Coagulation Testing for POCC

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<p>Coagulation TestingWhat is it? Why do we need it POC?.</p> <p>Coagulation Testingx</p> <p>Monitoring hemostasis</p> <p>Bleeding</p> <p>Clotting</p> <p>AnticoagulantsMonitor with PTH EP A R IN</p> <p>Monitor with aPTT or ACT</p> <p>t In s ic ri n y wa th Pa</p> <p>Extrinsic Pathway</p> <p>WARFARIN II IIa LMWH (thrombin) Hirudin &amp; DTI CLOT Xa DXaI</p> <p>X Common Pathway Monitor with ?????</p> <p>Coagulation is Complex</p> <p>Picture from DiaPharma.com</p> <p>Common(?) Coagulation Testsx</p> <p>Laboratory PT.. aPTT TT.. Fib. Anti Xa Anti IIa Factor Assays</p> <p>x</p> <p>Point of Care</p> <p> ACT Celite Kaolin Glass beads Silica thromboplastin</p> <p>Differences in test methodsx Standard</p> <p>Laboratory</p> <p>x Point</p> <p>of Care</p> <p> Platelet Poor Plasma Sodium Citrate Anticoagulant 1:9 Dilution Variable Preanalytical Delay</p> <p> Whole Blood No Added Anticoagulant No Dilution No Preanalytical Delay</p> <p>POC Coagulation Analyzersx x x x x x x x x</p> <p>HEMOCHRON 401 / 801 / Response HEMOCHRON Jr. Signature / Signature + ProTime / 3 Medtronic HMS/HMS+/ HemoTec ACT II / ACTPlus CoaguChek / S / Pro / Pro DM i-STAT Helena Actalyke Hemosense INRatio Others?</p> <p>POC Coag Analyzers Differx</p> <p>Test methodology Sample size and application Microliters to milliliters</p> <p> Sample measurement Manual vs automated</p> <p> Clot detection method Enzyme detection methodx</p> <p>Thrombin generation</p> <p> Reagent composition</p> <p> Results</p> <p>Clinical ApplicationsOperating Room Cardiac Surgery Interventional Cardiology and Radiology x Critical Care x Satellite Sites Dialysis ECMO</p> <p> Emergency Room Anticoagulation Clinic</p> <p>History of the ACTx Lee-White</p> <p>clotting time</p> <p> Manual No activator Very slowx 1966</p> <p>Hattersley- Activated Clotting Time</p> <p> Diatomaceous earth activator Operator defined mixing and clot detection Global assay - Contact activation of cascade</p> <p>Activated Clotting Time</p> <p>Particulate Contact Activationx</p> <p>Initiation of intrinsic coagulation cascade Factor XII (Hageman factor) Prekallikrein (Fletcher factor)</p> <p>Dramatically shortens contact activation period over Lee-White time x Proposed as both screening assay for coagulation defects and for heparin monitoringx</p> <p>ACT Automation - 1969x HEMOCHRON</p> <p>introduced</p> <p> semi-automated less operator dependence two assays CA510 (later FTCA510)x diatomaceous</p> <p>earth</p> <p>activated P214 glass bead activated</p> <p>2 assays for separate applications700 600C-ACT</p> <p>Clotting Time (sec)</p> <p>500 400 300 200 100</p> <p>P214</p> <p>CATH</p> <p>ECMO 0 Dialysis 1 0</p> <p>PTCA2 3</p> <p>CPB4 5</p> <p>Heparin (units/ml)</p> <p>1980s HemoTec ACTLiquid kaolin activator x Different technologyx</p> <p> Different results</p> <p>ACT Differencesx Recognized</p> <p>in literature &gt;20 years</p> <p> Clinical evaluations of Hemochron appeared in journals mid 1970s By 1981, papers appeared showing little correlation between ACT and heparin level By 1988, papers clearly showed clinically different results between Hemochron and HemoTecx Differences</p> <p>ignored by clinicians</p> <p>Why are there so many different ACTs?700 600 Clotting Time (sec) 500 400 300 200 100 0C-ACT K-ACT ACT+ P214 ACT-LR</p> <p>CATH1</p> <p>CCU 0 Dialysis</p> <p>PTCA2 3</p> <p>CPB4 5</p> <p>Heparin (units/ml)</p> <p>Monitoring - ACTx</p> <p>Benefits Industry Standard Since 1970s Recommended as primary method in AmSECT guidelines (perfusion) Easy to run</p> <p>x</p> <p>Disadvantages Each system yields different numbers High sensitivity to hypothermia and hemodilution (with exceptions) Little or no correlation to heparin level especially true for pediatric patients</p> <p>Heparinized ACT - CPB700 675 650 625 600 575 550 525 500 475</p> <p>H e m o c h ro n H e m o tec TA S HMS</p> <p>Seconds</p> <p>P re 15 30 45 60 75 90 105 C P B m in m in m in m in m in m in m inData from Huffman, et.al. 1998 AmSECT meeting</p> <p>Pharmaceutical Interventionx Amicar</p> <p>or Tranexamic Acid</p> <p> No effect on standard celite ACTx Aprotinin</p> <p> Significant elevation of celite ACT Two dosing regimens Full or Half Hammersmith Both independent of patient size</p> <p>ACT Monitoring-Aprotinin Treatmentx</p> <p>Celite ACT Not recommended Still used with target times of &gt;750 seconds</p> <p>x</p> <p>Kaolin ACT Unaffected by moderate doses of aprotinin Used with target times of &gt; 480 seconds</p> <p>x</p> <p>ACT+ Unaffected by ALL doses of aprotinin Used with target times of &gt; 400 seconds</p> <p>Monitoring in CPB - AprotininC-ACT1200 Trasylol 1000 800 600 400 200 0 Baseline PostBolus PostBolus2 OnPump OnPump2 OnPump3 PostProt. Placebo800 600 400 200 0 1200 1000</p> <p>ACT+Trasylol Placebo</p> <p>x</p> <p>Data from clinical evaluation, on file, ITC</p> <p>Baseline</p> <p>PostBolus</p> <p>PostBolus2</p> <p>OnPump</p> <p>OnPump2</p> <p>OnPump3</p> <p>PostProt.</p> <p>Other POC Coag in the ORx x x</p> <p>aPTT / PT Pre- and post-procedural screening</p> <p>Fibrinogen Pre- and post-procedural screening</p> <p>Dosing Assays Customize heparin and protamine for each patient HEMOCHRON HRT / PRT Hepcon HMS</p> <p> Measure heparin level Relationship to coagulation status unclear</p> <p>Other POC Coag in the ORx Heparin</p> <p>neutralization verification</p> <p> Ensure complete removal of circulating heparin aPTT PDA-O - ACT based TT / HNTT - Thrombin Time based heparinase ACT</p> <p>Outcome studies - POC in ORx x x</p> <p>Reduced Blood Loss/Transfusion Use of HRT and PRT (RxDx System)</p> <p>Reduced Cost Resulting from Use of POC Assays RxDx combined with TT / HNTT</p> <p>Reduced Complication Rates TT / HNTT Re-Exploration for Bleeding Reduced from 2.5% to 1.1% Re-Exploration for Coagulopathy Reduced from 1.0% to 0.0.</p> <p>Clinical ApplicationsOperating Room Cardiac Surgery Interventional Cardiology and Radiology x Critical Care x Satellite Sites Dialysis ECMO</p> <p> Emergency Room Anticoagulation Clinic</p> <p>Proceduresx Diagnostic</p> <p> Catheterization locate and map vessel blockage(s) determine need for interventional procedures</p> <p> Electrophysiology Interventional Radiologyx Interventional</p> <p> Balloon angioplasty Atherectomy (roto-rooter)</p> <p>Diagnostic Low dose heparinx Catheterization</p> <p>and Electrophysiology</p> <p> 2500 - 5000 unit bolus dose frequently not monitored if monitored ACT aPTT</p> <p>Interventional Moderate dosex</p> <p>Angioplasty and Atherectomy Heparin 10,000 unit bolus dose or 2 - 2.5 mg/kg target ACT 300 - 350 secondsx</p> <p>200 300 in presence of ReoPro</p> <p> Angiomax (bivalirudin) ACT &gt;300x</p> <p>Hemochron (ACT-LR or FTCA510) trials</p> <p> Measure post-bolus to ensure drug on board Required in patients with renal impairment</p> <p>Why use platelet inhibitors?x</p> <p>Angioplasty promotes aggregation3 sec</p> <p>Adhesion shape change release Aggregation</p> <p>ADP release</p> <p>10 sec Coagulation Fibrin formation 5 min</p> <p>Need to inhibit restenosis / reocclusion</p> <p>Platelet Inhibitorsx ReoPro</p> <p> elevates ACTs target time = 250 sec with ReoPro determined using FTCA510 tubex Integrelin</p> <p> No reported clinically significant effects on ACTx Aggrastat</p> <p> No reported effects on ACT</p> <p>Clinical ApplicationsOperating Room Cardiac Surgery Interventional Cardiology and Radiology x Critical Care x Satellite Sites Dialysis ECMO</p> <p> Emergency Room Anticoagulation Clinic</p> <p>ACT or aPTTx Determine</p> <p>when to pull the femoral sheath</p> <p> Premature sheath pull can lead to bleeding. Delayed removal can increase time in CCU. Target set at each site. ACT targets range from 150 220 seconds aPTT targets range from 40 70 secondsx</p> <p>Must be linked to heparin sensitivity of reagent used</p> <p>ACT vs aPTT120 110 100 aPTT (J103) (sec) 90 80 70 60 50 40 30 20 50 100 150 FTCA510 (sec) 200 250</p> <p>y = 0.57x - 28.44 R = 0.896</p> <p>Single site comparison, ACT tube vs HE Jr Sig aPTT</p> <p>ACT or aPTTx Monitor</p> <p>heparin therapy</p> <p> Target times determined by each facility APTT outcome study Reduce time to result (112 vs 200 &gt;200 &gt;200</p> <p>site 1 23 51 80 109 138 167 196</p> <p>Lot to Lot Reproducibility80 70 60</p> <p>Cuvette Lot ay = 1.35x - 14.2 R=.909</p> <p>50 40 30 20 20 40 60 80</p> <p>Signature</p> <p>Signature 30 40 50 60 70 80 90</p> <p>Lot a 26 40 53 67 80 93 107</p> <p>Lot b 29 43 57 70 84 98 112</p> <p>Lab</p> <p>80 70 Lab 60 50 40 30 20 20</p> <p>Cuvette Lot by = 1.39x - 12.8 R=0.934</p> <p>40</p> <p>Signature</p> <p>60</p> <p>80</p> <p>Clinical ApplicationsOperating Room Cardiac Surgery Interventional Cardiology and Radiology x Critical Care x Satellite Sites Dialysis ECMO</p> <p> Emergency Room Anticoagulation Clinic</p> <p>Dialysis / ECMOx ACT</p> <p>(or nothing in dialysis)</p> <p> Majority use P214 glass activated ACT Some use ACT-LR; HemoTec LR ACTx Better</p> <p>Control of Anticoagulation Leads to Increased Dialyzer Reuse Potential for Long Term Cost Savings No Compromise in Dialysis Efficacy (Kt/V) Ouseph, R. et.al. Am J Kidney Dis 35:89-94; 2000</p> <p>Emergency RoomACT; aPTT; PT; Fibrinogen x Immediate Identification of Coagulopathiesx</p> <p> Optimization of Critical Decision Pathwaysx</p> <p>ACT Allows Early Detection of Traumatic Coagulopathy Allows Early Treatment Decisions Aids Damage Control Decisions Aucar, J. et.al. 1998 SW Surgeons Congress</p> <p>x</p> <p>Optimize Staffing During Off Hours</p> <p>Anticoagulation Clinicsx</p> <p>Results Available While Patient is Present Improved Anticoagulation Management Improved Standard of Care Staff Efficiency</p> <p>x x</p> <p>Immediate Retesting (if needed) Fingerstick Sampling</p> <p>Same System for Clinic and Home Bound Patients Standardized ISI / PT normal Test System Specific</p> <p>Anticoagulation Clinicsx Potential</p> <p>for Self-Testing</p> <p> High Risk Patients Patients Who Travel Frequently Home-Bound Patients in Rural Areas Far from Clinicx Improved</p> <p>Outcomes Through More Frequent Testing</p> <p>Will POC Results Match the Lab?</p> <p>(It will be a lot closer than for aPTT) but it WILL Correlate</p> <p>How to Compare INR ResultsLower dose? x Keep same dose? x Raise Dose?x</p> <p>Test Again? x Test more often?x</p> <p>Lab to Lab Comparison1.5</p> <p>Mean difference = 0.3 INR1 Difference (TPC - INN) 0.5 0 0 -0.5 -1 -1.5 Mean Innovin and TPC INR 1 2 3 4 5 6 7</p> <p>INR ExpectationsINR within 0.4 of lab &gt; 80% INR within 0.7 of lab &gt; 90% INR within 1.0 of lab &gt; 95%(values shown are ranges) AACC 2002</p> <p>Pairs within 0.4 INR85.4 97.9 % 74.7 89.9 % 89.9 94.9 %</p> <p>Pairs within 0.7 INR94.8 99.0 % 87.9 99.0 % 97.0 99.5 %</p> <p>Lab to Lab</p> <p>POC to Lab POC to POC</p> <p>Why Bother with POC Coag?x Improved</p> <p>TAT - Turn Around Time</p> <p> Defined from the Clinician, not Lab view When is Turn Around Important Emergency Room ICU/CCU Dose Adjustments Operating Room / Cath Lab</p> <p> STAT Testing Turn Around</p> <p>STAT Testing TATLab (min) CPB (N=40) PVS (N=45) Median 90.0 90.0 Mean 78.5 74.0 Minimum 38.0 21.0 POC (min) All Groups Median 2.23 Minimum 0.33 Maximum 6.97Fitch, et.al, J. Clin Monit &amp; Comput. 1999. 15:197-204</p> <p>Standardized Clinical Interpretationx</p> <p>Defined Assay Sensitivity Requires Lot to Lot Reproducibility</p> <p>x</p> <p>Defined Reagent Variability Identical Instrumentation and Reagents at All Testing Sites</p> <p>x</p> <p>Defined Critical Clinical Decision Points No Change of Normal Ranges or Target Times Between Lots of Test Reagents or Testing Locations</p> <p>Whats the catch?1. 2.</p> <p>Regulatory compliance Connectivity</p> <p>Regulatory compliance - Who sets the rules? JCAHO Joint Commission on Accreditation of Health Care Orgs</p> <p> CAP College of American Pathologists</p> <p> FDA Food and Drug Administration CDRHx</p> <p>Center for Devices and Radiological Health</p> <p> CMS Centers for Medicare and Medicaid Services</p> <p> CDC Centers for Disease Control</p> <p>CLIA Applies to ALL Testing Areasx Central</p> <p>Laboratory x Satellite Labs Critical Care Surgical Suitex Clinics x Bedside</p> <p>testing x Doctors office</p> <p>CLIA Regulations for Coagulationx x x</p> <p>Central Laboratory can hold the CLIA license Satellites can have independent licensure</p> <p>Moderately Complex tests Except ProTime, Coaguchek, INRatio are waived</p> <p>Requires Certified Laboratory Director Record Keeping Training Quality Policy</p> <p>Implementing POC coag requires:x</p> <p>Method Validation - accuracy Comparison to current standard NCCLS Guideline EP-09 recommends 40 samples</p> <p> Linearity may be used if no current standard Is assay performance appropriate to clinical needs?x</p> <p>Precision Controls may be used to establish within and between run variability</p> <p>x</p> <p>Training Document training of all personnel high school equivalence or higher education level</p> <p> competency evaluations at predetermined intervals</p> <p>Implementing POC coag requires:x x</p> <p>x</p> <p>Linearity NOT required for coag Calibration does not apply to unit test systems that cannot be adjusted Calibration verification Current assumption: Equivalent to CAP POC.05450 If the laboratory has more than one method-system for performing tests for a given analyte, are they checked against each other at least twice a year for correlation of patient results?</p> <p> CLIA requires at least 3 point check</p> <p>New CLIA Regulationsx</p> <p>Work in progress New rules published January 2003 Rules in effect March 23, 2003 Interpretive guidelines published Jan 2004 Inspections using new regulations now 2 year grace period to adapt new rules Ends Jan 2005</p> <p>x</p> <p>Quality Assessment Program - Lab Responsibilities Establish &amp; follow policies/procedures addressing ongoing QA activity. Take corrective actions as necessary. Review their effectiveness. Revise policies/procedures as necessary to prevent recurrence.</p> <p> Communicate to staff. Document all assessment activities.</p> <p>New CLIA Regulationsx x</p> <p>Proficiency testing Changed consensus for PT program grading from 90% to 80%.</p> <p>Quality Assessment replaces Quality Assurance. Quality Assessment is interspersed throughout the regulation. Creates one set of nonwaived QC requirements.</p> <p>x</p> <p>Subpart K - Quality System for Nonwaived Testing Laboratory is ultimately responsible for ensuring that all components of the analytic process are monitored. Each laboratory that performs nonwaived testing must meet the applicable analytic systems requirements; unless HHS approves a procedure, specified in the Interpretive Guidelines, that provides equivalent quality testing</p> <p>Equivalent Quality Testingx</p> <p>Traditional: Testing two levels of external control materials each day of testing Except coag and blood gases every 8 hours of use</p> <p>x</p> <p>Equivalent QC Options #2 -Test systems with internal/procedural controls that monitor a portion of the analytic components, and if the lab successfully completes a thirty day evaluation process, the lab may reduce the frequency of external quality control materials to once per calendar week.</p> <p>Equivalent Quality Testingx</p> <p>Option #2 Perform the test systems internal control procedure(s) in accordance with the manufacturers instructions (but not less frequently than once each day of testing) and test two levels of external control material daily for 30 consecutive days of testing.</p> <p>x</p> <p>EQC AND LQC daily (NOT every 8 hours) for 30 days Then OK to use EQC daily, LQC weekly Unless manufacturer requires more</p> <p> Send comments to: Judith Yost Director, Division of Laboratory Services, CMS JYost@cms.hhs.gov (410) 786-3407</p> <p>Routine Quality Controlx</p> <p>Instrument Performance Verification Electronic Quality Control with Numeric Output Two levels per 8 hour shift (CLIA reg)</p> <p>x</p> <p>Assay Performance Verifi...</p>