College of American Pathologists
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  Clinical Abstracts





October 2012

Deborah Sesok-Pizzini, MD, MBA
Tina Ipe, MD, MPH

Low transfusion-related acute lung injury-risk plasma to reduce TRALI Low transfusion-related acute lung injury-risk plasma to reduce TRALI

A leading cause of transfusion-associated morbidity and mortality worldwide is transfusion-related acute lung injury. Despite TRALI being underdiagnosed and underreported, its incidence varies from one in 2,000 to one in 8,000 fresh frozen plasma units. Research on the pathogenesis of TRALI has resulted in the utilization of all-male donor plasma as a way to decrease its incidence. However, studies on TRALI incidence, especially look-backs, have produced conflicting results. The authors conducted a retrospective analysis to determine the incidence of TRALI after conversion to low-TRALI–risk plasma at three large university-affiliated academic medical centers. All-male donor plasma, male-predominant plasma, nulliparous female plasma, and HLA antibody-tested plasma were considered low-TRALI–risk plasma. The primary outcome measured was respiratory reactions that could be categorized as TRALI or possible TRALI 16 months before and after the institution of low-TRALI–risk plasma at the academic centers. A total of 99,986 plasma components were transfused, with 47,756 pre-conversion and 52,230 post-conversion. The authors demonstrated that there was not a significant reduction in overall transfusion reaction rates between the two periods (0.19 percent pre-conversion versus 0.17 percent post-conversion). In addition, there was not a significant reduction in respiratory reactions (0.046 percent pre-conversion versus 0.036 percent post-conversion). However, the results showed a significant decrease in the incidence of TRALI secondary to transfusion of low-TRALI–risk plasma (0.0084 percent to zero; P=.052). The authors noted that all cases of TRALI and possible TRALI were due to female donor plasma. The rate of TRALI in patients receiving red blood cells or platelets did not change significantly during the study period. Despite the significant reduction of TRALI, several study limitations require consideration, including the retrospective nature of the study and relative underdiagnosis of TRALI, as well as patients receiving female donor plasma during the post-conversion period and use of a screening method that does not detect HNA antibody in donors. Given these limitations, the true risk reduction of converting to low-TRALI–risk plasma is unknown, and additional clinical studies are required to ascertain the benefits of this strategy.

Arinsburg SA, Skerrett DL, Karp JK, et al. Conversion to low transfusion-related acute lung injury (TRALI)-risk plasma significantly reduces TRALI. Transfusion. 2012;52:946–952.

Correspondence: Dr. Melissa M. Cushing at

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MicroRNAs in CSF identify brain cancers and reflect disease activity MicroRNAs in CSF identify brain cancers and reflect disease activity

The ability to diagnose brain tumors without surgery would be a significant advancement in the care of patients with primary or metastatic brain cancers. Brain tumors are diagnosed by biopsy or cytological analysis of cerebrospinal fluid (CSF). However, CSF analysis has low sensitivity, and it’s possible to have negative findings and still have tumor present. Developing reliable biomarkers through the use of microRNAs (miRNAs) relies on the unique expression of miRNA in different types of brain cancer. The authors conducted a study to test if miRNA profiling of CSF allows detection of glioblastoma, helps distinguish between glioblastoma and metastatic brain tumors, and reflects disease progression. They examined CSF and brain tumor samples from 118 patients and divided the patients into a control group of non-neoplastic patients, glioblastoma patients, patients with brain metastasis from breast and lung cancer, and patients with breast or brain leptomeningeal metastasis. The authors used quantitative reverse-transcription polymerase chain-reaction analysis to detect miRNA biomarkers, including miR-10b and miR-21. The levels of miR-10b and miR-21 were found to be increased in the CSF of patients with glioblastoma and brain metastasis of breast and lung cancer compared with the levels in patients with non-neoplastic brain lesions and tumors in remission. Additional biomarkers in the miR-200 family were also shown to be expressed in the majority of patients with brain and leptomeningeal metastasis but not in the control group or glioblastoma patients. Absence of the miRNAs miR-10b and miR-200 in the CSF of patients in remission suggests that these miRNAs may be used to detect disease activity. The authors noted that additional unique miRNA signatures of tissues may be used as CSF biomarkers for disease monitoring and management. These may have implications in determining the most effective treatment strategy. A prospective study and further validation of miRNA biomarkers is recommended.

Teplyuk NM, Mollenhauer B, Gabriely G, et al. MicroRNAs in cerebrospinal fluid identify glioblastoma and metastatic brain cancers and reflect disease activity. Neuro-oncol. 2012;14(6):689–700.

Correspondence: Dr. Anna M. Krichevsky at

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Very early diagnosis of chest pain using point-of-care testing Very early diagnosis of chest pain using point-of-care testing

Early diagnosis of myocardial infarction is critical for improved outcomes. Multimarker cytoplasmic measurements, which include the MB isoenzyme of creatine kinase (CK-MB), myoglobin, and cardiac troponin I (cTnI), have been proposed for point-of-care testing (POCT). A multimarker approach to myocardial infarction diagnosis has been proposed due to concerns that cTnI cannot be detected in the early phases of myocardial infarction and myocyte necrosis. The RATPAC, or Randomised Assessment of Panel Assay of Cardiac markers study, is a prospective randomized trial of triple-marker testing by POCT. The RATPAC study showed that patients who underwent POCT received an earlier discharge with no increase in adverse coronary events compared to a control group. The purpose of this substudy was to determine if a full panel of cytoplasmic markers or troponin alone was necessary to diagnose an acute myocardial infarction. The study randomized 1,125 low-risk patients with chest pain to have a triple-marker panel performed on admission and 90 minutes after admission or to receive standard cardiac troponin measurement only through the local laboratory. The objective was to compare the accuracy of the different biomarkers for diagnosing acute myocardial infarction. The outcomes measured were comparison of the receiver operator characteristic (ROC) curve analysis and comparison of area under the curve (AUC) for individual marker values, change in CK-MB and myoglobin, and the combination of presentation or 90-minute value plus the change value. Results showed that cTnI was the most diagnostically accurate biomarker, with areas under the ROC curve statistically significant compared to CK-MB and myoglobin. The authors concluded that POCT cTnI measurements allowed for rapid diagnosis or exclusion of myocardial infarction. Use of myoglobin and CK-MB did not add value to the diagnosis. The enhanced performance of cTnI in detecting acute myocardial infarction is most likely due to the development of more sensitive cTnI measurements and more relevant diagnostic cutoff values. The RATPAC study is the first randomized controlled trial to evaluate the diagnostic and prognostic accuracy of a panel of biomarkers. Using a troponin assay that meets performance specifications for diagnosing myocardial infarction, the authors were able to show that POCT allows for a safe and accurate diagnosis of MI. The study also demonstrated that POCT biomarkers other than cTnI do not improve diagnostic efficiency.

Collinson P, Goodacre S, Gaze D, et al. Very early diagnosis of chest pain by point-of-care testing: comparison of the diagnostic efficiency of a panel of cardiac biomarkers compared with troponin measurement alone in the RATPAC trial. Heart. 2012;98:312–318.

Correspondence: Dr. Paul Collinson at

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Clinical pathology abstracts editors: Deborah Sesok-Pizzini, MD, MBA, associate professor, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, and medical director, Blood Bank and Transfusion Medicine, Children’s Hospital of Philadelphia; Tina Ipe, MD, MPH, resident, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania.