Introduction to Hemostasis
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153 Terms
What is hemostasis?
The mechanism by which blood flow is maintained and blood loss in prevented following vessel injury
What is the primary goal of hemostasis?
To keep blood within the arteries and veins, prevent blood loss from injuries, and help restore normal blood flow during healing
What components are involved in the hemostasis process?
It involves a combo of cellular and biochemical events, including vascular cells, platelets, and coagulation proteins:
1.Keep blood within arteries & veins
2.Prevent blood loss from injuries by formation of thrombi
3.Re-establish blood flow during healing process
What role does thrombus formation play in hemostasis?
It prevents blood loss at sites of injury by sealing the damaged vessels
How is blood flow re-established after injury?
By removal of the clot through fibrinolysis and restoration of vessel integrity
What are the four main components of the hemostasis system?
Blood vessels
Platelets
Plasma coagulation system
Fibrinolytic system
What is the role of blood vessels in hemostasis?
By vasoconstricting to reduce blood flow and by using endothelial cell functions to regulate clotting and maintain vessel integrity.
What role do platelets play in hemostasis?
They form the primary hemostatic plug by adhering to the injury site and aggregating to temporarily seal the wound
What is the function of the plasma coagulation system?
It leads to fibrin formation, which stabilizes the platelet plug to form a more durable clot
What does the fibrinolytic system do?
It is responsible for fibrin destruction, breaking down the clot after healing is complete to restore normal blood flow
What is the primary function of the endothelium in blood coagulation?
It acts as a barrier and plays a role in initiating the clotting process. It interacts with platelets and coagulation factors to regulate the formation and breakdown of clots.
How do platelets and the endothelium interact during the clotting process?
When blood vessel damage occurs, the endothelium exposed subendothelial structures, which attract platelets.
Platelets then adhere to damaged area, become activated, and release substances that enhance coagulation, facilitating the clotting process.
What triggers primary hemostasis?
It is triggered by small blood vessel injuries, such as pinpricks or the desquamation (shedding) of endothelial cells. These minor injuries stimulate a series of responses to minimize blood loss
How do blood vessels respond during primary hemostasis?
They contact to seal the wound, a process known as vasoconstriction. This helps reduce blood flow at the injury site and limits bleeding
What is the role of platelets in primary hemostasis?
They fill up the open space at the injury site, forming a temporary plug. These platelets adhere to the exposed subendothelial surface and aggregate, forming the primary blood clot
What triggers secondary hemostasis?
Primary hemostasis, It typically occurs in response to larger wounds, such as those caused by surgery or trauma.
What happens during secondary hemostasis?
The plasma coagulation system is activated. This system, composed of a series of enzyme proteins, generates a fibrin thrombus. This fibrin clot stabilizes the initial platelet plug formed during primary hemostasis
What is the purpose of the fibrin thrombus in secondary hemostasis?
It serves to reinforce and stabilize the temporary platelets plug formed during primary hemostasis, ensuring a more durable clot and preventing further blood loss
What are the major players in hemostasis
1.Blood vessel (Vascular Intima)
2.Blood platelets
3.Neutrophils & monocytes
4.Plasma coagulation system
5.Fibrinolysis
What is the event sequence in hemostasis
Vasoconstriction
Platelet adhesion
Platelet aggregation
Fibrin-Platelet Plug formation
Fibrin stabilization
What happens during the vasoconstriction stage?
The endothelium releases endothelin, which cases the blood vessels to constrict. This is a reflex response to injury. Which helps minimize blood loss by reducing blood flow to the injured area
What is the role of the endothelium in vasoconstriction?
It releases endothelin, a potent vasoconstrictor.
What are the functions of ADP and TXA2 in primary hemostasis
They are released from platelets within granules which activate other platelets and promote aggregation, forming a hemostatic plug.
What is the role of von Willebrand Factor (vWF) in primary hemostasis?
It helps platelets adhere to the exposed collagen of the damaged blood vessel and plays a crucial role in platelet aggregation during primary hemostasis.
What is the function of t-PA (tissue plasminogen activator) in clot formation
It activates fibrinolysis to break down the clot. Thrombomodulin is also released, which blocks further coagulation to prevent excessive clotting.
What are the primary components of blood vessels?
Endothelial cells – the inner lining of the blood vessel.
Collagen-rich basement membrane – providing structural support.
Connective tissue layer – containing fibroblasts that produce collagen and smooth muscle cells
What is the role of endothelial cells in blood vessels?
They form the inner lining of blood vessels, providing a smooth surface that prevents fluid turbulence and activation of platelets. This helps maintain efficient blood flow and prevents unnecessary clot formation.
What is the function of the collagen-rich basement membrane in blood vessels?
It provides structural support to the blood vessel and helps maintain the integrity of the endothelial layer. The collagen in this membrane plays a key role in vessel strength and tissue regeneration.
What cells are found in the connective tissue layer of blood vessels?
Fibroblasts, which produce collagen, and smooth muscle cells, which are present only in arteries. This layer provides additional support and elasticity to the blood vessels.
What anticoagulant properties are associated with the vascular intima?
Smooth, continuous surface
Nitric oxide (Vasodilator)
Prostacyclin
Tissue factor pathway inhibitor (TFPI)
Heparan sulfate
What is the role of the smooth, continuous surface of the vascular intima?
It prevents the activation of platelets and coagulation, ensuring smooth blood flow and reducing the risk of clot formation.
How does nitric oxide contribute to the anticoagulant properties of the vascular intima?
It is a vasodilator secreted by endothelial cells to help dilate blood vessels and maintain smooth blood flow.
What is the function of prostacyclin in the vascular intima?
It inhibits platelet activation and aggregation.
What role does tissue factor pathway inhibitor (TFPI) play in the vascular intima?
It regulates the coagulation cascade to prevent excessive clotting.
How does heparan sulfate contribute to the anticoagulant properties of the vascular intima?
It acts as an anticoagulant, preventing clot formation.
What role does thrombomodulin play in the anticoagulant properties of the vascular intima?
It acts as a cofactor in the thrombin-induced activation of Protein C. This process helps in inhibiting clot formation by deactivating coagulation factors.
How do smooth muscle cells (SMC) contribute to the procoagulant properties of the vascular intima?
It induce vasoconstriction via the release of endothelin, which reduces blood flow and supports clot formation at the site of injury.
How does the exposure of the basement membrane contribute to coagulation?
When the basement membrane is exposed, collagen binds to von Willebrand factor (vWF) and platelets, promoting platelet adhesion and aggregation, which are essential for clot formation.
What happens when endothelial cells are damaged in the vascular intima?
They secrete von Willebrand factor (vWF), which aids in platelet adhesion and aggregation, further promoting clot formation at the injury site.
What role does exposed smooth muscle cells (SMC) and fibroblasts (FB) play in the vascular intima’s procoagulant properties?
When smooth muscle cells and fibroblasts are exposed, tissue factor (TF) is released, which activates the coagulation cascade, further enhancing the clotting process.
What is the role of tissue plasminogen activator (tPA) in the fibrinolytic properties of the vascular intima?
It activates plasminogen, converting it into plasmin, which breaks down fibrin and helps to dissolve clots.
How does plasminogen activator inhibitor (PAI-1) contribute to the anti-fibrinolytic properties of the vascular intima?
It inhibits tissue plasminogen activator (tPA), thereby preventing excessive fibrinolysis and helping to stabilize the clot.
How are platelets produced in the body?
From the cytoplasm of megakaryocytes, which are large bone marrow cells responsible for the generation of platelets.
What happens as a megakaryocyte matures?
Granules in its cytoplasm begin to cluster in groups, and a network of tubules develops by invagination (DMS), which is crucial for platelet formation.
What is the role of the network of tubules in platelet production?
They fuse to create fissures. These fissures become the margins and plasma membranes of the platelets during their formation.
What occurs when the megakaryocyte's membrane fragments?
They make platelets, leaving behind only the nucleus. These platelets are then released into the bloodstream.
What do platelet cells interact with
Injured vascular walls
Plasma proteins
Circulating blood cells
What role do platelets play in hemostasis and thrombosis?
They form a temporary plug at the site of blood vessel injury and facilitate the coagulation cascade to prevent excessive blood loss or form pathological clots.
What happens during platelet adhesion?
Platelets stick to the exposed subendothelial matrix (such as collagen and von Willebrand factor) at the site of blood vessel injury. This step is essential for initiating the clotting process and forming the first layer of the platelet plug.
What is the platelet release reaction and secretion?
Platelets adhere to the injured vessel wall and activate, as they do this they release various granules such as ADP,TXA2, and serotonin which further activate and recruit additional platelets to the site of injury and promote vasoconstriction to control bleeding.
How does platelet aggregation occur?
It involves the clumping together of platelets at the site of injury. Activated platelets bind to each other via fibrinogen and other adhesive molecules, forming a stable, hemostatic plug that helps to seal the wound and prevent further blood loss.
Do platelets adhere to intact endothelial cells?
No, platelets do not adhere to intact endothelial cells. They only adhere to the exposed subendothelial structures, such as collagen, when there is damage to the vascular wall.
How does the platelet response vary based on the depth of the vessel injury?
For minor injuries, platelets adhere and spread over the damaged area, but they do not release their granules or promote aggregation and this process is reversible. In more severe injuries, platelets respond more aggressively and activate the clotting process.
What happens when there is major endothelial cell damage?
There is a release reaction, platelet aggregation, and the activation of blood coagulation, leading to the formation of a blood clot to prevent excessive bleeding.
What do some GP Ib/IX platelets require for adhesion to collagen
von Willebrand factor (vWF)
What is Bernard-Soulier syndrome and how does it affect platelet adhesion?
This is a genetic disorder where the GP Ib/IX receptor on platelets is absent, which impairs platelet adhesion to the vascular wall, particularly in response to damage. This results in bleeding disorders due to inadequate platelet attachment.
How does von Willebrand disease affect platelet adhesion?
This is a condition where there is either poor quality or an absence of von Willebrand factor (vWF). This impairs the ability of platelets to adhere to the damaged vessel wall, leading to bleeding problems.
What other molecules assist in platelet adhesion besides vWF?
albumin and fibrinogen also play a role in enabling platelet adhesion by interacting with platelet surface receptors and enhancing the platelet aggregation process.
What types of granules do platelets contain?
α-granules, dense bodies, and lysosomes, each containing various constituents involved in the clotting process and healing.
How do the constituents of platelet granules affect vessel tonicity and coagulation?
When released, the constituents of platelet granules affect vessel tonicity by inducing vasoconstriction and promoting coagulation by activating other platelets and initiating the coagulation cascade.
What biological factors trigger platelet granule release?
Collagen from the exposed subendothelial matrix
Thrombin, a key enzyme in coagulation
Epinephrine, which activates platelets
Thromboxane A2 (TxA2), which promotes vasoconstriction and platelet aggregation
Arachidonic acid, which is involved in the production of thromboxane A2 and other inflammatory mediators.
What factors induce platelet aggregation?
ADP, thrombin, thromboxane A2 (TxA2), collagen, and epinephrine
What happens to platelets before aggregation occurs?
There is a change in platelet shape. Platelets undergo a transformation from their disc-like shape to a more activated, spiky form, enhancing their ability to aggregate and form a stable clot.
How is ADP released from platelets during aggregation?
It is released from dense granules within platelets in response to factors such as collagen, epinephrine, and thromboxane A2 (TxA2)
What is the role of ADP in platelet aggregation?
It binds to specific platelet receptors (GP IIb-IIIa), which causes irreversible platelet aggregation. This interaction allows platelets to stick together, forming a platelet plug at the injury site.
What is the role of the GP Ib/IX receptor on platelets?
It is critical for platelet adhesion to the vascular injury site. It binds to von Willebrand factor (vWF) that is exposed on the damaged endothelial surface, which helps platelets adhere to the injury and initiate the clotting process.
What does the GP IIb/IIIa receptor do?
It plays a vital role in platelet aggregation. It binds to fibrinogen, linking platelets together to form a stable platelet plug at the site of injury. This receptor is essential for the final stages of clot formation.
What changes occur in the GP IIb-IIIa complex during platelet aggregation?
There is conformational changes in the receptor, which allows fibrinogen to bind to the receptor. This interaction is essential for platelets to aggregate and form a stable clot.
How does thrombin contribute to platelet aggregation?
It stimulates platelet aggregation by promoting the release of ADP from platelets, which further activates platelets. Thrombin also initiates the formation of thromboxane A2 (TxA2), a potent vasoconstrictor and platelet aggregator.
What is the bleeding time test and what are its limitations?
It measures how long it takes for bleeding to stop after a standardized injury. However, its predictive value is limited, as it does not accurately reflect platelet function or the overall hemostatic ability of the body.
What is the urinary thromboxane metabolic assay used for?
It is used to assess thromboxane A2 production, which plays a crucial role in platelet aggregation and vasoconstriction during the coagulation process.
What is platelet aggregometry and why is it considered technically demanding?
It is a test used to evaluate platelet function by measuring the extent of platelet aggregation in response to various stimuli. It is technically demanding and semiquantitative because it requires precise handling and interpretation, and results are not fully quantitative.
What role do red blood cells (RBCs) play in hemostasis?
They add bulk and structural integrity to the fibrin clot. They help reinforce the clot and provide stability to prevent excessive blood loss.
How do monocytes and lymphocytes contribute to coagulation?
They provide surface-borne tissue factor, which is essential for triggering the coagulation cascade. This helps initiate the clotting process at the site of injury.
What role do white blood cells (WBCs) play in wound healing?
They produce inflammatory materials that aid in the wound healing process by promoting inflammation, tissue repair, and immune response to prevent infection.
What are procoagulants in the plasma coagulation system?
They are also known as coagulation factors or clotting factors, are proteins involved in the coagulation cascade.
How many procoagulants are there and where are they produced?
There are 16 procoagulants in total, most of which are glycoproteins produced by the liver, with the exception of factor VIII, which is produced by endothelial cells.
Where are most procoagulants produced in the body?
Most procoagulants are produced by the liver, with the exception of factor VIII, which is produced by endothelial cells. Additionally, a few procoagulants are produced by monocytes and megakaryocytes.
How are procoagulants transported in the body?
They are transported in the plasma, where they circulate in an inactive form until they are activated during the coagulation process.
What type of enzymes are most procoagulants in the plasma coagulation system?
They are serine proteases, which are enzymes with a trypsin-like activity. These enzymes play a key role in the activation and amplification of the coagulation cascade.
What are zymogens in the context of the coagulation system?
They are the inactive precursors of enzymes. In the coagulation system, 8 procoagulants circulate in their inactive form as zymogens, and they are activated during the coagulation cascade to perform their enzymatic functions.
What are cofactors in the plasma coagulation system?
There are 6 other coagulation components that act as cofactors. Cofactors bind to and stabilize enzymes, enhancing their enzymatic activity during the coagulation process.
How does thrombosis affect the plasma coagulation system?
It activates procoagulants, leading to the formation of a thrombus (a blood clot)
What role do anticoagulants play in the plasma coagulation system?
At least 6 plasma glycoproteins act as anticoagulants in the coagulation system. These anticoagulants help regulate the coagulation process by preventing excessive clotting.
What is coagulation factor I (1)
Fibrinogen
What is coagulation factor II (2)
Prothrombin
What is coagulation factor III (3)
Tissue Factor
What is coagulation factor IV (4)
Ionic calcium
What is the coagulation factor for V (5)
Labile factor
What is the coagulation factor for VII (7)
Stable factor
What is the coagulation factor for VIII (7)
Antihemophilic factor (vWF)
What is the coagulation factor for IX (8)
Christmas factor
What is the coagulation factor for X
Stuart Prower
What is the coagulation factor for XI (10)
Plasma thromboplastin antecedent
What is the coagulation factor for XII (12)
Hageman factor
What is the coagulation factor for Prekallikrien
Fletcher
What is the coagulation factor for Fitzgerald factor
HMWK
What is the coagulation factor for XIII
Fibrin stabilizing factor
What is the coagulation factor for Platelet factor 3
phospholipids (PF3)
Which enzymes are considered serine proteases and belong to the trypsin family in the plasma coagulation system?
Thrombin
Factor VIIa (7)
Factor IXa (9)
Factor Xa (10)
Factor XIa (11)
Factor XIIa (12)
Prekallikerin