Discussion
DITP diagnosis is complicated owing to multiple causes of acquired
thrombocytopenia in ICU patients. Among thrombocytopenic patients who
present with severe infection, DITP is a very important distinction to
make. Firstly, we roughly excluded primary blood diseases and autoimmune
diseases through medical history and laboratory examination results.
Then we focused on the infection and medication factors. As a priority
factor suspected to thrombocytopenia, the severe infection had been
alleviating (Table 1) while PLT decreased. Thus, vancomycin caught our
attention. It offered further clinical evidence as thrombocytopenia
appeared when vancomycin was re-administered, and disappeared as
vancomycin discontinued.
Thrombocytopenia was occurred in 7.1 % patients treated with
vancomycin18, however, it could be easily overlooked
as its description and incidence have not been labelled. There were some
case reports of vancomycin-induced thrombocytopenia before. Back in
1985, Walker presented a 48-year-old female patient with secondary
peritonitis after peritoneal dialysis. During the treatment period,
vancomycin (500mg, i.v.gtt.) was given first, followed by
intraperitoneal injection of 120 mg/day, and the patient showed a
significant thrombocytopenia 6 days later.21 Howard
reported in 1997 that a 58-year-old male patient admitted to hospital
due to osteomyelitis caused by MRSA, who manifested thrombocytopenia
after vancomycin administration.22 In 2013, a
systematic review including pediatric patients (<18 years
old)23 found that 32 substances had potential
pathogenic effects in thrombocytopenia, including vancomycin (in 3 of 21
cases). In 2017, 30 case reports with 30 patients were included in a
scoping review reported vancomycin-induced
thrombocytopenia.24 It can occur on the 1st to 10th
days after drug exposure. The time window for the platelet count
dropping to the lowest point ranged from 4 hours to 10 days after drug
exposure. The median platelet count was often dropping < 20 ×
109/L25,26, with those <2
× 106/L to 1 × 108/L occurred
bleeding.27 The degree and occurring time (the time
for the platelet count to drop to 7 × 109/L was 2 days
of vancomycin use) of thrombocytopenia in our case was basically
consistent with the previous reports.
Significantly, it shows that vancomycin causing thrombocytopenia by
accelerating platelet destruction via drug-dependent platelet reactive
antibodies. Compared with linezolid, another agent commonly used for
MRSA, vancomycin-induced immunemediated thrombocytopenia occurs more
rapidly, while linezolid-induced
mye-losuppression-mediated
thrombocytopenia occurs for a longer time (usually 2
weeks).28 Previous experience showed that the
incidence of thrombocytopenia caused by linezolid was high. Notably,
based on our systematic review, there was no significant difference in
leading thrombocytopenia (defined as platelets<150 x
109/L) between vancomycin and linezolid (RR=1.01,
95%CI=0.64-1.58).
Usually, DITP was alleviative after vancomycin withdrawal, with the
severe one required platelet infusion.24 There is no
evidence for the efficacy of immunosuppression in treating DITP. In
previous reports, vancomycin was discontinued in 29 of 30 patients, and
platelet counts in 17 patients recovered within 5-6
days.25, 26 In this process, patients’ infection
control needs to be taken into account when discontinuing vancomycin. In
our case, luckily, the patient was definitely infected with Escherichia
Coli, and we decisively discontinued vancomycin after thrombocytopenia
was observed again. As thrombocytopenia leads to an increased risk of
bleeding, the transfusion of platelets was a common management though it
did not always result in expected increases in platelet counts of
affected patients (67% transfusion resistant of 20
patients).24 In this case, platelet infusion was given
when platelet count was at 8 × 109/L and 14 ×
109/L, and platelet 2U infusion was given at 3 ×
109/L.
There are some limitations in this study. Firstly, only postoperative
drainage fluid was collected for culture specimens after starting
antimicrobial therapy, but no blood samples obtained before at
emergency. We should continue to improve the implementation of sepsis
bundle, emphasizing the importance of retaining blood samples to monitor
and analyze the bacteria before the empirical antibiotic
treatment.27 Secondly, we couldn’t confirm whether the
cause was DITP or not, as our hospital doesn’t perform tests of
drug-dependent platelet reactive antibodies.29 In
order to better identify DITP and improve patient prognosis, it is
suggested to improve the accessibility of platelet reactive antibody
technology in the future. Thirdly, only three major databases were
searched for systematic reviewed, therefore some literatures might be
overlooked.