Antithrombotic Therapies Flashcards
When should you prophylax for TE dz pre-op?
Low risk pt’s don’t need it (minor procedure, otherwise healthy)
Moderate risk: abdominal surgery, thoracic surgery, medical pt
High risk: paraplegic, hemipletic, pelvic surgery, leg surgery, cancer pt’s
Heparin
True catalyst that binds & activates antithrombin which inactivates XI, IX, X, Thrombin
Monitor TTP
Cons: Variable bioavailability, short half life, requires monitoring, higher risk of complications especially HIP
Pros: cheap, effective in treatment & some prophylaxis, fully reversible with protamine
When you monitor heparin, what are you looking for?
Make sure you attain therapeutic anticoagulation
Monitoring is not to prevent bleeding
This is an important distinction
LMWH
More homogenous, predictable dosing without monitoring (except in renal dz, obesity, cachexia, pregnancy)
Pros: longer half life, can be given subcutaneously 1-2x/day, lower risk of HIT, as effective for treatment & more effective for prophylaxis
Cons: more expensive, longer acting, only partially reversible with protamine, renally excreted (dosing problematic in renal dz), cross reactive with HIT causing antibodies, more effective for prophylaxis if given pre-op
Black box warning vs. use with regional anesthesia
Enoxaparin
Has the most approvals:
VTE prophylaxis & treatment
Acute coronary syndrome
Dalteparin
Same as enoxaparin except VTE treatment only in cancer pt’s
Tinzaparin
Approved to treat VTE
Warfarin
Oral, doesn’t affect proteins already synthesized, takes several days to work: 5 day overlap
Inhibits Vit K reductase –> blocks synthesis of Vit K dependent factors (II, VII, IX, X, Protein C & S)
Monitor PT/INR
Lots of DDI and food interactions
Vitamin K = antidote
Start with 5-7.7 mg and adjust based on PT/INR
Factor Xa inhibitors:
Apixaban, Fondaparinux, Rivaroxaban
Woder therapeutic index, no overlap with parenteral agent needed
No food or DDI, dosing without monitoring ok but hard to follow pt compliance
Expensive, no reversal agent
Apixaban
Oral, 2x daily, approved for stroke prevention in nonvalvular AFib, superior to warfarin
Xa inhibitor
Fondaparinux
Subcutaneous, 100% bioavailability, daily injections
Possibility of post-op prophylaxis
No thrombocytopenia risk
Superior to LMWH when given post op and pre-op
Risk of wound hematoma but not if given >6h post-op
Approved fo VTE prophylaxis and treatment
Rivaroxaban
Xa inhibitor
Approved for VTE prophylaxis in ortho, stroke prevention in non-valvular AFib, treatment of VTE
Oral, takes effect immediately
Direct Thrombin Inhibitors
Blocks active site of thrombin –> inhibits both clot bound and free thrombin
More potent than heparin
Argatroban, bivalirudin, dabigatran, desirudin
Agatroban
Direct thrombin inhibitor
Oral, synthetic L-arginine molecule
Aprroved for HIT+prophylaxis and treatment of thrombosis
No cross-reactivity with heparin-induced antibodies
No antidote
Short half life
Problem in liver dz
Bivalirudin
Short acting, not reversible
Approved for unstable agina/angioplasty
Desirudin
Half life is 6-7 hrs
Approved for DVT prophylaxis in HIT
Dabigatran
Oral, the one in commercials
TE prevention in AFib, better than warfarin
150 mg 2x/day
Problem if pt has renal failure
Hematopoietic growth factors
Stimulate development & differentiation of blood cells
Thrombopoietin mimetics, Erythropoietin, G-CSF/GM-CSF
Romiplostim and Eltrombopag
Thrombopoietin mimetics
Stimulates differentiation & maturation of megakaryocytes to plts
Treats immunogenic thrombocytopenic purpura
Erythropoietin
Kidney makes this cytokine, necessary for erythroid proliferation and differentiation
Binds to erythropoietin receptor, transmembrane protein/cytokine receptor –> dimerization –> activates tyr kinase –> Jak/stat pathway –> nuclear signal to activate production of proteins –> proliferation & differentiation
Also signal to block apoptosis
Darbepoetin = synthetic version
Filgrastim (G-CSF)
Used in heme/onc
Increases differentiation & maturation of neutrophils
Most commonly used to increase WBC count post-chemo
SE= hyperleukocytosis, capillary leak syndrome)
Pegfilgrastim = synthetic version
Sargramostim = GM-CSF
Granulocyte-monocyte colony stimulating factor
Causes commitment to granulocyte/monocyte line
SE= fevers & capillary leak: bc it’s purified from E. coli & might have a little endotoxin the prep that leads to fever
