Haemostasis Flashcards
What is haemostasis?
What does the normal haemostatic response involve?
- the process that results in the stopping of bleeding following blood vessel injury
- complex interactions between activated clotting factors and platelets at the site of blood vessel injury
What is the sequence of events following blood vessel injury?
- Localised vasoconstriction at the sit of injury
1. Platelet adhesion to sub endothelium of damaged blood vessel
Platelet aggregation and activation
2. Activation of coagulation cascade
Fibrin formation - Thrombus Formation
- Fibrinolytic degradation of clot / blood vessel repair
What are the two glycoprotein receptors incorporated into the lipid bilayer of platelets?
GPIb and GPIIb/IIIa
What allows platelets to change shape?
actin and myosin fibrils which interact upon platelet activation
What are the 3 types of storage granules found in platelets? What are their purposes?
dense - mediators of activation including serotonin, ADP, catecholamines and calcium
alpha - contain clotting factors V, VIII, fibrinogen, VWF and other substances including platelet factor 4 and platelet-derived growth factor
glycogen - provide the energy source for platelet reactions
Draw the coagulation cascade
see booklet
Describe the role of platelets in the haemostatic response
- transient localised vasoconstricción –> platelets form a mechanical plug
- platelets adhere to exposed sub-endothelial collagen
- vWF adheres GP1b
- GPIIb/IIIa upgraded to membrane, binds to vWF and allows aggregation
- ADP is released from damaged blood vessel endothelial cells
- ADP and exposed collagen and thrombin activates platelets and they release aloha and dense granules
What are the bleeding tendency disorders and what causes them?
- Bernard-Soulier sundrome = deficiency of GPIb
- Glanzmann;s Thrombasthenia = deficiency of GPIIb/IIIa
- Haemophilia A - factor 8
- Haemophilia B - factor 9
- vWF deficiency
- autoimmune acquired thrombocytopenia
- vitamin K deficient
What factors are synthesised from vitamin K?
- 7, 9, 10
Describe the fibronolytic response and blood vessel repair
- tPa released from intact endothelial cells
- attaches to fibrin clot
- enables binding of plasminogen
- converted to plasmin
- proteolytic dissolution of clot
- degradation products removed by reticulo-endothelial system
- blood vessel repair occurs simultaneously
- smooth muscle of blood vessels and endothelial cells undergo mitosis - under control of PDGF
What are the 3 anticoagulant mechanisms?
- antithrombin
- protein C
- natural heparins
What does antithrombin do?
- inactivated thrombin and factor 9. 10, 11
- Where in the circulation is the protein C system most important?
- What does protein C do?
- venous side
- in the vicinity of clot formation, free thrombin binds to thrombomodulin
- enables binding of Protein C and thrombin activates it
- activates protein C complexes with protein S and inactive FV, and enzymatically degrades factor 5 and 8
- suppression of coagulation factors and restricts the thrombus to the site of injury
What do natural heparins do?
- operate at the level of the blood vessel endothelium
- present on endothelial surface which bind to and enhance the anticoagulant activity of anti-thrombin and the synthesis and relays of platelet inhibitory prostaglandin called prostacyclin
Give examples of causes of acquired thrombophilia states
- myeloproliferative disorders
- malignancy
- lupus anticoagulant
- surgery
- long haul flights
- prolonged periods of immobility
- pregnancy
- smoking
Give examples of hereditary thrombophilia states
- Factor V leiden mutation, factor V has impaired protein C cofactor activist and is resistant to neutralisation
- protein C, S and AT deficiencies
- mutation of prothrombin gene –> increased prothrombin levels
- hyperhomocysteinaemia
What routine tests are used to investigate the clotting cascade?
- platelet count
- prothrombin time
- activate partial thromboplastin time (APTT)
- fibrinogen level
- von Willebrand Factor levels
- platelet aggregation studies
What are the two most common test requested?
- prothrombin time (PT)
- activated partial thromboplastin time (APTT)
What does an prolonged prothrombin time indicate?
What are the possible causes?
- factor 7 deficiency Causes: - hereditary factor 7 deficiency - mild liver disease - mild VitK deficiency
What does an prolonged APTT indicate?
- requires further testing
- repeat, with mixing test
- if clotting time return to normal –> 8, 9, 11, 12 deficiency
- if clotting time fails to correct –> inhibitor present such as lupus anticoagulant or F8 antibodies
What does a prolonged prothrombin and APTT indicate?
- a single factor deficiency in the ‘common pathway’
e. g. 10, 5, prothrombin, or fibrinogen - of multiple factor deficiencies due to liver disease, VitK deficiency, warfarin therapy, DIC, dilutional coagulopathy
