mechanical clot detection stago’s viscosity-based clot detection system
TRANSCRIPT
Mechanical Clot Detection
Stago’s Viscosity-based Clot Detection System
Viscosity based Detection Viscosity based Detection SystemSystem
Viscosity based Detection Viscosity based Detection SystemSystem
Viscosity based Detection Viscosity based Detection SystemSystem
Viscosity based Detection Viscosity based Detection SystemSystem
Viscosity based Detection Viscosity based Detection SystemSystem
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
Platelets“Coagulation”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 monitoringneeded”!
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 INHIBITORSXimelagatran – 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 INHIBITORSXimelagatran – 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.