Anticoagulants: coag cascade and heparins Flashcards
What are coagulation factors?
Enzymes
What happens as the steps of coagulation go on?
The initial signal is amplified
Where is the coagulation cascade made?
In the liver
What does the final pathway of the coagulation cascade result in?
Conversion of prothrombin (II) to thrombin
What does the conversion of prothrombin to thrombin catalyze
Conversion of fibrinogen to fibrin
What does fibrin activate?
Plasmin and tissue plasminogen activator (t-PA)
What balance maintains homeostasis
The balance of procoagulants (coag factors) and endogenous anticoagulants
Give some examples of endogenous anticoagulants
Proteins C and S
Antithrombin III
What are proteins C and S important for
Warfarin dosing
What is antithrombin III important for?
Heparin dosing
What does the fibrinolytic system do?
Degrades fibrin
What does the degradation of fibrin result in?
Fibrin split products (FSP) Fibrin Dimers (d-dimer)
What are fibrin split products also known as
Fibrin degradation products (FDPs)
What do increased levels of FSP, FDPs, and d-dimers suggest?
Presence of thrombi
think DVT
What are some examples of venous thrombi?
DVT
“Red thrombus”
Venous stasis thrombi
What is a complication of venous thrombi?
Pulmonary embolus
What are some examples of arterial thrombi?
Platelet driven
“White thrombus”
What are some complications of arterial thrombi?
Stroke
MI
Recall virchow’s triad
Hypercoaguable state
Endothelial injury
Circulatory stasis
List some risks for thrombosis
Surgery Cancer Immobility Varicose veins Pregnancy
What is a potential complication of anticoagulation agents?
Bleeding
Is bleeding from an anticoagulant an allergy?
No!
Just an extension of their MOA
What is the MOA of heparin
It binds to antithrombin III
AT III
What is required for heparin binding
A specific pentasaccharide sequence
Heparin limitations
look at slides 20 and 21
What is unfractionated heparin (UFH)
A heterogeneous mix of sulfated glycosaminoglycans
What portion of UFH have the pentasaccharide?
1/3
How much more anticoagulant does UFH antithrombin complexes have than just antithrombin alone?
100-1000x more
What is UFH effective on?
Soluble fibrin -> not clot bound
What does UFH do to the thrombus?
Prevents growth/propagation
What does UFH allow the pt’s system to do?
Allows pt’s fibrinolytic system to degrade the clot
How do we measure UFH
By the activated Partial Thromboplastin Time (aPTT)
What kind of heparin is used as DVT prophylaxis
subq UFH
How much subq UFH is used as DVT prophylaxis
5000 units q12 or q8
What is the risk of heparin induced thrombocytopenia (HIT) with SubQ UFH for DVT prophylaxis?
It is that of IV UFH
*increased risk
List some advantages of UFH
Immediate anticoagulants
Measured by aPTT
Has a reversing agent (Protamine)
List some disadvantages of UFH
Non-linear kinetics
Frequent lab testing needed
Increased risk of bleeding
What is Protamine sulfate used for
Reverse UFH
What is the MOA of Protamine
combines w/ strongly acidic heparin
Is HIT I immune or non-immune
Non-immune
HIT I prevalence
10% of pts
HIT I description
Ok -> not very concerning
Transient due to clumping of platelets -> usually an artifact
How quickly does HIT I happen?
Immediately
Is HIT II immune or non-immune
Immune
Mediated by anti-platelet factor 4
Prevalence of HIT II
<3%
HIT II description
Happens 5-10 days after heparin
Platelet count falls by >50% from baseline
If pt has HIT II what do you test for?
PF4
How do you reduce the risk of HIT w/ a pt with low molecular weight heparin?
When this is the first heparin started in the pt
How is low molecular weight heparin (LMWH) dosed?
Weight based linear dosing
How do you administer LMWH?
SubQ
What is an available LMWH agent?
Enoxaparin
When are LMWH agents indicated?
ACS tx
DVT
PE
VTE prophylaxis in high risk populations
List some advantages of LMWH
More favorable benefit/risk ratio
More predictable dose response ratio
No IV access required
No routine testing
List some disadvantages of LMWH
SubQ administration causes pain
Testing requires anti-Xa -> not readily available
Possible upper weight max
No protamine reversal
Enoxaparin dosing for acute DVT w/ or w/o PE in an inpatient setting
1 mg/kg/dose (rounded) SubQ q12 hours
1.5 mg/kg (rounded) SubQ once daily
Enoxaparin dosing for acute DVT w/ or w/o PE in an outpatient setting
1 mg/kg/dose (rounded) SubQ q12
Is LMWH more or less costly than UFH?
Less
Is the risk of HIT higher or lower with LMWH than UFH?
Lower risk of HIT
