An Overview Of Haemostasis: Systems, Processes, And Laboratory Tests

Systems that Provide Haemostasis

Discuss about the Haemostasis for Pro-coagulation and Fibrinolysis.

Haemostasis can be defined as the psychological response of the body to stop bleeding and prevent haemorrhage. The aim of haemostasis is to ensure that blood remains in its state of fluidity within the vascular system (Hoppe, 2014). This process relies on a chain of events that involves platelets, blood cells and the activation of coagulation factors. Haemostasis is fundamental to maintaining the integrity of the vascular system. Understanding haemostasis helps in gaining an in-depth insight into some of the conditions that are associated with thrombosis. In this essay, we will discuss and explain haemostasis and provide an overview of the systems that interact to enhance haemostasis. Insufficient haemostasis can lead to hemorrhage while excessive haemostasis can cause thrombosis (Hoppe, 2014). It consists of primary haemostasis, secondary haemostasis and fibrinolysis. Additionally, we will talk about primary and secondary haemostasis. Furthermore, we will analyze the concept of fibrinolysis. Finally, the essay talks about the principles of routine laboratory tests that help in assessing haemostasis.

Haemostasis consists of a complex system that is regulated and that depends on a delicate balance among some other systems. Several systems interact to provide haemostasis to the body. Some of these systems include the vascular system, fibrinolytic system, coagulation system, platelets, and serine protease inhibitors among others (Marder et al., 2012). These systems interact and work in coordination when the endothelial lining of the blood vessels is damaged thus producing clot to stop bleeding. Below, we discuss some of these systems and how they provide haemostasis.

The vascular system consists of blood vessels and has some properties of anticoagulation, pro-coagulation, and fibrinolysis. The endothelial cells make up the innermost lining of the blood vessels. These endothelial cells form a smooth unbroken surface that enhances the passage of blood and prevents any disturbances that may trigger the release of plasma proteins and platelets (Marder et al., 2012). Any damage to the vascular system is repaired as fast as possible to maintain the integrity of the vascular system and blood flow. Prevention of bleeding happens through diversion of the flow of blood from the injured vessels, vessel contraction aggregation to initiate contact activation of platelets and activation of the coagulation system. The vascular system has some effective properties of anticoagulation that helps to prevent the initiation of the process of coagulation.

The coagulation system is where fibrin clot is formed through the interaction of coagulation factors. This system is responsible for the conversion of fibrinogen into insoluble fibrin fibres. The fibrin fibres are useful in the reinforcement of the platelet plug that is formed during the process of primary haemostasis (Marder et al., 2012). There are other protein factors that are present in the blood especially in an inactive state that participate in the coagulation system. Some of the coagulation factors include fibrinogen and prothrombin. These coagulation factors may be categorized as enzymes, cofactors, and substrates.

Haemostasis Systems

This system is responsible for the removal of the insoluble fibrin clots through the enzymatic digestion of the fibrin polymers. The fibrinogen and fibrin are digested through hydrolysis by the plasmin to form smaller fragments. The plasmin is generated from plasminogen. The fibrinolytic function is regulated by the renin-angiotensin-aldosterone system (Marder et al., 2012). The plasminogen activator system helps in controlling fibrinolysis.

The internal structure of platelets is complex which is a clear reflection of their hemostatic functions. Platelets are made up of two intracellular granules that include the dense bodies and α-granules. The α-granules are made up fibrinogen, platelet factor 4, fibronectin, and platelet thrombospondin. The dense bodies, on the other hand, are made up of adenosine triphosphate, ADP, and serotonin (Marder et al., 2012). Platelets release both dense bodies and α-granules when activated to support plasma coagulation which leads to the release of thrombin and deposition of fibrin fibres.

Primary haemostasis can be defined as the aggregation of platelets and the formation of platelet plugs. The activation of the platelets takes place in a multifaceted process and thus these platelets respond to the site of injury and plug the injury (Clemetson, 2012). During primary haemostasis, the von Willebrand factor is recruited to promote the attachment of platelets to the site of an injury. It also initiates the engagement of secondary haemostasis. Primary haemostasis is a very important defence mechanism against excessive bleeding.

The coagulation system which is part of the primary haemostasis is triggered due to damage to the endothelium which exposes blood to the extravascular tissues. The coagulation system responds by forming a platelet plug over the injured area (Broos et al., 2011). The main enzyme that controls coagulation is thrombin by activating platelets and aiding in the conversion of fibrinogen to fibrin fibres.

Primary haemostasis is made up of three main events that include platelet adhesion, activation of platelet and platelet plug formation (eClinpath, 2018). The events occur in s chronological manner as explained below. Firstly, upon the damage of the endothelium, the platelets, with the aid of the adhesion molecules, attach themselves to the sub-endothelial matrix proteins. The platelets adhere to the exposed collagen in the subendothelial matrix. Secondly, the platelet adhesion activates the platelets, causing several changes in the structure of platelets. During this process, the platelets change in shape to increase their surface area. Finally, there is the formation of platelet plug during which fibrinogen forms layers between the platelets that have been activated.

Primary Haemostasis

Secondary haemostasis is described as the formation of insoluble fibrin fibres by the thrombin enzyme. The fibrin is responsible for stabilizing the primary platelet plug especially in the larger blood vessels where these primary platelet plugs may not sufficiently stop bleeding (Levy et al., 2012). Secondary haemostasis can also be referred to as coagulation. The constituents of coagulation include cells, phosphatidylserine, enzymatic coagulation factors, and non-enzymatic coagulation factors.

Secondary haemostasis is divided into three major pathways that include extrinsic, intrinsic and common pathways (Monagle and Massicotte, 2011). The extrinsic pathway is made up of tissue factors, calcium, and the extrinsic tenase among others. The intrinsic pathway is made up of enzymatic coagulation factors, the cofactor, calcium and PS. The common pathway, on the other hand, is made up of prothrombin, fibrinogen, calcium and PS.

The coagulation process follows a sequence as described in this paragraph. Firstly, the generation of thrombin enzyme is initiated. It occurs in the extrinsic pathways through tissue factors expressed in fibroblasts. Secondly, the thrombin generation is amplified. This occurs when the thrombin enzyme activates Factor XI during which platelet polyphosphate acts as a cofactor. The third process is the propagation of thrombin generation (eClinpath, 2018). During this process, explosive thrombin burst is generated. The final event is the formation of fibrin. This process happens by the aid of the explosive thrombin burst that converts fibrinogen into fibrin fibres.

Fibrinolysis is the process by which blood clot is dissolved or prevented during the process of healing or in healthy blood vessels respectively. It is the final step of haemostasis and it occurs moments after the polymerization of fibrin (Chapin and Hajjar, 2015). The fibrinolytic system is primarily made up of three serine proteases. These serine proteases are present in blood as zymogens (Alzahrani and Ajjan, 2010). The efficiency of fibrinolysis is affected by the structure of the clot, the rate at which thrombin is generated, fibrinogen isoforms, the reactivity of platelets, and the overall biochemical environment (Chapin and Hajjar, 2015). The role of fibrin in haemostasis is very significant because it acts as the primary product in the coagulation cascade as well as being the ultimate fibrinolysis substrate.

The process of fibrinolysis begins when the endothelial cells release the Tissue plasminogen activator (Cesari, Pahor and Incalzi, 2020). Several factors stimulate the release of TPA that includes hypoxia. The TPA and plasminogen are both incorporated in the forming clot. The combination between fibrin-bound TPA and fibrin-bound plasminogen leads to the formation of active enzyme plasmin. Plasmin degrades both the fibrinogen and fibrin that are present in the clot (Gale, 2011). This degradation leads to the release of soluble fibrin degradation products. These soluble fibrin degradation products can be measured in the plasma. The result is that the clot is dissolved from inside out.

Coagulation System

Fibrinolysis is regulated by a series of inhibitors, cofactors, and receptors. The inhibitors are important because they help to prevent unregulated plasminogen activity (Collen, 2014). The serine protease inhibitors help to neutralize the circulating plasmin activators. Fibrinolysis can either be thrombin-based or cell surface.

Haemostasis is an intricate system that enhances the cooperation between pro-coagulant and anti-coagulant forces. These forces cooperate to either maintain the fluidity of blood under normal conditions or initiate the generation of a blood clot to limit bleeding if there is damage to endothelium cells. Excessive prevalence of anticoagulant forces may lead to haemorrhage (Dahlbäck, 2000). On the other hand, if pro-coagulant forces are excessively activated, there may be risks related to thrombosis.

Diagnostics in the laboratory is very crucial in the diagnosis of most cases of haemostasis disturbances. Laboratory haemostasis basically addresses the first, second and third line tests. These tests find their collocation within the diagnostic algorithms that are well established (Favaloro, Lippi and Koutts, 2011). The first line tests are also known as screening tests. They are made up of activated partial thromboplastin time, prothrombin time, fibrinogen, and platelets count. Secondary assays, on the other hand, help individuals to gain an in-depth understanding of the abnormalities that exist in the screening tests. They are also used to accurately monitor some antithrombotic therapies. The intention of the third line tests is to troubleshoot some of the most tasking conditions (Lippi and Favaloro, 2013). They also encompass analyses like von Willebrand factor collagen binding and von Willebrand factor ristocetin cofactor assay among others.

Laboratory diagnostic must be of high quality and obtaining false results from unsuitable specimen must be avoided. This is because these spurious results may negatively impact the credibility of clinical decision-making and jeopardize the safety of the patient (Lippi and Favaloro, 2013). Errors in the laboratory experiments can arise from any stage during the testing process. It is, however, important to note that these errors tend to be more prevalent in the pre-analytical phase where there are numerous manually intensive activities.

Conclusion

Haemostasis is important because it ensures that blood loss is minimized in the event of an injury to the vascular tissues. Several systems work in coordination to provide haemostasis. These systems cooperate to maintain the fluidity of blood within the vascular system or initiate the process of a blood clot to minimize blood loss. There are two types of haemostasis that include the primary and secondary haemostasis. Insufficient haemostasis can cause hemorrhage while excessive haemostasis can lead to coagulation. Primary haemostasis is responsible for the formation of platelet plugs while secondary haemostasis is responsible for coagulation that involves the formation of insoluble fibrin fibres in the injured area. The final step of haemostasis is known as fibrinolysis and it occurs moments after the polymerization of fibrin. Fibrinolysis is regulated by a series of inhibitors, cofactors and receptors. Haemostasis is a very significant aspect of life and enhances the cooperation between pro-coagulant and anti-coagulant forces.

References

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