Haemostasis and clot lysis Flashcards
Learning outcomes
- define the term haemostasis and list its stages •describe the extrinsic and intrinsic pathways of coagulation
- define the terms vascular spasm, platelet plugging, blood clotting and scar formation and explain the underlying processes
- briefly describe the processes of fibrinolysis & clot removal
- distinguish between bleeding and clotting time
Haemostasis- prevention of blood loss
Three phases occur in rapid sequence
Very important in minor vascular injury
1. Vascular spasms of smooth muscle–immediate vasoconstriction in response to injury- limits blood flow to site of injury
2. Platelet plug formation–platelet adhesion (stick to injured blood vessel) & aggregation
3. Coagulation–blood clotting (clotting cascade > thrombin- catalyses fibrinogen to fibrin, trapping RBCs onto surface of plug, forms mesh)
Phase 1: Vascular spasms
Damage to wall of blood vessel > vasoconstriction
Vasoconstriction
•Nervous reflexes- SNS and sensory nerve fibres (pain)
•Myogenic contraction
•Factors from damaged tissue and activated platelets e.g. endothelin (vasoconstriction), thromboxane A2, Serotonin (5-HT)
Collagen exposed on damage to BV wall> platelets adhere and release platelet factors > Platelets aggregate into loose platelet plug
Tissue factor exposed
Phase 2: Platelet Plug Formation
Platelets are activated by contact with: • von Willebrand factor (vWF) • collagen • thrombin • a negatively charged surface
Platelets do not normally stick to the vessel wall>
Endothelial surface
•Smoothness - prevents platelets and clotting factors sticking: furring up of vessels can cause sticking
•Glycocalyx- physically repels platelets and CFs
•Prostacyclin and NO- prevent activation
•Thrombomodulin: binds thrombin, cannot catalyse fibrinogen>fibrin
Activated platelets release these substances from granules- can cause further vasocontriction
- ADP- activates platelets in vicininity of forming plug
- Thromboxane A2
- Serotonin
Phases 1 and 2- Temporary haemostasis
positive feedback promotes formation of platelet plug
Phase 3: Coagulation
A set of reactions in which blood is transformed from a liquid to a gel Follows intrinsic (in BV) & extrinsic (tissue factor outside, initiates clotting cascade) pathways as well as a common pathway
Clotting cascade- intrinsic and extrinsic pathways end at F10.
EP- when tissue factor exposed, rapid progression to f10, happens faster than IP
IP- more reactions leading to factor 10-
both have f10 for common pathway
(PT activator> prothrombin> thrombin, fibrinogen>fibrin> cross linked fibrin polymer)
Clot retraction
- “Tightening” of clot
- Contraction of platelets ( actin and myosin)
- Damaged edges pulled closer together
- Serum (plasma w/out clotting factors) squeezed out
- Over time the clot is dissolved
- Healing occurs - fibrous tissue
Vessel rupture> clot formation (0-6 minutes)> clot retraction ( between cf and an hour), fibrous tissue formation ( may begin within 3 hours- between 1/2 weeks)
Role of Calcium ions in the Intrinsic/ Extrinsic pathways
Chelation of Ca2+ prevents clotting in blood samples
- Citrate/ EDTA
Oxalate can precipitate calcium out of blood
Vitamin K and Warfarin
-Many of clotting factors (Prothrombin, Factors VII, IX,X ) produced by liver are activated by vitamin K dependent reactions
Vit K, while activating CF’s, becomes oxidised Vit K (inactive)
Warfarin inhibits the activation of Vit K from inactive Vit K, clotting factors are not activated and no coagulation
Vitamin K is fat soluble- lipid disorder can lead to problems with coagulation ( other fat sol vits are A,D,E)
Anticoagulants in normal vascular system
Fibrin> binds thrombin
Heparin (mast cells/basophils) > Antithrombin III (liver protein) > Binds and inactivates thrombin
Ensures clots are not consistently formed
Aspirin is an anticoagulant through inhibition of cyclo- oxygenase, the enzyme forming cyclic endoperoxide> prostaglandins (painkilling) and thromboxane A2 (anticoagulant, no platelet activation)
Fibrinolysis and clot removal
Plasminogen in fibrin (activated to) > Plasmin by fibrin-specific plasminogen activators, produced by endothelial cells- production increased w inc. thrombin conc in blood ( thrombin inc. when clot forms)
Plasmin degrades fibrin (it is a protease, fibrinolysis), phagocytes act on debris
tissue Plasminogen activators used in thrombolytic therapy
- MI
- Stroke
- Pulmonary embolism
Bleeding vs clotting time
Bleeding time-
•the duration of bleeding after controlled, standardised puncture of the earlobe or forearm
•measures capillary & platelet function
•Normal: 1-3 minutes
- Phases 1 and 2 of haemostasis- Vasospasm and platelet plug formation
Clotting time, coagulation time–
•the time required for blood to clot in a glass tube
•mainly reflects the time required for generation of thrombin
•prolonged if plasma concentration of prothrombin or other clotting factors is low
•Normal: 4-10 minutes
Hypercoagulation: Thrombi and Emboli
•Endothelial damage
arteriosclerosis, infection, trauma
•Slowly flowing or static blood leg immobilisation, atrial fibrillation
Myocardial infarction, stroke, deep veinthrombosis, pulmonary embolism
Hypocoagulation •von WillebrandDisease •Deficiency of platelets: Thrombocytopenia purpura •Deficiency of coagulation factors Heamophilia A (lack of factor VIII) Heamophilia B (lack of factor IX) •Deficiency of vitamin K
