False Prolongation of Activated Partial Thromboplastin Time with Aminoglycoside Antimicrobial Agents: A Case Report

Authors

  • Hiroki Doi Department of Cellular and Molecular Biology, Fujita Health University School of Medical Sciences, Toyoake, Japan; Department of Clinical Laboratory, Fujita Health University Hospital, Toyoake, Japan https://orcid.org/0000-0002-3595-6235
  • Michiko Osawa Department of Clinical Laboratory, Fujita Health University Hospital, Toyoake, Japan
  • Ayane Ozaki Department of Clinical Laboratory, Fujita Health University Hospital, Toyoake, Japan
  • Seiko Sato Department of Clinical Laboratory, Fujita Health University Hospital, Toyoake, Japan
  • Takashi Fujita Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai, Japan
  • Hidehiko Akiyama Department of Cellular and Molecular Biology, Fujita Health University School of Medical Sciences, Toyoake, Japan
  • Hiroyasu Ito Department of Clinical Laboratory, Fujita Health University Hospital, Toyoake, Japan; Joint Research Laboratory of Clinical Medicine, Fujita Health University School of Medicine, Toyoake, Japan https://orcid.org/0000-0002-4836-4001

DOI:

https://doi.org/10.3889/oamjms.2023.11755

Keywords:

Activated partial thromboplastin time, Lupus anticoagulant, APTT prolongation, Aminoglycoside antimicrobial, Tobramycin

Abstract

BACKGROUND: Activated partial thromboplastin time (APTT) is a clotting time assay for screening bleeding tendency, evaluating coagulation factor production capacity, assessing preoperatively, monitoring anticoagulant drugs, and searching for blood coagulation abnormalities such as hemophilia and antiphospholipid syndrome.

CASE PRESENTATION: Here, we present a 77-year-old male patient with dyspnea who was suspected to have a drug-resistant Pseudomonas aeruginosa infection and pulmonary mycosis. The patient had no history of bleeding tendencies or anticoagulant medication use. The laboratory test results revealed an abnormally prolonged activated partial thromboplastin time (APTT) of 120.3 s using the Coagpia® APTT-N reagent. The APTT test is frequently used to evaluate blood clotting function and assess for bleeding disorders. Prolonged APTT can indicate coagulation factor deficiencies or the presence of certain conditions such as von Willebr and disease, hemophilia, and disseminated intravascular syndrome. However, APTT standardization has not been achieved, causing discrepancies in test results due to variations in the reagents used. The prolonged APTT, in this case, was initially suspected to be caused by contamination or other artifacts, but repeat blood collections and cross-mixing tests revealed the Coagpia® APTT-N reagent as the cause of false prolongation. The reagent was changed to HemosIL SynthASil APTT, which revealed a normal APTT result. The patient had been receiving the aminoglycoside antimicrobial agent tobramycin, and the blood sample taken at the peak tobramycin level demonstrated the longest APTT time. The APTT shortened over time, corresponding to the decrease in tobramycin blood levels.

CONCLUSION: Overall, this paper reports a case of false APTT prolongation due to a specific APTT reagent in the presence of aminoglycoside antimicrobial agents. The findings underscore the difficulties in standar PTT testing and the importance of considering reagent performance characteristics in result interpretations.

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References

Yasui Y, Ishii T, Tatebe J, Morita T. Comparative analysis on characteristics of two activated partial thromboplastin time reagents. J Clin Lab Anal. 2022;36(9):e24608. https://doi.org/10.1002/jcla.24608 PMid:35853032 DOI: https://doi.org/10.1002/jcla.24608

Condrey JA, Flietstra T, Nestor KM, Schlosser EL, Coleman- McCray JD, Genzer SC, et al. Prothrombin time, activated partial thromboplastin time, and fibrinogen reference intervals for inbred strain 13/N guinea pigs (Cavia porcellus) and validation of low volume sample analysis. Microorganisms. 2020;8(8):1127. https://doi.org/10.3390/microorganisms8081127 PMid:32726969 DOI: https://doi.org/10.3390/microorganisms8081127

Wada H, Shiraki K, Matsumoto T, Ohishi K, Shimpo H, Sakano Y, et al. The evaluation of APTT reagents in reference plasma, recombinant FVIII products; Kovaltry® and Jivi® using CWA, including sTF/7FIX assay. Clin Appl Thromb Hemost. 2021;27:1076029620976913. https://doi.org/10.1177/1076029620976913 PMid:33606948 DOI: https://doi.org/10.1177/1076029620976913

Kamal AH, Tefferi A, Pruthi RK. How to interpret and pursue an abnormal prothrombin time, activated partial thromboplastin time, and bleeding time in adults. Mayo Clin Proc. 2007;82(7):864-73. https://doi.org/10.4065/82.7.864 PMid:17605969 DOI: https://doi.org/10.4065/82.7.864

Tiede A, Collins P, Knoebl P, Teitel J, Kessler C, Shima M, et al. International recommendations on the diagnosis and treatment of acquired hemophilia A. Haematologica. 2020;105(7):1791-801. https://doi.org/10.3324/haematol.2019.230771 PMid:32381574 DOI: https://doi.org/10.3324/haematol.2019.230771

Bowyer AE, Gosselin RC. Factor VIII and factor IX activity measurements for hemophilia diagnosis and related treatments. Semin Thromb Hemost. 2023;49(6):609-20. https://doi.org/10.1055/s-0042-1758870 PMid:36473488 DOI: https://doi.org/10.1055/s-0042-1758870

Munsanje MM, Kaile T, Kowa S, Sinkala M, Simakando M, Ndhlovu J, et al. von Willebrand factor activity and activated partial thromboplastin time as proxy biomarkers for coagulopathies in women with menorrhagia in Zambia: A case-control study. Pan Afr Med J. 2021;39:13. https://doi.org/10.11604/pamj.2021.39.13.13742 PMid:34394804 DOI: https://doi.org/10.11604/pamj.2021.39.13.13742

Yasin H, Jamil MO, Williams Iii LA. Diagnostic pearls and clinical implications of prekallikrein deficiency. Cureus. 2020;12(5):e8349. https://doi.org/10.7759/cureus.8349 PMid:32617222 DOI: https://doi.org/10.7759/cureus.8349

Mutch NJ, Waters EK, Morrissey JH. Immobilized transition metal ions stimulate contact activation and drive factor XII-mediated coagulation. J Thromb Haemost. 2012;10(10):2108-15. https://doi.org/10.1111/j.1538-7836.2012.04890.x PMid:22905925 DOI: https://doi.org/10.1111/j.1538-7836.2012.04890.x

Watanabe Y, Kaneda T. Anesthetic management using epidural analgesia for emergency laparoscopic cholecystectomy in a patient with lupus anticoagulant positivity and prolonged activated partial thromboplastin time. Case Rep Anesthesiol. 2022;2022:6310630. https://doi.org/10.1155/2022/6310630 PMid:35087690 DOI: https://doi.org/10.1155/2022/6310630

Favaloro EJ, Pasalic L. Lupus anticoagulant testing during anticoagulation, including direct oral anticoagulants. Res Pract Thromb Haemost. 2022;6(2):e12676. https://doi.org/10.1002/rth2.12676 PMid:35316943 DOI: https://doi.org/10.1002/rth2.12676

Eljilany I, Elzouki AN. D-Dimer, fibrinogen, and IL-6 in COVID-19 patients with suspected venous thromboembolism: A narrative review. Vasc Health Risk Manag. 2020;16:455-62. https://doi.org/10.2147/VHRM.S280962 PMid:33223833 DOI: https://doi.org/10.2147/VHRM.S280962

Wu Q, Wang L, Zhao R. Neglected Vitamin K deficiency causing coagulation dysfunction in an older patient with pneumonia: A case report. BMC Geriatr. 2022;22(1):628. https://doi.org/10.1186/s12877-022-03327-6 PMid:35907829 DOI: https://doi.org/10.1186/s12877-022-03327-6

Kogan AE, Kardakov DV, Khanin MA. Analysis of the activated partial thromboplastin time test using mathematical modeling. Thromb Res. 2001;101(4):299-310. https://doi.org/10.1016/s0049-3848(00)00405-9 PMid:11248291 DOI: https://doi.org/10.1016/S0049-3848(00)00405-9

van den Besselaar AM, Chantarangkul V, Angeloni F, Binder NB, Byrne M, Dauer R, et al. International collaborative study for the calibration of proposed International Standards for thromboplastin, rabbit, plain, and for thromboplastin, recombinant, human, plain. J Thromb Haemost. 2018;16(1):142-9. https://doi.org/10.1111/jth.13879 PMid:29065247 DOI: https://doi.org/10.1111/jth.13879

Liu J, Li F, Shu K, Chen T, Wang X, Xie Y, et al. The analysis of false prolongation of the activated partial thromboplastin time (activator: Silica): Interference of C-reactive protein. J Clin Lab Anal. 2018;32(8):e22571. https://doi.org/10.1002/jcla.22571 PMid:29756266 DOI: https://doi.org/10.1002/jcla.22571

Kitchen S, Cartwright I, Woods TA, Jennings I, Preston FE. Lipid composition of seven APTT reagents in relation to heparin sensitivity. Br J Haematol. 1999;106(3):801-8. https://doi.org/10.1046/j.1365-2141.1999.01596.x PMid:10468876 DOI: https://doi.org/10.1046/j.1365-2141.1999.01596.x

Kumano O, Ieko M, Naito S, Yoshida M, Takahashi N. APTT reagent with ellagic acid as activator shows adequate lupus anticoagulant sensitivity in comparison to silica-based reagent. J Thromb Haemost. 2012;10(11):2338-43. https://doi.org/10.1111/j.1538-7836.2012.04906.x PMid:22909048 DOI: https://doi.org/10.1111/j.1538-7836.2012.04906.x

Lawrie AS, Kitchen S, Efthymiou M, Mackie IJ, Machin SJ. Determination of APTT factor sensitivity--the misguiding guideline. Int J Lab Hematol. 2013;35(6):652-7. https://doi.org/10.1111/ijlh.12109 PMid:23718922 DOI: https://doi.org/10.1111/ijlh.12109

Bowyer A, Kitchen S, Makris M. The responsiveness of different APTT reagents to mild factor VIII, IX and XI deficiencies. Int J Lab Hematol. 2011;33(2):154-8. https://doi.org/10.1111/j.1751-553X.2010.01261.x PMid:20840376 DOI: https://doi.org/10.1111/j.1751-553X.2010.01261.x

Asai H, Shirayama R, Oshida K, Honda Y, Sato T, Sakai M, et al. A pediatric case of acquired hemophilia A: The usefulness of the activated partial thromboplastin time (APTT) cross-mixing test for early diagnosis. J UOEH. 2018;40(4):331-7. https://doi. org/10.7888/juoeh.40.331 DOI: https://doi.org/10.7888/juoeh.40.331

PMid:30568085

Kato T, Hanawa T, Asou M, Asakawa T, Sakamaki H, Araki M. Autoimmune factor V deficiency that took 16 years to diagnose due to pseudodeficiency of multiple coagulation factors. Case Rep Med. 2021;2021:4657501. https://doi.org/10.1155/2021/4657501 PMid:33505468 DOI: https://doi.org/10.1155/2021/4657501

Devreese KM, de Groot PG, de Laat B, Erkan D, Favaloro EJ, Mackie I, et al. Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis: Update of the guidelines for lupus anticoagulant detection and interpretation. J Thromb Haemost. 2020;18(11):2828-39. https://doi.org/10.1111/jth.15047 PMid:33462974 DOI: https://doi.org/10.1111/jth.15047

Woo S, Kim B, Heo NH, Kim MS, Yoon YA, Choi YJ. Association of lupus anticoagulant status with disease course in SARS-CoV-2 (COVID-19) infection. Clin Appl Thromb Hemost. 2022;28:10760296221127276. https://doi.org/10.1177/10760296221127276 PMid:36172745 DOI: https://doi.org/10.1177/10760296221127276

Kaneko Y, Sugasaki M, Okada N, Niimi M, Yasui S, Hori T, et al. Artifactual prolongation of the activated partial thromboplastin time by amikacin or gentamicin with ellagic acid, but not silica activated reagent. Int J Lab Hematol. 2022;44(2):e72-5. https://doi.org/10.1111/ijlh.13718 PMid:34585530. DOI: https://doi.org/10.1111/ijlh.13718

Rosalia M, Chiesa E, Tottoli EM, Dorati R, Genta I, Conti B, et al. Tobramycin nanoantibiotics and their advantages: A minireview. Int J Mol Sci. 2022;23(22):14080. https://doi.org/10.3390/ijms232214080 PMid:36430555 DOI: https://doi.org/10.3390/ijms232214080

Hideo Y, Tadashi Y, Koichiro H, Yasuo K, Teruhisa I, Masayoshi D, et al. Absorption, excretion, distribution and metabolism of tobramycin. Chemotherapy. 1975;23(3):894-9.

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Published

2023-08-17

How to Cite

1.
Doi H, Osawa M, Ozaki A, Sato S, Fujita T, Akiyama H, Ito H. False Prolongation of Activated Partial Thromboplastin Time with Aminoglycoside Antimicrobial Agents: A Case Report. Open Access Maced J Med Sci [Internet]. 2023 Aug. 17 [cited 2024 Nov. 23];11(C):129-33. Available from: https://oamjms.eu/index.php/mjms/article/view/11755

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Case Report in Internal Medicine

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