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NEW ANTICOAGULANTS

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					Mechanical Clot Detection

 Stago’s Viscosity-based Clot
      Detection System
Viscosity based Detection System
Viscosity based Detection System
Viscosity based Detection System
Viscosity based Detection System
Viscosity based Detection System
NEW ANTICOAGULANTS
 Katy Whelchel MT(ASCP)SH

 Diagnostica Stago, Inc.
 Technical Support Specialist



 February 23, 2006
Maintain hemostatic balance
   the body must maintain a fluid
    equilibrium
   need to maintain balance between
    bleeding & clotting
                         vessels

         “Coagulation”             Platelets
         Proteins

                Fibrinolysis/ Inhibitors
ANTICOAGULANT THERAPY
   Decrease the risk of post-op thrombosis
   Decrease the risk of thrombosis in
    patients with risk factors
   Decrease the risk of spontaneous
    abortions in patients with Anti-
    Phospholipid Syndrome (APS) - lupus
    anticoagulants
STANDARD
ANTICOAGULANTS
   HEPARIN (UFH)
   COUMADIN (warfarin)
UFH – a few things to remember
   Will affect PTT- how much depends
    dosing and your reagent system
   Easily monitored (accurately!) with the
    Anti-Xa method
   Can be used in patients with renal
    failure
   HAS an antidote (protamine sulfate)
Coumadin –a few things to remember

   Can be monitored by the PT/INR
   Can be given long term for high risk
    patients
   Can be used in patients with renal
    failure
   HAS an antidote (Vitamin K)
St. Lucia Island flowers
2 classes of NEW
ANTICOAGULANTS
   Antithrombin Dependant
       LMWH – Lovenox, Fragmin, Innohep
         (tinzaparin – has been used on CAP surveys)
       DANAPROID (not available in US)
       FONDAPARINUX (Arixstra)
   Direct Thrombin Inhibitors
       HIRUDEN – LEPIRUDEN (Refludan)
       ARGATROBAN (Novastan)
       Bivalirudin
       Ximelagatran- the “new” coumadin
Why do we care about these new
anticoagulants??

They are advertised
as “no monitoring
needed”!
Why do we care about these new
anticoagulants??
   They can and DO interfere with our current
    coagulation tests
   Can you say how much of this new drug is in
    the patient’s system?
   What do you do for these patients?
       Patient is bleeding
       Patient is clotting – despite therapy
       Pre-op assessment?
       PT and PTT may or may not be “normal”
Why do we care about these new
anticoagulants??
   Special patient populations need special
    consideration:
       Pregnancy
       Renal dysfunction
       Liver dysfunction
       Anorexic or morbidly obese patients
Heparins
   UFH work on the activated factors
   LMWHs work where the extrinsic and
    intrinsic factors come together with
    Factor Xa
   Both use the patient’s ATIII to work
Coag Cascade
LMWH Action
LMWH HEPARINS
   LMWH – better bioavalibility than UFH
       Created from UFH
       Since it’s a smaller molecule it can be
        administered as a subcutaneous injection – given
        in fixed doses for MOST patients
       Therapeutic Ranges:
        0.5 – 1.1 (2 injections/day)
        1.0 – 2.0 (1 injection/ day)
       Timing of specimens - peak at about 4 hours
        after sub Q injection
Heparin Family picture
LMWH HEPARIN
   Doesn’t change the APTT (much) – an
    increased APTT may signify an
    overdose of LMWH or some other
    influence on the APTT (platelet
    antibodies)
   Difficult to reverse with protamine
    sulfate (antidote for UFH)
   Cleared through the kidneys
LMWH HEPARIN
   LMWH available in the US:
       Enoxaparin (Lovenox): prevent DVT/PE
        around surgery, treat DVT/PE, unstable
        angina
       Dalteparin (Fragmin): prevent and treat
        DVT/PE, treat unstable angina
       Tinzaparin(Innohep): treat DVT/PE
Who should be monitored for
LMWH?
   Patients with kidney problems
    (need to check creatinine
    clearance)
   Patients that are obese or have a
    very low body weight
   Children, burn patients
How should LMWH be
monitored?
   Monitor with an anti-Xa method,
    using LMWH calibrators and
    controls.
   Samples should be drawn 4 hours
    after dosing.
Marigot Bay, St. Lucia
Danaproid, Fonduparinux
DANAPROID            (not available in the US)

   Mixture of heparinoids
   Usually given to HIT patients
   Works through antithrombin to inhibit factor
    Xa (little effect on other factors)
   Administered twice a day – IV or Sub Q
   Therapeutic ranges – IV=0.5 – 0.8 Sub Q=
    0.13-0.35
   Monitored by anti-Xa (like LMWH) – using
    danaproid as the calibrator.
Danaproid (cont’d)
   It may prolong the PTT,as well as affect
    the PT, TT and ACT.
   Used successfully in HIT – however,
    platelet count should be monitored.
   No agent that will reverse the effects of
    the drug.
FONDAPARINUX (Arixtra)
   Synthetic pentasaccharide – accelerates the
    binding of AT to Xa – the “ultimate LMWH”
   Pure anti-Xa effect
   Commonly used to prevent VTE in orthopedic
    surgery
   Administered Sub Q
   Half-life of 13 – 15 hours, so only 1 dose per
    day.
   Excreted through kidney (check creatinine
    clearance…..)
Fondaparinux (cont’d)
   PT and PTT are relatively insensitive to this
    drug, but may be slightly prolonged.
   Low bleeding incidence.
   Has not been shown to cause HIT
   No direct inhibitor for Arixtra which can
    reverse it’s anticoagulant effect.
   May be monitored by an Anti-Xa method
    using the drug as a calibrator.
Fondaparinux (cont’d)
   Remember – there is no antidote. So if
    the patient has too much “on board”,
    the PT and PTT may be normal, but
    they may still be bleeding…….can use
    Factor VIIa concentrate (novoseven) or
    activated prothrombin concentrates to
    reverse effect.
Ship: The Brig Unicorn
DIRECT THROMBIN
INHIBITORS
   Hirudin – Lepirudin (Refludan)
       Hirudin: Medicinal Leech
       Refludan: recombinant polypeptide with same
        action
   Agatroban
   Bivalirudin (Angiomax)
       Do not cause thrombocytopenia; used successfully
        with HIT
       Directly blocks Thrombin
       Administered by IV or Sub Q
       REQUIRES MONITORING
Direct Thrombin Inhibitors
DIRECT THROMBIN
INHIBITORS
   These drugs have a very short half life.
   Agatroban cleared by the liver
   Lepirudin is cleared by the kidneys.
   Bivalirudin is cleared by the kidneys
       Have to be aware of these factors with the
        patient!
ARGATROBAN
   Derivative of amino acid arginine
   Directly binds to Thrombin
   Metabolized by the liver, and excreted
    through the kidney – so can be an alternate
    for patients with renal disease.
   Must be monitored by APTT (can also be
    monitored by the ACT). Therapeutic range is
    1.5-3.0 x Baseline APTT.
REFLUDAN - Lepirudin
   APTT – IV=1.5 – 3.0 x patient baseline
    Sub Q= 2.2 – 2.7 X baseline APTT
    (specimen drawn 3 hours after administration)
   HOWEVER, APTT reagents vary in their sensitivity to
    Refludin
   ECARIN CLOTTING TIME (used in some facilities)
   CHROMOGENIC ASSAY BASED ON THROMBIN
    INHIBITION (developed for research only at this
    point) – most accurate assay
DIRECT THROMBIN
INHIBITORS
   These drugs will affect the PT/INR – since they work
    at the bottom of the cascade
   Lepirudin: recommend stopping drug once INR>2.0
   Agatroban: recommend stopping drug once INR>4.0
   Levels are PT reagent dependent!! Literature says
    that reagents with a lower ISI have less variability in
    reactivity. Higher ISI reagents have greater variablity
    in response.
   Will affect results if patient is also on Coumadin!
DIRECT THROMBIN
INHIBITORS
   Since these drugs affect the PT/INR
    system – and since they have a very
    short half-life – the good news is that if
    they are discontinued for a couple of
    hours, the PT should return to normal.
   The bad news is that the kidneys and
    liver have to be working for this to
    happen.
Bivalirudin
   Approved for use in the cardiac cath lab
   Bivalent thrombin inhibitor
   Short half-life (20 -30 min)
   Exclude patients with creatinine >3.0
Live Volcano, St. Lucia
DIRECT THROMBIN
INHIBITORS
   Ximelagatran – the “new Coumadin”
       Oral tablet
       Direct thrombin inhibitor
       Converts to melagatran in the stomach
       Cleared by kidneys
       Irreversible – factor VII concentrate
        recommended for severe hemorrhage
DIRECT THROMBIN
INHIBITORS
Ximelagatran – the “new Coumadin” (cont’d)
 it’s supposed to work better than our current
  LMWHs in preventing DVTs in people who
  have had hip surgery
 Theoretically: NO MONITORING! It doesn’t
  matter how old you are, how much you
  weigh, etc. it is supposed to be
  safe…..however it causes liver damage in 6-
  10% of patients who take it long term. And
  remember – it is cleared by the kidneys.
DIRECT THROMBIN
INHIBITORS
Ximelagatran – the “new Coumadin” (cont’d)
 Not approved by FDA – yet.

 If you were going to monitor Ximelagatran,
  remember it is a thrombin inhibitor – so you’d
  have to monitor the APTT – NOT a PT even
  though it is the “new Coumadin”!!
 APTT’s response again will be variable

  depending on reagent system.
DIRECT THROMBIN
INHIBITORS
Ximelagatran – the “new Coumadin”
  (cont’d)
 So – for the time being, we’ll still be

  doing PT/INR for coumadin therapy.
Summary
   Many of these anticoagulants are currently in use.
   They may affect routine and specialty coagulation
    tests – remember where they affect the cascade!
   If abnormal results are obtained, and not expected –
    ask what drugs the patient is on.
   Remember many will act differently if the patient has
    renal or hepatic impairment.
   The “tried and true” may still be the easiest to use if
    monitored correctly.
St. Lucia Sunset
The end.

				
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