Laboratory Variables That May Affect Test Results in Prothrombin ...

More documents

Recommendations

Info

Summary of Mean INR Results on 25 Normal Patient Samples Before and After Local ISI Calibration Instrument Reagent Mean INR Using Mean INR Using Difference in Vendor-Assigned ISI Locally Calibrated ISI INR Means (%) Diagnostica Stago/STA Neoplastine CI+ 1.24 1.29 -3.9 Thromborel S 1.12 1.13 -0.9 Thromboplastin C+ 1.96 1.76 10.1 Innovin 0.92 1.00 -8.5 Sysmex CA 540 Neoplastine CI+ 1.24 1.09 11.9 Thromborel S 1.06 1.02 3.4 Thromboplastin C+ 1.95 1.81 7.4 Innovin 1.02 0.92 10.3 Dade-Behring BCS Neoplastine CI+ 1.24 1.16 6.9 Thromborel S 1.06 1.02 3.5 Thromboplastin C+ 1.77 1.57 11.1 Innovin 0.90 1.07 -18.9 Summary of Mean INR Results on 95 Patient OAT Samples Before and After Local ISI Calibration Instrument Reagent Mean INR Using Mean INR Using Difference in Results >10% Vendor-Assigned ISI Locally Calibrated ISI INR Means (%) Difference Diagnostica Stago/STA Neoplastine CI+ 2.58 2.69 4.1 0.0 Thromborel S 2.56 2.58 0.8 0.0 Thromboplastin C+ 2.39 2.15 10.0 37.1 Innovin 2.45 2.67 7.9 22.1 Sysmex CA 540 Neoplastine CI+ 3.46 2.90 16.1 63.9 Thromborel S 2.69 2.58 4.1 0.0 Thromboplastin C+ 2.82 2.60 7.8 27.8 Innovin 2.49 2.25 9.6 39.2 Dade-Behring BCS Neoplastine CI+ 2.81 2.60 7.5 20.6 Thromborel S 2.67 2.57 3.7 0.0 Thromboplastin C+ 2.86 2.51 12.6 52.6 Innovin 2.66 3.29 16.4 64.9 serious patient mismanagement during OAT. There is no current evidence that the heparin neutralizers may neutralize the presence of low molecular weight heparin. Each institution should check the effect of a therapeutic dose of unfractionated heparin against their reagent/instrument system. Possible Effect of a Lupus Anticoagulant (LA) on PT/INR The recommended therapeutic range of INR for OAT in patients with the presence of a LA is currently 2.5 to 3.5. This is still a controversial subject. It has been suggested that using the INR to monitor these patients may be inadequate due to interference by the presence of a LA on the clot-based PT assay. Some investigators have suggested using the prothrombin-proconvertin assay in lieu of the PT/INR for patients with this disorder since it doesn’t appear to be affected by a LAs inhibitory actions. 3 Others have suggested measuring coagulation factors II and X by either chromogenic or 1-stage clotting assays based on at least 3 dilutions to lessen the LA inhibitory effect. 3 Other investigators found little effect of the presence of a LA on PT/INR results using different thromboplastins and instruments. One small exception was a subgroup of 6 patients in which a recombinant thromboplastin © laboratorymedicine> february 2003> number 2> volume 34 T2 T3 (Innovin, Dade-Behring) was used. 3 One recent study performed a protocol to see if subjects who have the presence of anticardiolipin antibodies without the presence of an LA to see if the INR assay was affected using local specific ISIs with 11 different thromboplastins. No effect on the INR results was observed. 18 In another study using 11 different LA positive, 11 negative LA subjects, and 7 different thromboplastins, the presence of an LA did not disturb the laboratory tests for monitoring subjects on OAT. 19 Each institution should check their own reagent/instrument combination with positive LA plasmas to determine if the LA interference is an issue in their laboratory. 127
128 Reporting of PT/INR results There continues to be no consensus on the method of reporting INR values for conditions other than OAT. Many laboratories report only the INR for all PT measurements since the INR is simply a mathematical conversion of the PT using the ISI. 9 Many laboratories have been reluctant to convert to low ISI thromboplastins because the prolonged PTs are thought to be confusing to physicians used to shorter PTs with high ISI (less sensitive) reagents. This may be true when a PT is ordered for situations other than monitoring OAT. 9 A situation such as a preoperative coagulation screen or liver diseases can confuse the issue of INR reporting. It has been suggested by some clinicians to use 2 systems for reporting PT results. One result for patients on OAT and another for subjects not on OAT has been instituted at some facilities. There is data that suggests that the INR value is appropriate for use in patients beginning anticoagulation as well as in subjects with other coagulation disorders (eg, liver impairment). The range of PT prolongation appears to be greater for patients on OAT than for patients with liver disease or disseminated intravascular coagulation, but the PT and INR has been shown to correlate in a linear fashion when reagents of varying ISI were compared. Some experts have proposed reporting the INR in lieu of the PT for all patients, but suggested the best way to accomplish this would be to have an international consensus conference. This has still not been accomplished as recently as the 2001 International Society of Thrombosis and Hemostasis Conference in Paris, France. In the subcommittee conference that dealt with this issue, there was still no consensus on how to use the INR for other than those subjects on OAT. Some notable clinicians and researchers have publicly stated that the INR is recommended as the most appropriate means for reporting PT results in patients who are stable, orally anticoagulated. They have suggested that the INR is not appropriate for use in other clinical situations (eg, liver disease, hereditary factor deficiencies, routine screening, preoperative testing, and detecting vitamin K deficiency). There is little or no information available on the use of the INR reporting of drug-induced coagulation defects in subjects on OAT. Does a single coagulation factor deficiency, such as a factor FVII deficiency, have a significant effect on the INR? 9 This could present problems in clinical settings where the INR only is reported. Fairweather and colleagues 9 presented a further argument against the use of reporting INRs only. The presence of a mildly prolonged PT may be the only clue to a clinically significant coagulopathy. However, the upper range of normal is obscured by the exponential nature of the INR calculation. The example they used discussed the upper limit of normal for 2 reagents, which correspond to a PT ratio of 1.2. This would correspond to an INR of 1.2 for a reagent with an ISI of 1.0 and an INR of 1.4 for a reagent with an ISI of 2.0. The problem would then be in interpreting the INR values in the range of 1.3 to 1.4. One local hospital in our area went to INR value reporting because the surgeons would misinterpret what they perceived to be mildly prolonged PTs. Consequently, they would order freshfrozen plasma for surgeries unnecessarily. Final Notes The accuracy and precision of the INR is dependent on the PT assay and the ISI of thromboplastin. Other researchers have noted that since the ISI is the exponent of the INR equation, the higher the ISI assigned to thromboplastins the greater the imprecision of the INR as a result of the mathematical outcome. 20 In support of this information we discovered, in a study, that when the INR approaches 3.0 or greater the discrepancy in the INR value was between different reagent/instrument systems. Therefore the large difference in assigned ISI values is probably the most important variable that influences the poor correlation seen in different laboratories reagent/instrument combinations. Thromboplastins with an ISI less than 1.2 produce a wider range of values in the PT and PT ratio. Consequently, the precision of the INR is similarly improved. Since the calculation of the INR requires using the ISI exponentially, the farther the ISI value is from 1.0, the less accurate the INR values will be. laboratorymedicine> february 2003> number 2> volume 34 © Manufacturer assigned ISIs, not specific to the local reagent/instrument set-up, may introduce even more inaccuracy. Instrumentation can also greatly influence the INR values. Because manufacturers provide limited guidelines for instrument assigned ISIs, the laboratory should validate its coumadin influenced INR values by performing local on-site ISI calibration. If the laboratory in Pennsylvania had a protocol for locally calibrating their ISI values, the disaster that occurred with the inaccurate ISI being used may have been averted. 1. Adverse events and deaths associated with laboratory errors at a hospital-Pennsylvania, 2001. MMWR. 2001:710-711. 2. McCullough, Marie. Lab error deaths may now total five. The Inquirer (Philadelphia, PA), August 3, 2001. 3. McGlasson DL. A review of variables affecting PTs/INRs. Clin Lab Sci. 1999;12:353-358. 4. Cunningham MT, Johnson GF, Pennell BJ, et al. The reliability of manufacturer-determined, instrumentspecific international sensitivity index values for calculating the international normalized ratio. AJCP. 1994;102:128-133. 5. Ts’ao C, Swedlund J, Neofotistos D. Implications of use of low international sensitivity index thromboplastins in prothrombin testing. Arch Pathol Lab Med. 1994;118:1183-1187. 6. Duncan EM, Casey CR, Duncan BM, et al. Effect of concentration of trisodium citrate anticoagulant on calculation of the international normalized ratio and the international sensitivity index of thromboplastin. Thromb Haemost. 1994;72:84-88. 7. Adcock JM, Kressen DC, Marlar RA. Effect of 3.2% vs. 3.8% sodium citrate on routine coagulation testing. Am J Clin Pathol. 1997;107:105-110. 8. Dwyre AL, Giles AR, Key LA, et al. The effects of sodium citrate anticoagulant concentration, storage on or off cellular matrix, and specimen age on prothrombin time INR using a low ISI (1.06) rabbit brain thromboplastin. Thromb Haemost. 1995;73:1237. 9. Fairweather RB, Ansell J, Anton M, et al. College of American Pathologists Conference XXXI on laboratory monitoring of anticoagulant therapy: Laboratory monitoring of oral anticoagulant therapy. Arch Pathol Med. 1998;122:768-781. 10. NCCLS H21-A3. Collection, transport, and processing of blood specimens for coagulation testing and general performance of coagulation assays; approved guideline-3rd ed. 1998;18:20. 11. Van den Besselaar AMHP, Halem-Visser LP, Loeliger EA. The use of evacuated tubes for blood collection in oral anticoagulant control. Thromb Haemost. 1983;50:676-677. 12. Raskob GE, Durica SS, Owen WL, et al. Monitoring low-dose warfarin therapy be a central laboratory and implications for clinical trials and patient care: the coumadin aspirin reinfarction (CARS) pilot study group. Am J Cardiol. 1996;78:1074-1076. 13. Baglin T, Luddington R. Reliability of delayed INR determination: Implication for decentralized anticoagulant care with off-site blood sampling. Br J. Haematol. 1997;96:431-434. 14. Foubister Vida. Quick on the draw-coagulation tube response. CAP Today. 2002;16:38-42.
Page 1 and 2: 124 science [coagulation and hemato
Page 3: 126 Instrumentation There are over

Laboratory Variables That May Affect Test Results in Prothrombin ...

Create successful ePaper yourself

Delete template?

Save as template?