Hemostasis Flashcards
What is haemostasis?
- Complex set of interactions.
- divided into 3 processes
- a) primary hemostasis b) coagulation and 3 ) fibrinolysis
- main interacting components: blood vessels, platelet, plasma proteins. Erythrocyte and leucocyte play a role as well.
- After injury, vasospasm reduces blood flow
- exposed sub endothelium initiates platelet adhesions results in temporary platelet plug formation
- at the same time, coagulation cascade is activated by the vessel injury and substances released from platlet
- The coagulation cascade leads to fibrin formation, reinforce the initial platelet plug
- generation of fibrin leads to activation of fibrinolysis
In the event of vascular damage, tissue factor bearing surface is exposed which triggers formation of factor V, IX, and platelet activation, aggregation . This allows platelet plug formation, assembly of procoagulant enzymes and kickstart coagulation cascade.
Stages of haemostasis
Primary : platelet, vWf –> platelet plug formation. Shape changes allow adhesion, activation, aggregation of platelet to the site of injury, and assembly of procoagulant enzymes
Secondary: coagulation cascade ( extrinsic and intrinsic ) - propagation, amplification of coagulation -> formation of fibrin clot
Dissolution of fibrin clot by plasmin , antithrombin + protein C inactivates coagulation factor
Role of wvF
consequence of reduced wvf number or function
Types of wvf D
a adhesive glycoprotein, uncoiled and bind to exposed collagen in the fast blood flow vessel ( not capillaries ) , the other end has a receptor, to which platelet bind to.
a component of factor 8
has low, medium, high dimer
Platlet is unable to bind, be activated or release therefore no vasoconstriction, unable to form platelet plug and sustain coagulation.
clinical signs: bleeding during or after surgery. No petechiation ( surface bleeding) because vWF present in high blood flow vessel only , not essential in capillary hemostasis.
Type 1 : decreased in level but all dimer present
Type 2: decreased of high molecule dimer- the efficient one in clotting.
type 3: absent of wvf - in all dimers - most severe
What are the inhibitor of coagulation in body
tissue plasminogen activator; urokinase type plasmin ogen activator ( breakdown fibrin/ fibrinogen to FDP/ D-dimer )
ATIII ( antithrombin )
Protein C, protein S ( found in liver )
Factors in extrinsic pathway
Factors in intrinsic pathway
Factors in common pathway
7,
12 ( not essential ), 11 ( minimal bleeding if absent ), 9 ( Hemophilia B if absent ), 8 ( haemophilia A if absent )
10 , 5, 1 ( fibrinogen) , 2( prothrombin) , 13 ( link fibrin monomer to polymer )
How does clopidogel or aspirin prevent thrombus formation
clopidogel: prevent ADP from binding the receptor on platelet. This prevent activation and aggregation of platelet. Irreversible.
Aspirin: inhibit COX enzymes system, inhibit production of thromboxane and prostaglandin. Thromboxane has most stimulating effect in platelet aggregation. This enzymes inhibition is irreversible.
Common causes of bleeding
- thrombocytopenia
- thrombocytopathia
- vWf deficiency in quantity or function
- Defect in coagulation cascade ( congenital or acquired )
hypertension and hyperviscocity can also cause exudation of blood
what does tissue factor located
sub endothelium , only becomes active when endothelium is cut and expose sub endothelium collagen
subendothelium
monocyte and endothelial cell can also express under the influence of cytokines and endotoxin.
Why is cell based model of hemostasis make more sense ?
- factor 12 is not essential in clotting
- extrinsic pathway cannot replace intrinsic pathway
- primary and secondary homeostasis happen simultaneously
- events are interrelated
clinical features of bleeding in primary and secondary hemostasis disorder
primary hemostasis: ( small and shallow )
- petechia
- bruises
- immediate bleeding
- small bleed
Secondary hemostasis ( big and deep )
- hematoma
- big bleed into cavity/ joint
- delayed bleeding
DIC
what is it?
Pathophysiology?
Common disease associated with it?
What does it suggest in lab work?
- widespread coagulation in the system causing excessive thrombosis, consumptive large amount of clotting factors, inhibiting platelet function which in the end results in hemostasis disorder -> excessive bleeding.
- paralysis of MNP
- blood stasis
- hypoxia, acidosis( inhibit AT III, and heparin )
- blood hemolysis
- IMHA
- pancreatitis
- cushing disease
- shock
- sepsis
- heat stroke
- HSA spleen
- thrombocytopenia - dropping platelet
- high FDP/ d- dimer
- low fibrinogen
- prolonged APTT, PT, TT, ACT
- presence of shistocytes
How does rodenticide cause bleeding ?
common rodenticide
Rodenticide inhibit enzyme vit K epoxide reductase, which is essential in vit K recycling from vit K epoxide to vit K hydroquinone which is needed to activate via carboxylation of coagulation factors 2, 7, 9, 10 . If this enzymes is inhibited then large amount of vit K 1 needs to be supplied for a period of time. K 1 is high in green leafy, medium level in animal products.
The above cellular function is temp dependant. Hypothermia exacerbates clotting disorder.
Warfarin ( coumarin)
Brodicoferum
Test for
1) intrinsic coagulation,
2) extrinsic
3) common pathway
4) platelet function
5) wvf
Which is more sensitive for intrinsic ACT or APTT
1) APTT ( activated partial thromboplastin time ), ACT
2) PT ( prothrombin time ), ACT
3) ACT , APTT, PT
4) BMBT
5) Elisa assay melb uni
n/b vwf will have normal of the above except 4 )
APTT
