Sex: M
Vaccine: UNK, UNK
Symptoms: Agranulocytosis, Drug screen negative, HIV test negative, Metabolic function test normal, Neutropenia
Clinical narrative: Agranulocytosis; neutropenia; This case was reported in a literature article and described the occurrence of agranulocytosis in a 56-year-old male patient who received Flu Seasonal QIV Dresden  Co-suspect products included clozapine (Clozaril) for schizophrenia.   Concurrent medical conditions included hypertension, type ii diabetes mellitus, chronic obstructive pulmonary disease and schizophrenia (treated with clozapine (Clozaril) for more than 13 years). Concomitant products included simvastatin, acetylsalicylic acid (Aspirin), metformin hydrochloride (Metformin), metoprolol, lisinopril, haloperidol and benzatropine (Benztropine).   On 9th November 2018, the patient received Influenza vaccine Quadrivalent 2018-2019 season. On an unknown date, the patient started Clozaril at an unknown dose and frequency. On 2nd February 2019, 85 days after receiving Influenza vaccine Quadrivalent 2018-2019 season, the patient experienced agranulocytosis (serious criteria hospitalization, GSK medically significant and life threatening) and neutropenia (serious criteria hospitalization, GSK medically significant and life threatening). Clozaril was discontinued (Dechallenge was positive). On an unknown date, the outcome of the agranulocytosis and neutropenia were recovered/resolved.   The reporter considered the agranulocytosis and neutropenia to be possibly related to Influenza vaccine Quadrivalent 2018-2019 season.  Additional iformation was provided.  This case was reported in a literature and described the occurrence of severe clozapine-induced agranulocytosis (clozapine-induced neutropenia) in a 56-year-old male patient who was vaccinated with unspecified influenza vaccine (manufacturer unknown) for prophylaxis.   The patient's past medical history (PMH) included hypertension, type 2 diabetes mellitus, chronic obstructive pulmonary disease (COPD), and a history of schizophrenia for which he had been treated with clozapine (Clozaril) for more than 13 years. For more than 13 years of treatment with clozapine, the patient white blood cells (WBC) was stable. The patient had negative for human immunodeficiency virus (HIV). The patient was on active medications included simvastatin, metoprolol, lisinopril, aspirin, metformin, haloperidol, and benztropine, all of which he had been taking for more than 5 years with no adverse effect. No information on patient's family history was provided.  On 9 November 2018, the patient received unspecified influenza vaccine (administration route and site unspecified, dosage unknown; batch number not provided). The age of vaccination was not provided. It was reported that on 9 November 2018, the patient absolute neutrophil count (ANC) was 4100 cells/µl (normal value: 2,000-7,900 cells/µl).  On 7 December 2018, the patient ANC count was 3,400 cells/µl and on 4 January 2019, the patient ANC count was found to be 2400 cells/µl. On 1st, February 2019, the patient presented to the general medicine clinic with an acute drop of his white blood count (WBC) and at the current presentation ANC was reported to be 200 cells/µl. On 2nd February 2019, the patient ANC count was 200 cells/µl.  Review of systems was negative for any new symptoms, including fever, chills, asthenia, cough, or sore throat. Physical examination was unremarkable. The patient blood pressure was 136/99 mm Hg, the heart rate was 86 beats/min, and temperature was 97.2 deg. F. The patient was sent to the emergency department and was admitted. An HIV test, urine toxicology, and a complete metabolic panel were all unremarkable. On 5 February 2019, the patient ANC was measured and found 300 cells/µl and on same day clozapine was stopped. ANC was monitored closely after stopping the clozapine. On 6 February 2019, the patient ANC was found to be 200 cells/µl and on same day, the patient was cleared by the hematology team for discharge to follow-up as an outpatient. On 7 February 2019, the patient ANC was 100 cells/µl. On 8 February 2019, the patient ANC was 300 cells/µl. On 11 February 2019, the patient ANC was 700 cells/µl. On 13 February 2019, the patient ANC was 800 cells/µl. On 15 February 2019, the patient ANC was 400 cells/µl. On 19 February 2019, the patient ANC was 300 cells/µl. On 21 February 2019, the patient ANC was 400 cells/µl. On 3 April 2019, 7 weeks later, the patient ANC normalized to 4600 cells/µl, but the patient had a relapse of psychosis and had to be admitted to the psychiatric unit.  Treatment was unknown.  This case has been considered serious due to life threatening/hospitalisation.  The author's commented "We present the case of a late-onset of sudden severe agranulocytosis following an influenza vaccine, after more than 156 months of stable neutrophil counts on clozapine. After an exhaustive history and review of the patient chart, the only new event preceding the decline in WBC was the influenza vaccine in the previous seven weeks. Seven weeks after stopping clozapine, the ANC returned to normal. After the flu vaccine, there was a constant drop in the ANC. The likelihood that the flu vaccine was the triggering factor was considered because the patient had been stable for more than a decade on clozapine and suddenly experienced this drastic decline in ANC after being vaccinated. In view of the event sequence, it is reasonable to think that the influenza vaccine might have been the triggering event for the severe agranulocytosis in our patient taking clozapine.  The author's concluded "Clinicians must keep in mind that agranulocytosis can occur at any time during the treatment course with clozapine and may wish to increase the frequency of hematologic surveillance following an influenza vaccine or even consider a risk-benefit approach. Considering the importance of the influenza vaccination and the seriousness of agranulocytosis, further studies were needed to elucidate a potential increase in the risk of severe neutropenia in patients on clozapine who take the influenza vaccine.      Lab Comments: An HIV test, urine toxicology, and a complete metabolic panel were all unremarkable.