficiency Majority of clotting factors are precursors of proteolytic Aplastic anaemia enzymes known as zymogens that circulate in an Leukaemia inactive form. The activation of each zymogen is Chromic immune thrombocytopenic purpura depicted by suffixing letter “a” to the Roman numeral Leading to decreased platelet survival identifying that particular zymogen. Most of the Acute immune thrombocytopenic purpura Systemic lupus erythematosus procoagulants and anticoagulants are produced by Drug-associated: Quinidine, heparin, sulpha compounds liver except factor III, IV and VIII. These proteins Infections: HIV, dengue fever undergo a post translational modification