TY - JOUR AU - Murphy,, Colin AB - ABSTRACT Intraosseous (IO) devices are used for vascular access in settings where venous access is initially unobtainable, such as prehospital trauma care or cardiac arrest. While IO devices are effective for infusion of blood, fluids, and medications, there is limited data on the analytical equivalence of specimens taken out of IO devices and peripheral venous blood. Despite this, IO device manufacturers and clinical resources state that IO specimens can be submitted for laboratory analysis. As reported in this case, IO specimens may be drawn and labeled as ‘peripheral blood’. IO specimens are not always caught by automated sample quality testing and may proceed through analysis without any warning signal to the laboratory. There are potential regulatory risks in accepting IO samples for analysis without validation. IO infusion is a valuable technique for vascular access in critically ill patients, but clinical laboratories will need to determine their own policies for identifying and handling IO specimens. Clinical History A 32 year old male patient presented to the trauma unit with multiple gunshot wounds to the right side of his body, including to the axilla, posterior shoulder, arm, groin, and proximal lower extremity. On arrival, the patient had tachycardia and hypotension; accordingly, 2 units of uncrossmatched type O-positive red blood cells (RBCs) and 2 units of type A plasma were transfused. Imaging revealed a right sixth rib fracture; right middle lobe lung laceration with surrounding contusion, pericardial effusion, and bilateral pneumothoraces; liver laceration; right superior and inferior pubic ramus fractures; and several other bony injuries. The patient was sent immediately to the operating room and, in preparation for continued transfusion support, a specimen labeled as containing peripheral blood was drawn by a trauma unit staff member and sent to the blood bank. On receipt, the specimen initially appeared similar to a normal peripheral blood specimen. However, after centrifugation, the specimen had grossly hemolyzed plasma, a muddy-appearing buffy coat, and a superficial fat plug [Image 1]. The blood bank laboratory scientist initially encountering the specimen rejected it as being clotted. However, on review, another laboratory scientist suspected the specimen was most likely not peripheral blood. The trauma unit confirmed that the specimen had been taken from an intraosseous device placed in the right tibial plateau. Image 1 Open in new tabDownload slide A specimen taken from an intraosseous device placed in the right tibial plateau of a 32 year old male, after centrifugation. Image 1 Open in new tabDownload slide A specimen taken from an intraosseous device placed in the right tibial plateau of a 32 year old male, after centrifugation. Discussion The technique of intraosseous (IO) infusion into the bone marrow was discovered in 1922 and used in pediatric populations through the 1950s before being replaced in most cases by intravenous catheters.1,2 In current medical practice, IO devices are used for infusion of blood, fluids, and medications in hemorrhaging or critically ill patients without rapidly obtainable venous access.3 IO access is established via piercing the bony cortex with a needle and introducing a large-bore catheter to the richly perfused medullary space. Common sites of access include the proximal tibia, as happened in this case, in addition to the sternum, humerus, radius, ulna, and other locations.4 Although device manufacturers such as Teleflex Incorporated5 and clinical resources6,7 state that specimens drawn from IO devices can be submitted for laboratory analysis, paired studies of bone marrow or IO specimens have shown variable correlations to peripheral blood values, depending on the analyte.8–11 Laboratorians may find this variability less acceptable than clinicians or researchers.12 Also, accepting bone marrow or IO specimens interchangeably with peripheral blood could expose clinical laboratories to regulatory risks. For example, package inserts for anti-A and -B antisera specify ethylenediaminetetraacetic acid (EDTA) or citrate anticoagulated whole blood as acceptable specimen types.13 Planned deviations from package inserts require validation under College of American Pathologists (CAP) and Clinical Laboratory Improvement Amendments (CLIA) standards,14 which are typically performed using specimens from healthy volunteers (often, laboratory personnel). Given the risks and discomfort associated with IO device placement,15 performing this validation with volunteers may not be ethical or feasible. For the blood bank, the results of 2 studies16,17 have shown complete concordance in ABO concordance in ABO and RhD antigen typing between bone marrow aspirates and venous peripheral blood using tube testing and gel column agglutination testing. Issues reported with using bone marrow aspirate specimens in the blood bank included inadequate specimen material for reverse typing, hemolysis, bone marrow particles visible in the testing columns, and variable reaction strengths, although none of these factors prevented full ABO and RhD typing. Both studies utilized residual bone marrow specimens collected from patients in the hematologic/oncologic departments; these bone marrow specimens may not be equivalent to IO specimens collected from patients requiring rapid infusion. Laboratory Role in Diagnosis Some IO specimens can be detected in the laboratory by gross visual inspection after centrifugation, with a distinct appearance of hemolyzed plasma and a top layer of fat.18 However, other IO specimens may not have that classical appearance,19 and the appearance of fat droplets in blood-bank tube testing may be the sole indicator of an IO specimen. When using automated chemistry systems, specimens are not routinely visually inspected after centrifugation. In our experience, not all IO specimens fail the integrated hemolysis-icterus-lipemia (HIL) index testing that is present in automated chemistry analyzers. Accordingly, IO specimens submitted as peripheral blood may generate no warning signal before being processed, leading to result reports that are released with standard peripheral blood reference ranges. It can be especially challenging to identify IO specimens retrospectively using delta checks or other measures of variability between specimens because patients requiring IO access are critically ill and can have rapidly changing laboratory results. If a laboratory suspects IO specimens are being submitted as peripheral blood for a particular patient, nursing notes and documentation of patient lines can be helpful in determining what specimens to investigate further via repeat visual inspection after centrifugation. IO specimens can contain bone marrow elements, which may be visible on a manual differential. Wright Giemsa stained smears of the fat layer from the specimen in this case demonstrated a marrow spicule [Image 2]. Image 2 Open in new tabDownload slide A bone marrow spicule in a Wright Giesma stained smear prepared from the superficial fat plug of the specimen in Image 1. Image 2 Open in new tabDownload slide A bone marrow spicule in a Wright Giesma stained smear prepared from the superficial fat plug of the specimen in Image 1. Patient Follow Up Because neither IO nor bone marrow specimens had been validated for ABO and RhD typing, the blood bank rejected the IO specimen. A subsequent venous peripheral blood specimen established the blood type of the patient as being A positive, with a mixed field due to previous transfusion of group-O RBCs and a negative antibody screening result. Nonclinical testing of the IO specimen showed concordant forward and reverse reactions consistent with an A positive blood type. The patient underwent an exploratory laparotomy and was successfully resuscitated with a balanced ratio of 10 RBC units, 10 thawed plasma units, and 1 apheresis platelet unit, along with operative repair of critical injuries. The patient underwent several additional procedures during the hospital stay and was successfully discharged to home 28 days later. Personal and Professional Conflicts of Interest None reported. Abbreviations Abbreviations RBCs red blood cells IO intraosseous EDTA ethylenediaminetetraacetic acid CAP College of American Pathologists CLIA Clinical Laboratory Improvement Amendments HIL hemolysis-icterus-lipemia References 1. Drinker CK , Drinker KR, Lund CC. The circulation in the mammalian bone marrow . Am J Physiol 1922 ; 62 ( 1 ): 1 – 92 . Google Scholar Crossref Search ADS WorldCat 2. Doan CE . The circulation of the bone marrow . Contrib Embryol. 1922 ; 12 : 27 . Google Scholar OpenURL Placeholder Text WorldCat 3. Reades R , Studnek JR, Vandeventer S, Garrett J. Intraosseous versus intravenous vascular access during out-of-hospital cardiac arrest: a randomized controlled trial . Ann Emerg Med. 2011 ; 58 ( 6 ): 509 – 516 . Google Scholar Crossref Search ADS PubMed WorldCat 4. Luck RP , Haines C, Mull CC. Intraosseous access . J Emerg Med. 2010 ; 39 ( 4 ): 468 – 475 . Google Scholar Crossref Search ADS PubMed WorldCat 5. Arrow® EZ-IO® Intraosseous Vascular Access System. Teleflex Incorporated website, via the Internet Archive. https://web.archive.org/web/20171005130451/http://www.teleflex.com/usa/product-areas/ems/intraosseous-access/arrow-ez-io-system/. Accessed April 28, 2020. 6. Perron CE. Intraosseous Infusion. In: UpToDate, AM Stack, AB Wolfson and JF Wiley, eds. Waltham, MA: UpToDate ; 2020 . Google Scholar Google Preview OpenURL Placeholder Text WorldCat COPAC 7. Petitpas F , Guenezan J, Vendeuvre T, Scepi M, Oriot D, Mimoz O. Use of intra-osseous access in adults: a systematic review . Crit Care. 2016 ; 20 : 102 . Google Scholar Crossref Search ADS PubMed WorldCat 8. Grisham J , Hastings C. Bone marrow aspirate as an accessible and reliable source for critical laboratory studies . Ann Emerg Med. 1991 ; 20 ( 10 ): 1121 – 1124 . Google Scholar Crossref Search ADS PubMed WorldCat 9. Ummenhofer W , Frei FJ, Urwyler A, Drewe J. Are laboratory values in bone marrow aspirate predictable for venous blood in paediatric patients? Resuscitation. 1994 ; 27 ( 2 ): 123 – 128 . Google Scholar Crossref Search ADS PubMed WorldCat 10. Miller LJ , Philbeck TE, Montez D, Spadaccini CJ. A new study of intraosseous blood for laboratory analysis . Arch Pathol Lab Med. 2010 ; 134 ( 9 ): 1253 – 1260 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 11. Strandberg G , Larsson A, Lipcsey M, Eriksson M. Comparison of intraosseous, arterial, and venous blood sampling for laboratory analysis in hemorrhagic shock . Clin Lab. 2019 ; 65 ( 7 ): doi: 10.7754/Clin.Lab.2019.181214. Google Scholar OpenURL Placeholder Text WorldCat 12. Cervinski MA . Laboratory analysis of intraosseous blood: bad to the bone? Clin Chem Lab Med. 2014 ; 52 ( 8 ): e187 – e189 . Google Scholar Crossref Search ADS PubMed WorldCat 13. Anti-A (ABO1) Seraclone® Murine Monoclonal, (A003) Anti-B (ABO2) Seraclone® Murine Monoclonal (B005) Anti-A,B (ABO3) Seraclone® Murine Monoclonal Blend (BS63/BS85) [package insert]. Dreieich, Germany : Bio-Rad Laboratories, Inc. ; 2020 . 14. Department of Health and Human Services, Centers for Medicare and Medicaid Services . Clinical laboratory improvement amendments of 1988; final rule. 42 CFR 493.1252: Standard: Test systems, equipment, instruments, reagents, materials, and supplies . Chicago, IL : Federal Register (US Government Publishing Office) ; 2003 . Google Scholar 15. Philbeck TE , Miller LJ, Montez D, Puga T. Hurts so good: easing IO pain and pressure . JEMS. 2010 ; 35 ( 9 ): 58 – 62, 65 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 16. Brickman KR , Krupp K, Rega P, Alexander J, Guinness M. Typing and screening of blood from intraosseous access . Ann Emerg Med. 1992 ; 21 ( 4 ): 414 – 417 . Google Scholar Crossref Search ADS PubMed WorldCat 17. Bäckman S , Ångerman-Haasmaa S, Jousi M, Siitonen S, Salmela K. ABO and D typing and alloantibody screening in marrow samples: relevance to intraosseous blood transfusion . Transfusion. 2018 ; 58 ( 6 ): 1372 – 1376 . Google Scholar Crossref Search ADS PubMed WorldCat 18. Pac LJ , Rossi HA, Theyagarajan KV, et al. Blood sample from an intraosseous device . Transfusion. 2018 ; 58 ( 11 ): 2472 – 2473 . Google Scholar Crossref Search ADS PubMed WorldCat 19. Mayer R , Ward M, Merrill V, Peisach N, Shimer L, Murphy C. An intraosseous sample initially resembling peripheral blood [epub ahead of print] . Transfusion . 2020 ; doi: 10.1111/trf.15772. Google Scholar OpenURL Placeholder Text WorldCat © American Society for Clinical Pathology 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) TI - Intraosseous Specimens Submitted to the Laboratory: A Case Report and Review JF - Laboratory Medicine DO - 10.1093/labmed/lmaa029 DA - 2020-11-02 UR - https://www.deepdyve.com/lp/oxford-university-press/intraosseous-specimens-submitted-to-the-laboratory-a-case-report-and-GtmOA5zwrE SP - e75 EP - e77 VL - 51 IS - 6 DP - DeepDyve ER -