Procoagulants Flashcards
name the two synthetic antifibrinolytic agents available (lysine analogs)
epsilon aminocaproic (EACA)
tranexamic acid (TXA)
antifibrinolytic agents- such as EACA and TXA competitively inhibit activation of?
plasminogen to plasmin
EACA has been removed from many european countries D/t?
safety concerns
when comparing aprotinin, EACA, TXA -what is the MI risk
no risk
aprotinin, EACA, TXA were effective in reducing the need for
RBC transfusions
specifically aprotinin was effective in reducing
need for reoperation d/t bleeding
aprotinin, TXA, EACA have also reduced blood loss during ____surgeries
orthopedic surgeries
what is the function of plasmin
breaks down fibrin clots
what does TXA inhibit
plasminogen- which limits plasmin that breaks down coagulated functions
at higher doses what does TXA inhibit
plasmin
TXA dosing
loading and scheduled
1g/10min
1g/8hrs
oral TXA is used in the US for
heavy menstrual bleeding
TXA potential complications include
seizures:
TXA blocks GABA receptors in frontal cortex is thought to be the moa
what is aprotinin
polypeptide serine protease inhibitor
*what does aprotinin inhibit
plasmin and other serine proteases
when are we allowed to give aprotinin since it is removed from the market
available for compassionate use.
*in which situation is aprotinin used as an investigational drug under a special treatment protocol
in patients undergoing CABG surgery. it has been shown to decrease the need for RBC transfusion
*what does canada use aprotinin for
basic cabg surgery. but poor outcomes noted from higher risk cardiovascular surgeries. canada sites benefits outweigh risk
what is protamine
polypeptide containing approximately 70% arginine residues
*what medication is the only available reversal agent for UFH
protamine (polypeptide)
why do most patients receive too much protamine
plasma levels of heparin decrease overtime. and the protamine dose is not accounted for in the dosing
*excess protamine can contribute to
coagulopathy
& prolongs ACT
*how does protamine increase(wouldn’t it be decrease??) coagulation
inhibits platelets and serine proteases
oddly enough- excess protamine prolongs what level? and causes additional platelet dysfunction
ACT!
when protamine is given in the exact amount needed to reverse circulating heparin what is the act value
produces the lowest act values
when can heparin rebound occur
after initial reversal
when is heparin rebound observed
2-3 hours after first dose of protamine when pt is in ICU
the initial dose of protamine produces a
large drop in ACT time
if exact dose of protamine is not given, what may ensue
coagulopathy
a repeat dose of protamine may well be less than
50mg commonly administered
most patients may not need additional protamine
within 30 minutes of initial administration
the ACT is not a sensitive indicator of low heparin concentrations because…
platelet counts and fibrinogen levels may also affect values
protamine adverse reaction include (4)
anaphylaxis
acute pulmonary vasoconstriction (PHTN)
RV failure
hypotension
patients at an increased risk for adverse reactions are sensitized from exposure to the neutral protamine -where do patients get exposure to protamine
NPH
make up
Other patients at risk for protamine reactions include
vasectomy
drug allergies
prior exposure (eye make up/ mascara?)
DDAVP is an arginine vasopressin analog of
V2
what specific surgical patient might benefit from DDAVP
not clear
dose of DDAVP
0.3mg/kg over 15-30 minutes to avoid hypotension
what is the most frequently inherited bleeding disorder
VWD
ddavp may stimulate release of vWF
effect is likely minimal except in type 1 (maybe 2a)
*Type 3 and severe types 1 and 2, dDAVP is NOT EFFECTIVE
fibrinogen (1) synthesized where
in the liver
half life of fibrinogen is
3.7 days (4 days)
what do the platelets do with clot formation
enmeshed within the fibrin strands stabilizing the growing clot
fibrinogen acts as the binding site for glycoprotein IIb /IIIa receptors - found on platelet surface which are
responsible for platelet aggregation.
cross linking of fibrin polymers induced by what factor
XIIIa
factor XIIIa is fundamental to the coagulation process increasing elasticity of the clot and its resistance to
fibrinolysis
what is the binding site for glycoprotein IIb/IIIa receptor
fibrinogen
Fibrinogen also acts as the binding site (ligand) for glycoprotein IIb/IIIa receptors found on platelet surface which are responsible for
platelet aggregation
what substance is key to normalizing clotting function
fibrinogen supplementation
*what is the underregocnized coagulation factor that is critical for producing effective clot in surgical patients
fibrinogen
normal levels of fibrinogen
200-400 mg/dL
when do we expect fibrinogen to be elevated
greater than 400 m/dL in pregnancy
what is the important final step in clot formation
plasma XIII- stabilizes initial clot
what relationship does post operative blood loss have for factor XIII in cardiopulmonary bypass
inverse relationship
recombinant activated factor VIIa is
recombinant rFVIIa (7)
rFVIIa is approved for
hemophilia but known for off label use to procoagulant in massive hemorrhage
*
1 unit of cryoprecipitate per 10kg increases fibrinogen by
50-70mg/dl
in CABG- more factor XIII=
in CABG less factor XIII=
more factor XIII=less blood loss
Less factor XIII=more blood loss
• Warfarin reversal in the US is typically achieved
with FFP
most other countries use ___for warfarin reversal
PCC’s
Gelatin sponges (Gelfoam) what is it made from
purified pork skin gelatin- increases contact activation helps create topical clot
Surgicel or Oxycel
oxidized regenerated cellulose works like gelfoam
*work like gelfoam
where should gelatin foam NOT be used near
nerves or in confined spaces
when is coseal used
where swelling and expansion are not a concern
what has been used in cardiac surgery
bioglue
• BioGlue has been used in cardiac surgery but it contains a glutaraldehyde component
Cross-links proteins to fix tissues it is applied to
bovine thrombin should be avoided due to its potential for
anti-bovine thrombin antibody formation and immune mediated coagulopathy
cow=bovine have allergic reactions
where is unfractionted heparin extracted from
porcine (pig)intestine the majority or bovine (cow) lungs where heparin is stored in mast cells.
how are anticoagulant effects are produced by binding to
Anti thrombin (AT) previously known as at 3
heparin binds to AT enhancing the rate of thrombin at complex formation by how many times
1,000-10,000
how many fold increase in the risk for VTE
20 fold
in general surgery patients - what is the DVT % incidence
10-40%
name the 4 surgery categories that have the higher risk for DVT
orthopedic
thoracic
cardiac
vascular
general surgery have a higher risk of
DVT
in patients with renal failure or renal dysfunction- are heparin and warfarin affected?
minimally- due to non renal clearance
who has a risk of DVT higher than general surgery
hip surgery
DANAPAROID—Orgaran (LMWH)
no longer used in the US- due to?
shortage but used in other countries
danaparoid-orgaran how does it work?
this low molecular weight heparinoid compound attenuates fibrin formation by binding to AT
danaparoid- orgaran derived from procaine intestinal mucosa consisting of a mixture of
dermatan sulfate and chondroitin sulfate.
danaparoid -orgaran is eliminated
primarily in the kidneys
fondaparinux -Arixtra-metabolism occurs
metabolism Does not Occur! but it is eliminated by the kidneys and should not be used in patients with renal dysfunction
clinical uses of fondaparinux- arixtra
DVT
PE
alternative treatment for Hit positive
what factor does fondaparinux arixtra inhibit
Xa-stuart-has no direct activity against thrombin
if patient has renal failure what type of heparin do we use
LMWH is greatly prolonged in renal failure.
UFH should be used in kidney failure
for protection against venous thromboembolism in high risk medical and surgical patients- its thought to be better treated with
LMWH than heparin
what are the two commonly administered LMWH
enoxaparin and dalteparin
what pharmacokinetics of enoxaparin and dalteparin between patient are more consistent than heparin- why
because they bind less to proteins than does heparin
where do we find protamine
salmon sperm
what charges is protamine and heparin
protamine is positively charged alkaline
combines with the negatively charged acidic heparin to form a stable complex that is devoid of anticoagulant activity
protamine dosing example
o Example from class: If you gave 10,000 units 1 hour ago how much will you give? 5,000 units will be circulating (1 mg for every 100 units) so = 50 mg
protamine dose 1mg for how much heparin circulatin
1mg for every 100 units of heparin circulating
what is the half life of heparin
1 hours
if there is an immediate reaction to heparin what should be suspected
HIT
• For cardiac surgery, a baseline ACT is determined:
(before & 3 min after administration and 30 min intervals thereafter)
- Treating Fibrinogen Deficiency is important for survival and has a POSITIVE correlation with reductions in mortality of trauma patients.
- Consider transfusion before fibrinogen drop to
< 100 mg/dL may not be fixed by FFP.
PCC’s are concentrations of coagulation factors that include factors:
K-1972
II, VII, IX, X
Two PCC used worldwide are KCENTRA and Octaplex. the MOA :
Vit K antagonist-induced (Warfarin) reversal
3 other PCC approved in the usa for hemophilia are Feiba VH, Profilnine SD, Bebulin VH. These contain mainly what factor:
Factor IX (9)
PCC’s are recommended in guidelines are primary treatement of reversal in patients with:
- Life threatening bleeding
- and increased INR when URGENT REVERSAL IS REQUIRED
these agents are used intraoperatively to promote hemostasis at the site of vascular injury
Topical hemostatic agents
Currently there are 2 human thrombins available for
clinical use:
- plasma derived thrombin
- recombinant human thrombin
