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70 Cards in this Set
- Front
- Back
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What are the three components of Virchow's Triad
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1.Vascular injury- surgery, injury, indwelling catheter
2.Stasis- immobility, paralysis, atrial fibrillation, left ventricular dysfunction 3.Hypercoagulability- protein C or S deficiency, pregnancy, cancer (Objective 1, pg 4) |
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What are clinical complications of pulmonary embolism?
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PE is a type of venous thromboembolism (VTE).
Death pulmonary hypertension cor pulmonale recurrent VTE (objective 2, page 5) |
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What factors lead to an increased risk of cardioembolic stroke in a patient with a prosthetic heart valve? (there are 7)
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1. >1 prosthetic valve
2. atrial fibrillation 3. low ejection fraction 4. hypercoagulable state 5. atherosclerotic disease 6. ST-elevation MI 7. Left atrial enlargement (objective 3, pg 5) |
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What are complications of deep vein thrombosis (DVT)?
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DVT is a type of VTE.
PE post-thrombotic syndrome recurrent VTE chronic venous insufficiency (objective 2, page 5) |
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What factors are associated with increased risk for cardioembolic stroke in a patient with atrial fibrillation?
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CHADS2
C- Congestive heart failure H- hypertension A- Age >75 D- Diabetes S- history of Stroke/TIA A patient gets a point for each risk factor except S (stroke or TIA) counts for 2 points. (Objective 3, pg 4) |
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What is the mechanism of action for heparin?
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Heparin increases by >1000 fold the effect of antithrombin on factors IIa (thrombin), IXa, Xa, XIa, and XIIa.
Heparin binds to both antithrombin and the activated clotting factor expediting clotting factor neutralization. Factor II1 is most sensitive to the effect, followed by factor Xa. (only available through IV or subcutaneous) |
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What is the onset of action for heparin?
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onset of action- starts working immediately when given IV. Time to full therapeutic effect varies and requires monitoring with subsequent dosing adjustment. With appropriate monitoring an dose adjustment this should be achieved in less than 24hrs.
Onset of action SC= 1-2 hrs |
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What is the offset of action for heparin
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half life: 45 minutes (average)
discontinue about 4 hrs prior to a surgical procedure |
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What is the optimal timing for heparin monitoring effect?
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Should check every 6 hours until stable, then once daily
(objective 6, pg 7) (the tests used are PTT and activated clotting time, it does not say we need to know specific names of the tests) |
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True or False? Renal impairment does not necessitate dosing adjustments for heparin?
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True!! (this was not an objective, but was bolded and underlined)
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What are adverse effects of heparin?
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Bleeding- major bleeding depends on clinical scenario, can be as high as 1-5%. Minor bleeding is common (ex epitaxial). Common sites: surgical site, GI, soft tissue
Osteoporosis with vertebral fractures- associated with long term use of UFG (>3-6 mo) Thrombocytopenia |
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4 basic treatment pathways for treatment of VTE
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1. Thrombolytics
2. Anticoagluants 3. Thrombectomy 4. Inferior vena cava filter |
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Effects of vitamin K-containing food on warfarin therapy
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• Dietary vitamin K intake influences the amount of warfarin needed to achieve the target INR.
• If a consistent quantity of dietary vitamin K is consumed, the warfarin dose can be adjusted to produce the desired effect. • The more dietary vitamin K, the higher the warfarin dose to produce the desired INR. • If a patient increases dietary vitamin K intake, the INR will go down. If less, the INR will go up. • If an inconsistent amount of vitamin K is consumed the INR will fluctuate. • Examples of high vitamin K foods: green leafy vegetables. These include: broccoli, cabbage, greens (turnip or mustard), romaine lettuce. Liver also has significant vitamin K. • The message to patients should be consistency of vitamin K, not aversion. |
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UFH reversal agent
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Protamine Sulfate
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Fondaparinux reversal agent
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None
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LMWH Reversal Agent
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Protamine Sulfate
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Warfarin (Coumadin) reversal agent
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Vitamin K
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Dabigatran (Pradaxa) reversal agent
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None
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Orally active Factor X inhibitor reversal agent
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None
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Advantages and disadvantages of heparin
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• Effect has a quick onset and offset and easy to monitor.
• Good when tight control over; anticoagulation status is needed (quick onset and offset of action). This is particularly useful prior to and during some surgical procedures. • Less expensive than many alternatives. • Complicated by the need to monitor. • Not limited in renal failure as opposed to LMWH and fondarpinux |
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Advantages and disadvantages of LMWH
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• int-erpatient variability in dosing requirements, resulting in the need to monitor when used for tx of acute VTE
• With the specified outpatient indication for VTE treatment, enoxaparin is the most common drug used for acute anticoagulation in VTE. • LMWHs are more commonly used for inpatient treatment than UFH. • Monitoring for efficacy is infrequently needed. • Cost is a significant barrier to access, even for many insured patients (due to high copay). |
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Advantages and disadvantages of Fondaparinux (Arixtra)
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• Similar in efficacy to LMWH, although less frequently used.
• Shares advantages of LMWH over UFH (and greater benefit in area of HIT). • UFH or LMWH favored in renal impairment. • Alternative in patients with porcine allergy or who desire to avoid porcine products. • Longer half-life makes offset longer. Less preferred in patients with pending surgery. • Another disadvantage is lack of a reversal agent. |
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Advantages and disadvantages of Warfarin (Coumadin)
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• Warfarin takes several days or more to produce its full effect following initiation
• has a very narrow therapeutic index, substantial inter-patient variability in dosing requirements, and a large number of factors influence the magnitude of its effect • Regular INR monitoring is needed as long as the patient is treated with warfarin • Many drug ineractions |
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Advantages of Dabigatran (pradaxa) over warfarin
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• No laboratory monitoring required.
• Limited inter-patient variability (standard doses can be used). • No dietary limitations. It is not influenced by dietary vitamin K, a substantial advantage. • Few drug interactions |
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Disadvantages of Dabigatran (pradaxa) to warfarin
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• Expensive (~$260/month).
• No reversal agent. • Twice daily dosing. • No test accurately measuring effect is available. • Less time on the market (unknown side effects or other unknown problems). • No evidence-based dosing in CrCl < 15ml/min. |
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Characteristics of a good patient for dabigatran
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• Anticoagulation indication is atrial fibrillation.
• Monitoring INR is cumbersome for the patient (i.e. poor access to INR monitoring). • INR is frequently outside of therapeutic range. • Cost is not prohibitive. |
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Advantages of orally active factor X inhibitors over warfarin
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• No laboratory monitoring required.
• Limited inter-patient variability (standard doses can be used). • No dietary limitations. It is not influenced by dietary vitamin K, a substantial advantage. • Few drug interactions |
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Disadvantages of orally active factor X inhibitors to warfarin
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Same as dabigatran
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Advantages of rivaroxaban over dabigatran and apixaban
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Once daily dosing
FDA approval for tx of DVT & PE |
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Indications for primary and secondary prevention of thromboembolism (was not sure on this one)
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hospitalized medicine and surgical patients
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Risk factors for a major hemorrhagic event: HAS-BLED Risk Score
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H: Hypertension
A: Abnormal renal and liver function S: Stroke history B: Bleeding history L: Labile INRs E: Elderly D: Drugs that increase bleeding risk (aspirin, NSAID’s, etc) or alcohol use |
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What is the treatment for HIT?
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• Discontinue heparin
• Initiate anticoagulation with a non-heparin product (lepirudin, bivalirudin, argatroban, or fondaparinux) • Warfarin should not be used in these patients until thrombocytopenia is resolved (associated with venous limb gangrene or skin necrosis in patients with HIT). • Platelet transfusions are relatively contraindicated because they can aggravate the problem (adding fuel to the fire). |
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What is mechanism of action for LMWH?
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Interacts with antithrombin (similar to UFH) to accelerate the inactivation of clotting factors Xa (predominant) and IIa (modest). This predominance of effect on factor Xa represents a difference between UFH and LMWH.
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Goals of therapy for a pt experiencing VTE
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• Prevent pulmonary embolism (venous thromboembolism)
• Prevent extension of thrombus (venous or arterial thromboembolism) • Prevent post-thrombotic syndrome (venous or arterial thromboembolism) • Prevent recurrence of thromboembolism (venous or arterial thromboembolism) |
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What is the onset of offset of action for LMWH?
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• Onset of action: 2-4 hours
• Offset of action: half-life is about 7 hours, hold for 24 hours prior to a procedure |
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What drugs are classified as LMWH?
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• Enoxaparin (Lovenox), dalteparin (Fragmin), and tinzaprin (Innohep)
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What are adverse effects of LMWH?
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• Bleeding – similar to UFH
• Epidural hematoma around spinal procedures (can lead to paralysis) • HIT – substantially less common than in UFH |
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When does monitoring need to be done for LMWH?
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• Generally, monitoring for efficacy is unnecessary.
• Circumstances in which monitoring may be appropriate: o Renal insufficiency (CrCl < 30 ml/min) o Pregnancy o Weight < 50 kg or > 150 kg o Pediatrics |
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What drug is classified as Factor Xa Inhibitor?
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fondaparinux
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What is the mechanism of action for fondaprinux?
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It is a synthetic pentasaccharide based on the structure of heparin. It enhances antithrombin’s effect on Xa but does not have an effect on IIa. It is administered subcutaneously.
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What is the onset and half life of fondaparinux?
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• Onset in 2 hours
• Renally eliminated • Minimal inter-patient variability in dose response • Half-life: 17-21 hours |
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What are the adverse effects of fondaparinux?
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• Bleeding: similar to UFH/LMWH
Thrombocytopenia but NOT HIT |
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Does monitoring for fondaparinux need to be done?
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No!
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What drug is classified as vitamin K antagonist?
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Warfarin
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What is mechanism of action for warfarin?
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• Warfarin is a vitamin K antagonist. It inhibits vitamin K epoxide reductase and, to a lesser extent, vitamin K reductase. These enzymes are important in the preparation and recycling of vitamin K for its role in producing biologically active clotting factors II, VII, IX, and X. Synthesis of fully active vitamin K-dependent clotting factors requires carboxylation in the presence of reduced vitamin K.
• Warfarin inhibits the production of new, fully functional clotting factors II, VII, IX, and X. • Proteins C & S (natural anticoagulants) also require vitamin K for production. Warfarin inhibits these also, inhibiting our natural anticoagulant process. |
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What is the onset of action for warfarin?
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• Onset: Warfarin takes several days or more to produce its full effect following initiation. The onset of warfarin’s effect is limited by the metabolism of clotting factors present at the time of warfarin initiation. Vitamin K-dependent clotting factor half-lives range from 4 to 100 hours. Factor II, the most important, is the longest (60-100 hours):
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What is offset of action and half life for warfarin?
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• Warfarin half-life (mean): 40 hours
• Offset: Warfarin offset is dependent on its own long half-life and the time required to synthesize new vitamin K-dependent clotting factors. For a patient therapeutically anticoagulated with warfarin, this is typically about 3-5 days. |
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What is the normal INR and INR for patient on warfarin?
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Normal=1
Warfarin=2-3 |
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What is the subtherapeutic range for warfarin?
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INR Below 2, patient is at increased risk of thromboemolic event
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What is the supratherapeutic range for warfarin?
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INR above 3, patient is at increased risk for bleeding event
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When should monitoring be done when patient is first started on warfarin?
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By day 3 and titrated based on resposne
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When patient is stable on warfarin, how often should monitoring be done?
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At least every 4 weeks. Should be done more frequently if INR is out of range and the etiology of out of range INR values should be assessed as transient or ongoing in nature
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What are adverse effects of Warfarin?
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• Major bleeding
o Estimated incidence: 1-10%/year; improved INR control reduces bleeding rate. o Notable sites: GI (most common), intracranial hemorrhage (most morbidity/mortality) • Minor bleeding o Estimated incidence: > 15%/year o Notable sites: GI, epistaxis, urinary track, soft tissue • Rare adverse effects: Purple toe syndrome, warfarin-induced skin necrosis, alopecia. |
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What is classified as direct thrombin inhibitor?
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Dabigatran
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What is mechanism of actino for Dabigatran?
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• Dabigatran is a competitive direct thrombin inhibitor. As such, it inhibits the conversion of fibrinogen into fibrin, a key step in the formation of a stable thrombus.
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What is onset of action and half life for Dabigatran?
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• Onset: 2-4 hours.
• Elimination is primarily renal. • Half-life (t1/2) is 12-17 hours No lab monitoring required!!! |
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What are adverse effects of Dabigatran?
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• Major bleeding. Comparable to warfarin and possibly less than warfarin.
• GI upset. More common than warfarin, sometimes requiring discontinuation. |
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What Is classified as orally active factor Xa inhibitor?
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• Rivaroxaban (Xarelto®)
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What is the mechanism of action for Rivaroxaban?
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• Selectively blocks the active site of factor Xa, thereby inhibiting its activation within the intrinsic and extrinsic pathways. Unlike heparin, LMWH, and fondaparinux, the mechanism is independent of antithrombin.
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What is a huge warning of using Rivaroxaban?
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Discontinuation increases risk of thrombotic events (black box)
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What is the onset of action for Rivaroxaban?
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2-4 hours; no lab monitoring required
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What are adverse effects of rivaroxaban?
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major bleeding
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What is the effect of fluconazole on warfarin therapy?
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increases INR, increased bleeding risk
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What is the effect on trimethroprim/sulfamethoxazole-- SMZ/TMP on warfarin therapy?
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(bactrim) increased INR, increase bleeding risk
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What is the effect on metronidazole on warfarin therapy?
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increased INR, increase bleeding risk
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what is the effect amiodarone on warfarin therapy?
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increased INR, increase bleeding risk
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What is the effect of aspirin on warfarin therapy?
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no change. platelet inhbition
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What is the effect of carbamazepine on warfarin therapy?
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decreases INR, decreased bleeding risk
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What are indications for primary prevention of thromboembolism?
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Many hospitalized and surgical patients
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HAS-BLED risk score
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o H: Hypertension
o A: Abnormal renal and liver function o S: Stroke history o B: Bleeding history o L: Labile INRs o E: Elderly o D: Drugs that increase bleeding risk (aspirin, NSAID’s, etc) or alcohol use |
