lab control of anticagulant & therapy

7/30/2019 Lab Control of Anticagulant & Therapy

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Lab control of anticoagulant and

therapy

Dr. Kashmiri Lal Sharma


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Hemostasis

Hemostasisblood in fluid state

Blood vessel wall

Platelets Coagulation cascade


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Antithrombotic Agents Anticoagulants: prevent clot formation and

extension

Antiplatelet drugs: interfere with platelet

activity

Thrombolytic agents: dissolve existing thrombi


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XII XIIa

XI

XIa

IX

IXa

X

Xa

II

IIa

X

Xa

VII

VIIa

V Va

VIIIa

Fibrinogen

Fibrin CLOT

monomers

IIa

IIa

XIII

HMWK

TF

The Chemical Process of Clotting

Desai, U. R., VCU (2005)

IIa

Note:

IXa and VIIIa work together to

convert X into Xa.

Xa and Va work together to

convert II into IIa.

IIa works on a number of steps.

HMWK and TF are initiation points

CLOT is the end point

XIIIa

VIII


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Warfarin: Indications

Prophylaxis and/or treatment ofVenous thrombosis and its extension

Pulmonary embolism

Post MI

To reduce the risk of death, recurrent MI, andthromboembolic events such as stroke or

systemic embolization Prevention and treatment of cardiac embolism


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Warfarin

Major Adverse effect is Hemorrhage

Factors that may influence bleeding risk

Intensity of anticoagulationConcomitant clinical disorders

Concomitant use of other medications

Quality of management


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Special Considerations in the elderly

Increased age associated with increased

sensitivity at usual doses

Comorbidity

Increased drug interactions


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Elderly patients need less warfarin

Age 20 needs 10-15 mg

Age 40 needs 5-10 mg

Age 70 needs 2.5 mg

Always begin warfarin at the expectedmaintenance dose ( 2-5 mg), avoid large loadingdoses


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Prothrombin Time (PT)

Proliferation of thromboplastin reagents with widely

varying sensitivities to reduced levels of vitamin K

dependent clotting factors has occurred Problem addressed by use of INR (International

Normalized Ratio)


10/33J Clin Path 1985; 38:133-134; WHO Tech Rep Ser. 7. 983.

International Normalized Ratio

A mathematical correction (of the PT ratio)for differences in the sensitivity ofthromboplastin reagents

Relies uponreference

thromboplastins withknown sensitivity to antithrombotic effects of

oral anticoagulants

INR is the PT ratio one would have obtained if

thereference

thromboplastin had been used

Allows for comparison of results between labsand standardizes reporting of the prothrombintime


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( )Patients PT in Seconds

Mean Normal PT in SecondsINR =

ISI

INR = International Normalized Ratio

ISI = International Sensitivity Index

INR Equation


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MeanNormal(Seconds)

PTR ISI INR

12

12

13

11

14.5

1.3

1.5

1.6

2.2

2.6

A

B

C

D

E

Blood froma singlepatient Patients

PT(Seconds)

16

18

21

24

38

ThromboplastinReagent

How Different Thromboplastins

Influence the PT Ratio and INR


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MeanNormal(Seconds)

PTR ISI INR

12

12

13

11

14.5

1.3

1.5

1.6

2.2

2.6

3.2

2.4

2.0

1.2

1.0

2.6

2.6

2.6

2.6

2.6

A

B

C

D

E

Blood froma singlepatient Patients

PT(Seconds)

16

18

21

24

38

Thromboplastinreagent

How Different Thromboplastins

Influence the PT Ratio and INR


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Potential Problems with the INR

Limitations

Unreliable during induction

Loss of accuracy with highISI thromboplastins

Solutions

Use thromboplastin reagents withlow ISI values (less than 1.5)

Use thromboplastin reagents withlow ISI values


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Warfarin: Dosing Information

Individualize dose according to patient

response

(as indicated by INR)

Use of large loading dose not recommended

May increase hemorrhagic complications

Does not offer more rapid protection Low initiation doses are recommended for

elderly/frail/liver-diseased/malnourished

patients


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Conversion from Heparin to Warfarin

May begin concomitantly with heparin therapy

Heparin should be continued for a minimum offour days

Time to peak antithrombotic effect of warfarinis delayed 96 hours

When INR reaches desired therapeutic range,

discontinue heparin (after a minimum of fourdays)


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Warfarin: Dosing & Monitoring

Start low

Initiate 5 mg daily

Educate patient

Stabilize

Titrate to appropriate INR

Monitor INR frequently (daily then weekly)

Adjust as necessary

Monitor INR regularly (every 14 weeks) andadjust


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Signs of Warfarin Overdosage

Any unusual bleeding:

Blood in stools or urine

Excessive menstrual bleedingBruising

Excessive nose bleeds/bleeding gums

Persistent oozing from superficial injuriesBleeding from tumor, ulcer, or other lesion


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Warfarin: Current Indications/Intensity

Indication INR Range Target

Prophylaxis of venous thrombosis (high-risk surgery) 2.03.0 2.5

Treatment of venous thrombosis

Treatment of PE

Prevention of systemic embolism

Tissue heart valves

AMI (to prevent systemic embolism)

Valvular heart disease

Atrial fibrillation

Mechanical prosthetic valves (high risk) 2.5

3.5 3.0

Certain patients with thrombosis and the antiphospholipid syndrome

AMI (to prevent recurrent AMI)

Bileaflet mechanical valve in aortic position 2.03.0 2.5


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Patient education & information


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Effective Patient Education

Teach basic concepts of safe, effective

anticoagulation

Discuss importance of regular INR monitoring

Counsel on use of other medications, alcohol

Develop creative strategies for improving

compliance


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PATIENT EDUCATION

Inform patients about the mechanism of action ofwarfarin and caution them about diet and druginteractions

Advise patients to avoid alcohol

Instruct patients to report any drug changes to thephysician monitoring the INR Counsel women to avoid pregnancy while on

warfarin


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LAB MONITORING OF HEPARIN

THERAPY Essential because of complicated pharmaco-

kinetics.

Response is affected by

body weight

event of thrombosis

heparin binding to plasma and endothelial

cell proteins


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Monitoring is performed to achieve a targeted

therapeutic range1.5 to 2.5 times the mean lab control aPTT value

Plasma heparin level of 0.2-0.4 u/m1

(Protamine titration) or 0.35 to 0.7 u/m1(antifactor Xa methods)

Low-does prophylactic therapy with either UFH

or LMWH is given by subcutaneous injectionand usually not monitored except in some

circumstances like pregnancy and renal failure


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Test Advantages

Whole blood

clotting

time

Simple

inexpensive

No equipment needed

APTT Simple

many tests can be carried out in parallel

TT Simple

many test can be carried out in parallel

Protamine

neutralization

Sensitive to all concentrations

Anti-Xa

assays

Sensitive to all concentrations and to LMWT heparin

Tests used


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ACTIVATED PARTIAL

THROMBOPLASTIN TIME

The test measures the clotting time of plasmaafter activation of contact factors but withoutadded tissue thromboplastin indicates overallefficiency of intrinsic pathway

Very sensitive to heparin but few short comings

Different aPTT reagents have different

sensitivities to heparin


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HEPARIN MONITORING AT BEDSIDE

Wholeblood activated clotting time (ACT)

Determined by using clotting cascade

activators such as kaolin and end - pt detection

by optical or electromagnetic method.

Not specificaffected by factors like

hypothermia, hemodilution and platelet

dysfunction.


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Indications for LMWH monitoring

Renal Dysfunction

Body Wt < 60 Kg

Body Wt > 100 Kg High Risk patients (Recent bleeding)

Consider it in elderly patients above age 70 yrs

Pregnancy


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Failing Anticoagulants

Things to Consider

Short duration of antithrombotic Rx

Heparin induced thrombocytopenia

Poor control of INR

Drug interactions

Non-compliance


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Reversal of anticoagulantsUnfractionated heparin

Protamine 1 mg per 100 units, risksbradycardia and hypotension

Allergic reactions due to previous exposure toprotamine containing insulin, vasectomy andfish allergies

LMWH

Protamine less effective due to shorter heparin

chains Normal dosing acutely reverses 42% of factor

Xa activity and 92% of anti-factor IIa actvity


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Warfarin

Oral vitamin K reduces INR in 24 hrs

Low dose IV doses effective (0.5 to 2.5mg),

higher doses (>10mg) associated withtemporary warfarin resistance onreintroduction


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Warfarin

INR lowering or

omitting a dose INR >5 and withhold

1 to 2 doses +/- 1 to 2.5mg of oral vitamin K

INR >9 3 to 5mg of oral vitamin K

For serious bleeding => FFP and slow IV

administration of 10mg vitamin K

In preparation for surgery, most patientsrequire 4 days to reach an INR


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Thanks

lab control of anticagulant & therapy

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