242141416-Anticoagulant-Therapy-pppt.ppt

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1. Anticoagulant Therapy

2. Definition of Anticoagulation
•Therapeutic interference ("blood-thinning")
with the clotting mechanism of the blood
to prevent or treat thrombosis and
embolism.

3. Overview
•Indications
•A basic case study
•Heparin/heparin like drugs and their
complications
•Warfarin
•Newer anticoagulant drugs

4. Indications of Anticoagulant
Therapy
•Treatment and Prevention of Deep Venous
Thrombosis
•Pulmonary Emboli
•Prevention of stroke in patients with atrial
fibrillation, artificial heart valves, cardiac
thrombus.
•Ischaemic heart disease
•During procedures such as cardiac
catheterisation and apheresis.

5. Pertinent Questions from this
case
•How do heparin drugs work?
•How does warfarin work?
•Why start both clexane and warfarin?
•What is an INR and how is heparin
monitored?
•What are the risks of both of these
types of drugs?

6. Standard Heparin
•Heterogenous mixture of polysaccharide
chains
•MW 3k to 30k
•Active in vitro and in vivo
•Administration - parenteral- Do not inject IM -
only IV or deep s.c.
•Half-life 1 - 2 hrs - monitor APTT
•Adverse effect - haemorrhage - antidote -
protamine sulphate

7. Enhances
Antithrombin Activity

8. Monitoring Heparin
•Activated Partial Thromboplastin Time
(APTT)
•Normal range: 25-40 seconds
•Therapeutic Range: 55-70 seconds
•Timing
–4-6 hours after commencing infusion
–4-6 hours after changing dosing regimen

9. Low Molecular Weight Heparin
•Changed management of venous
thromboembolism
•Standard (Unfractionated) heparin 3k to
30k
•LMWH contains polysaccharide chains
MW 5k
•Enriched with short chains with higher
anti-Xa:IIa ratio

10. Differences in Mechanism of
Action
•Any size of heparin chain can inhibit the
action of factor Xa by binding to antithrombin
(AT)
•In contrast, in order to inactivate thrombin
(IIa), the heparin molecule must be long
enough to bind both antithrombin and
thrombin
•Less than half of the chains of LMWH are
long enough

13. Heparin-Induced
Thrombocytopaenia
•Most significant adverse effect of
heparin after haemorrhage
•Most common drug-induced
thrombocytopenia
•A large number of patients receive
heparin in the hospital environment.

14. Trreatment of HIT
•Discontinue all heparin
•If need to continue anti-coagulation, use
danaparoid (orgaran).
•Avoid platelet transfusions
•Thrombosis: use danaparoid or
thrombin inhibitor

15. Enhances
Antithrombin Activity
Warfarin

16. Warfarin: Major Adverse Effect—
Haemorrhage
•Factors that may influence bleeding
risk:
–Intensity of anticoagulation
–Concomitant clinical disorders
–Concomitant use of other medications
–Quality of management

17. Warfarin-induced Skin Necrosis

18. Prothrombin Time (PT)
•Historically, a most reliable and “relied upon”
clinical test
However:
–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 Normalised Ratio)

19. (( ))
Patient’s PT in SecondsPatient’s PT in Seconds
Mean Normal PT in SecondsMean Normal PT in Seconds
INR =INR =
ISIISI
INR = International Normalised Ratio


ISI = International Sensitivity Index
INR Equation
Target INR
•DVT, PE, Atrial Fibrillation: 2-3
•Artificial Cardiac Valve: 3-3.5

20. Changing over from Heparin to
Warfarin
•May begin concomitantly with heparin therapy
•Heparin should be continued for a minimum
of four days
–Time to peak antithrombotic effect of
warfarin is delayed 96 hours (despite INR)
•When INR reaches desired therapeutic
range, discontinue heparin (after a minimum
of four days)

21. Warfarin: Dosing & Monitoring
•Start low
–Initiate 5 mg daily
–Educate patient
•Stabilise
–Titrate to appropriate INR
–Monitor INR frequently (daily then weekly)
•Adjust as necessary
•Monitor INR regularly (every 1–4 weeks) and adjust

22. Relative Contraindications to
Warfarin Therapy
•Pregnancy
•Situations where the risk of hemorrhage
is greater than the potential clinical
benefits of therapy
–Uncontrolled alcohol/drug abuse
–Unsupervised dementia/psychosis

23. Signs of Warfarin Overdosage
•Any unusual bleeding:
–Blood in stools or urine
–Excessive menstrual bleeding
–Bruising
–Excessive nose bleeds/bleeding gums
–Persistent oozing from superficial injuries
–Bleeding from tumor, ulcer, or other lesion

24. Reversing action of warfarin
•Plasma
–Rapid but short-lasting
•Vitamin K
–Not rapid, but lasts 1-2 weeks. Do not use
if wishing to restart warfarin within next
week.

25. New Anticoagulation Drugs
•Direct Thrombin Inhibitors
–Ximelagatran, hirudin, bivalirudin, and
argatroban
•Synthetic pentasaccharide
•Acivated Protein C
•Tissue Factor Pathway Inhibitor (TFPI)

26. Enhances
Antithrombin Activity
Ximelagatran