2ary Haemostasis Flashcards
What is goal of 2ary haemostasis?
Produce a fibrin clot network
What is the coagulation cascade driven by?
By coagulation factors which normally circulate in the plasma as inactive proenzyme
What is the final product of coagulation cascade?
Conversion of fibrinogen to fibrin by thrombin. Fibrin polymerises and forms a network
What are the pathways involved in coagulation?
Intrinsic, extrinsic, common
What is the extrinsic pathway triggered by?
Injury - tissue factor is exposed to the blood
Where is tissue factor produced?
On the cell membrane of the perivascular cells (SMCs, fibroblasts)
Describe extrinsic pathway
- TF binds to XII from the blood and activates it, forming XIIa on surface of platelet
- X can also bind to TF-VIIa complex, activating it to F10a (amplification of response)
Describe the common pathway
- Xa converts prothrombin (II) into thrombin (IIa)
- Thrombin (IIa) converts the soluble molecule fibrinogen (I) into fibrin (Ia)
- Fibrin (Ia) is converted into cross-linking fibrin
What factor is prothrombin?
Factor II (F2)
What factor is fibrinogen?
Factor I (F1)
What is purpose of FXIIIa
Acts as superglue, making more reactions between fibrin sheets
What is intrinsic pathway triggered by?
Negatively charged surfaces e.g. glass, collagen, polyphosphates
What are steps in intrinsic pathway?
Injury to blood vessel
- XII –> XIIa
- XIIa converts XI –> XIa
- XIa converts IX into IXa
- IXa converts X –> Xa (with help of VIIIa)
Why is Vitamin K essential for coagulation?
Is a cofactor for an enzyme that allows the maturation of coagulation factors
What is the extrinsic pathway activated by?
External trauma that causes blood to escape from the vascular system. This pathway is quicker than the intrinsic pathway. It involves factor VII.
What is the intrinsic pathway activated by?
Trauma inside the vascular system, and is activated by platelets, exposed endothelium, chemicals, or collagen. This pathway is slower than the extrinsic pathway, but more important. It involves factors XII, XI, IX, VIII.
What is VIII (FVIII)?
An essential blood clotting protein which circulates in the bloodstream in an inactive form, bound to another vWf, until an injury that damages blood vessels occurs.
What is FVIII response to injury?
Is activated and separates from vWf, becoming VIIIa
What is role of VIIIa?
Is a cofactor for factor IXa, which, in the presence of Ca2+ and phospholipids, forms a complex that converts factor X to the activated form Xa.
What are people with high levels of VIII at risk of?
Pulmonary embolism and DVT
What is role of FXIII?
Stabilises fibrin clot –> activated to XIIIa
What is role of FV?
Essential cofactor in coagulation cascade
Activated to Va and helps Xa convert prothrombin to thrombin
What is Factor 5 Leiden?
Mutation in FV which causes an increase in blood clotting (hypercoagulability)
