Haemostasis: Pathways, Systems, and Laboratory Tests

This essay provides an overview of haemostasis, including primary and secondary haemostasis, fibrinolysis, and laboratory tests used to assess haemostasis. It discusses the systems that provide haemostasis, such as the vascular system, coagulation system, fibrinolytic system, and platelets. The essay also explains the principles of routine laboratory tests used to assess haemostasis.

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HAEMOSTASIS
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Haemostasis 2
Haemostasis
Abstract
Haemostasis is a very important aspect of life that helps to minimize the loss of blood that may
be caused by a damage to the blood vessels. It 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. It is clearly evident that blood coagulation
and primary haemostasis are some of the most significant defence mechanisms against excessive
bleeding. Coagulation is initiated due to damage to the endothelium cells. Anticoagulation, on
the other hand, ensures that the process of coagulation is carefully controlled. It is important to
note that fibrin is a very crucial product in haemostasis that acts as the primary product of
coagulation and the most important substrate for fibrinolysis. In this review, we summarize the
pathways of haemostasis that include primary and secondary haemostasis. We also talk about
fibrinolysis in addition to the laboratory tests used to assess haemostasis.
Keywords: haemostasis; primary haemostasis; secondary haemostasis; fibrinolysis; laboratory
test for haemostasis.
Introduction
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

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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.
Systems that Provide 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
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

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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
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.
The Fibrinolytic System
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.
Platelets
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

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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
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

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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.
Secondary 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.

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This process happens by the aid of the explosive thrombin burst that converts fibrinogen into
fibrin fibres.
Fibrinolysis
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.
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

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serine protease inhibitors help to neutralize the circulating plasmin activators. Fibrinolysis can
either be thrombin-based or cell surface.
The Principles of Routine Laboratory Tests used to Assess Haemostasis
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

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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.

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