Everyday anticoagulation for

the intern

22 January 2018

Important to get it right!

Too much anticoagulation

= Bleeding,

delayed surgery

Too little anticoagulation

= DVT/PE, stroke

What do I need to know? • Frequently used anticoagulants

–Names –Mechanisms of action –Understand differences in

pharmacokinetics • How to start anticoagulation • Monitoring and adjusting heparin, warfarin

and clexane dosing • What can go wrong? • Where to find guidance

The short answer……….

WSLHD anticoagulation guidelines

Click on ‘Policies and Procedures’ button on the right hand side of the intranet homepage click on ‘Search Here’ type ‘Anticoagulation’ in the search bar open document titled “Anticoagulation Guidelines

(Adult) - WSLHD“.

Ask if you are not sure!

• Your registrar/consultant • Your ward pharmacist • Thrombosis & Haemostasis registrar in hours

(pager 22926) • Oncall haematologist after hours • Transfusion registrar for anticoagulation

reversal (pager 27150 or transfusion mobile 0409392151)

Anticoagulants used at Westmead Generic name Brand name Drug formulation Indication

Apixaban Eliquis Oral tablet Non valvular AF, VTE prophylaxis and treatment

Bivalirudin Angiomax IV infusion PCI for coronary artery disease, HIT

Dabigatran Pradaxa Oral capsules Non valvular AF, VTE prophylaxis

Dalteparin Fragmin IV infusion or SC injection Cancer associated VTE, unstable CAD

Danaparoid Orgaran SC injection VTE prophylaxis

Enoxaparin Clexane SC injection Pregnancy, cancer associated VTE

Fondaparinux Arixtra SC injection VTE prophylaxis and treatment, HIT

Rivaroxaban Xarelto Oral tablets Non valvular AF, VTE prophylaxis and treatment

Unfractionated heparin

Heparin sodium IV infusion or SC injection Peri op anticoagulation, renal impairment

Warfarin Coumadin or Marevan Oral tablets Arterial and venous thromboembolism, mechanical heart valves

Frequently used anticoagulants you should be familiar with

Generic Name Trade names

Enoxaparin Clexane

(Unfractionated) Heparin Heparin sodium

Warfarin Marevan, Coumadin

Dabigatran Pradaxa

Rivaroxaban Xarelto

Apixaban Eliquis

Different targets

10

Fibrin

IX

IXa

X

VIIIa

Thrombin

Fibrinogen

Direct Factor Xa inhibitors: Apixaban, Rivaroxaban

Va

Xa

II

AT

Direct thrombin inhibitors: Dabigatran, Bivalirudin

Indirect Factor Xa inhibitors: Heparins: LMWH, UFH Pentasaccharides: Fondaparinux Heparinoids: Danaparoid

Tissue factor/VIIa Vitamin K antagonist: Warfarin

Different effect on coagulation tests Anticoagulant Coag screening tests Drug specific lab test

Apixaban Minimal effect “Apixaban level” = anti Xa level with apixaban calibrator

Bivalirudin APTT Not available

Dabigatran TT, APTT (PT less) “Dabigatran level” = dilute thrombin time

Dalteparin Minimal effect Anti Xa level Danaparoid Minimal effect Anti Xa level

Enoxaparin Minimal effect “Clexane level” = anti Xa level with enoxaparin calibrator

Fondaparinux Minimal effect “Fondaparinux level” = anti Xa level with fondaparinux calibrator

Rivaroxaban PT (APTT less) “Rivaroxaban level” = anti Xa level with rivaroxaban calibrator

Unfractionated heparin

APTT “Unfractionated heparin level” = anti Xa level with heparin calibrator

Warfarin INR Not available

Different reversal ability/methods

Anticoagulant Reversal

Apixaban (Prothrombinex)

Bivalirudin Nil specific

Dabigatran Idarucizumab (Praxbind)

Dalteparin Protamine + FFP

Danaparoid Nil specific

Enoxaparin Protamine + FFP

Fondaparinux Nil specific

Rivaroxaban (Prothrombinex)

Unfractionated heparin Protamine

Warfarin Vitamin K, prothrombinex

NOACs (DOACs)

Dabigatran (Pradaxa)

Rivaroxaban (Xarelto)

Apixaban (Eliquis)

NOAC PBS indications

Dabigatran Rivaroxaban Apixaban

Stroke prevention in non-valvular AF with ≥ 1 risk factor

PBS authority PBS authority PBS authority

VTE prevention after THR or TKR

PBS authority PBS authority PBS authority

VTE treatment and prevention of recurrence

TGA registered. Not PBS reimbursed.

PBS authority PBS authority

Like all anticoagulants, NOACs have pros and cons

PROs • Less major bleeding

(especially ICH) • Rapid onset of action, no

bridging • Few drug and no food

interactions • Fixed dosing without

monitoring • Idarucizumab for dabigatran

reversal (at Westmead and Blacktown Hospitals)

CONs • No specific reversal agent

for rivaroxaban and apixaban.

• Renal elimination • Relatively short t1/2

– Rapid decline in effect if doses missed

• Limited availability of assays to measure drug levels

• Absence of validated monitoring strategies for special circumstances

Who should NOT be on a NOAC • Mechanical heart valve - Warfarin • Significant renal or liver impairment - Warfarin • Pregnant - Clexane • Breast feeding - Warfarin or Clexane • VTE at unusual sites – Warfarin • Antiphospholipid syndrome – Maybe (warfarin first choice) • Cancer – Maybe (LMWH first choice, NOAC studies

ongoing) • Extremes of weight – maybe

• Other …active bleeding, at risk of bleeding, bleeding disorder…

CHARTING THERAPEUTIC ANTICOAGULATION

Look at the med chart for everyone EVERY day

• You need to look at every patients’ medication chart everyday

• For every medication you should consider the ongoing indication, interaction and whether it has actually been given.

Charting anticoagulants

• Use generic names – Do not use trade names. Some health professionals

are not familiar with trade names – Some patients have been doubly anti-coagulated

because of this – Patients usually know trade names

• Doses depend on indication • Should only be initiated after discussion with

senior clinician

Different doses for prophylactic and therapeutic anticoagulation

• Enoxaparin – Prophylaxis: 20mg or 40mg S/C daily – Therapeutic: 1mg/kg BD or 1.5mg/kg S/C daily

• Heparin

– Prophylaxis: 2500 or 5000 units S/C BD or TDS – Therapeutic: Continuous IV infusion

Different doses for prophylactic and therapeutic anticoagulation

• Apixaban – VTE secondary prophylaxis: 2.5mg PO BD – VTE therapeutic: 5mg or 10mg PO BD – AF: 2.5mg or 5mg PO BD – Dose depends on indication!

• Fondaparinux

– Prophylaxis: 2.5mg S/C daily – Therapeutic: 5mg or 7.5mg or 10mg S/C daily

Prescribing therapeutic anticoagulation

• Why does the patient need anticoagulation? – VTE – DVT/PE etc – Atrial fibrillation – Acute coronary syndrome

• Is the patient safe to anti-coagulate? – What baseline tests should you perform?

• What drugs are available? • Which drug is best for this patient? • Do we need to dose reduce? • CHECK WITH SOMEONE MORE SENIOR • Then prescribe

Safety: Risks are increased by

• Bleeding disorder, recent bleeding • Renal or liver dysfunction • High blood pressure • Extremes of age • Extremes of body weight • Concurrent medications eg: dual antiplatelet

therapy

CASE 1

Case 1: Samantha Stosur • 36 yo female • Presents with acute onset right leg pain and

swelling • Doppler USS shows occlusive femoral vein

thrombus • What is the diagnosis? • What baseline tests should be performed? • Prescribe anticoagulation for this patient • Weight 70kg, Creat 75 micromol/L, Height

172cm

1.1 Not pregnant

1.1 Not pregnant

Options: • Rivaroxaban

– 15mg BD for 3 weeks then 20mg daily

• Apixaban – 10mg BD for 1 week then 5mg BD

Have a go at charting a NOAC

1.2 Pregnant

Options • Enoxaparin

Have a go at charting Enoxaparin

• Weight 70kg

1.3 Breast feeding

Options • Enoxaparin • Warfarin

Have a go at charting warfarin

1.4 Renal impairment

The patient had creatinine clearance of 28 mL/min? • Reduce enoxaparin dosing to 70 mg (1mg/kg)

daily – Check Anti Xa levels

• Transition to warfarin • Use Cockroft-Gault creatinine clearance

– Apps available on phone e.g. MDCalc, QxMD – Use ideal body weight for obese for CrCl calculation

(but actual body weight for dosing of enoxaparin)

Warfarin

• Complex to use • Not able to use in NBM, albumin<30 , frequently

changing drugs – ie many inpatients • Doesn’t work instantly – therefore overlap with a

heparin if instant anti-coagulation is required • If recommencing after a procedure in some

circumstances overlap is not used – check this with each consultant directly

Starting warfarin Treatment day

Warfarin dose (first INR on day 3)

1

10mg Age < 70

5mg Age >70 years OR Weight <50kg OR Chronic or intercurrent illness

2 5mg

3 INR < 2.0 INR 2.0 – 3.0 INR > 3.0

5mg 4mg Omit dose

4 INR – adjust warfarin dose according to schedule below. Continue LMWH

Brands of warfarin – Coumadin® vs Marevan® (not interchangeable, not bioequivalent) *Initiation for new patients = Coumadin®

LMWH or Heparin is co-prescribed

• Therapeutic doses (adjust as per CrCl) until INR is >2.0 for two consecutive days

Monitoring • Request an INR • Target 2.0-3.0 in most cases • 2.5-3.5 in some artificial valves

Case 1 continued:

• Patient receives warfarin 10mg, then 5mg and 5mg

• On day 4 the INR is 1.7, write up the next dose

Sending a patient home on Clexane/warfarin

• Contact PACC nurse & pharmacist early

• HITH/PACC – nurses will go to homes, inject Clexane, take INRs and adjust with LMO, team or haem.

• On Discharge: Enoxaparin: 3-7 days supply

Take home kit includes sharps bin. (Some patient may be able to self-administer.)

Warfarin • If INR is unstable, provide starter pack (1mg,

2mg, 5mg - 5 tabs of each strength) until GP review.

• If stable, 3-7 days supply until GP review.

CASE 2

Case 2: Thanasi Kokkinakis

• 65yo male with mechanical mitral valve • Presents with an acute bowel obstruction and

rectal mass on CT scan • Warfarin is reversed and he proceeds to bowel

resection • He has acute renal failure with CrCl 20 mL/min • Weight 80kg • What anticoagulation would you prescribe

postoperatively?

Heparin infusion protocol

• VTE or cardiology modified protocol? • Bolus or no bolus?

– Ask your senior

• Need to know patient’s weight

Heparin protocols - starting

Have a go at charting heparin infusion

• Weight 80kg

Charting Heparin infusion

UNITS (not “U”) Specify: Diluent infusion rate

Case 2 continued:

• 4 hours after starting IV heparin, the APTT is >150 sec – What questions must you ask? – What would you prescribe next? – When should you repeat the APTT?

Take blood for APTT when required (on time)

What can go wrong?

• Dual anti-coagulation for too long or unrecognized (NOACs)

• Not adjusting for renal function • Using warfarin in sick patients • Using inappropriate dose for indication • Not considering other bleeding risk factors

– Dual antiplatelet agents – Surgery

• Not using VTE prophylaxis enough

Ask if you are not sure!

• Your registrar/consultant • Your ward pharmacist • Thrombosis & Haemostasis registrar in hours

(pager 22926) • Oncall haematologist after hours • Transfusion registrar for anticoagulation

reversal (pager 27150 or transfusion mobile 0409392151)