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Results of the Survey of Hospital Coagulation Laboratory Practices, United States-2001
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Laboratory Practices, United States-2001

Shahram Shahangian, Ph.D.; Ana K. Stanković, M.D., Ph.D.; Ira M. Lubin, Ph.D.;James H. Handsfield, M.P.H.; Mark D. White, B.S.
 

Also available in a print-friendly PDF version

 
bullet Executive Summary
bullet Introduction
bullet Methods
bullet Results and Discussion
bullet Concluding Remarks
bullet References
bullet Appendix (PDF)
    

EXECUTIVE SUMMARY

 

We present findings from a 2001 survey of U.S. hospital coagulation laboratories. (See the Appendix for a copy of the actual survey used.) We sent this questionnaire to 800 hospital laboratories, stratified into large (> 200 beds) and small (<200 beds) hospitals. Study sample was a random selection of the large and small hospitals from the 1999 directory of the American Hospital Association (AHA). The selected large and small hospitals constituted 26% and 9% of the large and small hospitals listed in this directory, respectively. We administered this survey and collected results between June and October 2001. Respondents had the option of mailing a completed survey or submitting one via the Internet. We received 632 responses (corresponding to a response rate of 79% including 20 responses submitted electronically).

Our findings show great variability in certain laboratory practices. Although in most cases, response patterns from the large and small hospital laboratories were not significantly (P > 0.050) different, several questions solicited significantly different responses from these 2 groups. For most of these questions, a greater proportion of large hospitals adhered to published laboratory practice recommendations and guidelines. The following is a summary of major findings.

Performance of Coagulation Testing

Ninety-seven percent of the respondents performed coagulation testing.

Test Requisition and Specimen Management

Test requisition. The respondents noted the following usage information on their test requisition forms: coumadin, 53%; unfractionated heparin, 39%; heparinoid, 33%; low molecular weight heparin (LMWH), 23%; and salicylate, 16%. The large hospital respondents noted significantly more requests for information on requisition forms for using unfractionated heparin (P = 0.003), heparinoid (P = 0.044) and LMWH (P = 0.045).

Rejection of specimens. The proportions of the respondents below did not note the following reasons for rejecting a coagulation specimen in their laboratories: specimen collected via indwelling catheter, 68%; label not having hospital medical record number, 55%; specimen stored at an inappropriate temperature, 15%; specimen hemolyzed, 14%; requisition form and specimen label having conflicting patient information, 8%; and specimen transport time exceeding recommended time frame, 8%. The College of American Pathologists (CAP) has recommended that specimens used for monitoring heparin therapy be collected from a different extremity than the one used for heparin infusion (Arch Pathol Lab Med. 1998;122:782798). A significantly greater proportion of the large hospital respondents (59%) rejected coagulation specimens because of the lack of hospital medical record number compared to the small hospital respondents (31%); P < 0.001. These results suggest a need for improvement in certain laboratory practices relating to test requisition and specimen collection procedures.

Practices Relating to Prothrombin Time (PT) Assay

Anticoagulant concentration. Based on the recommendation of the World Health Organization (WHO) and the NCCLS guidelines, 3.2% (109 mmol/L) citrate is the anticoagulant of choice for coagulation testing (Arch Pathol Lab Med. 1998;122:768781). Eighty percent of the large hospital respondents stated exclusively using 3.2% sodium citrate as the anticoagulant compared to 66% of the small hospital respondents (P < 0.001).

Reporting of results. Reporting PT results in seconds may lead clinicians to inappropriately compare results between institutions (Am J Clin Pathol. 1998;109:589594) and relying on PT ratio has been documented to cause errors in anticoagulant therapy (Arch Intern Med. 1992;152:278282). Almost all the respondents (99.8%) used international normalized ratio (INR) to report PT; however, 97% also reported PT in seconds and/or as therapeutic PT ratio. Three percent of the respondents reported PT results in INR only.

Reference interval. Ninety-two percent of the respondents conducted in-house evaluations to establish the reference interval for their PT assay. Most respondents (46% of the large hospitals and 74% of the small hospitals, P < 0.001) used less than 40 subjects to establish their PT reference intervals. According to the NCCLS, a minimum of 120 subjects for each reference population or subclass is recommended to establish reference intervals for quantitative laboratory tests (NCCLS approved guideline2nd edition. Document C28-A2. Vol 15; No. 4). Five percent of the respondents noted using at least 120 subjects to establish their reference ranges for PT assay.

Sensitivity of PT assay to heparin. According to the CAP, laboratories should determine sensitivity of their PT assays to heparin (Arch Pathol Lab Med. 1998;122:782798). Seventeen percent of the respondents determined the sensitivity of their PT assays to heparin. Also according to the CAP guideline, laboratories should, where possible, select a thromboplastin that is insensitive to heparin in the therapeutic range (Arch Pathol Lab Med. 1998;122:768781). Fifty-nine percent of the large hospital respondents selected a PT-thromboplastin reagent that was insensitive to heparin in the heparin therapeutic range, compared to 40% of the small hospital respondents (P < 0.001).

The CAP recommends that thromboplastins with a manual ISI between 0.9 and 1.7 be used (Arch Pathol Lab Med. 1998;122:768781). The large hospital respondents reported an average ISI of 1.52 (median, 1.56) while the small hospitals reported an average of 1.70 (median, 1.89). Of the large hospital respondents, 50% reported ISI values of < 1.70 compared to 36% of the small hospital respondents (P = 0.001). Forty-two percent of the large hospital respondents reported ISI values of < 1.20 compared to 24% of the small hospital respondents (P < 0.001) as recommended by the American College of Chest Physicians (Chest. 1995;108(4 Suppl):231S246S).

Practices Relating to Activated Partial Thromboplastin Time (aPTT) Assay

Therapeutic range. According to the CAP guideline, adjusted dose and therapeutic heparin require anticoagulant monitoring using a method with a defined therapeutic range (Arch Pathol Lab Med. 1998;122:782798). Seventy-three percent of the large hospital respondents noted having an aPTT therapeutic range for heparin compared to 53% of the small hospital respondents (P < 0.001). While 64% of the respondents stated they reported the aPTT therapeutic range for heparin when monitoring heparin therapy, 9% included the corresponding heparin concentration with aPTT results.

How the aPTT therapeutic range for heparin was determined. The CAP recommends that therapeutic range of unfractionated heparin for the aPTT reagent-instrument system should be determined with each change in reagent (lot number or manufacturer) or instrument (Arch Pathol Lab Med. 1998;122:782-798). This may be accomplished by (1) comparison of ex vivo specimens with an appropriately validated heparin assay or (2) comparison of ex vivo specimens to a previously calibrated aPTT using a method to control for reagent drift. The respondents adhered to the following practices to determine the aPTT therapeutic range for heparin:

  • using samples from patients on heparin therapy to compare a new to an old reagent lot, 59% (66% of the large hospital respondents versus 50% of the small hospital respondents, P = 0.007);
  • using heparin-spiked samples to compare a new to an old reagent lot, 46%;
  • using heparin-spiked samples to compare a new to an old heparin lot, 15% (12% of the large hospital respondents versus 21% of the small hospital respondents, P = 0.038);
  • using samples from patients on heparin therapy to compare a new to an old heparin lot, 12%;
  • performing anti-Xa assay, 37% (47% of the large hospital respondents versus 18% of the small hospital respondents, P < 0.001); and
  • performing protamine sulfate titration, 9%.

When the aPTT therapeutic range for heparin was reconfirmed. The respondents reconfirmed the aPTT therapeutic range for heparin under the following circumstances:

  • when new instrumentation is used, 79%;
  • when new reagent lots are used, 75%;
  • when new reagents are used, 51%; and
  • after a specified time period, 22%.

Specimen management. According to the NCCLS, samples can be assayed up to 4 hours after phlebotomy if centrifuged within 1 hour of collection (NCCLS approved guideline3rd edition. Document H21-A3. Vol 18; No. 20). The respondents indicated they adhered to the following practices to manage specimens before aPTT analysis:

  • specimens assayed within 4 hours after phlebotomy, 96%;
  • specimens centrifuged within 1 hour of collection, 88% (84% of the large hospital respondents versus 92% of the small hospital respondents, P = 0.007);
  • specimens kept at room temperature prior to testing, 82%; and
  • specimens kept at 4 C prior to testing, 22%.

Practices Relating to Assays for von Willebrand Disease (vWD)

Performance of von Willebrand factor (vWF) assays. Ten percent of the large hospital respondents stated that they provided results for von Willebrand factor antigen (vWF Ag) compared to 0.4% of the small hospital respondents (P < 0.001). Fourteen percent of the large hospital respondents noted that they provided results for von Willebrand factor activity (Ristocetin cofactor activity) compared to 0.3% of the small hospital respondents (P < 0.001). Finally, 3% of the large hospital respondents stated that they provided results for vWF multimers compared to 0.4% of the small hospital respondents (P = 0.007). The following proportions of the respondents performed the 3 vWF assays:

  • 38% for vWF Ag and vWF activity,
  • 25% for vWF activity only,
  • 15% for vWF Ag, vWF activity and vWF multimers,
  • 15% for vWF Ag only, and
  • 6% for vWF multimers only.

Reporting of ABO specific reference interval for vWF antigen assay. Nineteen percent of the respondents that performed vWF Ag assay reported an ABO specific reference interval for this assay.

Provision of vWF multimers results. Eighty-nine percent of the respondents noted that they performed vWF multimers assay only when ordered by a clinician; 38% did so when Ristocetin cofactor was decreased; 29% performed this assay when Ristocetin cofactor was disproportionately decreased relative to vWF Ag; 25% did so when vWF Ag and vWF activity were both low; and 13% did so only if Ristocetin-induced platelet aggregation indicated a Type II B vWD.

Practices Relating to Thrombosis/Hypercoagulability Workup

Protein S assays. Ten percent of the large hospital respondents usually performed the assay for protein S activity (functional test) before the antigenic assay compared to 0.3% of the small hospital respondents (P < 0.001). If the results of the functional test were decreased, 17% performed antigenic assay to differentiate Type I deficiency from Type II while 20% performed free and total protein S antigen assay.

Performance of activated protein C (APC) resistance and factor V Leiden mutation assays. Eleven percent of the large hospital respondents performed activated protein C (APC) resistance assay compared to 1% of the small hospital respondents (P < 0.001). If, after performing the APC resistance assay, results indicated resistance to APC, 61% obtained results for factor V Leiden mutation. Long-term anticoagulation in carriers of factor V Leiden, on the basis of the carrier state alone, is not indicated (Blood. 1997;89:19631967).

Algorithm for Diagnosing a Lupus Anticoagulant (LA)

Offering an LA profile. Eighteen percent of the respondents stated that they offered an LA profile.

Practices leading to mixing studies. When a PT result was prolonged, 37% of the respondents did not offer mixing studies for PT, and 56% did so only if there was an additional order for the mixing study. When an aPTT result was prolonged, 33% of the respondents did not offer mixing studies for aPTT, and 59% did so only if there was an additional order for the mixing study.

Workup to diagnose an LA. If the results of the mixing study for aPTT did not correct to normal, 17% of the respondents initiated a workup to diagnose an LA. Those routinely initiating a workup to diagnose an LA most commonly performed the following tests:

  • dilute Russell viper venom time, 79%;
  • hexagonal phase phospholipid (Staclot LA) assay, 51%;
  • lupus sensitive aPTT, 40%; and
  • platelet neutralization procedure, 35%.

Practices Relating to Monitoring for Low Molecular Weight Heparin (LMWH) Therapy

Monitoring of LMWH therapy. Fourteen percent of the respondents (19% of the large and 10% of the small hospitals, P = 0.002) noted that they monitored LMWH therapy.

Assays used. The CAP recommends the chromogenic antifactor Xa method for monitoring LMWH (Arch Pathol Lab Med. 1998;122:799807). In this survey, those monitoring LMWH therapy did so most commonly by using aPTT (72%) and anti-Xa (53%) assays. While 65% of the large hospital respondents used an anti-Xa assay to monitor for LMWH therapy, 18% of of the small hospital respondents did so (P = 0.001). Fifty-eight percent of the large hospital respondents used an aPTT assay to monitor LMWH therapy compared to 96% of the small hospital respondents (P = 0.001). The observation that 17% of the large hospital respondents reportedly performed in-house anti-Xa assay compared to 2% of the small hospital respondents (P < 0.001) may help to explain these findings.

Calibrators used. According to the CAP guideline, a hospital pharmacy should dispense heparin of a single manufacturer and lot number (Arch Pathol Lab Med. 1998;122:782798). The most common calibrators for anti-Xa assay were reportedly

  • LMWH supplied by pharmacy, 53%;
  • internal standard LMWH, 22%;
  • unfractionated heparin, 14%; and
  • internal standard unfractionated heparin, 11%.

The CAP recommends that a calibrated LMWH be used to establish the standard curve for an assay to measure LMWH and that unfractionated heparin not be used to establish the standard curve for monitoring LMWH (Arch Pathol Lab Med. 1998;122:799807). While 74% of the respondents used different calibration curves for LMWH and unfractionated heparin, 42% did so for each type of LMWH.

Timing of anti-Xa assay. The CAP recommends that when LMWH is monitored, the sample be obtained 4 hours after subcutaneous injection (Arch Pathol Lab Med. 1998;122:799807). Forty-six percent of the respondents did not recommend a time for anti-Xa testing after subcutaneous administration of LMWH, 32% performed anti-Xa testing 4 hours after injection, and 14% did so between 2 and 4 hours after injection.

Availability of Specific Coagulation Tests

The top 8 most commonly performed coagulation tests were PT (100%), aPTT (99%), bleeding time (90%), fibrinogen (78%), D-dimer (66%), fibrin(ogen) degradation products (52%), activated clotting time (43%), and thrombin time (38%). We found no significant differences between the large and small hospital respondents in terms of the proportions performing in-house testing of the 3 most commonly assayed coagulation tests: PT, aPTT and bleeding time. Except for plasminogen antigen assay (performed by 2 large hospitals), a significantly greater proportion of the large hospital respondents performed all other tests in-house compared to the small hospital respondents (P < 0.001, P = 0.035 for vWF multimers with 5 large hospitals performing this assay).

Test Result Information, Interpretations and Recommendations

From 90% to 98% of the respondents provided measurement units and 7687% provided needed specimen comments for PT, aPTT, vWF Ag and protein C assays. From 93 to 97% of the respondents supplied reference intervals for these assays. The following proportions of respondents provided therapeutic ranges: PT, 54%; aPTT, 38%; aWF Ag, 5%; and protein C, 5%.

From 4 to 6% of the respondents noted that they specified testing methodology/reagent on coagulation test reports for these 4 tests. One percent noted possible drug interactions for PT and aPTT assays; 7% did so for vWF Ag assay; and 21% stated drug interactions in reporting protein C results.

Two percent of the respondents suggested diagnoses for PT and aPTT assays compared to 10% and 12% for protein C and vWF Ag assays, respectively. The proportions providing written interpretations were as follows: aPTT, 4%; PT, 6%; vWF Ag, 21%; and protein C, 22%.

While 2% of the respondents provided recommendations for further testing for PT and aPTT assays, 12% and 14% did so for vWF Ag and protein C assays, respectively. The proportions providing recommendation for treatment were as follows: PT, 1%; aPTT, 1%; protein C, 3%; and vWF Ag, 5%. The proportions providing recommendation to test family members were as follows: PT, 0.2%; aPTT, 0.2%; protein C, 8%; and vWF Ag, 10%.

From 29% to 33% provided no result interpretation for any of these 4 tests, and 4651% provided no testing/treatment recommendations.

Process of Reporting Results

Reporting of critical values. Ninety-nine percent of the respondents reported critical values. Of those noting that they reported critical values, the respondents adhered to the following practices:

  • critical values telephoned to the clinician and the call documented, 99%;
  • critical values repeated and documented as confirmed, 91%;
  • critical values telephoned to the clinician and the call not always documented, 6%; and
  • critical values indicated on the report, but no further action taken, 5%.

Repeating a coagulation test. Circumstances under which a coagulation test was usually repeated were reportedly as follows:

  • control(s) out of range, 98%;
  • results outside instrument technical ranges, 98%;
  • results being critical values, 95%;
  • results not agreeing with previous results, 73%; and
  • results outside of the reference interval, 16%.

These data suggest a need for improved reporting of laboratory test results.

Quality Assurance (QA) Procedures

Respondents usually took the following QA steps:

  • critical values brought to immediate attention of the clinician, 99%;
  • calibration of all instruments periodically verified, 99%;
  • critical values reviewed, 99%;
  • new analytical methods validated, 98%;
  • patient information on specimen tube and laboratory-generated labels matched, 93%;
  • specimen label and requisition form matched, 90%;
  • instrument printout compared to reported value, 82%;
  • patients previous results checked, 76%;
  • specimens run in duplicate, 39%;
  • controls run in duplicate, 38%; and
  • plasma checked for platelet count after centrifugation, 23%.

According to the Clinical Laboratory Improvement Amendments of 1988 (CLIA) regulations, a laboratory report must be sent promptly to the authorized person, the individual responsible for using the test results or the laboratory that initially requested the test (CLIA Subpart K Sec. 493.1253 Condition: Hematology.  One percent of the respondents did not adhere to this practice (P = 0.005).

Patient and control specimens must be tested in duplicate for manual coagulation tests; duplicate testing is not required for automated coagulation tests (CLIA Subpart K Sec. 493.1253 Condition: Hematology). Patient and control specimens were reportedly run in duplicate by 39% and 38% of the respondents, respectively. We did not ask whether this duplicate testing was performed using manual or automated methods.

Two percent of the respondents reportedly did not validate new analytical methods (P < 0.001); and 1% of the respondents indicated that they did not periodically verify calibration of all of their instruments (P = 0.003).

These data suggest a need for improvement in performing certain QA procedures.

Coagulation Laboratory Personnel and Resources

Testing location. Respondents performed coagulation tests in the following locations: core laboratory, 55%; hematology laboratory, 38%; coagulation laboratory, 16%; point of care, 11%; and stat laboratory, 5%. Two percent noted that coagulation testing was done at none of these locations.

Number of full time equivalents (FTEs). Seventy-one percent employed less than 4 FTEs to perform coagulation testing, while 17% employed 49 FTEs and 12% employed > 10 FTEs.

Components of competency assessment program. The respondents included the following components in their competency assessment program for coagulation testing personnel:

  • successful performance of QC with documentation of remedial actions, 92%;
  • review of procedure manuals, 86%;
  • analysis of unknown samples, 80%;
  • direct observation of a task, 74%;
  • participation in continuing education, 61%; and
  • periodic written examination, 30%.

Educational degrees of coagulation laboratory director. Ninety-one percent of the respondents noted that the laboratory director had an M.D., while 7% stated that this individual had a Ph.D. Both M.D. and Ph.D. degrees were noted by 4% of the respondents. Eight percent of the respondents noted other degrees, and 27% of this group also noted that the laboratory director possessed an M.D.

Certifications of coagulation laboratory director. The proportions of the laboratory directors with specific professional board/society certifications were as follows:

  • in clinical pathology, 76%; 81% of the large versus 71% of the small hospital respondents (P = 0.002);
  • in anatomical pathology, 63%; 73% of the large versus 53% of the small hospital respondents (P < 0.001);
  • by the American Society of Clinical Pathologists (ASCP), 25%; 21% of the large versus 29% of the small hospital respondents (P = 0.020);
  • in medicine (18%);
  • in hematopathology, 8%; 14% of the large versus 1% of the small hospital respondents (P < 0.001); and
  • in hematology, 5%; 9% of the large versus 1% of the small hospital respondents (P < 0.001).

Coagulation service capacities. A clinician was reportedly available for consultation having expertise in coagulation disorders in 57% of the responding hospitals (74% of the large versus 38% of the small hospitals, P < 0.001). An anticoagulation outpatient clinic specializing in the adjustment of oral anticoagulants reportedly existed at the institutions of 20% of the respondents (27% of the large versus 12% of the small hospitals, P < 0.001). Nine percent of the respondents stated that they had an outpatient clinic specializing in the diagnosis and treatment of coagulation disorders (17% of the large versus 2% of the small hospitals, P < 0.001).

Point-of-Care Testing (POCT) for PT Assay

Availability of POCT for PT assay. Nine percent of the respondents (15% of the large versus 3% of the small hospitals, P < 0.001) had POCT for PT assay.

Laboratory oversight of coagulation POCT. The laboratory reported having oversight of coagulation POCT (including certification and regulatory compliance) in 93% of cases (98% of the large versus 67% of the small hospital respondents, P = 0.001).

Location of coagulation POCT. The respondents noted the following sites for performing coagulation POCT: coagulation clinic, 64%; cardiac catheterization laboratory, 27%; satellite laboratory, 23%; operating rooms, 21%; bedside, 18%; dialysis clinic, 13%; and other sites, 2%.

Integration of POCT results. Forty percent of the respondents stated that coagulation POCT results were integrated into the laboratorys results reporting system. Of these, 95% noted that coagulation POCT results were integrated into the laboratorys reporting system in the order of collection time.

Reference interval for POCT of PT. Reference interval for the POCT PT assay was reported to be the same as the laboratory PT reference interval for 45% of the respondents. Of the remaining, 36% noted that the POCT reference interval was established by the same method used to establish the PT reference interval for the laboratory.

Type of quality control (QC) material/method. Seventy-four percent of the respondents used electronic QC, 52% employed lyophilized QC material, and 44% used liquid QC material. Sixty-seven percent used 2 or more types of QC. Those using 2 or more types of QC reported they used electronic QC methods along with liquid QC material (33%), lyophilized QC material (30%), or both (4%).

Frequency of QC runs. According to the CLIA regulations, for all non-manual and CLIA non-waived coagulation testing systems, the laboratory must include 2 levels of control each 8 hours of operation, i.e. once per an 8-hour shift, and each time a change in reagents occurs (CLIA Subpart K. Sec. 493.1253 Condition: Hematology. Thirty-nine percent of the respondents performed QC once per shift, while 54% did so once per day. Ninety-three percent of the respondents performed QC either once per day or once per shift.

Our findings show substantial variability exists in certain coagulation laboratory practices. To our knowledge, this is currently the only report of a broad and comprehensive survey of nationally based coagulation-specific and general laboratory practices in hospitals. We believe these results present a representative and accurate snapshot of hospital coagulation laboratory practices in the United States in 2001.

 

This page last reviewed: 7/12/2004
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