Blood Clotting Pathways Flashcards
what is haemostasis
the arresting of bleeding after everyday trauma
what are the 3 steps in haemostasis
- VASCULAR SPASM
- FORMATION OF A PLATELET PLUG
- BLOOD COAGULATION (CLOTTING)
why must haemostasis be controlled
to avoid inappropriate clot formation
describe stage 1 of haemostasis
what is it mediated by
Vasoconstriction of blood vessel after injury
- muscle cells contract
- this constriction reduces blood flow, limits blood loss
- Opposing endothelial surfaces are pressed together and adhere on contact
platelet-derived products serotonin and thromboxane A2
Normal ENDOTHELIUM produces
vasodilators and inhibitors of
platelet aggregation
e.g. prostacyclin (prostaglandin I 2 )
nitric oxide (a vasodilator)
what are platelets (thrombocytes)
what do they contain
small fragments derived from megakaryocytes (bone marrow cells)
megakaryocyte cytoplasm and intracellular granules
how can platelets be activated
- ADP (adenosine diphosphate) - released by platelets, erythrocytes & endothelial cells
- COLLAGEN – in the connective tissue, exposed by vessel damage
- THROMBIN – made by enzymatic cleavage of prothrombin
- PAF – platelet activating factor (phospholipid) from the vessel wall & other cells
what is the effect of activation of platelets
- changes shape from disc to sphere
- granules release compounds involved in haemostasis
- aggregate
- adhere to vessel wall
- Synthesise thromboxane A2 (TXA2 ) a potent, labile, mediator of platelet activation and
vasoconstriction
Activated
platelet
describe stage 2 of haemostasis
formation of platelet plug
- platelet activated and adhesion to vessel wall at sight of injury
- this mass forms the primary haemostatic plug
- plug can be washed away by local blood flow when vasoconstriction eases
- the plug must be stabilised by fibrin
what are vWF
von Willebrand Factor
What is the most common platelet related bleeding disorder
what do less common disorders affect
von Willebrand disease - group of autosomal disease affecting vWF
receptors found in platelet membrane that are involved in platelet adhesion and aggregation
what are antiplatelet drugs used to treat
how do they work
what are some examples of these drugs
arteriole thrombosis (blood clot within a vessel)
they decrease platelet aggregation and inhibit thrombus formation
- aspirin
- platelet receptor antagonists
- platelet ADP receptor antagonist
what does collagen play an important role in
structure and function of small blood vessels
Vascular causes of excessive bleeding include congenital or acquired
deficiencies in collagen synthesis
- CONGENITAL DISORDERS
e.g. Ehlers-Danlos Syndrome - ACQUIRED DISORDERS
e.g. Vitamin C Deficiency and
excessive exogenous or
endogenous Glucacorticoids
(steroid hormones)
MAKE FLASHCARD
describe the third stage in haemostasis
blood coagulation factors interact to form secondary, fibrin rich, haemostatic plug in small vessels and secondary fibrin thrombus in arteries and veins
describe both the intrinsic pathway and extrinsic pathway and the final common pathway in blood coagulation
INTRINSIC PATHWAY:
activated by the exposure of
flowing blood to sub-
endothelial COLLAGEN,
exposed by vessel damage
EXTRINSIC PATHWAY:
activated by tissue damage
which exposes flowing
blood to a protein called
TISSUE FACTOR (TF)
FINAL COMMON PATHWAY:
resulting in conversion of
FIBRINOGEN to FIBRIN
what are the main factors in blood coagulation
Clot formation - fibrin clot formed by interaction between intrinsic, extrinsic and final common pathways. the clot on top of platelet plug strengthens the plug and reinforces the seal
fibrin - insoluble, threadlike molecule. Forms loose mesh that traps blood cells. Generated from fibrinogen, a large soluble plasma protein.
thrombin
- catalyses conversion of fibrinogen to fibrin
- activates factor XIII
cross links - form between adjacent fibrin strands, strengthens and stabilises the clot. catalysed by factor XIII
Describe the blood clotting cascade - Intrinsic pathway
- initiates clotting in damaged vessels and in a test tube
- activated when factor XIII comes into contact with collagen or foreign surface
- aggregated platelets secrete platelet factor (PF3) which is essential for the cascade and platelet aggregation
- Results in activation of Factor X, a
protease which can digest
PROTHROMBIN -> active
THROMBIN
describe Blood Clotting Cascade - Extrinsic Pathway
- Requires contact with tissue factors
external to the blood - Traumatised tissue releases TISSUE
FACTOR, a polypeptide (also called TF,
Factor III, thromboplastin) - TF (with Factor VII) activates Factor X
- To clot blood which has escaped into
tissues
what is a common factor for both intrinsic and extrinsic pathways
Both Intrinsic and Extrinsic
Pathways activate FACTOR X -> COMMON PATHWAY
what is fibrinogen
a soluble plasma protien that consists of 6 polypeptide chains.
describe the process of thrombin converting fibrinogen into fibrin
- when thrombin cleaves 4 peptide bonds in fibrogen and releases fibrinopeptides, the cleaved molecule is called fibrin monomer
- The monomers spontaneously assemble into ordered fibrous arrays called
FIBRIN which are INSOLUBLE - The Fibrin is cross-linked by the action of ACTIVATED FACTOR XIII (XIIIa)
what are the regulation of the clotting process
- Clotting factors are labile and once activated are short-lived due to dilution
by blood flow, removal by the liver and degradation by proteases - thrombin catalyses the formation of fibrin
but also initiates the deactivation of the clotting cascade - Specific inhibitors of the clotting cascade e.g. anti-thrombin III, a plasma protein that forms an irreversible
complex with thrombin
what stops blood from clotting
fibrinogen is always present in blood but thrombin is present as inactive prothrombin, if not, blood would always clot
