Anticoagulation

Halley Willson
PGY-1 Resident, IU Health Arnett
hwillson@iuhealth.org
About Me
Objectives

Describe the pathophysiology, clinical presentation and clinical findings of the acute coronary syndromes (ACS)

Differentiate between unstable angina (UA), non ST-elevation myocardial infarction (NSTEMI) and ST-elevation myocardial
infarction (STEMI)

Identify the pharmacologic classes and agents within each class used to treat ACS

Discuss the indications, doses, precautions/contraindications, and monitoring of pharmacologic agents used to treat ACS

Describe the similarities and differences among the antiplatelet and thrombolytic agents. Understand the pros and cons
of using each for a given patient

Develop a therapeutic care plan for a patient with UA, NSTEMI or STEMI and explain the rationale for each medication you
would or would not recommend

Recommend a pharmacotherapy regimen for secondary prevention of MI and explain the rationale for each medication you would
or would not recommend
Objectives

Describe the pathophysiology, clinical presentation and clinical findings of the acute coronary syndromes (ACS)

Differentiate between unstable angina (UA), non ST-elevation myocardial infarction (NSTEMI) and ST-elevation myocardial
infarction (STEMI)

Identify the pharmacologic classes and agents within each class used to treat ACS

Discuss the indications, doses, precautions/contraindications, and monitoring of pharmacologic agents used to treat ACS

Describe the similarities and differences among the antiplatelet and thrombolytic agents. Understand the pros and cons
of using each for a given patient

Develop a therapeutic care plan for a patient with UA, NSTEMI or STEMI and explain the rationale for each medication you
would or would not recommend

Recommend a pharmacotherapy regimen for secondary prevention of MI and explain the rationale for each medication you would
or would not recommend
Anticoagulation
Recommended in addition to
antiplatelet therapy to improve vessel
patency and prevent re-occlusion
Coagulation Cascade
Anticoagulants

Unfractionated Heparin (UFH)

Low Molecular Weight Heparin (LMWH)

Bivalirudin

Fondaparinux
Unfractionated Heparin (UFH)

 Anti-Xa and anti-IIa activity

 Risk of heparin induced thrombocytopenia (HIT)
 Drop in platelet count AND increased thrombosis
 Caused by formation of antibodies that activate platelets
 If suspected  Calculate 4T Score (What are the 4 T’s?)
 Screening tests available if HIT suspected
 Enzyme-linked immunosorbent assay (ELISA)- quick, high false positive rate
 Serotonin release assay (SRA)- gold standard for diagnosis, often a “send-out” lab
Unfractionated Heparin (UFH)

 Question: Is unfractionated heparin the only anticoagulant that can cause

HIT?
Unfractionated Heparin (UFH)

 Question: Is unfractionated heparin the only anticoagulant that can cause

HIT?
 No, LMWH can also cause HIT but there is a lower risk than with UFH

 Question: Can a patient with a history of HIT be re-challenged with

unfractionated heparin or LMWH?
Unfractionated Heparin (UFH)

 Question: Is unfractionated heparin the only anticoagulant that can cause

HIT?
 No, LMWH can also cause HIT but there is a lower risk than with UFH

 Question: Can a patient with a history of HIT be re-challenged with

unfractionated heparin or LMWH?
 No, patients should not be re-challenged with either
Unfractionated Heparin (UFH)

 Unfractionated heparin (UFH)

 Quick onset and short half life
 Administered as a continuous infusion
 Dosing of UFH is based on the activated partial thromboplastin time (aPTT) or activated
clotting time (ACT)
aPPT Level IV push loading dose Infusion IV rate change units/hr Repeat aPTT

Less than 39 seconds 60 units/kg Continue Increase 4 units/kg/hr 6 hours

39-54 seconds 30 units/kg Continue Increase 2 units/kg/hour 6 hours

55-90 seconds 0 Continue No change Next AM

91-99 seconds 0 Continue Decrease 1 unit/kg/hr 6 hours

100-110 seconds 0 Continue Decrease 2 units/kg/hr 6 hours

111-139 seconds 0 Stop for 1 hour Decrease 2 units/kg/hr 6 hours after resumed

140-180 seconds 0 Stop for 1 hour Decrease 3 units/kg/hr 6 hours after resumed

Greater than 180 seconds 0 Stop for 2 hours Decrease 4 units/kg/hr 6 hours after resumed
Enoxaparin

 Low molecular weight heparin (LMWH)

 Anti-Xa and anti-IIa activity
 Higher ratio of anti-Xa/anti-IIa than UFH
 Eliminated by kidneys
 Accumulates in renal impairment

 Question: Do we routinely check anti-Xa levels for patients on enoxaparin?

 No. Usually not necessary and difficult to interpret results. Consider in certain
cases- very high or low body weight, renal impairment, development/worsening
clot, etc.
Bivalirudin

 Direct thrombin inhibitor

 Not used together with GPIIb/IIIa inhibitors (except
”bail out”)
 Conflicting results vs unfractionated heparin
 Many studies used GPIIb/IIIa inhibitors with
heparin
 Difficult to determine if differences were
due to bivalirudin vs heparin
 May not be as effective for MACE and stent
thrombosis
 HEAT-PPCI trial
 May have lower bleeding risk
 BRIGHT trial and MATRIX trial
Fondaparinux

 Factor Xa inhibitor
 Not commonly used
 Can use in patients with a history of HIT
 Do not use alone for PCI
 High rates of thrombosis
 Not drug of choice if planning PCI
 If already giving fondaparinux and patient needs
PCI, need to give unfractionated heparin or
bivalirudin also

 Contraindicated for CrCl < 30mL/min

Anticoagulation Dosing

Bolus Dose Maintenance Dose Renal Dosing

UFH 60 units/kg IV 12 units/kg/hr infusion titrated to
(max 4000 units) institutional aPTT target
50-100 units/kg during PCI No maintenance dose during PCI

Enoxaparin 30 mg IV 1 mg/kg subcutaneously q12h CrCl < 30 mL/min: 1 mg/kg q24h

(first dose 15 minutes after bolus)
(reduce to 0.75 mg q12h if > 75 years)

Bivalirudin 0.75 mg/kg IV 1.75 mg/kg/hr infusion CrCl < 30 mL/min: 1 mg/kg/hr
Dialysis: 0.25 mg/kg/hr

Fondaparinux 2.5 mg IV 2.5 mg subcutaneously q24h CrCl < 30 mL/min:

Contraindicated
Anticoagulation

UA/STEMI STEMI
Ischemia Guided Strategy Early Invasive Strategy Fibrinolytic PCI

UFH Yes (48 hours) Yes (Until PCI) Yes (48 hours) Yes (Until PCI)

Bivalirudin No Yes (Until PCI) No Yes (Until PCI)

Consider using for HIT (Prefer in high
bleeding risk)

Enoxaparin Yes (Duration of hospital stay, Yes (Until PCI) Yes (Duration of hospital stay, No
up to 8 days) up to 8 days)

Fondaparinux Yes (Duration of hospital stay, Not ideal Yes (Duration of hospital stay, No
up to 8 days) Do not use alone for PCI up to 8 days)
Question

 Patient is an 82-year-old female that presented with NSTEMI and the

cardiologist has opted for ischemia guided therapy. Temp 37.2, BP is 125/71,
HR 67bpm, RR 16, O2 sat 96% on room air. SCr = 0.58mg/dL. Patient weighs
58kg. Patient received ASA 325mg x 1, clopidogrel 600mg x 1. What
recommendation would you made regarding this patient’s anticoagulation?

1. Fondaparinux 2.5mg subq q24h

2. UFH 60 units/kg IV, followed by 12 units/kg per hour titrated to aPTT
3. Enoxaparin 45 mg subq bid
4. Enoxaparin 60 units/kg subq daily
Question

 Patient is an 82-year-old female that presented with NSTEMI and the

cardiologist has opted for ischemia guided therapy. Temp 37.2, BP is 125/71,
HR 67bpm, RR 16, O2 sat 96% on room air. SCr = 0.58mg/dL. Patient weighs
58kg. Patient received ASA 325mg x 1, clopidogrel 600mg x 1. What
recommendation would you made regarding this patient’s anticoagulation?

1. Fondaparinux 2.5mg subq q24h

2. UFH 60 units/kg IV, followed by 12 units/kg per hour titrated to aPTT
 This is an option, but less convenient that LMWH
3. Enoxaparin 45 mg subq bid
4. Enoxaparin 60 units/kg subq daily
Question

 Patient is an 82-year-old female that presented with NSTEMI and the

cardiologist has opted for ischemia guided therapy. Temp 37.2, BP is 125/71,
HR 67bpm, RR 16, O2 sat 96% on room air. SCr = 0.58mg/dL. Patient weighs
58kg. Patient received ASA 325mg x 1, clopidogrel 600mg x 1. Based on your
selection in the last question, how long would you continue anticoagulation
for?
1. 24 hours
2. 48 hours
3. Until hospital discharge (up to 8 days)
4. Until PCI
Question

 Patient is an 82-year-old female that presented with NSTEMI and the

cardiologist has opted for ischemia guided therapy. Temp 37.2, BP is 125/71,
HR 67bpm, RR 16, O2 sat 96% on room air. SCr = 0.58mg/dL. Patient weighs
58kg. Patient received ASA 325mg x 1, clopidogrel 600mg x 1. Based on your
selection in the last question, how long would you continue anticoagulation
for?
1. 24 hours
2. 48 hours
3. Until hospital discharge (up to 8 days)
4. Until PCI
What
questions do
you have?
Review –
Patient Case
Patient Case

 A 59-year-old male presents to the ER reporting severe, crushing chest pain

that radiates down his left arm. The chest pain started 30 minutes ago while
landscaping his yard outside on a hot summer day. The pain has not subsided
with rest. His past medical history includes GERD and COPD. He smokes ½
PPD of cigarettes.
 ECG
 ST segment elevation is present on ECG
 Troponin = 2.5ng/mL
Patient Case

 A 59-year-old male presents to the ER reporting severe, crushing chest pain that
radiates down his left arm. The chest pain started 30 minutes ago while landscaping
his yard outside on a hot summer day. The pain has not subsided with rest. His past
medical history includes GERD and COPD. He smokes ½ PPD of cigarettes.
 ECG
 ST segment elevation is present on ECG
 Troponin = 2.5ng/mL
 Early hospital care?
 Morphine
 Oxygen
 Nitrates
 Aspirin
Patient Case

 A 59-year-old male presents to the ER reporting severe, crushing chest pain

that radiates down his left arm. The chest pain started 30 minutes ago while
landscaping his yard outside on a hot summer day. The pain has not subsided
with rest. His past medical history includes GERD and COPD. He smokes ½
PPD of cigarettes.
 Reperfusion
 PCI (preferred)
 Fibrinolytic
Patient Case

 A 59-year-old male presents to the ER reporting severe, crushing chest pain

that radiates down his left arm. The chest pain started 30 minutes ago while
landscaping his yard outside on a hot summer day. The pain has not subsided
with rest. His past medical history includes GERD and COPD. He smokes ½
PPD of cigarettes.
 P2Y12 inhibitor
 Loading dose
 Ticagrelor 180mg x 1 (preferred with PCI)
 Prasugrel 60mg x 1 (preferred with PCI)
 Clopidogrel 600mg x 1
 Clopidogrel 300mg x 1 (preferred with fibrinolytic)
 Cangrelor?
Patient Case

 A 59-year-old male presents to the ER reporting severe, crushing chest pain

that radiates down his left arm. The chest pain started 30 minutes ago while
landscaping his yard outside on a hot summer day. The pain has not subsided
with rest. His past medical history includes GERD and COPD. He smokes ½
PPD of cigarettes.
 P2Y12 inhibitor
 Maintenance dose
 Ticagrelor 90mg bid
 Prasugrel 10mg daily
 Clopidogrel 75mg daily

 Duration?
Patient Case

 A 59-year-old male presents to the ER reporting severe, crushing chest pain

that radiates down his left arm. The chest pain started 30 minutes ago while
landscaping his yard outside on a hot summer day. The pain has not subsided
with rest. His past medical history includes GERD and COPD. He smokes ½
PPD of cigarettes.
 GPIIB/IIIA inhibitor?
 Not used routinely. Consider for large thrombus burden or bail out
 Abciximab
 Eptifibatide
 Tirofiban
Patient Case

 A 59-year-old male presents to the ER reporting severe, crushing chest pain

that radiates down his left arm. The chest pain started 30 minutes ago while
landscaping his yard outside on a hot summer day. The pain has not subsided
with rest. His past medical history includes GERD and COPD. He smokes ½
PPD of cigarettes.
 Anticoagulation
 PCI
 Heparin or bivalirudin

 Fibrinolytic
 Heparin, enoxaparin or fondaparinux
What
questions do
you have?
Evaluation