Professional Documents
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Hemostasis
Hemostasis blood in fluid state Blood vessel wall Platelets Coagulation cascade
Antithrombotic Agents
Anticoagulants: prevent clot formation and extension Antiplatelet drugs: interfere with platelet activity Thrombolytic agents: dissolve existing thrombi
XI IX X
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
VIII
IIa
Fibrinogen IIa
XIII
Warfarin: Indications
Prophylaxis and/or treatment of Venous thrombosis and its extension Pulmonary embolism
Post MI To reduce the risk of death, recurrent MI, and thromboembolic events such as stroke or systemic embolization Prevention and treatment of cardiac embolism
Warfarin
Major Adverse effect is Hemorrhage Factors that may influence bleeding risk Intensity of anticoagulation Concomitant clinical disorders Concomitant use of other medications Quality of management
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 expected maintenance dose ( 2-5 mg), avoid large loading doses
INR Equation
Patients PT in Seconds ISI INR = Mean Normal PT in Seconds
INR = International Normalized Ratio ISI = International Sensitivity Index
(Seconds)
PTR 1.3
ISI
INR
16 18 21 24 38
12
B C D
E
12 13 11
14.5
(Seconds)
PTR 1.3
ISI 3.2
INR 2.6
16 18 21 24 38
12
B C D
E
12 13 11
14.5
Mechanical prosthetic valves (high risk) 2.53.5 Certain patients with thrombosis and the antiphospholipid syndrome AMI (to prevent recurrent AMI) Bileaflet mechanical valve in aortic position 2.03.0
3.0
2.5
PATIENT EDUCATION
Inform patients about the mechanism of action of warfarin and caution them about diet and drug interactions Advise patients to avoid alcohol Instruct patients to report any drug changes to the physician monitoring the INR Counsel women to avoid pregnancy while on warfarin
Essential because of complicated pharmacokinetics. Response is affected by body weight event of thrombosis heparin binding to plasma and endothelial cell proteins
Monitoring is performed to achieve a targeted therapeutic range 1.5 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 injection and usually not monitored except in some circumstances like pregnancy and renal failure
Tests used
Test Advantages Whole blood Simple clotting inexpensive time No equipment needed APTT Simple many tests can be carried out in parallel Simple many test can be carried out in parallel Sensitive to all concentrations Sensitive to all concentrations and to LMWT heparin
TT
Failing Anticoagulants
Things to Consider Short duration of antithrombotic Rx Heparin induced thrombocytopenia Poor control of INR Drug interactions Non-compliance
Reversal of anticoagulants
Unfractionated heparin Protamine 1 mg per 100 units, risks bradycardia and hypotension Allergic reactions due to previous exposure to protamine containing insulin, vasectomy and fish 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
Warfarin Oral vitamin K reduces INR in 24 hrs Low dose IV doses effective (0.5 to 2.5mg), higher doses (>10mg) associated with temporary warfarin resistance on reintroduction
Warfarin INR <5 and no bleeding => lowering or omitting a dose INR >5 and <9 and no bleeding => 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 patients require 4 days to reach an INR <1.5 after discontinuation of therapy
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