Thrombocytopenia in refractory delirium tremens: A cause or a consequence?

Dear Editor, Recent interest has been growing toward the consideration of thrombocytopenia as a potential prognostic marker determining the progression of noncomplicated to complicated alcohol withdrawal or delirium tremens (DT). Refractory DT (RDT) can be termed if the symptoms are not controlled after 50 mg of diazepam or 10 mg of lorazepam in the first hour or diazepam (>200 mg) or lorazepam (>40 mg) in the first 3–4 h of management, as cited in the article.[1,2] However, no such finding of thrombocytopenia has been reported in RDT and we report such cases. A 39-year-old married male, a retired veteran, presented to us with history of alcohol dependence and alcohol withdrawal symptoms from the past 1 day. In alcohol, the patient gave a history of consuming beer, approximately 300–400 mL, rum = 90–120 mL per day, from the past 11 years, whiskey = approximately 300–500 mL per day, regular, from the past 3 years, and last usage was 2 days before. The patient also had a medical history of alcohol-induced pancreatitis and hepatitis B. During admission, he was anxious with bilateral tremors, and investigations (complete blood count, serum electrolytes, liver function test, renal function test, blood sugar, and triple serology) were sent. The patient was then prescribed an injection of lorazepam 4 mg intravenously (i.v.) but before receiving it, he had an episode of the generalized tonic-clonic seizure (GTCS) for 30 s, and injection of lorazepam 8 mg i.v. stat was given, just 4 min later, the patient again had an episode of GTCS for 30 s and an injection of lorazepam 4 mg i.v. was given stat. seizures were controlled and the Clinical Institute Withdrawal Assessment of Alcohol scale (CIWA-Ar) was 17. Then, the patient received 48 mg of injection lorazepam i.v., an injection of thiamine 1000 mg/day i.v. in normal saline (NS) on day 1, tablet of melatonin 20 mg at bedtime, with frequent vitals monitoring. Meanwhile, reports of his baseline investigations arrived, as presented in Table 1. Urine drug screening for other substances was negative. On day 2, CIWA-Ar = 18, with agitation, bilateral tremors and was not oriented to place and had received an injection of lorazepam 68 mg i.v., injection of haloperidol 2.5 mg intramuscular (i.m.) for agitation, tablet melatonin 20 mg bedtime, and injection of thiamine 1000 mg/day i.v. in NS. Despite this, the patient had not slept and got worsened the next day (CIWA-Ar = 22) and was given an injection of lorazepam 136 mg i.v., injection of midazolam 3cc i.v., injection of haloperidol 2.5 mg i.m. in the morning and afternoon, injection of thiamine 1000 mg/day i.v. in NS, on day 3. On the next day morning, light sedation was achieved. Meanwhile, a non-contrast computed tomography brain was performed, which was normal, and repeat blood investigations were performed, presented in Table 1. On the next day, he was cooperative, oriented to time, place, and person (CIWA-Ar = 8 → 4), and was shifted to oral medications. Repeat blood counts were sent on day 7 in Table 1, and he was subsequently discharged with tapering of medications.Table 1: Blood investigation resultsBecause of his chronic alcohol usage history, there is a suppression of gamma-aminobutyric acid GABA receptor neurotransmission and upregulation of N-methyl-d-aspartate receptor activity, which becomes evident during withdrawal causing excitotoxicity by glutamate, in addition to the role of kindling phenomena.[3] Chronicity of alcohol use can lead to confirmational structural change in GABA receptors, thus requiring a high dose of benzodiazepine to control withdrawal symptoms.[2,4] Thrombocytopenia can be seen in chronic alcohol users in the presence of deranged liver enzymes, but its presence with normal liver function enzymes needs exploration of other medical and substance use comorbidities, which was absent in our case. The previous study[5] has shown thrombocytopenia as a cause of alcohol-induced hepatotoxicity, but in our case, we did not find a hepatic system to be much involved as values of alkaline phosphatase, aspartate transaminase, and alanine transaminase were within range. Thus, the involvement of the hepatic system could not be considered as the potential cause of thrombocytopenia. Even the cause of bone marrow suppression due to chronic alcoholism is ruled out, as other blood parameters are near range. A study has shown high sensitivity and specificity of thrombocytopenia for the development of severe alcohol withdrawal symptoms,[5] instead of liver function test and carbohydrate-deficient transferrin.[5-7] From baseline till the control of withdrawal symptoms, there has been an increase in platelet count, a phenomenon known as reverse thrombocytosis, which has been demonstrated earlier[8] and is present in our case. All these factors pointing toward understanding it as a cause or consequence of thrombocytopenia in alcohol-induced delirium need a detailed exploration for considering it as a potential biomarker for assessing withdrawal severity. Declaration of patient consent We obtained written informed consent from the patient and attendant regarding publishing this data maintaining confidentiality of the patient in all respects. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.