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What factors influence initiation of coagulation following blood vessel endothelial injury?
Exposure of platelets to collagen and the VonWillebrand factor.
tPA becomes clot-specific only at pharmacologic levels. True or False?
- False. At pharmacologic levels tPA becomes systemically specfic leading to increased bleeding and decreased clot formation and stability in the entire body.
- tPA is clot specific at physiologic levels only.
What is the risk of developing HIT in patients using UFH?
- Fequency 1-4% in patients receving UFH for a minimum of seven days (5-10 days, Gillman and Goodman)
- More common with use of bovine UFH > porcine UFH > LMWH.
How UFH is reversed?
- Two options are available:
- - Stopping UFH;
- - Protamine Sulphate.
How Protamine Sulphate is dosed?
- - 1mg of PS for every 100IU of UFH;
- - Infusion not more than 50mg in 10 minutes.
How LMWH is reversed?
- Protamine Sulphate incompletely reverses Enoxaparine (Clexane).
- The dose is 1mg of Protamine Suphate for every 1IU of LMWH.
How does Warfarin work?
Warfarin blocks gamma-carboxylation of glutamate residues in prothrombin, factors VII, IX, X and anticoagulant proteins C and S. This results in production of ineffective coagulation molecules. It also blocks reduction of oxydated vtamin K to its active (hydroquinone) form. carboxylation reaction of clotting factors is coupled to oxydation of vit K with deoxydation and recycling of vit K for another carboxylation..
The onset of acton of Warfarin is almost immediate when given in 5-10mg dosess. True or False?
False. The onset of action of Warfarn is eight to 12hrs.
What causes the delay in the onset of action of Warfarin?
The delay in the onset of action is caused by the presence of already activated and vit K dependent factors and their half-lives.
What are the vitamin K-dependent clotting factors?
They are factors VII, IX, X and II.
Name thrombolytic agent with longer T1/2, more fibrin specific than Reteplase that can be given as IV bolus.
Reteplase is more fibrin specific than Alteplase. True or False?
False. Reteplase is less fibrin specific than Alteplase because it lacks the specific fibrin-binding domain that is present in Alteplase.
What is Heparin?
It is a mixture of sulphated mucopolysacharides.
How does Heparin work?
Following binding to ATIII - it allows protease binding site to be more exposed for binding and inhibits thrombin. UFH accelerates this, normally very slow, reaction by the factor of 1000.
What is the importance of Thromboxane A2 in coagulation?
- TxA2 causes platelets to
- - change shape,
- - release granules and
- - aggregate.
How coagulation process is affected by Aspirin?
Aspirin causes irreversible acetylation of CycloOXygenase. This prevents synthesis of TxA2. This leads to prolonged bleeding time in vivo and prevents aggregation of the platelets in vitro.
What is the duration of the antiplaelet effect of Clopidogrel?
The duration of the effect is 7-10 days.
With regard to Clopidogrel, what is the loading dose, the maintenance dose and duration of action of the agent?
- - The loading dose is 300mg;
- - The maintenance dose is 75mg and
- - The duration of actioin is 7-10 days.
How Clopidogrel exerts its action?
Clopidogrel bloks ADP receptors on platelets prevetion them from adhesion.
Clopidogrel reversibly blocks prostaglandin synthesis and blocks ADP receptors in platelets thus preventing adhesion of platelets. True or False?
False. Clopidogrel has no effect on the synthesis of prostaglandins.
What are the advantages of using LMWH over UFH?
- When using LMWH, the advantages are few:
- - No need to monitor APTT;
- - More uniform absorption when given SC;
- - Lower rates of HIT;
- - Lower risks of bleeding;
- - Lower risks of osteopenia;
- - Easier wight adjusted dosing for outpatients.
What is HIT?
- Immune-mediated reaction against Heparin-Platelet Factor IV complexes.
- Derease in platelets to <150,000/uL or a 50% decrease from pretreatment value.
- Predominantly venous thrombotic complications (gangrene), but arterial thrombosis also occurs.