coagulation testing for pocc

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Coagulation TestingWhat is it? Why do we need it POC?.

Coagulation Testingx

Monitoring hemostasis

Bleeding

Clotting

AnticoagulantsMonitor with PTH EP A R IN

Monitor with aPTT or ACT

t In s ic ri n y wa th Pa

Extrinsic Pathway

WARFARIN II IIa LMWH (thrombin) Hirudin & DTI CLOT Xa DXaI

X Common Pathway Monitor with ?????

Coagulation is Complex

Picture from DiaPharma.com

Common(?) Coagulation Testsx

Laboratory PT.. aPTT TT.. Fib. Anti Xa Anti IIa Factor Assays

x

Point of Care

ACT Celite Kaolin Glass beads Silica thromboplastin

Differences in test methodsx Standard

Laboratory

x Point

of Care

Platelet Poor Plasma Sodium Citrate Anticoagulant 1:9 Dilution Variable Preanalytical Delay

Whole Blood No Added Anticoagulant No Dilution No Preanalytical Delay

POC Coagulation Analyzersx x x x x x x x x

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?

POC Coag Analyzers Differx

Test methodology Sample size and application Microliters to milliliters

Sample measurement Manual vs automated

Clot detection method Enzyme detection methodx

Thrombin generation

Reagent composition

Results

Clinical ApplicationsOperating Room Cardiac Surgery Interventional Cardiology and Radiology x Critical Care x Satellite Sites Dialysis ECMO

Emergency Room Anticoagulation Clinic

History of the ACTx Lee-White

clotting time

Manual No activator Very slowx 1966

Hattersley- Activated Clotting Time

Diatomaceous earth activator Operator defined mixing and clot detection Global assay - Contact activation of cascade

Activated Clotting Time

Particulate Contact Activationx

Initiation of intrinsic coagulation cascade Factor XII (Hageman factor) Prekallikrein (Fletcher factor)

Dramatically shortens contact activation period over Lee-White time x Proposed as both screening assay for coagulation defects and for heparin monitoringx

ACT Automation - 1969x HEMOCHRON

introduced

semi-automated less operator dependence two assays CA510 (later FTCA510)x diatomaceous

earth

activated P214 glass bead activated

2 assays for separate applications700 600C-ACT

Clotting Time (sec)

500 400 300 200 100

P214

CATH

ECMO 0 Dialysis 1 0

PTCA2 3

CPB4 5

Heparin (units/ml)

1980s HemoTec ACTLiquid kaolin activator x Different technologyx

Different results

ACT Differencesx Recognized

in literature >20 years

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

ignored by clinicians

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

CATH1

CCU 0 Dialysis

PTCA2 3

CPB4 5

Heparin (units/ml)

Monitoring - ACTx

Benefits Industry Standard Since 1970s Recommended as primary method in AmSECT guidelines (perfusion) Easy to run

x

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

Heparinized ACT - CPB700 675 650 625 600 575 550 525 500 475

H e m o c h ro n H e m o tec TA S HMS

Seconds

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

Pharmaceutical Interventionx Amicar

or Tranexamic Acid

No effect on standard celite ACTx Aprotinin

Significant elevation of celite ACT Two dosing regimens Full or Half Hammersmith Both independent of patient size

ACT Monitoring-Aprotinin Treatmentx

Celite ACT Not recommended Still used with target times of >750 seconds

x

Kaolin ACT Unaffected by moderate doses of aprotinin Used with target times of > 480 seconds

x

ACT+ Unaffected by ALL doses of aprotinin Used with target times of > 400 seconds

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

ACT+Trasylol Placebo

x

Data from clinical evaluation, on file, ITC

Baseline

PostBolus

PostBolus2

OnPump

OnPump2

OnPump3

PostProt.

Other POC Coag in the ORx x x

aPTT / PT Pre- and post-procedural screening

Fibrinogen Pre- and post-procedural screening

Dosing Assays Customize heparin and protamine for each patient HEMOCHRON HRT / PRT Hepcon HMS

Measure heparin level Relationship to coagulation status unclear

Other POC Coag in the ORx Heparin

neutralization verification

Ensure complete removal of circulating heparin aPTT PDA-O - ACT based TT / HNTT - Thrombin Time based heparinase ACT

Outcome studies - POC in ORx x x

Reduced Blood Loss/Transfusion Use of HRT and PRT (RxDx System)

Reduced Cost Resulting from Use of POC Assays RxDx combined with TT / HNTT

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.

Clinical ApplicationsOperating Room Cardiac Surgery Interventional Cardiology and Radiology x Critical Care x Satellite Sites Dialysis ECMO

Emergency Room Anticoagulation Clinic

Proceduresx Diagnostic

Catheterization locate and map vessel blockage(s) determine need for interventional procedures

Electrophysiology Interventional Radiologyx Interventional

Balloon angioplasty Atherectomy (roto-rooter)

Diagnostic Low dose heparinx Catheterization

and Electrophysiology

2500 - 5000 unit bolus dose frequently not monitored if monitored ACT aPTT

Interventional Moderate dosex

Angioplasty and Atherectomy Heparin 10,000 unit bolus dose or 2 - 2.5 mg/kg target ACT 300 - 350 secondsx

200 300 in presence of ReoPro

Angiomax (bivalirudin) ACT >300x

Hemochron (ACT-LR or FTCA510) trials

Measure post-bolus to ensure drug on board Required in patients with renal impairment

Why use platelet inhibitors?x

Angioplasty promotes aggregation3 sec

Adhesion shape change release Aggregation

ADP release

10 sec Coagulation Fibrin formation 5 min

Need to inhibit restenosis / reocclusion

Platelet Inhibitorsx ReoPro

elevates ACTs target time = 250 sec with ReoPro determined using FTCA510 tubex Integrelin

No reported clinically significant effects on ACTx Aggrastat

No reported effects on ACT

Clinical ApplicationsOperating Room Cardiac Surgery Interventional Cardiology and Radiology x Critical Care x Satellite Sites Dialysis ECMO

Emergency Room Anticoagulation Clinic

ACT or aPTTx Determine

when to pull the femoral sheath

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

Must be linked to heparin sensitivity of reagent used

ACT vs aPTT120 110 100 aPTT (J103) (sec) 90 80 70 60 50 40 30 20 50 100 150 FTCA510 (sec) 200 250

y = 0.57x - 28.44 R = 0.896

Single site comparison, ACT tube vs HE Jr Sig aPTT

ACT or aPTTx Monitor

heparin therapy

Target times determined by each facility APTT outcome study Reduce time to result (112 vs 200 >200 >200

site 1 23 51 80 109 138 167 196

Lot to Lot Reproducibility80 70 60

Cuvette Lot ay = 1.35x - 14.2 R=.909

50 40 30 20 20 40 60 80

Signature

Signature 30 40 50 60 70 80 90

Lot a 26 40 53 67 80 93 107

Lot b 29 43 57 70 84 98 112

Lab

80 70 Lab 60 50 40 30 20 20

Cuvette Lot by = 1.39x - 12.8 R=0.934

40

Signature

60

80

Clinical ApplicationsOperating Room Cardiac Surgery Interventional Cardiology and Radiology x Critical Care x Satellite Sites Dialysis ECMO

Emergency Room Anticoagulation Clinic

Dialysis / ECMOx ACT

(or nothing in dialysis)

Majority use P214 glass activated ACT Some use ACT-LR; HemoTec LR ACTx Better

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

Emergency RoomACT; aPTT; PT; Fibrinogen x Immediate Identification of Coagulopathiesx

Optimization of Critical Decision Pathwaysx

ACT Allows Early Detection of Traumatic Coagulopathy Allows Early Treatment Decisions Aids Damage Control Decisions Aucar, J. et.al. 1998 SW Surgeons Congress

x

Optimize Staffing During Off Hours

Anticoagulation Clinicsx

Results Available While Patient is Present Improved Anticoagulation Management Improved Standard of Care Staff Efficiency

x x

Immediate Retesting (if needed) Fingerstick Sampling

Same System for Clinic and Hom