Haemostasis and Thrombosis Flashcards
What is Haemostasis?
Hemostasis is the physiological process by which blood vessels constrict, platelets adhere to the injured vessel wall, and blood coagulation occurs, ultimately leading to the cessation of bleeding.
What is Thrombosis?
Thrombosis is the pathological process in which blood clots (thrombi) form abnormally within intact blood vessels, leading to obstruction of blood flow and potentially causing tissue damage or ischemia (lack of blood supply) to affected organs or tissues.
It is essentially haemostasis occurring within non-damaged blood vessels.
What is blood coagulation and what does it involve?
Blood coagulation is an enzyme cascade. It involves:
- Coagulation factors (plasma proteins - activated by proteolytic cleavage to become, in turn, active proteases)
- Phospholipid on the surface of activated platelets
- Calcium ions
- This leads to the generation of the enzyme thrombin which converts soluble fibrinogen to gel-like fibrin. Fibrin provides the strength of a blood clot.
What normally suppresses Intravascular blood coagulation and platelet activation?
- Non-thrombogenic surface of endothelium
- Production by endothelium of prostacyclin (PGI2) and nitric oxide which inhibit platelet aggregation; nitric oxide also inhibits adhesion of platelets to vascular wall
- Presence in plasma of natural anticoagulants, e.g. antithrombin III
When blood vessel damaged occurs, what occurs?
- Platelets adhere to exposed sub-endothelial collagen and become activated
- Coagulation is initiated by exposure of blood to tissue factor (Factor III) and facilitated by exposure of pro-coagulant phospholipid on platelet surface
- Platelets release agents which promote vasoconstriction and platelet aggregation, i.e. thromboxane A2, 5-HT and ADP
- Fibrin strands enmesh the platelet aggregate to consolidate the haemostatic plug
- The haemostatic plug is dissolved by the fibrinolytic system to allow tissue repair
What are the stages of platelet activation?
- Vessel is cut/an atherosclerotic plaque ruptures - this leads to activation of platelets by the now exposed sub-endothelial collagen
- Platelet surface integrin (glycoprotein GPIb) permits adhesion to collagen in the vessel wall via a Von Willebrand factor bridge
- Platelets then change shape (from discoid to spherical) with development of pseudopodia
- Platelets aggregate (stick to each other) and fibrinogen cross-links GPIIb/III receptors on adjacent platelets
- Arachidonic acid metabolism is initiated. This forms thromboxaneA2 which activates adjacent platelets and promotes vasoconstriction
- Platelets degranulate -releasing stored ADP and 5-HT which again activates adjacent platelets and promotes vasoconstriction
- Exposure of pro-coagulant phospholipid on platelet surfae activates the coagulation cascade (intrinsic pathway)
Describe in detail the coagulation cascade
What is a clotting disorder?
A clotting disorder is a deficiency of a clotting factor that can lead to uncontrolled bleeding
What are examples of clotting disorders and what do these involve?
- Von Willebrand Disease (most common) - deficiency of Von Willebrand factor - binds to and stabilises factor VIII and binds platelets to collagen
- Haemophilia A – deficiency of factor VIII
- Haemophilia B – deficiency of factor IX
- Haemophilia C – deficiency of factor XI- “Rosenthal syndrome”
- Genes encoding factors VIII and IX are located on the X chromosome because of this, Haemophilia A and B are more common in males – as they only need a single copy due to having only one X chromosome
How are clotting disorders treated
Via replacement of the deficient facotr
What is the fibrinolytic system and what is its purpose?
The Fibrinolytic System is the physiological repair system for removing blood clots. It involves the generation of the enzyme plasmin which digests fibrin.
What is Venous Thrombosis? What are the causes and risks? How would it be treated?
- Venous thrombosis is intravascular blood clots which form in deep veins, particularly at the legs where flow is sluggish.
- The risks of venous thrombosis are that it may bud off (embolus) and block vessels (often the pulmonary artery)
- It is treated using anticoagulant drugs
What is Arterial Thrombosis? What are its causes and risks? How would it be treated?
- Arterial Thrombosis is when platelets aggregate and are then encapsulated by a clot.
- Arterial thrombosis is usually at the site of ruptured atherosclerotic plaque
- Arterial Thrombosis is treated short term by dissolving existing clots with fibrinolytics and long term using anti-platelet drugs.
Difference between arterial and venous thrombosis? Why is there this difference in mechanism?
Venous Thrombosis is driven by activation of the coagulation cascade whereas Arterial Thrombosis is driven by platelet aggregation/activation.
This difference is because flow in veins is more laminar (straight) than in arteries. In arteries, due to variations in vessel diameter caused by vasoconstriction, the flow of blood can go more towards the vessel wall rather than straight forward - leading to increased shear stress and more interaction between the circulating platelets and vessel walls than in veins.
What are Heparin and Low Molecular Weight Heparin (LMWH) and how do these work work?
They are both anticoagulants which both form a complex with antithrombin III.
For standard Heparin, this complex inhibits thrombin (factor IIa), factors Xa, IXa, XIa and XIIa (all of the intrinsic pathway and the common pathway upto thrombin). Standard Heparin is monitored by APTT.
For LMWH, this complex inhibits factor Xa.
