Chapter 34: Anticoagulation, Chapter 35: Anemia, Chapter 36: Sickle Cell Disease Flashcards
Anticoagulants are used to prevent blood clots from forming and to keep existing clots from becoming larger. They DO NOT break down clots (like thrombolytics). Anticoags. are used in the prevention and treatment of VTE = which referes to either DVT or PE. Anticoags are also used in the immediate treatment of acute coronary syndromes (ACS) and for the prevention of cardioembolic stroke. Most common side effects include bleeding (which can be fatal) = high alert med!
Clot Formation: what is it? how does it occur? where can blood clot form?
Coagulation is the process by which blood clots form. A number of factors can lead to activation of the coagulation process such as blood vessel injury, blood stasis (stopping or slowing of blood flow) and pro -
thrombotic conditions. Coagulation involves activation of platelets and the clotting cascade. Blood clots can form anywhere in the body and cause serious conditions that can be fatal…if the clot (or a piece of it) travels to another location it is called an embolus!
Blood clots in different parts of the body and what they can lead to…
1. brain
2. heart
3. lungs
4. legs
- brain: stroke
- heart: ACS
- lungs: PE
- legs: DVT
Coagulation Cascade: general, where are these clotting factors made?, what is produced at the end of clotting cascade? what are the two pathways of the cascade?
The Coagulation cascade is a process that occurs through activation of a series of clotting factors (proteins made mainly in the liver).
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All clotting factors have an inactive and active form (the “a” next to a factor means “activated”. Once activated, a clotting factor will active the next clotting factor in a sequence until fibrin is formed.
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The coagulation cascade has two pathways that lead to fibrin formation: contact activation pathway (aka intrinsic pathway) and the tissue factor pathway (aka extrinsic pathway). Anticoagulation inhibit the coagulation cascade and prevent clot formation
List the steps of the Coagulation Cascade, and where does all the different anticoags work on then pathway?
DOACs VS. Warfarin
DOACs have less drug-drug interactions , less or
comparable bleeding and a shorter half-life compared to warfarin!
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DOAC dosing is based on the indication and kidney/liver function - there is no need to adjust the
dose based on the INR (as with warfarin )
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DOACs are preferred for stroke prevention in AF… BUT - if there is moderate-to-severe mitral stenosis or
a mechanical heart valve, use WARFARIN!
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Use DOACs for VTE treatment… BUT if the patient has antiphospholipid syndrome or mechanical heart valve use WARFARIN
Anticoag Drugs
Warfarin: What is it, what clotting factors does it work on? monitoring?
Warfarin is a** vitamin K antagonist**. Vitamin K is required for the carboxylation (activation) of clotting factors II, VII, IX and X. Without adequate vitamin K, the liver produces the clotting factors, but they have reduced coagulant activity. Warfarin has
a narrow therapeutic range and requires careful monitoring of the international normalized ratio (INR), which is affected by many drugs and changes in dietary vitamin K
Anticoag Drugs
FACTOR Xa INHIBITION: Unfractionated heparin (UFH), low molecular weight heparins (LMWHs) and fondaparinux: How do they work? what factor do they effect?
Unfractionated heparin (UFH), low molecular weight heparins (LMWHs) and fondaparinux work by binding to antithrombin (AT) and causing a conformational change which increases AT activity 1,000-fold! LWMHs inhibits Xa more specifically than UFH. Fondaparinux (Arixtra) has selective inhibition of Xa.
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AT is an endogenous (naturally occuring in the body) anticoagulant; it inactivates thrombin (factor IIa) and other proteases (eg. Factor Xa) involved in blood clotting!
Anticoag Drugs
THROMBIN INHIBITION: UFH, LWMHs and Direct thrombin inhibitors (DTIs)
UFH and LMWH indirectly inhibit thrombin and Factor Xa through antithrombin binding. Direct thrombin inhibitors (DTIs) block thrombin directly, decreasing the amount of fibrin available for clot formation. The** intravenous DTIs** (ie. argatroban) are important clinically since they do not cross-react with heparin-induced thrombocytopenia (HIT) antibodies. Dabigatran (Pradaxa) is an oral DTI
Anticoag Drug
FACTOR Xa INHIBITION: DOACs: how do they work? Do they need monitoring?
Apixaban (Eliquis), edoxaban (Savaysa) and rivaroxaban (Xarelto) work by** inhibiting factor Xa directly**. These oral medications are taken once or twice daily and require no laboratory monitoring for efficacy.
Key points: When studying anticoag, ACS, and ischemic heart disease and stroke chapters of NAPLEX it can be hard to determine when a fibrinolytic, antiplatelet or anticoag would be appropriate! What is the general overview of when to use what?
- Oral anticoags: used mainly in AF (for stroke prevention) and for DVT/PE (treatment and prevention). Oral med like xarelto or eliquis are not indicated for the acute management of an ACS when platelet aggregation is the main target!
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Fibrinolytics break down existing clots but are associated with very high risk of bleeding. They are used to immediatly treat acute ischemic stroke or STEMI when patient could die without rapid restoration of blood flow!
3.** Antiplatelet drugs** (ASA, clopidogrel, ticagrelor) are mainly used for coronary artery disease (including ACS) and to prevent recurrent ischemic stroke/ TIA. Dual antiplatelet therapy (DPAT) refer to the use of ASA + P2Y12 inhibitor (eg. clopidgrel) togetehr, which is very common for patients with ACS. Antiplatelet drugs are not sufficient for treating DVT/PE!
**Anticoags are high alert medications! ** Why? what needs to be done to ensure patient safety when recieving anticoags?
All anticoagulants can cause significant bleeding and are classified as “high-alert” medications by the Institute for Safe Medication Practices (ISMP). Bleeding events with anticoagulants put patients at increased risk for death. The Joint Commission’s National Patient Safety Goals require policies and protocols to properly initiate and manage anticoagulant therapy. Patients receiving anticoagulants should receive individualized care through a defined process that includes standardized ordering, dispensing, administration, monitoring and patient/caregiver education (for treatment doses)
Anticoag Drugs
List The common types of visible bleedings/ locations
- Epistaxis (nose bleed)
- Gums, worsening or new gingivitis
- Brusing
- Hematoma
- Hematuria (blood in urine)
- Blood in emesis/ Hematemesis - from GI bleeding;’ vomit may have red or ground coffee like appearance.
- Blood from the anus: lighter/ red blood = from hemorrhoids/ rectal tear. Black/ tarry sticky stool = blood from esophagus/ stomach or duodenum (upper GI region)
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Note: In some cases, bleeding will not be visible, but identified from symptoms and/or labs. An acute drop in hemoglobin (e.g., > 2 g/dL) could signify that bleeding is occurring (visible or not). Internal bleeding could be from anywhere.
UNFRACTIONATED HEPARIN: Dosing for Prophylaxis VTE and Treatment VTE
- Prophylaxis VTE: 5000 units sc Q8-12hs
- Treatment VTE: 80 units/kg IV bolus; 18 units/kg/hr infusion. If outpatient? 333 units/kg x 1 dose sc then 250 units/kg sc q12hrs
UNFRACTIONATED HEPARIN: Dosing for treatment of ACS/ STEMI
60 units/kg IV bolus then 12 units/kg/hr infusion… use TBW for dosing!
UNFRACTIONATED HEPARIN: Contraindications, warnings, side effects
- Contraindications: Uncontrolled active bleed (intracranial hemorrhage), severe thrombocytopenia, history of HIT, hypersensitivity to pork products. Some products contain benzyl alcohol as a preservative (do not use in neonates, infants, pregnancy and breastfeeding)
- Warnings: Fatal medication errors! verify the correct concentration is chosen!
- Side Effects: Bleeding (epistaxis, ecchymosis, gingival, GI), thrombocytopenia, HIT, hyperkalemia and osteoporosis (with long-term use), alopecia
UNFRACTIONATED HEPARIN: Monitorings
- aPTT or anti-Xa level- check 6 hours after initiation and every 6 hrs until therapeutic, then every 24 hrs and with every dosage change
- aPTT therapeutic range is 1.5-2.5x control (specific to each hospital), anti-Xa therapeutic range typically 0.3-0.7 units/ml
- Platelets, Hgb, Hct at baseline and daily (decrease in platelets > 50% from baseline suggests possible HIT)
UNFRACTIONATED HEPARIN: Other important information to note - onset, antidote, heparin lock flushes, etc
- Onset: Onset: IV: immediate; SC: 20-30 min; t½ = 1.5 hrs.
- Antidote: protamine
- UFH has unpredictable anticoagulant response
- Continuous IV infusions are common for treating VTE and ACS because heparin has a very short half-life
- Do not give IM due to hematoma risk
- Heparin lock-flushes (HepFlush) are only used to keep IV lines open. Fatal errors, especially in neonates, occurred when the incorrect heparin strength (higher dose) was chosen. Heparin injection 10,000 units/ml and flushes 10 or 100 units/ml look and sound alike!
LOW MOLECULAR WEIGHT HEPARINS: Enoxaparin - list the doses that are avalible
Multidose vial (300 mg/3 ml) and prefilled syringes:
30mg/0.3 ml
40mg/0.4 ml
60mg/0.6ml
80 mg/0.8 ml
100mg/ml
120 mg/0.8 ml
150mg/ml
- 1 mg = 100 units anti-Xa activity
LOW MOLECULAR WEIGHT HEPARINS: Enoxaparin: Dosing for Prophylaxis of VTE and Treatment of VTE/UA/NSTEMI
- Prophylaxis of VTE: 30mg SC q12hrs or 40mg SC QD (if CrCl < 30: use 30mg SC QD)
- Treatment of VTE/UA/NSTEMI: 1mg/kg SC Q12hrs or 1.5mg/kg SC QD (inpatient VTE treatment only)! If CrCl is < 30 use 1mg/kg SC QD
LOW MOLECULAR WEIGHT HEPARINS: Enoxaparin: Dosing for Treatment of STEMI in patients < 75 y/o and Treatment of STEMI in patients > 75 y/o
- Treatment of STEMI in patients < 75 y/o: 30 mg IV bolus + 1 mg/kg SC dose followed by 1 mg/kg SC Q12H (max 100 mg for the first two SC doses only). CrCI < 30 ml/min : 30 mg IV bolus + 1 mg/kg SC dose, followed by 1 mg/kg SC QD
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Treatment of STEMI in patients > 75 y/o: 0.75 mg/kg SC Q12H (no bolus - max 75 mg for the first two SC doses only). CrCI < 30 ml/min : 1 mg/kg SC daily (no bolus)
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USE TBW!
LOW MOLECULAR WEIGHT HEPARINS: Dalteparin (Fragmin) - dosing for prophylaxis VTE and treatment of UA/NSTEMI
- Prophylaxis VTE: 2500-5000 units sc QD
- Treatment of UA/NSTEMI: 120u/kg (max 10000u) sc q 12hrs
LOW MOLECULAR WEIGHT HEPARINS: Boxed warnings, Contraindications, SEs
- Boxed warnings: Patients receiving neuraxial anesthesia (epidural, spinal) or undergoing spinal puncture are at risk of hematomas and subsequent paralysis
- Contraindications: Hx of HIT, active major bleed, hypersensitive to pork
- SEs: Bleeding, anemia, injection site reactions (e.g., pain, bruising, hematomas), decrease platelets (thrombocytopenia, including HIT)
LOW MOLECULAR WEIGHT HEPARINS: Monitoring
- Platelets, Hgb, Hct, SCr
- More predictable anticoag response than UFH; does not require anti-Xa level monitoring in most cases!
- Anti-Xa level monitoring is recommended in pregnancy
- Monitoring can be useful in obesity, low body weight, pediatrics, elderly or renal insufficiency
- aPTT is not used
- Obtain peak anti-Xa levels 4 hours post SC dose
LOW MOLECULAR WEIGHT HEPARINS: Important notes/ consideration
- antidote: protamine
- Do not expel air bubble from syringe prior to injection (can cause loss of drug)
- Do not admin IM
- Store at room temp
- Patients managed with percutaneous coronary intervention (PCI); if the last SC enox dose was given 8-12 hrs before balloon inflation, give .3mg/kg IV bolus
HEPARIN-INDUCED THROMBOCYTOPENIA: What is it? MOA, What complications can occur if not treated?
Heparin-induced thrombocytopenia (HIT) is an immune-mediated IgG drug reaction that has a high risk of venous and arterial thrombosis (clot). The immune system forms antibodies against heparin bound to platelet factor 4 (PF 4), the antibodies then
join with heparin + PF 4 to create a complex, and this complex binds to the Fc receptors on platelets. This causes platelet activation and a release of pro-coagulant microparticles.
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HIT is a prothrombotic state- left untreated, can cause many complications, including heparin-induced
thrombocytopenia and thrombosis (HITT). HITT leads to amputations, post-thrombotic syndrome and/or death.
HEPARIN-INDUCED THROMBOCYTOPENIA: The probability of HIT can be assessed by calculating the 4 Ts Score, which includes an evaluation of the following:
- Thrombocytopenia: an unexplained > 50% drop in platelet count from baseline
- Timing of platelet count drop: typical onset of HIT is 5-10days after starting heparin or within hours if a patient has been exposed to heparin within past 3 months.
- Thrombosis: can be a new suspected or confirmed thrombosis or skin lesions that are necrotizing or non necrotizing
- Other causes
If HIT is suspected, a heparin-PF4 antibody enzyme linked immuno assay (ELISA) test is completed. Results may confirmed with a serotonin release assay or heparin induced platelet aggregation assay.
MANAGEMENT OF HIT COMPLICATED BY THROMBOSIS (HITT)
- If HIT is suspected/ confirmed , stop all forms of heparin and LMWH. If the patient is on warfarin and diagnosed with HIT, the warfarin should be d/c. and vitamin K should be administered. Although the patient is at a high risk of thrombosis, warfarin use with a low platelet count has a high correlation with warfarin-induced limb gangrene and necrosis!
- In patients with HIT, non-heparin anticoagulants are recommended (in particular, argatroban)
- Do not start warfarin therapy until the platelets have recovered to >150,000 cells/mm3. Warfarin should be initiated at lower doses (5 mg maximum). Overlap warfarin with a non-heparin anticoagulant for a minimum of five days and until the INR is within target range for 24 hours. Argatroban can increase the INR; the value must be interpreted cautiously.
- If urgent cardiac surgery or PCI is required, bivalirudin is the preferred anticoagulant
ORAL DIRECT FACTOR Xa INHIBITORS
Apixaban (Eliquis): Dosing for nonvalvular AF (stroke prophylaxis)
5 mg PO BID
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If patient has at least 2 of the following: age greater or equal to 80 y/o, body weight equal to or less than < 60kg or SCr equal to or greater than 1.5mg/dL = THEN GIVE 2.5mg BID (this rule only apply to stroke! NOT VTE!)
ORAL DIRECT FACTOR Xa INHIBITORS
Apixaban (Eliquis): Dosing for Treatment of DVT/PE
- Initial: 10 mg PO BID for 7 days then 5mg PO BID
- Extended phase (after 3 months or more of initial treatment): 2.5 mg PO BID
ORAL DIRECT FACTOR Xa INHIBITORS
Apixaban (Eliquis): Dosing for Prophylaxis for DVT (after knee or hip replacement surgery)
**2.5mg PO BID **(for 12 days after knee or 35 days after hip replacement); give first dose 12-24hrs after the surgery!
ORAL DIRECT FACTOR Xa INHIBITORS
Rivaroxaban (Xarelto): Dosing for Nonvalvular AF (stoke prophylaxis)
- CrCI > 50: 20 mg PO daily with evening meal
- CrCI 15-50: 15 mg PO daily with evening meal
- CrCI < 15 : avoid use
ORAL DIRECT FACTOR Xa INHIBITORS
Rivaroxaban (Xarelto): Dosing for Treatment of DVT/PE
- Initial: 15 mg PO BID x 21 days, then 20 mg PO daily with food
- Extended phase (after 3 or more months of initial treatment): 10 mg PO QD (no need to take with food. only 15 mg and up need food!)
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CrCl < 30: avoid use
ORAL DIRECT FACTOR Xa INHIBITORS
Rivaroxaban (Xarelto): Dosing for Prophylaxis for DVT (after knee/ hip replacement) and VTE (in acutely ill medical patients)
- 10 mg PO daily (for 12 days after knee or 35 days after hip replacement surgery or 31-39 days in acutely ill patients).
- Give first dose 6-10 hours after surgery!
- CrCl < 30: avoid use
ORAL DIRECT FACTOR Xa INHIBITORS
Rivaroxaban (Xarelto): Dosing for Reduction in the risk of major CVD events in CAD/PAD
- 2.5 mg PO BID in combination with low-dose aspirin
- CrCl < 15: Avoid use
ORAL DIRECT FACTOR Xa INHIBITORS
Edoxaban (Savaysa): Dosing for Nonvalvular AF (stroke prophylaxis)
- CrCI > 95: do not use (due to reduced effectiveness)
- CrCI 51-95: 60 mg daily
- CrCI 15- 50: 30 mg daily
- CrCI < 15: not recommended
ORAL DIRECT FACTOR Xa INHIBITORS
Edoxaban (Savaysa): Dosing for Treatment of DVT/PE
- 60 mg daily, start after 5-10 days of parenteral anticoagulation
- CrCI 15-50 ml/min or body weight < 60 kg or on certain P-gp inhibitors: 30 mg daily
- CrCI < 15 ml/min: not recommended
Apix, Riva, Edoxa
ORAL DIRECT FACTOR Xa INHIBITORS: Boxed warnings, Contraindication, Warnings, SEs
- Boxed warnings: All: patients receiving neuraxial anesthesia (epidural, spinal) or undergoing spinal puncture are at risk of hematomas and subsequent paralysis; Premature d/c increase risk of thrombotic events; Edoxaban only - reduced effectiveness in nonvalv AF patient if CrCl > 95 so do not use!
- Contraindication: Active pathological bleeding
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Warnings: Not recommended with prosthetic
heart valves, antiphospholipid syndrome (use warfarin for these!); avoid in patients with moderate to severe hepatic impairment - Side Effects: Generally well tolerated. unless bleeding occurs. Edoxaban only: rash and increase LFT
Apixa, Riva, Edoxa
ORAL DIRECT FACTOR Xa INHIBITORS: Monitoring, Any additional notes
- Monitoring: Hgb, Hct, SCr, LFTs; no monitoring of efficacy required
- Additional Notes:
1. Antidote for apixaban and rivaroxaban:
andexanet alfa (Andexxa)
2. All: can be crushed and put in applesauce or h2o to be admin via NG tube
3. Apixaban only: can be crushed and mixed in h2o, D5W or apple juice
4. Elective surgery: discontinue 24 hours prior to elective surgery (rivaroxaban, edoxaban); Discontinue 48 hours prior to elective surgery with moderate-high bleeding risk or 24 hours prior with a low bleeding risk (apixaban)
5. Dosage for avalibility: Apix (tab, blister packet for DVT/PE), Riva (tab, suspension, blister packet for DVT/PE), Edoxa (tab)
Apixa, Riva, Edoxa
ORAL DIRECT FACTOR Xa INHIBITORS: Missed dose?
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Apixaban: Take immediately on the same
day, then twice daily administration should be resumed; DO NOT DOUBLE UP DOSE! - Rivaroxaban: Administer the dose as soon as possible on the same day as follows: If taking 15 mg BID: take immediately to ensure intake of 30 mg/day. In this particular instance, two 15 mg tablets may be taken at once. Then resume regular schedule on the following day If taking 10, 15 or 20 mg once daily: take immediately on the same day; otherwise skip.
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Edoxaban: Take immediately on the same
day; DO NOT DOUBLE UP DOSE!
INJECTABLE INDIRECT FACTOR Xa INHIBITOR (SC)
Fondapainux (Arixtra): dosing availibility, dosing for: prophylaxis of VTE, Treatment of VTE, renal consideration?
- Dosings: Prefilled syringes: 2.5 mg/0.5 ml, 5 mg/0.4 ml, 7.5 mg/0.6 ml, 10 mg/0.8 ml (all stored at room temp)
- Prophylaxis of VTE: > or = 0kg: 2.5 mg SC QD, less than 50 kg: contraindicated!!
- Treatment of VTE: < 50kg: 5mg SC QD, 50-100kg: 7.5 mg SC QD, > 100kg: 10mg SC QD
- Renal consideration?: CrCI 30-50 ml/min: use caution; CrCI < 30 ml/min: contraindicated
INJECTABLE INDIRECT FACTOR Xa INHIBITOR (SC)
Fondapainux (Arixtra): Boxed warnings, Contraindication, SEs
- Boxed warnings: Patients receiving neuraxial anesthesia (epidural, spinal) or undergoing spinal puncture are at risk of hematomas and subsequent paralysis
- Contraindication: Severe renal impairment (CrCI < 30 ml/min), active major bleed, bacterial endocarditis, thrombocytopenia with positive test for anti-platelet antibodies in presence of fondaparinux
- SEs: Bleeding (epistaxis, ecchymosis, gingival , GI, etc.), anemia, local injection site reactions (rash, pruritus, bruising), thrombocytopenia, hypokalemia, hypotension
INJECTABLE INDIRECT FACTOR Xa INHIBITOR (SC)
Fondapainux (Arixtra): Monitoring and Additional Notes
- Monitoring: Anti -Xa levels (3 hrs post-dose), platelets, Hgb, Hct , SCr
- NOTES Do not expel air bubble from syringe prior to injection; No antidote; Do not administer IM
Factor Xa Inhibitor Drug Interactions
General Interactions to be mindful of for all anticoags
Avoid using with other anticoagulants (unless benefit
outweighs risk). Monitor for additive effects with other
drugs that can i bleeding risk (antiplatelet drugs, some
herbals. NSAIDs, SSRls, SNRis, thrombolytics)
Factor Xa Inhibitor Drug Interactions: Apixaban
Apixaban is a substrate of CYP450 3A4 (major) and
P-gp. Avoid use with strong dual inducers of CYP3A4
and P-gp (e.g., carbamazepine, phenytoin, rifampin, St.
John’s wort). For patients receiving doses > 2.5 mg BID, the dose of apixaban should be decreased by 50% when coadministered with drugs that are strong dual inhibitors of CYP3A4 and P-gp (e.g., clarithromycin, itraconazole, ketoconazole, or ritonavir). For patients taking 2.5 mg BID, avoid these strong dual inhibitors.
Factor Xa Inhibitor Drug Interactions: Rivaroxaban
Rivaroxaban is a substrate of CYP3A4 (major) and P-gp. Avoid use with drugs that are combined P-gp and strong CYP3A4 inducers (e.g., carbamazepine, phenytoin, rifampin, St. John’s wort) or combined P-gp and strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, lopinavir/ritonavir, ritonavir, and Conivaptan).
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The benefit must outweigh the potential risks in these
situations: CrCI 15 - 80 mL/min who are receiving
combined P-gp and moderate CYP3A4 inhibitors (e.g.,
diltiazem, verapamil, dronedarone, erythromycin)
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Stribild, Genvoya (each containing cobicistat) and Cobicistat (Tybost) can increase exposure to the factor Xa inhibitors. Rivaroxaban should not be used with any of these medications!
Factor Xa Inhibitor Drug Interactions: Edoxaban
Edoxaban is a substrate of P-gp; avoid use with rifampin.When treating DVT/PE, reduce dose to 30 mg daily with verapamil, macrolides (azithromycin, clarithromycin, erythromycin) and oral itraconazole or ketoconazole.
Conversion Between Anticoags
Direct Thrombin Inhibitors: MOA and list of drugs
MOA: These agents directly inhibit thrombin (Factor Ila); they bind to the active thrombin site of free and clot-associated thrombin.
Drugs: Dabigatran (oral), Argatroban (inj), Bivalirudin (inj)
Oral Direct Thrombin Inhibitor
Dabigatran (Pradaxa): dosage forms, dosing for nonvalvular AF (stroke prop), Treatment for DVT/PE and reduction of risk of recurrent DVT/PE, and prop of DVT/PE following hip/knee replacement
- Dosage forms: capsule/ pellets oral packets
- Dosing for nonvalvular AF (stroke prop): 150 mg BID (CrCl 15-30 - 75mg BID and avoid use if CrCl less than 15)
- Treatment for DVT/PE and reduction of risk of recurrent DVT/PE: 150 mg BID, start after 5-10 days of parenteral anticoagulation; CrCI less than 30: do not use!
- Prop of DVT/PE following hip/knee replacement: 110 mg on day 1, then 220 mg daily; CrCl less than 30: do not use!
Oral Direct Thrombin Inhibitor
Dabigatran (Pradaxa): Boxed Warning, Contraindication, Warnings, SEs
- Boxed Warning: Patients receiving neuraxial anesthesia (epidural, spinal) or undergoing spinal puncture are at risk of hematomas and subsequent paralysis; Premature discontinuation increase risk of thrombotic events
- Contraindication: Active pathological bleeding, treatment of patients with mechanical prosthetic heart valve
- Warnings: No recc. for antiphospholipid syndrome
- SEs: Dyspepsia, gastritis -like symptoms, bleeding (including more GI bleeding)
Oral Direct Thrombin Inhibitor
Dabigatran (Pradaxa): Monitoring, Missed dose?, Additional Notes/ Consideration
- Monitoring: Hgb, Hct, SCr; no monitoring of efficacy required
- Missed dose: Take immediately unless it is within 6 hours of next scheduled dose; the dose should not be doubled to make up for a missed dose
- Notes:
1. Antidote: idarucizumab (Praxbind)
2. Swallow capsules whole (do not break, chew, crush or open); do not administer by NG tube
3. Can increase aPTT, PT/INR
4. Discontinue if undergoing invasive surgery (1-2 days before if CrCI > or equal to 50, 3-5 days before if CrCI < 50)
Injectable Direct Thrombin Inhibitors
Argatroban: Indication, dosing, special note
- Indicated for HIT and in patients undergoing PCI who are at risk for HIT
- Dosing for HIT: 2mcg/kg/min (then tritrate to target aPTT) (max dose is 10mcg/kg/min)
- Dosing for PCI: IV bolus followed by infusion; weight based dosing…decrease dose in hepatic impaired patients
- Note: can increase INR!!!
Injectable Direct Thrombin Inhibitors
Bivalirudin (Angiomax): Indication, general dosing
- Indicated for patients with ACS undergoing PCI, including those with HIT
- General dosing: IV bolus followed by infusion; weight based dosing…decrease dose in CrCl < 30
Injectable Direct Thrombin Inhibitors (Argatroban and Bivalirudin): Contraindication, SEs, Monitoring, Notes
- Contraindication: Active major bleed
- SEs: Bleeding, anemia
- Monitoring: aPTT and/or activated clotting time, platelet, Hbg, Hct, LFT
- Notes: Safe for patients with history of HIT; no cross-reaction with HIT antibodies; No antidote
Dabigatran Drug Interactions
Dabigatran is a substrate of P-gp
- avoid concurrent use with rifampin or other P-gp inhibitors if Crcl < 50 (or CrCl 15-30 when taking dabigatran or nonval AF)
- reduce dose to 75mg BID if CrCl 30-50 and there is concurrent use of dronedarone or systemic ketoconazole
- Avoid use with other anticoag (unless benefit > risk)
- Cobicistat and conbicistat containing drug can increasae exposure to dabigatran
Warfarin: MOA, brand names, dosage form
- MOA: Warfarin competitively inhibits the C1 subunit of the multi-unit vitamin K epoxide reductase (VKORCl) enzyme complex, thereby reducing the regeneration of vitamin K epoxide and causing depletion of active clotting factors II, VII, IX and X and proteins C and S
- Brand names: Coumadin, Jantoven
- Dosage Form: Tablets
Warfarin: Dosing and missed dose?
- Healthy outpatients: 10 ms daily for first, then adjust dose per INR values
- Lower doses (less than or equal to 5 mg) for elderly, malnourished, taking other drugs which can increase warfarin levels, liver disease, heart failure, or have a high risk of bleeding
- Take at the same time each day! Highly protien bound (99%)
- Missed Dose: Take immediately on the same day. DO NOT DOUBLE UP DOSE!
Warfarin: Boxed Warnings, Contraindication, Warnings, SEs
- Boxed Warnings: Major or fatal bleeds
- Contraindication: Pregnancy (except with mechanical heart valves at high risk for clots, hemorrhagic tendencies, blood dyscrasias, uncontrolled hypertension, noncompliance, recent or potential surgery of the eye or CNS, major regional lumbar block anesthesia or traumatic surgery, pericarditis, endocarditis, preeclampsia/eclampsia, possible misscarriage
- Warnings: tissue necrosis/gangrene, HIT (contraindicated as monotherapy in initial treatment) systemic atheroemboli and cholesterol microemboli, presence of CYP2C92 or ‘3 alleles and or polymorphism of VKORC1 gene may increase bleeding risk (routinegenetic testing is not currently recommended)
- SEs: Bleeding/bruising (mild to severe), skin necrosis, purple toe syndrome
Warfarin: Monitoring/ ideal INR goals, Additional Notes/ Considerations
- Monitoring:
1. Goal INR 2-3 (target 2.5): most indications (DVT, AFib, bioprosthetic mitral valve, mechanical aortic valve, antiphospholipid syndrome)
2. Goal INR 2.5-3.5 (target 3): high-risk indications such as a mechanical mitral valve, 2 mechanical heart valves, or mechanical aortic valve with one additional risk factors (eg. previous DVT, AF, hypercoag. state)
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Begin INR monitoring after the initial 2 or 3 doses, or if on a chronic, stable dose of warfarin, monitor at intervals every 4-12 weeks; Hct, Hgb, signs of bleeding
- Notes: Antidote: vitamin K! Dental cleanings and single tooth extraction do not generally require a change in warfarin dosing, if INR is in therapeutic range
Warfarin Tablets Colors and Their Doses
Use of Vitamin K (pref choice) for overanticoagulation in warfarin: List the different symptoms and what to do.
Afib/Aflutter
CHA2DS2-VASc Scoring System: what is the scoring system, what is the reccomended therapy based on each score?
Afib/Aflutter
HAS-BLED Scoring System: what is it? what is the scoring system
- Assesses bleeding risk in patients requiring anticoagulation for stroke prevention in AF. The higher the score the greater the risk of bleed
Identifying the causes of anemia; based off of MCV, what are the 3 different types of anemia and their main causes?
What are the % elemental iron in the different oral iron products?
All Oral Iron Products: Boxed Warning, Contraindication, SEs, Monitoring, Notes/ antidote
Key Vaccines in Sickle Cell Disease
