LESSONS LEARNT FROM INAPPROPRIATE D-DIMER TESTING – CASE REPORT

Nikola M Pantić; Nikica Sabljić; Andrija  Bogdanović; Ljubomir Jaković; Mirjana Mitrović

doi:10.5937/smclk5-51180

Nikola M Pantić Clinic of Hematology, University Clinical Center of Serbia https://orcid.org/0000-0001-7798-4026
Nikica Sabljić University Clinical Center of Serbia, Clinic of Hematology, Belgrade, Serbia https://orcid.org/0000-0001-5488-126X
Andrija Bogdanović University Clinical Center of Serbia, Clinic of Hematology, Belgrade, Serbia; University of Belgrade, Faculty of Medicine, Belgrade, Serbia https://orcid.org/0000-0002-8288-7308
Ljubomir Jaković University Clinical Center of Serbia, Clinic of Hematology, Belgrade, Serbia https://orcid.org/0000-0003-2400-0112
Mirjana Mitrović University Clinical Center of Serbia, Clinic of Hematology, Belgrade, Serbia; University of Belgrade, Faculty of Medicine, Belgrade, Serbia https://orcid.org/0000-0001-8313-3754

DOI: https://doi.org/10.5937/smclk5-51180

Keywords: acute monoblastic leukemia, D-dimer, heparin-induced thrombocytopenia

Abstract

Introduction: Since the beginning of the COVID-19 pandemic, D-dimer testing has been widely used in not-yet-approved indications. This has led to misdiagnosis, overuse of diagnostic procedures, and unnecessary costs.

Case report: Herein, we report the case of a 50-year-old female patient who came to the emergency department with chest pain, shortness of breath, fatigue, and pain in her right leg. Because of an elevated level of D-dimer (4.73 mg/l (N:<0.5)), deep vein thrombosis and pulmonary embolism, as well as COVID-19 were excluded. Therapy with rivaroxaban, 10 mg/day, was initiated. Seven days later, the D-dimer level continued to rise (17.52 mg/l), which was why rivaroxaban was replaced with low molecular weight heparin (LMWH). After another five days, the level of D-dimer continued to rise (27.26 mg/l). A complete blood count revealed significant thrombocytopenia (54 x 109/l). As the 4Ts score for heparin-induced thrombocytopenia was 5, the anti-heparin/PF4 antibody test was performed, and it came back strongly positive (4+). LMWH was replaced with fondaparinux sodium, and the patient was referred to a hematologist. On examination, cutaneous bleeding and gingivorrhagia were present. Laboratory analyses registered pancytopenia (hemoglobin = 101 g/l; white blood cell count = 1.7 x 109/l; platelet count = 29 x 109/l) and consumption coagulopathy (INR = 1.7; aPTT = 27.1 s; fibrinogen = 0.8 g/l; D-dimer = 30.9 mg/l). Bone marrow aspirate was analyzed and the diagnosis of acute monoblastic leukemia, 47, XX, +12 [4] / 46, XX [16], FLT3-ITD, wild-type NPM1, was established.

Conclusion: D-dimer is a powerful diagnostic tool when used properly. It should never be treated as a single, isolated result and the decision to introduce anticoagulant therapy should never be made based on its value alone.

References

Innocenti F, Lazzari C, Ricci F, Paolucci E, Agishev I, Pini R. D-dimer tests in the emergency department: current insights. Open Access Emerg Med. 2021 Nov 11;13:465-79. doi: 10.2147/OAEM.S238696.

Johnson ED, Schell JC, Rodgers GM. The D‐dimer assay. Am J Hematol. 2019 Jul;94(7):833-9. doi: 10.1002/ajh.25482.

Thachil J, Lippi G, Favaloro EJ. D-dimer testing: laboratory aspects and current issues, Methods Mol Biol. 2017;1646:91-104. doi: 10.1007/978-1-4939-7196-1_7.

Auditeau C, Khider L, Planquette B, Sanchez O, Smadja DM, Gendron N. D‐dimer testing in clinical practice in the era of COVID‐19. Res Pract Thromb Haemost. 2022 May 25;6(4):e12730. doi: 10.1002/rth2.12730.

Wells PS, Anderson DR, Rodger M, Forgie M, Kearon C, Dreyer J, et al. Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis. N Engl J Med. 2003 Sep 25;349(13):1227-35. doi: 10.1056/NEJMoa023153.

Wells PS, Anderson DR, Rodger M, Ginsberg JS, Kearon C, Gent M, et al. Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer. Thromb Haemost. 2000 Mar;83(3):416-20.

Lo GK, Juhl D, Warkentin TE, Sigouin CS, Eichler P, Greinacher A. Evaluation of pretest clinical score (4 T’s) for the diagnosis of heparin‐induced thrombocytopenia in two clinical settings. J Thromb Haemost. 2006 Apr;4(4):759-65. doi: 10.1111/j.1538-7836.2006.01787.x.

Taylor FB, Toh CH, Hoots WK, Wada H, Levi M; Scientific Subcommittee on Disseminated Intravascular Coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH). Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost. 2001 Nov;86(5):1327-30.

Levi M, Toh CH, Thachil J, Watson HG. Guidelines for the diagnosis and management of disseminated intravascular coagulation. Br J Haematol. 2009 Apr;145(1):24-33. doi: 10.1111/j.1365-2141.2009.07600.x.

Kamolratanapiboon K, Tantanate C. Inappropriate use of D-dimer and impact on the test characteristics for deep vein thrombosis exclusion. Scand J Clin Lab Invest. 2019 Oct;79(6):431-6. doi: 10.1080/00365513.2019.1658214.

Oliver M, Karkhaneh M, Karathra J, Goubran M, Wu CM. A Review of inappropriate D-dimer ordering at a Canadian tertiary care centre. Blood 2019;134(Suppl 1):5778. doi: 10.1182/blood-2019-122617.

Jones P, Elangbam B, Williams NR. Inappropriate use and interpretation of D-dimer testing in the emergency department: an unexpected adverse effect of meeting the “4-h target.” Emerg Med J. 2010 Jan;27(1):43-7. doi: 10.1136/emj.2009.075838.

Thachil J, Fitzmaurice DA, Toh CH. Appropriate use of D-dimer in hospital patients. Am J Med. 2010 Jan;123(1):17-9. doi: 10.1016/j.amjmed.2009.09.011.

Schutte T, Thijs A, Smulders YM. Never ignore extremely elevated D-dimer levels: they are specific for serious illness. Neth J Med. 2016 Dec;74(10):443-8.

Ten Cate H, Leader A. Management of disseminated intravascular coagulation in acute leukemias. Hamostaseologie. 2021 Apr;41(2):120-6. doi: 10.1055/a-1393-8302.

Greinacher A, Selleng K, Warkentin TE. Autoimmune heparin‐induced thrombocytopenia. J Thromb Haemost. 2017 Nov;15(11):2099-114. doi: 10.1111/jth.13813.