ANTICOAGULANT THERAPY - Used with the following condition to prevent clot formation:

Aim of the anticoagulant therapy o Percutaneous transluminal coronary angioplasty

- Prevention of thrombus formation or extension (PTCA)
Thrombosis o Cardiopulmonary bypass (CPB)
- Implies an abnormal mass that partially or totally obstructs a vein Activated clotting time (ACT) – used to assess the degree of
or artery anticoagulation in heparinized patients
- Thrombi usually begins in 2 ways: - First coagulation test be offered at the point of care
o Attached to an injured vessel wall;./ (operating room, cardiac catherization, hemodialysis, etc.)
o Unattached intravascular masses Low-Molecular-Weight Heparin
Anticoagulant - New family of compounds produced by the controlled
- Most clinical laboratories are accustomed to monitoring patients fragmentation of heparin
who are receiving Warfarin (coumadin) or Heparin anticoagulant - Examples:
therapy. o Tinzaparin (Innohep)
Warfarin (Coumadin) o Dalteparin (Fragmin)
- Traditional oral anticoagulant o Enoxaparin (Lovenox)
- Vitamin K antagonist that interfere with the normal synthesis of - It react with the regulatory protein AT-III to inhibit activated
Factors II, VII, IX, and X, Protein C and S. factor X (factor Xa) but not thrombin (factor IIa)
o Incomplete coagulation because they lack Calcium-binding - Less capable than standard heparin to activate resting platelets
sites and cannot form enzyme substrate complexes so that they release platelet factor 4, and it binds less well to
o Unable to function as anticoagulant platelet factor 4
Biological Activity: Decreased PT Method of Chromogenic Assay
Onset of Action: Between 8-12 hrs Monitoring: – based on inhibition of factor Xa
Maximum Effect: Approximately 36 hrs Peaks: About 4 hours after subcutaneous injection
Duration of Action: Approximately 72 hours Peak -0.5 to 1.0 IU/ml for px who receive the drug
PT (Prothrombin Time) therapeutic twice a day
- Used to adjust the dose of oral anticoagulants levels, Values: -1.0 ro 2.0 IU/ml for those receiving one
o Should be reported according to the INR, not the PT ratio dose a day
or the PT expressed in seconds.
- Can be prolonged in patients with antiphospholipid syndrome Other Antithrombin-Dependent Inhibitors
o Antibodies produced in this syndrome are directed Danaparoid (Orgaran)
toward phospholipid-binding proteins including - Mixture of heparinoids which only accelerates the binding of
prothrombin Factor Xa to antithrombin
o Lupus Anticoagulant or inhibitor interferes with the - Possesses no anticoagulant activity of its own
phospholipid in the vitro assays of PT and aPTT - Monitored: Chromogenic Assay
- (>1) Inc. INR = Good dosage Fondaparinux (Arixtra)
Heparin - Synthetic pentasaccharide that accelerates the binding of
- First agent administered as an anticoagulant antithrombin to actives factor Xa
- Can be used to prevent the formation of thrombin in veins or to - No antithrombin activity
prevent the propagation of previously formed thrombi in veins - Requires no monitoring
and arteries o But if monitoring is needed it is recommended that
- Used extremely for the treatment: it be assayed by a system based on the inhibition
o Venous thrombosis of factor Xa
o Pulmonary thrombosis Direct Thrombin Inhibitors
- Recommended treatment: Lepirudin (Refludan)
o active thrombophlebitis - Recombinant product
o arterial thrombosis - Same anticoagulant activity as Hiruden
- *For apheresis o Produced by medicinal leech
- Immediate therapy: - Act as direct thrombin inhibitors by blocking both the active site
o Pulmonary Embolism and the substrate binding site on the thrombin molecule.
- No anticoagulant activity of its own but acts as an anticoagulant - Monitoring:
by accelerating the binding of antithrombin to target enzymes. o aPTT – most widely used
o Thrombin and Factor Xa  Target range: 1.5-2.5 times the baseline aPTT
- Termed an antithrombin because it helps to prevent new o ECARIN clotting time
thrombus formation and buys time for endogenous fibrinolytic o Chromogenic assay
mechanisms to lyse the clot - Disadvantage: Need to monitor patients with a laboratory assay.
- Can cause the following: Argatroban
o Bleeding - Binds to thrombin directly
o Thrombocytopenia - Acts as an anticoagulant by blocking the active site on the
o Osteopenia thrombin molecule
- Before initiating heparin, patients should be screened for clinical - Monitoring:
evidence of active bleeding o aPTT
- Laboratory Evaluation:  Therapeutic Level: 1.5 to 3.0 greater than
o Complete Blood Count (CBC) with platelet count baseline aPTT
o PT - Disadvantages:
o aPTT o No known inhibitor to reverse the anticoagulant
o Stool analysis for occult blood effect
o Urine dipstick for hematuria o Need to monitor patients with a laboratory assay
 New Thromboplastins
- New types of thromboplastins for measuring the PT
o Mixtured of phospholipids
o Recombinant derived human tissue factor
- More sensitive (Typical ISI, 1.0)
o Traditional North American ones (ISIs, 1.8 to 3.0)
- PTs for patients with inherited or acquired deficiencies of
coagulation factors – prolonged
- Therapeutic range (in seconds) of the PTs in patient receiving
orally administered anticoagulant agents is wider with the
sensitive thromboplastins
- The INR, will be the same
[ISI – International System Index]
Recombinant Thromboplastin Advantages
1. It is made from a human protein, not from the protein of a
different species,
2. The material is pure, and the concentration can be readily
adjusted, unlike currently available rabbit brain
thromboplastins. Adjustment will minimize variation
between different lots of reagent; thus, the normal and
therapeutic ranges of the PT will remain the same.
3. The reagent is free of contamination with noxious viruses
because it is a recombinant product.
4. When the ISI is approx.. 1.0, the PTs will be the same as
those obtained with use of the WHO reference
thromboplastins. Therefore, the PT ratio (PT of Px/ Mean
Normal PT) will be the same as the INR
5. The new reagents are more sensitive to mild deficiencies of
coagulation factors than are the traditional thromboplastins.
Pxs with hemostatically adequate levels of coagulation
factors II, V, VII, or X (30% to 40% of mean normal activity)
will have INRs or 1.4 or less
SUMMARY
HEPARIN
- Intravenous anticoagulants
- ACTION: Inhibits Thrombin
- NEUTRALIZED BY: Protamine Sulfate
- MONITORING: aPTT or ACT
WARFARIN/COUMADIN/COUMARIN
- Oral anticoagulants
- ACTION: Vitamin K antagonist that interferes with synthesis
of II, VII, IX, X as well as Protein C & S
- NEUTRALIZED BY: Vitamin K or FFP
- MONITORING: PT ( because the first factor to depress is VII
which is an extrinsic factor)