Pharmacology: Anticoagulation Flashcards
What is the mechanism of action of heparin and how does LMWH vs Unfractionated heparin differ?
Bind antithrombi III (think of the AT3 cage) to facilitate deactivation of factors IIa and Xa
Shorter polysaccharide chain makes it more difficult for LMWH to bind thrombin (beaver) at same time as factor X (FoX). Thus, LMWH binds thrombin at a much lower ratio than UFH.
What monitoring is required for UFH and LMWH?
UFH - aPTT, much more sensitive to changes in factor II levels
LMWH - blood monitoring not required
How are the pharmacokinetics of LMWH different from UFH? Antidote?
LMWH is more bioavailable, longer half life, and eliminated renally (tapering flag sticking into kidney from LMWH daughter)
Furthermore, UFH can be reversed totally be protamine sulfate, but cannot fully reverse LMWH (Daughter can get thru the PRO fence)
What is bridge therapy and what heparin is typically used for this?
Use of subcutaneous anticoagulant (LMWH is best because of high bioavailability) for the purpose of keeping anticoagulant while warfarin comes online, or patient needs to stop warfarin for a surgical procedure and needs some anticoagulation in the meantime
Who are the only patients who should get bridge therapy for surgery? Why?
Patients with high risk for thromboembolism and low risk for bleeding
-> studies have shown it causes significantly more bleeding in a patient during procedures
What are common and rarer side effects of UFH / LMWH outside of HIT?
Bleeding
Rarer:
Osteoporosis - due to stopping of bone deposition, think of bone sticking from tree with termites
Hyperkalemia - due to hypoaldosteronism
Elevated LFTs due to liver damage from metabolism of heparins
What is HIT and what is the mechanism? What types of heparin tend to cause it?
Heparin-induced thrombocytopenia, from forming antibodies against heparin + PF4. These antibodies bind and activate platelets, cause a hypercoagulable state and low platelet count
UFH most commonly causes it - think of dad shooting four plates
LMWH can cause it but it is rare - she throws up four plates but doesn’t shoot them
Fondaparinux never causes it
What is the typical onset time of HIT?
after day #4 of heparin therapy
Can be more rapidly if patient has previously been exposed to heparin, or rarely delayed onset (Greater than 3 weeks after cessation of therapy)
What is the clinical presentation of HIT & its most common complication?
Drop in platelet count greater than 50% below baseline
Most common complication is venous thrombosis. Almost 50% will get DVT / PE if untreated.
Arterial thrombosis is less common. Arterial thrombosis can cause limb gangrene, skin necrosis, and organ infarction (MI, stroke).
What is the most acute reaction which can occur with heparin?
Acute systemic anaphylactic reactions within 30 minutes of IV heparin bolus
-> fever, chills, hypertension, dyspnea, cardiorespiratory arrest
What scoring system is used to determine the diagnosis of HIT?
The 4Ts scoring system, including Thrombocytopenia Timing of platelet count fall Thrombosis or other sequellae oTher possible causes of thrombosis present
What drug is given in the management of HIT?
Direct thrombin inhibitors, i.e. espectially argatroban (gator eating thrombeaver)
Bivalirudin if patient needs PCI
What enzyme does warfarin inhibit and why is bridge therapy required when you first start it?
VKOR - vitamin K epoxide reductase
Therapy is required because proteins C and S have shorter halflives than some of the 2,7,9,10. Thus, there will be a transient procoagulant state until those clotting factors are lost from the blood (warfarin only inhibits synthesis) -> 5 days needed
Remembers proteins C and S inactivate factors 5 and 8 respective and thus are natural anticoagulants which are lost
What are the adverse effects of warfarin?
Bleeding, skin necrosis and purple toe syndrome could occur due to protein C deficiency
Contraindicated in pregnancy
- > fetal bone malformation
- > LMWH should be used instead
What is the target INR for warfarin? What dietary considerations need to be made to maintain this?
INR = 2 to 3
Keep eating vitamin K containing foods consistently
Separate soy protein and fiber from warfarin as they inhibit absorption
