Anticoagulation & Blood Disorders* Flashcards
Anticoagulant Use
-Prevention and treatment of venous thromboembolism (VTE)
–> Deep vein thrombosis (DVT)
–> Pulmonary embolism (PE)
-Acute coronary syndrome (ACS)
–> STEMI
–> NSTEMI
EX: heparin to prevent further blood clot formation
-Cardioembolic stroke prevention
Anticoagulants & where they work on the coagulation cascade
-Unfractionated heparin: inhibit equally factors X a and IIa via antithrombin (indirect inhibition)
-LMWH: shorter structure so it inhibits factor Xa > IIa via antithrombin
-Rivaroxaban,apixaban,endoxaban: direct factor Xa inhibitors
-Fondaparinux: indirect factor Xa inhibitor
-Warfarin: inhibits factos II, VII, IV, and x
-Direct thrombin inhibitors: directly inhibit factor IIa/thrombin
–> IV: argatroban, bivalirubin
–> PO: dabigatran
Unfractionated Heparin dosing
–> Prophylaxis of VTE: 5,000 units SC Q 8-12 h
–> Treatment of VTE: 80 units/kg IV bolus; 18 units/kg/hr infusion
–> Treatment of ACS/STEMI: 60 units/kg IV bolus; infusion at 12 u/kg/hr
CI: uncontrolled active bleed, hx of HIT, hypersensitivity to pork products
SE: bleeding, thrombocytopenia, hyperkalemia, osteoporosis (with long term use)
-monitor: aptt: baseline, q 6hr then q 24 hrs once therapeutic
Antidote = protamine
Enoxaparin(Lovenox)/LMWH dosing *
-Prophylaxis of VTE: 30 mg SC Q12h or 40 mg daily
–> crcl < 30: 20 mg sc daily
-Treatment of VTE and Unstable Angina/NSTEMI: 1 mg/kg q12h or 1.5 mg/kg daily
–> crcl: < 30: 1 mg/kg daily
-Treatment of STEMI in pts < 75 y/o: 30 mg IV bolus + 1 mg/kg SC dose followed by 1 mg/kg q12h
–> Crcl < 30: 30 mg IV bolus + 1 mg/kg dose, followed by 1 mg/kg sc daily
-Treatment of STEMI in pts > 75 y/o: 0.75 mg/kg sc q12h (no bolus)
–> crcl: < 30 : 1 mg/kg sc
Enoxaparin(Lovenox)/LMWH SE/warnings
BBW: neuraxial anesthesia/spinal puncture use = risk of spinal hematoma
CI: uncontrolled active bleed, hx of HIT, hypersensitivity to pork products
SE: bleeding, anemia, injection site reaction, thrombocytopenia
monitor: Xa levels , 4-6 hrs after
Antidote = protamine
Heparin drug interactions (additive bleed risk)
-anticoagulants
-antiplatelets
-NSAIDs
-SSRIs
-SNRIs
Enoxaparin preparations
-300 mg/3 ml vial
-prefilled syringes: 30, 40, 60. 80, 100, 120 & 150 mg
Heparin Induced Thrombocytopenia diagnosis (4 Ts) & lab tests
4 Ts:
–> Thrombocytopenia (>50% drop in platelets)
–> Timing of platelet count fall
–> Thrombosis development
–> other causes of thrombocytopenia (meds, conditions?)
Lab Tests:
-ELISA
-SRA
-heparin induced platelet aggregation assay
Treatment of HIT
1) stop all heparin products
2) reverse warfarin with vitamin K (if on warfarin)
-start a non-heparin anticoagulant: argatroban, bivalirudin (if urgent cardiac surgery or PCI: bivalirudin preferred)
-fondaparinux used off-label for HIT
–> do not restart/start warfarin until the platelets have recovered to > 150,000
Apixaban (Eliquis) dosing
Stroke prevention in nonvalvular afib: 5mg PO BID
Treatment of VTE: 10 mg po BID x 7days then 5 mg po BID
–> decrease to 2.5 mg PO BID if pt has at least 2 of the following:
- age > 80 y/o
-body weight < 60 kg
-scr >1.5 mg/dL
Rivaroxaban (xarelto) dosing
-stroke Prophylaxis in nonvalvular Afib:
–> crcl > 50 ml/min: 20 mg PO daily with evening meal
–> crcl 15-50 ml/min: 15 mg PO daily with evening meal
–> crcl < 15 ml/min: avoid use
-Treatment of VTE:
–> initial: 15 mg PO BID x 21 days, then 20 mg PO daily with food
–> crcl < 30 ml/min: avoid use
-15 mg BID missed dose: take the missed dose ASAP, 2 tabs at once is ok
Endoxaban (Savaysa) dosing
–> stroke prophylaxis in nonvalvular afib: crcl > 95; DO NOT USE
–> tx of venous thromboembolism: start 60 mg PO daily after 5-10 days of parenteral anticoagulation
Apixaban (Eliquis), rivaroxaban(xeralto) and endoxaban (Savaysa) Safety/SE
BBW: pts recieving neuraxial anesthesia (spidural, spinal) or undergoing spinal puncture are at risk of hematomas and paralysis
-premature d/c increases risk of thrombotic events
CI: active pathological bleeding
Warnings: not rec with prosthetic heart valves or antiphospholipid syndrome
SE: bleeding
–> antidote to apixaban and rivaroxaban is andexant alfa (andexxa)
Fondaparinux (Arixtra) SEs
CI: severe renal impairment (crcl < 30), major active bleeding, bacterial endocarditis
SE: bleeding, anemia, local injection site reactions, thrombocytopenia
Conversion from warfarin to oral anticoagulant, stop warfarin and convert to:
Rivaroxaban when INR < 3
Endoxaban when INR <2.5
Apixaban when INR < 2
Dabigatran when INR < 2
Converting from Xa inhibitor to warfarin
stop the Xa inhibitor, start parenteral anticoagulant and warfarin at next scheduled dose
Converting from dabigatran to warfarin
start warfarin 1-3 days before stopping dabigatran
Dabigatran (Pradaxa) indications
-tx and prevention of VTE –> start after 5-10 days of parenteral anticoagulation
-stroke prophylaxis in pts with nonvalvular afib
-prophylaxis of VTE following hip replacement surgery
Dabigatran (Pradaxa) safety/SEs
BBW: pts receiving neuraxial anesthesia , premature d/c can increase risk of thrombotic events
CI: active pathological bleeding, pts with mechanical heart valves
SE: dyspepsia, gastritis-like symptoms, bleeding (including GI)
–> antidote = Idarucizumab (Praxbind)
–> dispense in the original container and discard bottle after 4 months after opening
Argatroban and Bivalirudin (Angiomax) IV direct thrombin inhibitors
A: used for HIT, in pts w/ or at risk for HIT that are undergoing PCI
B: in pts undergoing PCI, including those at risk for HIT
CI: major active bleed
SE: bleeding, anemia
–> safe for pt w/ HIT, short 1/2 life
Indications for INR goal 2-3 (target 2.5)
-a fib
-bioprosthetic mitral valve
-clotting disorder (factor V Leiden)
-mechanical aortic valve
-venous thromboembolism
Indications for INR goal of 2.5-3.5 (target 3)
-mechanical mitral valve
-2 mechanical heart valves
Warfarin dosing
-healthy pts: < 10 mg daily for the first 2 days then adjust per INR
-other pts: based on hospital protocol, usually 5 mg and adjusted
Warfarin (Jantoven, Coumadin)
BBW: major or fatal bleeding
CI: pregnancy (except with mechanical heart valves at high risk for VTE)
Warnings: tissue necrosis/gangrene, HIT
SE: bleeding/bruising, skin necrosis, purple toe syndrome
–> antidote= vitamin K
CYP2C9 inducer drugs & warfarin interactions
-inc warfarin metabolism = dec serum levels + INR (under coagulated)
Rifampin
Phenytoin
Phenobarbital
Carbamazepine
St. Johns wort
CYP2C9 inhibitors and warfarin interactions
- dec warfarin metabolism = inc serum levels & INR = over coagulated
Aminodarone
Azole antifungals (fluconazole, ketoconazole, voriconazole)
select anti-infectives (metronidazole, sulfamethoxazole/trimethoprim)
Dietary Supplement Interactions with Warfarin
-can increase the risk of bleeding with or without increasing the INR :
-Chamomile, chondroitin, dong quai, high doses of fish oils, vitmain E, willow bark, 5 G’s (garlic, ginger, ginkgo, ginseng, glucosamine)
Select foods that are high in vitamin K
Spinach (cooked)
Broccoli
Brussel sprouts
Collard greens
kale
turnip greens
swiss chard
parsley
- Warfarin tablet colors & doses (Please Let Greg Brown Bring Peaches To Your Wedding)
Pink: 1 mg
Lavender: 2 mg
Green: 2.5 mg
Brown/tan: 3 mg
Blue: 4 mg
Peach: 5 mg
Teal: 6mg
Yellow: 7.5 mg
White: 10 mg
Warfarin Reversal: No bleeding
–> INR < 4.5: hold or decrease dose, resume warfarin when INR is therapeutic
–> INR 4.5-10: hold 1-2 doses of warfarin, resume warfarin at a lower dose when INR is therapeutic
–> INR > 10: hold warfarin and administer 2.5-5 mg oral vitamin K, resume warfarin at a lower dose when INR is therapeutic
Warfarin reversal with major bleeding
ANY INR!
-hold warfarin
-administer IV vitamin K 5-10 mg and 4 PCC
PCC = four-factor prothrombin complex concentrate (Kcentra)
–> contains factos VII, IX, X, II, protein C and protein S
Vitamin K/phytonadione (Mephyton) - warfarin antidote
BBW: severe reactions resembling hypersensitivity reactions after IV admin
SE: anaphylaxis, flushing, dizziness, rash
Notes:
-SC route not rec due to variable absorption
-do not use IM administration due to risk of hematoma
-protect from light during administration
Preoperative management of warfarin
-stop warfarin ~ 5 days before surgery
-High risk for thromboembolism: bridge with LMWH or UFH
–> d/c LMWH 24 hrs before surgery
–> d/c UFH 4-6 hrs before surgery
Post surgery:
-resume warfarin after hemostasis (stopped bleeding)
Antidotes for reversal of anticoagulants
Protamine –> Heparins
Andexant alfa (Andexxa) –> Apixaban/Rivaroxaban
Idarucizumab (Praxbind) –> Dabigatron
Protamine Sulfate
-mixture of proteins derived from fish sperm
Reverses: LMWH, UFH
BBW: hypersensitivity
SE: hypotension, bradycardia, flushing, anaphylaxis
–> administer as a slow IV push or infusion (max 50 mg over 10 mins)
–> rapid IV infusion causes hypotension
Protamine dosing
UFH: 1 mg protamine reverses ~100 units of heparin; max 50 mg
LMWH: (less effective, reverses the enoxaparin given in the last 8 hrs): 1 mg protamine is given per 1 mg of enoxaparin
Andexanet alfa (Andexxa)
-used to reverse apixaban and rivaroxaban
BBW: thromboembolic risk, ischemic events, cardiac arrest adn sudden death
Idarucizumab (Praxbind)
-humanized monoclonal antibody fragment that binds to and reverses the effects of dabigatran
Warning: thromboembolic risk, risk of serious reactions due to the excipient of sorbitol
Modifiable risk factors for Venous Thromboembolism
-acute medical illness
-immobility
-medications: estrogen contianing, selective estrogen receptor modulator and ESAs
-obesity (BMI > 30)
-pregnancy and postpartum
-recent surgery or trauma
non modifiable risk factors for Venous Thromboembolism
-increasing age
-cancer
-heart failure
-known thrombophilia: antiphospholipid syndrome, antithrombin deficiency, factor V leiden mutations, protein C or S deficiency
-previous VTE
-respiratory failure
VTE tx for pts with cancer
-for the first 3 months:
–> oral factor Xa inhibitors: rivaroxaban, apixaban, edoxaban
-dabigatran
VTE tx in pts with cancer
- Preferred: rivaroxaban, apixaban, edoxaban
-then, other oral anticoagulants and LMWHs
Warfarin Initation and Bridging
Initial tx period: Warfarin and LMWH/UFH for 5 days
Maintenance period: dose adjust warfarin to goal INR
–> continue parenteral anticoagulation for a minimum of 5 days AND until the INR is therapeutic for a min of 24 hrs
VTE Prophylaxis in Pregnancy
Pharm: LMWH preferred
–> monitor with anti-Xa levels
non-pharm: Intermittent pneumatic compression devices
Chronic anticoagulation in pregnancy with warfarin
-positive preg test: STOP warfarin, start LMWH
-13 weeks: optional to resume warfarin
-3rd trimester: close to delivery, switch to LMWH
Anticoagulation in pts with AF undergoing cardioversion
–> in AF < 48 hrs: initiate AC at cardioversion and continue AC for 4 weeks
–> in AF > 48 hrs: AC for 3 weeks before planned cardioversion, do cardioversion then continue AC for 4 weeks
CHA2DS2VASc scoring system
Congestive heart failure 1
Hypertension 1
Age > 75 - 2
Diadetes 1
Prior stroke/TIA/thromboemboslim 2
Vascular disease 1
Age 65-74 1
Sex (female) 1
> 2 males, > 3 females: Oral anticoagulation is rec (DOAC)
HAS-BLED Scoring System
Hypertension (SBP > 160) (1)
Abnormal liver or kidney function
Stroke (1-2)
Bleeding tendency or predisposition
Labile INR (if on warfarin) (1)
Elderly (> 65) (1)
Drugs (asa, NSAIDs. or extensive alcohol use (1-2)
Causes for Iron deficiency anemia
–> low iron intake: veg or vegan diet, malnutrition
–> blood loss: acute (hemorrhage), chronic (heavy menses), drug induced (anticoagulation)
–> decreased iron absorption: high gastric pH, GI disease
–> Increased iron requirements: pregnancy, lactation, infants and adolescents
Lab tests for iron deficiency anemia
-reticulocytes: dec
-serum iron: dec
-ferritin: dec
-TSAT: dec
-TIBC: (amount of transferrin available to bind iron) increase
Oral Iron therapy points
-1 tablet daily or every other day
-take on an empty stomach
-avoid H2RAs and PPIs, seperate from antacids
-sustained-release or enteric coated not rec due to poor absorption
Oral iron supplements: Ferrous sultafe
325 mg = 65 mg elemental iron
160 mg = 50 mg elemental iron (slow fe)
Warning: accidental overdose; leading cause of fatal poisoning in children < 6 y/o
–> antidote = deferoxamine (Desferal)
SE: constipation, dark tarry stool
Indications for IV iron
-unable to tolerate oral iron
-CKD on hemodialysis
-Severe anemia
-acute blood loss or life-threatening anemia AND blood transfusions are not accepted by the pt
IV Iron drugs: Iron Sucrose (Venofer), Ferumoxytol (Feraheme)
NNW: Iron dextra and ferumoxoytol: serious and sometimes fetal anaphylactic reactions
Warning: hypersensitivity reactions
SE: hypotension (give slow IV injections or infusions to dec hypotension)
Causes of Macrocytic anemia (MCV > 100, low Hgb)
caused by folate or vitamin B12 deficiency
-veg or vegan diet
-alcohol use disorder
-GI disease or surgery
-drug induced
–> methotrexate- folate
–> metformin/PPI: B12
–> Vit B12: pernicious anemia = due to antibodies against intrinsic factor, which is required for vitmain B12 absorption
Treatment of macrocytic anemia
–> Cyanobalamin (B12): IM, deep SC
AE: pain with injection
–> Folic acid (B9) PO
When to use Erythropoiesis-stimulating agents (ESAs)?
-stimulate production and release of reticulocytes
-used most often in pts with CKD or cancer
-initiate when Hgb < 10
-decrease or d/c when Hgb > 11
-requires sufficient iron stores
ESAs: Epoetin alfa (Epogen, Procrit), Darbepoetin alfa (Aranesp)
BBW:
-inc risk of death, MI, stroke, WTE, thrombosis
-CKD: inc risk of death if Hgb > 11
-Cancer: dec survival, inc risk of tumor progression/recurrence (not indicated if intent to cure)
–> use lowest effective dose
Warnings: HTN
SE: arthalgia, bone pain
S&S of hemolysis
-jaundice
-dark urine
-splenomegaly
Drug-induced hemolytic anemia: Immune-mediated
drug binds to RBC –> development of antibodies –> RBC destruction
-positive coombs test
-d/c causative drug - avoid drug- list as an allergy
Drug-induced hemolytic anemia: G6PD deficiency
deficiency of protective enzyme –> hemolysis under conditions of oxidative stress
-low G6PD levels
-d/c causative drug- AVOID all potential causative drugs
Drugs that can cause hemolytic anemia: Immune mediated
–> + Coombs test
-penicillins
-cephalosporins
-Isoniazid
-levodopa
-methyldopa
-rifampin
-quinidine
-quinine
-sulfonamides
Drugs that can cause hemolytic anemia: G6PD deficiency
-dapsone
-methylene blue
-nitrofurantoin
-pegloticase
-rasburicase
-primaquine
-quindine
-quinine
-sulfonamides
Functional asplenia
-RBC sickling causes infarctions (ischemic attacks) of the spleen
-the spleen shrinks and becomes fibrotic (no longer functions)
-pts are at increased risk for infections –> strep. pneumoniae, h. influenzae and n. meningitidis
Key vaccines in sickle cell disease
Routine childhood series
–> h. influenzae (Hib)
–> Pneumococcal conjugate (PCV13, Prevnar 13)
Additional vaccines for functional asplenia:
–> meningococcal conjugate + routine booster
–> meningococcal serogroup B (Bexsero)
–> Prevnar 20 (PCV20) x1
–> PCV15 x1 then PPSV23 x1 > 8 weeks later
Hydroxyurea (for Sickle cell disease)
-reduces pain episode and acute chest syndrome - stimulates production of HgbF
–> use when > 3 moderate-severe pain crisis in 1 yr (and in all children age > 9 months)
BBW: myelosuppression (monitor CBC with differential, calculate ANC and hold if < 2000), malignancy (leukemia, skin cancer)
Warnings: embyro-fetal toxicity (contraception required)
-no live vaccines
-folic acid supplementation
-hazardous drug (wear gloves when handeling med, skin protection)
L-Glutamine (Endari) for SCD
-amino acid (decreases oxidative stress)
-approved for children > 5 y/o and adults
-better safety than hydroxyurea
Iron chelation tx
-iron overload (from blood transfusions) damages organs, such as the heart and liver
-chelation tx removes excess iron
–> oral deferasirox (Exjade, Jadenu) preferred
