Flashcards in Disorders of Platelets and Coagulation Deck (115)
What are endothelial cells?
Flattened cells that line blood vessels and have pro and anticoagulant properties
What are the functions of endothelial cells?
Normally anticoagulant inhibiting coagulation and platelet aggregation
Act as a barrier to sub-endothelial collagen which is procoagulant
What produced Von Willebrand's Factor (vWF)?
Endothelium and platelets
Where is vWF stored?
Weibel Palade bodies
Where is vWF located?
On sub-endothelial surface
When is vWF released and what is its function?
Early in the haemostatic process and is responsible for platelet adhesion to collagen
What do platelets look like?
Small discoid anuclear cells found in the circulation, 3-5um, pale basophilic with small red granules
Where do platelets originate from?
Megakaryocytes in the bone marrow during a process called thrombopoiesis
What mediates platelet production?
How long do platelets circulate for?
5-9 days in most species
What is the functional structure of platelets?
Outer membrane has receptors important for adhesion and aggregation
Cytoplasm has actin and myosin allowing shape change
What are the two different types of granules in platelets?
Alpha granules (red) that contain vWF, fibrinogen and factors V and VII
Dense granules which contain ADP and calcium
What glycoprotein receptors are associated with platelet membrane?
GP Ib binds vWF
GP IIbIIIa binds fibrinogen on adjacent platelets and allows platelets to aggregate
What happens if there are defects in receptors?
Abnormal platelet function and clot formation occurs
What is primary haemostasis?
Formation of the primary platelet plug
What is the first step in primary haemostasis?
Damage to the endothelium and exposure of sub-endothelial collagen results in vWF release
What is the second step in primary haemostasis?
Platelet adhesion occurs and platelets bind to collagen via receptor GP Ib and vWF from the endothelium
What is the third step in primary haemostasis?
Platelets undergo shape change and become spherical with filipodia which exposes additional GP Ib and GP IIbIIIa
What is the fourth step in primary haemostasis?
Platelets bind fibrinogen via GP IIbIIIa between adjacent platelets forming a clump/aggregate of platelets
Where is fibrinogen generated from?
What is the fifth step in primary haemostasis?
Aggregating platelets rapidly degranulate releasing ADP, fibrinogen and vWF as well as thromboxane A2 from the platelet membrane which increase platelet adhesion and aggregation
What is the final step in primary haemostasis?
Platelets release factors V and VIII which are involved in coagulation
What is secondary haemostasis?
Activation of the coagulation cascade simultaneously with platelet plug formation
What are the different pathways the coagulation cascade split into?
Intrinsic, extrinsic and common pathways but only for lab testing purposes not in vivo
What is the function of the extrinsic pathway of coagulation cascade?
Initiates coagulation cascade and is most important in vivo
What is the process of extrinsic pathway of coagulation cascade?
Tissue factor is released from damaged tissue binds to and activates FVII in the presence of calcium
TFFVII complex activates FX of the common pathway and FIX of the intrinsic pathway
What is the function of the intrinsic pathway of the coagulation cascade?
Amplifies the coagulation cascade
What is the process of intrinsic pathway of the coagulation cascade?
FXII is activated by contact with a negatively charged surface (co factor HMWK)
Activated FXII cleaves and activates FXI which in turn activates FIX which requires calcium
Activated FIX in turn activates FX of the common pathway
What is the process of the common pathway of the coagulation cascade?
Starts with activation of FX which binds activated FV and calcium on the platelet surface which converts prothrombin (FII) to thrombin (FIIa)
Thrombin converts fibrinogen (FI) to fibrin (FIa) and fibrin is cross-linked by activated FXIII