Severe thrombocytopenia caused by vancomycin in the intensive care unit: a case report and systematic review

Guanru Wang ^{1a, 2†}, Xiaoxiao Li ^{1a, 2†}, Qinggang Ge^1b, Chao Li ^1b, Na He ^1a,2, Peng Yao ², Chuhui Wang^{1a, 2}, Min Yi ^1b, Zongyu Wang^1b, Luwen Shi ²*, and Rongsheng Zhao^{1a, 2}*

1 a Department of Pharmacy, b Department of Intensive Care Unit, Peking University Third Hospital, Beijing 100191, China

2 Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China

*Correspondence: Lu-wen Shi MHPE, Email: Shilu@bjmu.edu.cn, Add: 38 Xueyuan Rd., Haidian District, Beijing, P. R. China (100191), Tel: 86-10-82265740

Rong-sheng Zhao Ph.D., Email: zhaorongsheng@bjmu.edu.cn, Add: 49 North Garden Rd., Haidian District, Beijing, P. R. China (100191), Tel: 86-10-82265810

† These authors contributed equally to this work.

Acknowledgments : We sincerely thank the patient for willing to share his therapy information and thank the multidisciplinary therapy team for offering the profound skill and high-quality patient care.

Conflicts of Interest : The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Abstract : Thrombocytopenia can cause substantial morbidity and mortality in critically ill patients. There are multiple etiology factors and various mechanisms associated with thrombocytopenia, of which drug-induced thrombocytopenia (DITP) deserves attention. Herein, we describe a case of severe thrombocytopenia during intensive care unit (ICU) hospitalization that was probable to be associated with vancomycin. In addition, clinical studies evaluating thrombocy-topenia caused by vancomycin were systematically reviewed and 6 studies with acceptable quality were included and analyzed. By revealing the process of identifying this case of DITP and re-viewing relevant clinical studies, a risk alert of vancomycin related severe hematotoxicity should be focused on.

Keywords: Vancomycin; thrombocytopenia; adverse drug reaction; critically illness; systematic review

Thrombocytopenia is defined as a platelet count below the lower limit of normal (<150 × 10⁹/L for adults). Degrees of thrombocytopenia can be further subdivided into mild (100 × 10⁹/L to 150 × 10⁹/L), moderate (5 × 10⁹/L to 9.9 × 10⁹/L), and severe (under 5 × 10⁹/L). In the setting of immune thrombocytopenia, a platelet count <3 × 10⁹/L is considered to represent severe thrombocytopenia.¹ Thrombocytopenia can cause substantial morbidity and mortality in critically ill patients. The incidence of thrombocytopenia in adult critically ill patients can reach 8.3% to 67.6%.² Meanwhile, thrombocytopenia is associated to significantly increased bleeding and blood transfusion and even mortality events.^3,4

There are multiple etiology factors and various mechanisms that can cause thrombocytopenia, and clinical decision-making is quite complicated. Common causes of thrombocytopenia are bone marrow suppression, primary hematological diseases, autoimmune diseases, severe infections and medications. As an increasingly cause of isolated thrombocytopenia, drug-induced thrombocytopenia (DITP) can be attributed to foods and herbal remedies besides medications.⁵Among the intensive care unit (ICU) patients with new-onset thrombocytopenia, medications cause can account for 16%.⁶ DITP is an important clinical problem for physicians, of which drug-dependent anti-body-mediated platelet destruction is one of the main mechanisms. The most implicated medications include quinine, sulfamethoxazole, penicillin and linezolid, etc.⁷ Vancomycin is used for gram-positive cocci infections, especially in methicillin-resistant staphylococcus aureus (MRSA) infection.⁸ Severe renal impairment, hypersensitivity reactions and infusion-related reactions caused by vancomycin have been widely recognized in clinical practice, while adverse reactions such as agranulocytosis and thrombocytopenia are rare and can easily be ignored.

Herein, we present a case with probable vancomycin-induced severe thrombocytopenia during ICU hospitalization. We aim to provide evidence-based references for the diagnosis and treatment of vancomycin-induced thrombocytopenia in critically ill patients.