Abstract
Thrombocytopenia has been reported as an adverse reaction of numerous drugs. Vancomycin is often overlooked as a culprit but has been associated with several cases of thrombocytopenia that were not well described in the literature. A literature search was conducted to find reports of thrombocytopenia induced by vancomycin. Biomedical databases including ‘PubMed’, ‘Scopus’, and ‘Web of Science’ were searched using terms ‘vancomycin’, ‘platelet’, ‘pancytopenia’, ‘thrombocytopenia’, and ‘bleeding’. English language articles published before July 2015 were included. Thirty-nine papers including 29 case reports (30 cases), five observational studies, two clinical trials, two letters, and one case series remained for final analysis. The main route of administration was intravenous infusion. This adverse reaction seems to be duration dependent with the mean time to platelet nadir count of 8 days in reported cases. The interval may be significantly shorter in re-exposure to the drug. Platelet nadir counts ranged from 2000 to 100,000/mL in patients who experienced bleeding. Vancomycin-specific antibodies were detected in 13 of 17 patients who were tested in the case reports. Based on the Naranjo Adverse Drug Reaction Probability Scale, reaction was ‘definite’, ‘probable’, and ‘possible’ in 1, 15, and 14 patients, respectively. Among 30 cases, vancomycin was discontinued in 29 patients and platelets returned to normal counts within 5–6 days in 17 of them; in one patient, vancomycin was not discontinued, but platelet count recovered 11 days after the nadir time. Transfusion might be recommended if severe thrombocytopenia and bleeding occurs. Intravenous immunoglobulins, corticosteroids, rituximab, and plasma exchange should be reserved for patients with resistant thrombocytopenia and severe bleeding as mentioned in a number of reports.
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References
Aster RH, Curtis BR, McFarland JG, Bougie DW. Drug-induced immune thrombocytopenia: pathogenesis, diagnosis, and management. J Thromb Haemost. 2009;7(6):911–8. doi:10.1111/j.1538-7836.2009.03360.x.
Rondina MT, Walker A, Pendleton RC. Drug-induced thrombocytopenia for the hospitalist physician with a focus on heparin-induced thrombocytopenia. Hosp Pract (1995). 2010;38(2):19–28.
van den Bemt PM, Meyboom RH, Egberts AC. Drug-induced immune thrombocytopenia. Drug Saf. 2004;27(15):1243–52. doi:10.2165/00002018-200427150-00007.
Aster RH, Bougie DW. Drug-induced immune thrombocytopenia. N Engl J Med. 2007;357(6):580–7. doi:10.1056/NEJMra066469.
Kenney B, Stack G. Drug-induced thrombocytopenia. Arch Pathol Lab Med. 2009;133(2):309–14. doi:10.1043/1543-2165-133.2.309.
Arnold DM, Kukaswadia S, Nazi I, et al. A systematic evaluation of laboratory testing for drug-induced immune thrombocytopenia. J Thromb Haemost. 2013;11(1):169–76. doi:10.1111/jth.12052.
Priziola JL, Smythe MA, Dager WE. Drug-induced thrombocytopenia in critically ill patients. Crit Care Med. 2010;38(6 Suppl.):S145–54. doi:10.1097/CCM.0b013e3181de0b88.
Patnode NM, Gandhi PJ. Drug-induced thrombocytopenia in the coronary care unit. J Thromb Thrombolysis. 2000;10(2):155–67.
Von Drygalski A, Curtis BR, Bougie DW, et al. Vancomycin-induced immune thrombocytopenia. N Engl J Med. 2007;356(9):904–10. doi:10.1056/NEJMoa065066.
Levine DP. Vancomycin: understanding its past and preserving its future. South Med J. 2008;101(3):284–91. doi:10.1097/SMJ.0b013e3181647037.
Black E, Lau TT, Ensom MH. Vancomycin-induced neutropenia: is it dose- or duration-related? Ann Pharmacother. 2011;45(5):629–38. doi:10.1345/aph.1P583.
Ganly P, Downing J, Stiven P, et al. Clinical and serological diagnoses of a patient with vancomycin-induced thrombocytopenia. Transfus Med. 2011;21(2):137–9.
Anand A, Chauhan HK. Piperacillin and vancomycin induced severe thrombocytopenia in a hospitalized patient. Platelets. 2011;22(4):294–301. doi:10.3109/09537104.2010.549973.
Apiwattanakul N, Wanitkun S, Chongtrakool P, Sirinavin S. A patient with penicillin-resistant viridans group streptococcal endocarditis and unusual reactions to vancomycin. Southeast Asian J Trop Med Public Health. 2008;39(6):1088–91.
Bay A, Oner AF, Dogan M, Çaksen H. A child with vancomycin-induced thrombocytopenia. J Emerg Med. 2006;30(1):99–100.
Candemir B, Aribuca A, Koca C, et al. An unusual case of vancomycin-related systemic reaction accompanied with severe thrombocytopenia mimicking pacemaker-related infective endocarditis: a case report and review of literature. J Interv Card Electrophysiol. 2013;38(2):143–5. doi:10.1007/s10840-012-9738-6.
Carmichael A, Al-Zahawi M. Drug points: pancytopenia associated with vancomycin. BMJ. 1986;293(6554):1103.
Christie DJ, van Buren N, Lennon SS, Putnam JL. Vancomycin-dependent antibodies associated with thrombocytopenia and refractoriness to platelet transfusion in patients with leukemia. Blood. 1990;75(2):518–23.
Govindarajan R, Baxter D, Wilson C, Zent C. Vancomycin-induced thrombocytopenia. Am J Hematol. 1999;62(2):122–3.
Kenney B, Tormey CA. Acute vancomycin-dependent immune thrombocytopenia as an anamnestic response. Platelets. 2008;19(5):379–83. doi:10.1080/09537100802082280.
Kuruppu JC, Le TP, Tuazon CU. Vancomycin-associated thrombocytopenia: case report and review of the literature. Am J Hematol. 1999;60(3):249–50.
Lee JH, Kim DS, Lee HS, et al. A case of vancomycin-induced thrombocytopenia. Korean J Hematol. 2009;44(4):294–7.
Marraffa J, Guharoy R, Duggan D, et al. Vancomycin-induced thrombocytopenia: a case proven with rechallenge. Pharmacotherapy. 2003;23(9):1195–8.
Mizon P, Kiefel V, Mannessier L, et al. Thrombocytopenia induced by vancomycin-dependent platelet antibody. Vox Sang. 1997;73(1):49–51.
O’Donnell E, Shepherd C, Neff A. Immune thrombocytopenia from vancomycin in orthopedic cement. Am J Hematol. 2007;82(12):1122.
Ortín BP, Solis MA, Ramos VB, et al. Thrombocytopenia in a patient on peritoneal dialysis. Nefrologia. 2008;28(4):453–5.
Pauldine R, Pustavoitau A. Case report: vancomycin-induced thrombocytopenia in a burn patient. Eplasty. 2008;8:e39.
Peel RK, Sykes A, Ashmore S, et al. A case of immune thrombocytopenic purpura from intraperitoneal vancomycin use. Perit Dial Int. 2003;23(5):506–8.
Rocha JL, Kondo W, Baptista MI, et al. Uncommon vancomycin-induced side effects. Braz J Infect Dis. 2002;6(4):196–200.
Ruggero MA, Abdelghany O, Topal JE. Vancomycin-induced thrombocytopenia without isolation of a drug-dependent antibody. Pharmacotherapy. 2012;32(11):e321–5. doi:10.1002/phar.1132.
Shah RA, Musthaq A, Khardori N. Vancomycin-induced thrombocytopenia in a 60-year-old man: a case report. J Med Case Rep. 2009;3:7290. doi:10.4076/1752-1947-3-7290.
Shahar A, Berner Y, Levi S. Fever, rash, and pancytopenia following vancomycin rechallenge in the presence of ceftazidime. Ann Pharmacother. 2000;34(2):263–4.
Winteroll S, Kerowgan M, Vahl C-F, Leo A. Vancomycin-mediated drug-induced immune thrombocytopenia. Transfus Med Hemother. 2004;32(1):20–3.
Zenon GJ, Cadle RM, Hamill RJ. Vancomycin-induced thrombocytopenia. Arch Intern Med. 1991;151(5):995–6.
Dilli D, Oguz SS, Dilmen U. A newborn with vancomycin-induced thrombocytopenia. Pharmacology. 2008;82(4):285–6. doi:10.1159/000163099.
Walker RW, Heaton A. Thrombocytopenia due to vancomycin. Lancet. 1985;1(8434):932.
Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30(2):239–45. doi:10.1038/clpt.1981.154.
George JN, Aster RH. Drug-induced thrombocytopenia: pathogenesis, evaluation, and management. Hematol Am Soc Hematol Educ Program. 2009:153–8. doi:10.1182/asheducation-2009.1.153.
George J, Raskob G, Shah S, et al. Drug-induced thrombocytopenia: a systematic review of published case reports. Ann Intern Med. 1998;129(11):886–90.
Bonfiglio MF, Traeger SM, Kier KL, et al. Thrombocytopenia in intensive care patients: a comprehensive analysis of risk factors in 314 patients. Ann Pharmacother. 1995;29(9):835–42.
Howard CE, Adams LA, Admire JL, et al. Vancomycin-induced thrombocytopenia: a challenge and rechallenge. Ann Pharmacother. 1997;31(3):315–8.
Linder N, Edwards R, MeClead R, et al. Safety of vancomycin with or without gentamicin in neonates. Neonatal Netw. 1993;12(8):27–30.
Wood MJ. Comparative safety of teicoplanin and vancomycin. J Chemother. 2000;12(Suppl. 5):21–5.
Ahmed Y, Sartin C, Umer I, et al. Vancomycin-induced severe asymptomatic immune thrombocytopenia; a rare cause. Southwest Respir Crit Care Chronicles. 2015;3(9):42–5.
Arnold DM, Nazi I, Warkentin TE, et al. Approach to the diagnosis and management of drug-induced immune thrombocytopenia. Transfus Med Rev. 2013;27(3):137–45. doi:10.1016/j.tmrv.2013.05.005.
Lobo N, Ejiofor K, Thurairaja R, Khan MS. Life-threatening haematuria caused by vancomycin-induced thrombocytopenia. BMJ Case Rep. 2015;2015. doi:10.1136/bcr-2014-208192.
Rowland SP, Rankin I, Sheth H. Vancomycin-induced thrombocytopaenia in a patient with severe pancreatitis. BMJ Case Rep. 2013;2013. doi:10.1136/bcr-2013-200830.
Wetzel DR, Njathi CW, Telesz BJ, et al. Thrombocytopenia of unusual etiology in the intensive care unit. J Med Cases. 2013;4(12):792.
Marinho DS, Huf G, Ferreira BL, et al. The study of vancomycin use and its adverse reactions associated to patients of a Brazilian university hospital. BMC Res Notes. 2011;4:236. doi:10.1186/1756-0500-4-236.
Moenster RP, Linneman TW, Finnegan PM, McDonald JR. Daptomycin compared to vancomycin for the treatment of osteomyelitis: a single-center, retrospective cohort study. Clin Ther. 2012;34(7):1521–7. doi:10.1016/j.clinthera.2012.06.013.
Domen RE. Vancomycin-induced cytopenias. Arch Intern Med. 1992;152(2):413–4.
Bougie DW, Wilker PR, Aster RH. Patients with quinine-induced immune thrombocytopenia have both “drug-dependent” and “drug-specific” antibodies. Blood. 2006;108(3):922–7. doi:10.1182/blood-2006-01-009803.
Patel N, VanDeWall H, Tristani L, et al. A comparative evaluation of adverse platelet outcomes among Veterans’ Affairs patients receiving linezolid or vancomycin. J Antimicrob Chemother. 2012;67(3):727–35. doi:10.1093/jac/dkr522.
Rybak M, Lomaestro B, Rotschafer JC, et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm. 2009;66(1):82–98. doi:10.2146/ajhp080434.
Vandecasteele SJ, De Vriese AS. Recent changes in vancomycin use in renal failure. Kidney Int. 2010;77(9):760–4. doi:10.1038/ki.2010.35.
Wilson AP. Comparative safety of teicoplanin and vancomycin. Int J Antimicrob Agents. 1998;10(2):143–52.
Jaksic B, Martinelli G, Perez-Oteyza J, et al. Efficacy and safety of linezolid compared with vancomycin in a randomized, double-blind study of febrile neutropenic patients with cancer. Clin Infect Dis. 2006;42(5):597–607. doi:10.1086/500139.
Kohno S, Yamaguchi K, Aikawa N, et al. Linezolid versus vancomycin for the treatment of infections caused by methicillin-resistant Staphylococcus aureus in Japan. J Antimicrob Chemother. 2007;60(6):1361–9. doi:10.1093/jac/dkm369.
Young LS. Hematologic effects of linezolid versus vancomycin. Clin Infect Dis. 2004;38(8):1065–6. doi:10.1086/382364.
Hsiao SH, Chou CH, Lin WL, et al. High risk of cross-reactivity between vancomycin and sequential teicoplanin therapy. J Clin Pharm Ther. 2012;37(3):296–300. doi:10.1111/j.1365-2710.2011.01291.x.
Rao N, Ziran BH, Wagener MM, et al. Similar hematologic effects of long-term linezolid and vancomycin therapy in a prospective observational study of patients with orthopedic infections. Clin Infect Dis. 2004;38(8):1058–64. doi:10.1086/382356.
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Mehdi Mohammadi, Zahra Jahangard-Rafsanjani, Amir Sarayani, Molouk Hadjibabaei, and Maryam Taghizadeh-Ghehi have no conflicts of interest that are directly relevant to the content of this article.
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Mohammadi, M., Jahangard-Rafsanjani, Z., Sarayani, A. et al. Vancomycin-Induced Thrombocytopenia: A Narrative Review. Drug Saf 40, 49–59 (2017). https://doi.org/10.1007/s40264-016-0469-y
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DOI: https://doi.org/10.1007/s40264-016-0469-y