A 64-year-old male patient was admitted to hospital on 21 April 2021 (Day 1, hereafter referred to as D1) with 3-day paroxysmal abdominal cramps, accompanied by diarrhea, nausea, and vomiting. The diagnosis was transverse colon perforation on admission, with rectal mass, septic shock, and hypokalemia. An emergency surgery was performed to repair the laparotomy perforation as well as radical treatment of rectal cancer. After the operation, he was transferred to an intensive care unit (ICU) (D1). The scores of the sequential organ failure assessment, acute physiology and chronic health evaluation, and Richmond agitation-sedation scale were 8, 19, and -2 scores, respectively. To treat sepsis, ICU physicians implemented bundle strategies including antimicrobial therapy (imipenem and cilastatin sodium injections, 0.5 g q6h), fluid resuscitation (20% human albumin, 40 g; crystoloid solution, 3,000 ml), and sedation therapy (remifentanil, propofol, and midazolam).
During the ICU hospitalization (D1-D9), his blood routine examinations, body temperature, coagulation, procalcitonin, renal, and liver function laboratory markers were measured, as shown in Table 1. On D2, an operative recording showed a serious fecal contamination in his abdominal cavity. According to the 2019 epidemiological data of the surgical system in our hospital (among 23 samples of Gram-positive cocci isolated from blood bacterial cultures, there were 5 samples of Enterococcus faecium and 1 sample of Enterococcus faecalis), we considered the possible risk of bloodstream infection of Enterococcus faecium or Enterococcus faecalis; thus, vancomycin (1 g, q12 h) was administrated intravenously. Here, we used a VCM-TDM tool (Pharmvan, http://www.pharmado.net/) to predict the appropriate vancomycin dosage with a minimal concentration (Cmin) of 10-20 mug/ml; and follow-up monitoring of Cmin also proved its feasibility (D4, 11 ug/ml). Unexpectedly, his platelet count (7 x 109/L) severely decreased on D4 (Figure 1).
To find the causes of thrombocytopenia, as Figure 2 shows, firstly, we excluded the possibility of laboratory error or pseudothrombocytopenia by examining the peripheral blood smear for platelet clumping and repeating the platelet count test. Then, we roughly excluded hematological disease and autoimmune diseases, according to the blood routine test (Table 1) combined with medical history and laboratory markers. For instance, myelodysplastic syndrome or nutritional disorder rarely presents as isolated thrombocytopenia; usually, it combines with the abnormal level in laboratory markers, such as serum iron, vitamin B12, folic acid, reticulocyte count, corpuscular volume, and megakaryocytes. However, no exceptions in above tests occurred in this patient. After that, the result of sonography helped us exclude an enlarged spleen, which might be induced by liver cirrhosis or exhibited as a common clinical manifestation in such primary immune diseases as primary immune thrombocytopenia (ITP). Yet, an alcohol naive status and a negative result of liver ultrasound helped us further exclude chronic liver diseases. Besides, primary ITP usually persisted for months or years and could be detected in the medical history. We further excluded thrombotic microangiopathy (TMA) as there was no indication for acute kidney injury or hemolytic anemia. Although total bilirubin (TBIL) was elevated, as shown in Table 1, it was dominated by direct bilirubin instead of indirect bilirubin, and fragmented red blood cells were not found in the blood smear. Meanwhile, hepatic failure and disseminated intravascular coagulation (DIC) were put aside according to liver function laboratory and coagulation markers. Although there were fluctuations in coagulation markers, the trend was not synchronized with the platelet count trend, and the protamine anticoagulant test (3P test) suggested a low probability of DIC. Thus, thrombocytopenia was a major concern, which might be caused by infection or medications. After transfusion of platelets (1 U) and blood cells (2 U) on D4, his platelet count recovered a little (26 x 109/L). However, it went down again in the morning of D5 (14 x 109/L). Patients with severe infection, such as sepsis, generally have laboratory abnormalities indicative of systemic infection (leukocytosis or neutropenia) and ongoing coagulation (prolonged prothrombin time and activated partial thromboplastin time, low fibrinogen, and elevated D-dimer). In this case, we found that the patient's severe infection was alleviated by the above markers during D1-D5. Therefore, thrombocytopenia was less likely caused by infection, and we started to focus on medications. Among all the medications used between D1-D5, there was no administration records of systemic heparin or linezolid, and antitumor therapy had not been started. Vancomycin aroused suspicion as a previous study had shown that it could cause thrombocytopenia at the initial exposure without prior sensitization. Thus, vancomycin was discontinued on D5 in the morning (the overall diagnostic diagram is shown in Figure 2), and a platelet transfusion (1U) was given to prevent hemorrhage.
In the evening of D5, as the body temperature increased to 38.7 C, the patient had to be re-administered vancomycin. As a result, his platelet count reduced from 61 x 109/L to 3 x 109/L within 8 h rapidly. He had to receive another platelet (2 U) transfusion in the morning of D6. As the drainage fluid culture suggested only a extended spectrum beta-lactamase-negative (ESBL-) Escherichia coli infection, we completely discontinued vancomycin but kept the patient on imipenem and cilastatin sodium. The platelet count returned to 135 x 109/L on D7 and did not drop again after that. He was transferred back to the general ward after being extubated (D9). On D14, he stopped using antibiotics and was discharged with a better health condition. According to the Naranjo adverse reaction evaluation scale (Table 2), the total score was 6, and the relationship between vancomycin and thrombocytopenia was judged as "probable."