Flashcards in Hemostatis agent Deck (52):
What is Tisseel
Topical sealant containing fibrinogen and thrombin (small amount of aprotinin)
What is FLOSEAL?
topical agent that consists of gelatin matrix hemotstatic sealant that is composed of human thrombin and a proprietary gelatin matrix.
Augment the coagulation cascade at multiple site. It has proven efficiacy in cardiac surgery.
Best to use with arterial bleeding
What is COSEAL?
Surgical sealant composed of polyethylene gycol (PEGS)
What is surgicel?
provides a platform for hemostasis to occur
What is dose of protamine for reversal of heparin?
1 gram of protamine per 100 units of heprain
What is the range of dosing for factor VII
According to body weight
65ug/Kg to 100ug/k--NovoSeven is available in the hospital at 1.2, 2.4, and 5 mg Vials.
How does factor VII work
stimulates the coagulation cascade by activation of thrombin at the site of tissue injury by tissue factor-dependent and independent mechanisms.
Tissue-factor dependent mechanism results in production of FactorX which leads to the generation of thrombin.
The tissue factor independent mechanisms include activation, aggregation, recuitment and stablization of platelets that are resistant to fibrinolysis.
What is BioGlue
Has two components---purified bovine serum albumin (BSA) and glutaraldehyde.
polymerize reaction in 20 to 30 seconds and reaches full strength in 2 minutes
Name 2 new anitplatelet durgs
What study and dosing is important regarding ASA and bypass grafts
Antiplatelet trialists Collaboration
restarting ASA before surgery or withing 24 hours after surgery had a similar benefit on vein graft patency.
75 to 325 mg.
Effect of ASA on mortality
Study from mayo clinic in 16 3 patients showed preoperative asa pts had a significantly lower post operative mortality (1.7% vs 4.4). No difference in bleeding.
NEJM study showed that preoperative ASA in isoalted CABG patients resulted in 27% reduction in-hospital mortality.
Name 3 thienopyridines
prodrugs that are biotransformed into molecules that bind irrecversible to P2Y12 receptor.
Why plavix in pts with ACS
CURE: clopidogrel in Unstable ANgina to precent recurrent events---ASA + plavix
This resulted in a reduced cardiovascular death, myocardial infarction, or stroke in patients with ACS
11% relative risk reduction.
benefit was mainly before surgery.
What is Prasugrel
Associated with increased bleeding risk
surgery should be delayed by 7 days.
similar active metabolite to plavix
What is Ticagrelor
Nonthienopyridine, pyrimidine derivative, direct-acting, and reversible antagonis of the ADP receptor P2Y12 with a plasma half-life of about 12 hours
More rapid, potent and consistent effect on platelet function compared with clopidogreal.
Currently indicated for the treatment of patients with ACS on the basis of the PLATO trial.
What is PLATO trial
Large, multicenter trial, with pts in ACS with/without ST MI.
Composite of death, MI, stroke, at 12 months was signficant reduced with ticagrelor compared to clopidogrel. 4.5% vs 5.9%
According to recent recommendations of the 2011 ESC guidelines for NSTEM with ACS
Ticagrelor is considered first line therapy.
Prasugrel is recommended only for P2Y12 inhibitor naive patients whom coronary antomy is known and are who are proceeding with PCI
Plavix is for pts who cannot receive ticagrelor or prasugrel.
How long should you stop ticagrelor
5 days before surgery
ticagrelor higher potency; platelet inhibition is the same as plavix in first 24 to 28 hour
only 3 to 5 days from discontinuation is there less platlete inhibiton compared to plavix.
What is the evidence for GPIIbIIIa
PURSUIT study in patients with NSTEMI and ACS
30 day mortality was 26.1% vs 30.8%
When do you stop Eptifibatide and tirofiban before cardiac surgery
2 to 4 hours
When you stop Abciximab?
It has a short plasma half-life of about 10 minutes but it dissociated slowly from the platelet receptors
12 hours before CABG, if not you have to give platelets..
List the stages of hemostasis
1. Vascular phase--immediate response (local and myogenic spasm)
2. Platelet phase--goal to make a platelet plug
3. Clotting phase (turns loose platelet plug into a stable fibrin clot)
3 pathways that are involved in clotting cascade
intrinsic---(contact activation pathway)
extrinsic pathway--(tissue factor), activated by TG released by endothelium follow vessel damage
Final common pathway and results in fibrin formation
List co-factors involved in coagulation cascade
Calcium---required to convert tenase to prothrombinase to covert prothrombin to thrombin
Vitamin K---required for the production of factors II, VII, IX and X
What is fibrinolysis
process of clot break down and primarily controlled by plasmin
Plasminogen is inactive form
activated by tPA
inactivated by alpha 2 antiplasmin and serine protease inhibitors
What happens with Anti-thrombin levels
ATIII levels are usually 100% active but with heparinization activity is reduced to 30%
If you have resistance of heparin in OR, then one of the key step is to give FFP to replenish your ATIII store and have your heparin effect.
How is Argatroban cleared
How are lepirudin and Bivalidudin cleared
What is Thromboelasography and what does it measure
TEG monitors hemostasis as a whole
The life of a clot
time to initial clot formation
Evaluation of clot in the acceleration
Assess clot strengthening and retraction
Detect clot lysis
TEG parameters of interest
R value - time from initiation of the test to the initial fibrin formation
K value- time from the beginning of clot formation until the amplitude of the TEG reaches 20 mm
maximal amplitude (MA) repsents clot strength which is depentedn on the number of function of platelts and its intercation
What is action and potential role for DDAVP?
increase factor VIII and VwF
Appropriate for pts with kidney disorders (Uremic bleeding)
May have a role in pts who were taking ASA pre-op
Meta analysis showed a 9% reduction in blood loss (not clinically signficant)
What are 3 stages of hemostasis
What two things should be corrected before giving factor VIIa
Hypothermia and acidosis reduced ability of Factor VII
What percentage of patients do not respond to plavix
a. How is Bivalirudin and Lepirudin cleared from body?
b. How is Argatroban cleared?
b. Liver *So you can use if a pt has HIT and renal insufficiency
List two Anti-Factor Xa oral medication
What is mechanism of action of Dabigitran
Oral, direct competitive thrombin, inhibitor
Re-Ly study showed in AF that 110 vs warfarin was equal and 150 vs warfarin resulted in less stroke 1.69 vs 1.11% with similar bleeding
Limitation was the time spent in therapeurtic range on warfarin was limited for pt. when pts were in therapeutic range greater >70%) of time there was no difference
How does heparin work
Heparin potentiates the action of ATIII (which normally acts by inhibiting thrombin) by 1000 time so it inhibits thrombin and the subsequent anticoagulation effect.
How is Ticragrelor different from plavix
Like the thienopyridines prasugrel, clopidogrel and ticlopidine, ticagrelor blocks adenosine diphosphate (ADP) receptors of subtype P2Y12.
In contrast to the other antiplatelet drugs, ticagrelor has a binding site different from ADP, making it an allosteric antagonist, and the blockage is reversible.
Moreover, the drug does not need hepatic activation, which might work better for patients with genetic variants regarding the enzyme CYP2C19 (although it is not certain whether clopidogrel is significantly influenced by such variants).
What is abicimab
Abciximab is made from the Fab fragments of an immunoglobulin that targets the glycoprotein IIb/IIIa receptor on the platelet membrane.
Abciximab has a plasma half-life of about ten minutes, with a second phase half-life of about 30 minutes. However, its effects on platelet function can be seen for up to 48 hours after the infusion has been terminated
What is factors help regulate the coagulation cascade
inactivates factors V and VIIIa in the presence of Protein S
Anti-thrombin III--inhibits thrombin and factors IX, A and XI
Prostayclin, inhibits platelet aggregation and causes vasodilation
What is mechanism of action of Fondaparinux
Pentasaccharide Factor Xa inhibitor.
Within heparin and heparan sulfate this monomeric sequence is thought to form the high affinity binding site for the anti-coagulant factor antithrombin III (ATIII). Binding of heparin/HS to ATIII has been shown to increase the anti-coagulant activity of antithrombin III 1000 fold. In contrast to heparin, fondaparinux does not inhibit thrombin.
What is mechanism of action of Bilvalirudin
reversible direct thrombin inhibitor
Chemically, it is a synthetic congener of the naturally occurring drug hirudin (found in the saliva of the medicinal leech Hirudo medicinalis).
Bivalirudin, overcomes many limitations seen with indirect thrombin inhibitors, (heparin)
is a short, synthetic peptide that is potent, highly specific, and a reversible inhibitor of thrombin, inhibits both circulating and clot-bound thrombin, while also inhibiting thrombin-mediated platelet activation and aggregation.
Bivalirudin has a quick onset of action and a short half-life. It does not bind to plasma proteins (other than thrombin) or to red blood cells.
No risk for Heparin Induced Thrombocytopenia/Heparin Induced Thrombosis-Thrombocytopenia Syndrome (HIT/HITTS).
Does not require a binding cofactor such as antithrombin and does not activate platelets.
Name inibition of coagulation cascade
Natural anticoagulants---ATIII, Protein C and Protein S
Fibrinoytic system (Plasmin--degrades fibrinogen)
What degree is platlete aggregability reduced after CPB
by about 60%
and bleeding time is longer
these outcome persist for more then 24 hours
What is normal weight of Heparin (UF) and LWMH (Enoxaprin)
half life of heparin
half life of Enoxaparin
UF = 750 - 1000 kDA
LMWH 1- 10 kDA
UF = 60 to 90 min
LMWH = 4.5 hours * only partially reverses protamine
What are complications of warfarin
Vit K antagonist
Half life is 36 to 42 hours
Vit K causes reversal in 8 to 24 hours
Complications: Bleeding/ Skin necrosis (Vit C and S deficiency), fetal abnormalities
What is loading dose and time of action for plavix
Research showing 600 mg of Plavix is better (900 mg made no difference)
onset of action is within 2 hours
Inhibits ADP induced aggregation
Requires 5 days for platelet activity to return
Inhibits ADP induced platelet aggregation
with 60 mg of oral loading dose
onset of action is < 30 minutes
peal effect in 4 hours
greater risk of bleeding: not in pts with previous stroke, age > 75; or pts with PUD
Details of the GPIIb/IIIa inhibitors
Antiplatelet agents--inhibit aggregation by preventing fibrinogen, von Willebrand factor, and other adhesive ligands to bind to GP IIb/IIA
What is Octaplex
Prothrombin Complex Concentrate (PCC) is a combination of blood clotting factors II, VII, IX and X, as well as protein C and S.
It reverses the effect of warfarin (a coumarin anti-coagulant) and is used in cases of significant bleeding in patients with a coagulopathy (INR > 8.0, prolonged prothrombin time, raised d-dimer).
lasts for 6 to 12 hours. only 25 to 50 ml, no risk of TRALI