Pancytopenia is a triad of findings which is characterized by decrease in all three major formed elements of blood. It can be defined as hemoglobin (Hb):<9 g/dl, total leukocyte count (TLC) <4000/mm3, and platelets <10,000/mm3.
There can be multiple etiological factors implicated in the causation of the same. These factors can be broadly classified into the reduction of blood cell production, bone marrow infiltration by abnormal cells, bone marrow suppression, abnormal hematopoiesis with cell destruction, antibody-mediated cell destruction, and cell sequestration in the reticuloendothelial system.
A wide array of factors which attribute to the same include infections (malaria, leishmaniasis, AIDS, etc.), toxins, autoimmune diseases, neoplasia, storage disorders, etc.[2–4]
Certain drugs have also been notoriously known to cause pancytopenia by various mechanisms such as bone marrow suppression, immune-mediated idiosyncratic reaction, and dose-dependent effect. Some examples include chloramphenicol, thiazides, sulfonamides, cytotoxics, phenytoin, etc.[2,5] Carbamazepine is one of the rare causes of pancytopenia.[2,5,6]
The Food and Drug Administration approved indications for carbamazepine include partial seizures, generalized tonic-clonic seizures, mixed seizure patterns, and pain associated with trigeminal neuralgia and acute manic and mixed manic states.[7–9]
Carbamazepine has also been used as an adjunctive treatment in patients with schizophrenia who do not achieve satisfactory treatment responses with just antipsychotic drugs.[10,11]
There are multiple proposed mechanisms of action of carbamazepine which include sodium channel blockade, interaction with calcium and potassium channels, reducing glutamate release, enhancing effect of gamma aminobutyric acid and decreasing dopamine and noradrenaline turnover.[9,12]
Common side effects of carbamazepine include nausea, vomiting, diarrhea, dizziness, diplopia, hyponatremia, headaches, dry mouth, and edema. Around 3% patients would develop generalized erythematous rash.
Serious hematological disorders may also be rarely associated with the administration of carbamazepine, including pancytopenia, aplastic anemia, and thrombocytopenia, with estimated incidence rate that ranges from 1:20,000.
In this case report, we wish to discuss a known case of schizophrenia on adjunctive carbamazepine therapy who presented to the medical intensive care unit (MICU) with pancytopenia and its sequelae which resolved on tapering off carbamazepine.
A 29-year-old unmarried female, who is a known case of schizophrenia for the past 10 years, was admitted to the MICU of our institute.
She was on tablet risperidone 6 mg, tablet aripiprazole 15 mg, and tablet carbamazepine 800 mg for the past 1 year as prescribed by a psychiatrist from another institute. The patient had presented with complaint of gradually progressive generalized weakness, loss of appetite, lethargy, and giddiness for the past 6 months, with increasing severity from the past 1 month, with a history of fever for 4 days. There was no history of any chronic illness and substance use. A family history of pancytopenia was absent.
General physical examination revealed pallor and generalized swelling all over the body. Pulse rate was 102/min, blood pressure 78/40 mmHg, respiratory rate 16/min, temperature 102°F, and SpO2 97% on room air. Systemic examination was within normal limits.
On laboratory investigations, there was severe anemia (Hb: 4.4g%), thrombocytopenia (60,000/mm3), and decreased TLC (3940/mm3). Urine routine microscopy revealed 4–6 pus cells/high-power field. Malaria serology, dengue serology test, Widal test, and viral markers tested negative. Renal function test, liver function test, and serum electrolytes were within normal limits. Vitamin B12 and B9 levels were low (82 pg/ml and 1.8 ng/ml, respectively). Based on the above clinical and laboratory data patient was diagnosed with carbamazepine-induced pancytopenia.
During hospitalization, the following medications were prescribed; tablet folic acid 5 mg once daily (OD), tablet calcium + Vitamin d3 (500 mg + 250IU) OD, tablet B complex OD, injection of Neurobion forte two ampules intravenous of (IV) in normal saline (NS), three units packed red blood cells were transfused, IV fluids (NS altering with Ringer Lactate) were being transfused hourly, to treat hypotension, and injection noradrenaline four ampules were administered in NS. A combination injection of piperacillin and tazobactam was administered for 5 days and fever had then subsided. Subsequently, the tablet carbamazepine was tapered off in 1 week. After cessation of the drug, the platelet count showed a significant improvement to 113, 000/mm3, Hb 8.3 g%, and TLC count 4650/mm3.
In the above-discussed case, after excluding all common possible causes of pancytopenia, carbamazepine-induced pancytopenia was thought of, after which, on tapering off carbamazepine, the blood counts gradually returned to normal levels.
The mechanism by which carbamazepine may induce pancytopenia has been postulated to be an immune-mediated idiosyncratic action where patients on carbamazepine tend to develop drug-dependent reactive antibodies.[2,13]
To our knowledge, there are few studies which have reported carbamazepine-induced pancytopenia.[5,14,15]
In a case study by Mathur et al., A known patient of seizure disorder had been prescribed carbamazepine 400 mg/day for 1 year. She developed pancytopenia (Hb: 5.4 gm%, white blood cell [WBC]: 3960/mm3, and platelet count: 35,000/mm3). Carbamazepine was discontinued, and symptomatic management was provided. The antiepileptic drug was changed to tablet phenytoin, and her counts had improved.
In a study by Prajapati et al., A known case of schizophrenia was on carbamazepine 200 mg/day for 2 months. She was also on tablet risperidone 4 mg/day, tablet trihexyphenidyl 4 mg/day. On developing pancytopenia (Hb: 3.7 gm%, WBC: 3900/mm3, and platelet count: 59,000/mm3), carbamazepine was stopped and she was managed conservatively, after which her counts improved.
Jeong et al. had discussed a traumatic brain-injured patient who developed pancytopenia (Hb: 7.9 gm%, platelet count: 54,000/mm3) just after 3 weeks of taking carbamazepine for prophylactic management of seizure. On discontinuation, patient’s counts had returned to normal (Hb: 12.5 gm%, WBC: 6120/mm3, and platelet count: 251,000/mm3).
In our case, the patient was on carbamazepine 800 mg/day for the past 1 year, which is much higher dose than the cases discussed above. There were no past reports of blood monitoring available during the titration of the medication. If there would have been regular monitoring, the decreasing blood counts could have been detected early.
Thus, it becomes essential that patients who are taking carbamazepine should take medications as prescribed and get regular monitoring of complete blood count (CBC), which often gets neglected apart from the baseline workup of CBC. By ensuring such simple preventive measures, such serious and unusual side effects may be averted through early detection of warning signs.
The patient was not rechallenged with carbamazepine to reconfirm the diagnosis after the complete resolution of pancytopenia as the patient and family members refused to take the drug because of fear of impairment in the quality of life.
While it is necessary for clinicians to rule out common causes of pancytopenia, they should also keep in mind this unusual and serious side effects of carbamazepine. Psycho educating patients regarding regular blood monitoring, the importance of adherence and early warning signs holds considerable importance as it enhances their compliance for regular monitoring and to take the medication as prescribed.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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