haemostasis Flashcards
coagulation & anticoagulation
what are primary and secondary haemostasis?
primary: formation of platelet plug
secondary: formation of blood clot
what is thrombopoiesis?
the process of forming thrombocytes/platelets in the bone marrow
what is the process of thrombopoiesis?
thrombopoietin (TPO) activates myeloid stem cells→ megakaryocytes→ thrombocytes→ negative feedback (↓TPO)
what is the process of formation of platelet plug (primary haemostasis)?
exposed collagen→ platelets adhere & activate→ platelets form appendages to increase attachment surface, and release granules containing platelet agonists for aggregation→ attract more platelets→ platelets aggregate to form plug→ positive feedback loop (release more platelets)
how do platelets adhere to exposed collagen
- primary haemostasis
- mediated by Von Willebrand’s Factor (vWF) (plasma proteins produced by platelets)
- vWF binds platelets to exposed collagen via Gp1b
what factors mediate platelet aggregation? (3)
platelets release granules containing agonists:
1. ADP: attracts & activates more platelets
2. Thromboxane A2: promotes aggregation & further vasoconstriction
3. fibrinogen: links platelets through glycoprotein receptors (link r WEAK! need secondary haemostasis)
what are the triggers of intrinsic pathway? (2)
- exposure to collagen fibres
- exposure to foreign surface eg glass
what are the triggers of extrinsic pathway? (1)
damaged tissues releasing tissue factor or thromboplasin
what is the process of coagulation cascade?
extrinsic: 12a→ 11a→ 9a→(+8a)→ 10a
intrinsic: 7→ (+ tissue factor/thromboplastin/3)→7a→ 10a
common pathway: 10a→ (+5a)→ thrombin/2a→ fibrin/1a→ (+13)→ fibrin meshwork
what are the actions of thrombin? (2)
- activates factor 13→ 13a (fibrin stabilising factors for fibrin→ meshwork)
- cleaves & activates fibrinogen (fibrin→ fibrin monomer)
what is the process of fibrin meshwork formation?
10→ 10a→ prothrombin→ thrombin→ fibrinogen→ fibrin monomer (→ fibrin strand)→ + factor 13 (crosslinks strands)→ fibrin meshwork
what are the measures of coaguation cascade? (2)
- PT (prothrombin time)
- aPTT (partial thromboplastin time)
what does PT evaluate?
extrinsic pathway
normal time: ~10s (less time)
what does aPTT evaluate?
intrinsic pathway
normal time: ~25-35s (more time)
what factors require Vit K for production? (4)
2, 7, 9, 10
(2+7=9)+1=10
what are (most) common factors made of?
plasma protein
(except factor 3/tissue factor/thromboplastin that is a mixture of glycoprotein & phospholipids)
where are (most) common factors of coagulation cascade produced in?
liver
(except factor 3 that’s produced by damaged tissues)
what is the pathology of non-palpable/blanchable rashes + frequent nose bleeding
problem with primary haemostasis (small damages in capillary are usually healed by platelet plugs)→ vWF disease?
what are the 3 processes of anticoagulation?
- plug prevention (primary haemostasis): NO + prostacyclins
- clot prevention (secondary haemostasis): TFPI + APC/S + AT
- clot removal (fibrinolysis)
how are aberrant plug & clot prevention carried out? (3)
intact & smooth endothelial cells release:
1. Nitric Oxide (NO) & prostacyclins that inhibit platelet activation/aggregation
2. TFPI (Tissue Factor Pathway Inhibitor) to inhibit extrinsic pathway
3. thrombomodulin & protein C receptor that sequesters/inactivates thrombin & activates protein C/S
what is the process of protein C & S activation?
thrombomodulin binds to thrombin and EPCR binds Protein C→ bring Protein C to thrombin-thrombomodulin complex→ activate Protein C→ binds circulating Protein S→ forms APC-PS complex (active protease)→ cleaves & inactivates factor 5a & 8a (common pathway)
what are anti-thrombins (AT) and its functions?
- plasma protein produced by liver
- binds & inhibits thrombins & 10a & 9a that leak from clots (ensure clotting is localised to damaged site)
what is the process of clot removal (fibrinolysis) after wound healing?
intact endothelial cells release Tissue Plasminogen Activator (TPA)→ binds to plasminogen in presence of fibrin→ forms plasmin (protease)→ fibrin degradation products (FDP) released into circulation
how is fibrinolysis regulated? (3)
- no TPA from damaged vessels (only INTACT endothelial cells)
- low TPA affinity to plasminogen in absence of fibrin
- circulatory PAI (plasminogen activator inhibitor) & anti-plasmin inhibits TPA & plasmin that strays into circulation
