anticoag, anemia, sickle cell

MOA of Heparins

bind to AT= increase AT activity= inactivates IIa (prothrombin) + other proteases like Xa

UFH vs. LMWH

both bind to AT, but LMWHs inhibit Xa more= more predictive response

Factor Xa Inhibitors

• apixaban

• rivaroxaban

• edoxaban

• fondaparinux

Direct Thrombin Inhibitors:

• dabigatran

• argatroban

• bivalirubin

Situations warfarin > DOAC

• stroke prevention- mitral stenosis or mechanical heart valve

• VTE tx- triple-positive antiphospholipid syndrome or mechanical heart valve

MORAL OF THE STORY—> MECH HEART VALVE= WARFARIN

heparin calculations use what weight

TBW

UFH dosing:

• VTE pro

• VTE tx

• ACS/STEMI tx

• VTE pro: 5,000 units SQ q8-12h

• VTE tx: 80 units/kg IV bolus, 18 units/kg/hr inf

• ACS/STEMI tx: 60 units/kg IV bolus, 12 units/kg/hr inf

LMWH dosing:

• VTE pro

• VTE tx + UA/NSTEMI tx

• STEMI <75 tx

• STEMI ≥75 tx

• VTE pro: 40 units SQ daily, 30 units SQ q12h

  • CrCl <30: 30 units SQ daily

• VTE tx + UA/NSTEMI tx: 1 mg/kg SQ q12h

  • VTE inpatient only: 1.5 mg/kg SQ daily

  • CrCl <30: 1mg/kg SQ daily

• STEMI <75 tx: 30mg IV bolus, 1 mg/kg SQ q12h

  • CrCl <30: 30mg IV bolus, 1 mg/kg SQ dose, then 1 mg/kg SQ daily

• STEMI ≥75 tx: no bolus, 0.75 mg/kg q12h

  • CrCl <30: 1 mg/kg SQ daily

LMWH dosing tips:

• CrCl <30—> always only daily dosing

• when in doubt—> 1mg/kg

4T

• Thrombocytopenia: drop in platelets 50%

• Timing: 5-10 days after hep

• Thrombosis: clot?

• oTher?—> can it be anything else?

4T management:

• stop what?

• warfarin?

  • restart?

• which anticoags?

  • preference in cardiac surgery/PCI?

• stop ALL HEPARINS ASAP

• Warfarin

  • reverse w/ vit K

  • only restart when platelets >150

• argatroban for tx asap

  • bivalirudin if cardiac surgery/PCI

eliquis nonvalvular AF dosing

• 5mg PO BID

• 2.5mg PO BID if—> ≥80 YO, SCr >1.5, Wt ≤60kg

eliquis DVT/PE tx dosing

10mg PO BID x 7 days, 5mg PO BID

eliquis DVT prophylaxis dosing after hip/knee replacement

2.5mg PO BID x 12 days for knee, 35 days for hip

rivaroxaban + food

doses ≥15

Xarelto nonvalvular AF dosing

CrCl >50: 20mg daily w/ evening meals

CrCl ≤50: 15mg daily w/ evening meals

Xarelto DVT/PE tx dosing

15mg PO BID x 21 days, then 20mg daily w/ food

• CrCl <15: do not use

Xarelto DVT prophylaxis dosing after hip/knee replacement

10mg PO daily x 12 days for knee, 35 days for hip

• CrCl <15: do not use

xarelto and funky missed dose

if on 15mg PO BID and miss dose—> take both asap do not skip

Special BBW on edoxaban

if CrCl >95: do not use for nonvalvular AF

Edoxaban nonvalvular AF dosing:

CrCl 51-95: 60mg daily

CrCl: 15-50: 30mg daily

CrCl: <15: not recommended

Edoxaban DVT/PE tx dosing

• 60mg daily—> must start after 5-10 days of parenteral

• same dose reductions as in stroke dosing

BBW on all DOACs

pts. receiving neuraxial anesthesia or spinal puncture—> hematoma and paralysis risk

Fondaparinux CrCl cutoff

<30 is CI

DOACs and CYP interactions

eliquis & xarelto—> avoid w/ strong CYP3A4 and Pgp inducers (inhibitors for xarelto as well)

Pradaxa DVT/PE tx dosing

150mg BID —> must start after 5-10 days of parenteral

• CrCl<30: avoid use

converting from warfarin to DOAC:

“READ”—> stop warfarin and convert to DOAC when…

• Rivaroxaban: INR<3

• Edoxaban: INR<2.5

• Apixaban: INR <2

• Dabigatran: INR <2

converting from DOAC to warfarin:

stop DOAC, start parenteral anticoagulant and warfarin at next dose (doesn’t apply to edoxaban)

converting from dabigatran to warfarin:

start warfarin 1-3 days before stopping dabigatran (refer to package insert)

MOA of warfarin:

competitively inhibits VKORC1—> inhibits 2,7,9,10

BBW of warfarin

bleeding. duh.

warfarin warnings

tissue necrosis/gangrene, purple toe syndrome

warfarin phamacogenomics

CYP2C9*2 or 3* alleles= increase bleed risk

goal INR

2-3 for most, 2.5-3.5 if mechanical

more potent warfarin isomer

S

Warfarin D/I

• PK—> CYP2C9

  • decrease INR: CYP inducers (phenytoin, carb, phenobarb, rifampin, st. johns wort)

  • increase INR: CYP inhibitors (fluconazole, metronidazole, bactrim, AMIODARONE, tamoxifen)

• PD—> anything that can increase bleed risk or clot risk like NSAIDs, SSRIs, antiplatelets, estrogens

• Diet—> 5G’s, alcohol, foods with vit K (leafy green veggies)

Which anticoagulant is C/I in pregnancy?

warfarin —> (think: HD for a reason)

warfarin tab colors: 1,2, 2.5, 3, 4, 5, 6, 7.5, 10

pink, purple, green, tan, blue, peach, teal, yellow, white

Protamine dosing for UFH and LMWH reversal:

UFH: 1mg protamine will reverse 100 units, reverse amount given in last 2-2.5 hours, max 50mg

LMWH: 1mg protamine/1mg enoxaparin within last 8 hours

BBW of protamine and vit K

hypersensitivity/ anaphylaxis (warfarin IV only)

administer what with vit K?

Four Factor Prothrombin Complex Concentrate (Kcentra, Balfaxar) —> has 2,7,9,10, C,S

oral vs. IV Vit K

oral—> when no sig bleeding

IV—> major bleeding

don’t do IM or SC

Warfarin Reversal per INR:

• <4.5 w/ no major bleeding: reduce/skip dose, monitor INR

• 4.5-10 w/ no major bleeding: hold 1-2 doses, monitor INR (maybe oral vit K if having surgery)

• >10 w/ no major bleeding: hold warfarin, oral vit K, monitor INR

• major bleeding: hold warfarin, IV vit K slowly + 4-factor PCC

perioperative warfarin management:

• stop ~5 days before surgery

• if mechanical heart valve or high VTE risk bridge w/ heparin

• d/c LMWH 24 hrs before/UFH 4-6 hrs before surgery

do not bridge for low risk

CHA-DS-VASc Scoring System:

≥2 (males) and ≥3 (females)= anticoag rec

anticoagulation for pts. with AF undergoing cardioversion

• AF> 48 hrs or unknown duration= 3w before, 4w after

• AF ≤ 48 hrs= 4w after

HAS-BLED Scoring System:

Anticoagulation in pregnancy:

• LMWH PREFERRED

• Warfarin- C/I

• DOACs- not studied

VTE provoked and unprovoked tx duration:

unprovoked: 3 months+

provoked: 3 months

identifying the cause of anemia via MCV:

• microcytic (<80): iron deficiency

• normocytic: acute blood loss, hemolysis, CKD, malignancy, bone marrow failure

• macrocytic (>100): vit b12/ folate deficiency

causes of iron deficiency anemia:

• diet

• blood loss (acute, chronic— heavy periods, PUD)

• decreased absorption (high gastric pH—- PPI use or GI disorders)

  • THINK: IRON LIKES ACIDITY

• increased requirements (pregnant, lactating, infants)

iron deficiency anemia tx—- oral vs. IV

• oral iron—> GO TO

• IV iron- due to ADRs, cost, etc.—> reserved typically for CKD or cancer

oral iron counseling:

• when to take?

• D/I?

• BBW

• ADRs

• Admin: TAKE ON EMPTY stomach (unless GI upset)

  • take w/ vit C—> increase absorption

• D/I: quinolones, tetracycline, bisphosphonates, levothyroxine, INSTIs

• BBW: overdose in kids

• ADRs: constipation, dark tarry stools

iron overdose antidote

deferoxamine (Desferal)

IV iron names:

• Iron sucrose (Venofer)

• Ferumoxytol (Feraheme)

• Iron dextran complex (INFeD)

Main BBW/ warnings with IV iron

Hypersensitivity rxns—- on ALL IV iron products

• BBW for Feraheme and INFeD—- must give test dose for INFeD

ESA initiated when Hgb < ___ g/dL

10

ESA d/c’ed when Hgb > ___ g/dL

11

BBW on ESAs

↑ risk of death, MI, stroke, VTE, thrombosis AKA INCREASES CLOT RISK

Epoetin brand

Epogen, Procrit

Darbepoetin brand

Aranesp

Epoetin vs. Darbepoetin

darb has 3x longer half life… allows for once weekly dosing vs. trice weekly dosing

what is hemolytic anemia?

when RBCs are destroyed prematurely (10-20 days instead of 120)

2 types of drug-induced hemolytic anemia

• immune-mediated: + Coombs test

• GP6D deficiency: - Coombs test

Key drugs that can cause immune-mediated hemolytic anemia:

• penicillins, cephalosporins

• isoniazid

• methyldopa, levodopa

• rifampin

• quinidine, quinine

• sulfonamides

Key drugs that can cause G6PD Deficiency hemolytic anemia:

• Dapsone

• Methylene blue

• nitrofurantoin

• Pegloticase, Resburicase

• Primaquine, Quinidine, Quinine

• Sulfonamides

ESA storage considerations

• fridge

• do NOT SHAKE