Evidence of myelosuppression has been negatively correlated with patient outcomes following cases of high dose sulfur mustard (SM) exposure. These hematologic complications can negatively impact overall immune function and increase the risk of infection and life-threatening septicemia. Currently, there are no approved medical treatments for the myelosuppressive effects of SM exposure.

Leveraging a recently developed rodent model of SM-induced hematologic toxicity, post-exposure efficacy testing of the granulocyte colony-stimulating factor drug Neupogen® was performed in rats intravenously challenged with SM. Before efficacy testing, pharmacokinetic/pharmacodynamic analyses were performed in naïve rats to identify the apparent human equivalent dose of Neupogen® for efficacy evaluation.

When administered 1 d after SM-exposure, daily subcutaneous Neupogen® treatment did not prevent the delayed onset of hematologic toxicity but significantly accelerated recovery from neutropenia. Compared with SM controls, Neupogen®-treated animals recovered body weight faster, resolved toxic clinical signs more rapidly, and did not display transient febrility at time points generally concurrent with marked pancytopenia.

Collectively, this work corroborates the results of a previous pilot large animal study, validates the utility of a rodent screening model, and provides further evidence for the potential clinical utility of Neupogen® as an adjunct treatment following SM exposure.

To minimise infection during COVID-19, the clozapine haematological monitoring interval was extended from 4-weekly to 12-weekly intervals in South London and Maudsley NHS Foundation Trust.

To investigate the impact of this temporary policy change on clinical and safety outcomes.

All patients who received clozapine treatment with extended (12-weekly) monitoring in a large London National Health Service trust were included in a 1-year mirror-image study. A comparison group was selected with standard monitoring. The proportion of participants with mild to severe neutropenia and the proportion of participants attending the emergency department for clozapine-induced severe neutropenia treatment during the follow-up period were compared. Psychiatric hospital admission rates, clozapine dose and concomitant psychotropic medication in the 1 year before and the 1 year after extended monitoring were compared. All-cause clozapine discontinuation at 1-year follow-up was examined.

Of 569 participants, 459 received clozapine with extended monitoring and 110 controls continued as normal. The total person-years were 458 in the intervention group and 109 in the control group, with a median follow-up time of 1 year in both groups. During follow-up, two participants (0.4%) recorded mild to moderate neutropenia in the intervention group and one (0.9%) in the control group. There was no difference in the incidence of haematological events between the two groups (IRR = 0.48, 95% CI 0.02–28.15, P = 0.29). All neutropenia cases in the intervention group were mild, co-occurring during COVID-19 infection. The median number of admissions per patient during the pre-mirror period remained unchanged (0, IQR = 0) during the post-mirror period. There was one death in the control group, secondary to COVID-19 infection.

There was no evidence that the incidence of severe neutropenia was increased in those receiving extended monitoring.

We discuss the case of a 75-year-old man with no psychiatric history, presenting with complex auditory hallucinations, both commentary and imperative, delusions of persecution and prejudice, severe anxiety, modified behaviour, and altered sleep patterns.

The patient was started on oral risperidone, with favourable evolution of symptoms after reaching a daily dose of 3 mg/day. After three weeks of treatment, the laboratory results showed a low number of neutrophils. Interdisciplinary approach and examinations which included both clinical and paraclinical evaluation concluded that another cause of neutropenia was highly unlikely.

The patient was switched to olanzapine, with gradually increasing doses up to 10 mg/day. A significant improvement of the neutrophils’ level was noticed, with a return to normal parameters after a few days. Nevertheless, the clinical course was unfavourable, with reoccurrence of auditory hallucinations and delusions in two weeks’ time. Decision to rechallenge was made, with careful monitoring of the blood test results, particularly neutrophil levels. Risperidone was started at low doses of 0.5 mg/day and gradually increased up to 2 mg/day.

Seven days after risperidone reinitiation laboratory tests showed normal absolute neutrophil count. However, another week later, neutrophils fell again out of the normal range.

The patient was discharged with haloperidol, with adequate control of symptoms and no adverse reactions.

No significant relationships.

Valproic acid (VPA) is considered a well-tolerated antiepileptic drug used in Bipolar Disorder as a mood stabilizer. Nevertheless, VPA has been related to several adverse effects. Neutropenia is included as a potential adverse effect, although in clinical practice it is not often measured with regularity.

To report a case of a patient with Bipolar Disorder type 2 and Personality Disorder Cluster B treated with VPA with a neutropenia caused by VPA.

A 61-year-old woman assists to the outpatient psychiatric unit in order to a pharmacological treatment adjustment. A blood test is performed showing a decrease in the levels of neutrophiles in comparison with previous tests. Psychiatric history is revised finding and association between the prescription of VPA and the reduction of neutrophile levels. When this drug was removed, neutrophile levels had increased again up to normal levels.

Due to the relationship between neutropenia and VPA treatment, we decided to discontinue this drug. At the beginning the patient doesn’t agree with the withdrawal of VPA treatment due to its effectiveness in her mood stabilization. Psychoeducation sessions are performed in order to explain risk and benefits of potentials treatment alternatives versus maintaining the same prescription. Finally the patient accepts the switch of the mood stabilizer treatment to oxcarbazepine with a good tolerability and effectiveness.

Periodical blood test monitoring is needed in order to study adverse effects as neutropenia in patients with VPA treatment.

The author has received support from Janssen-Cilag, Otsuka-Lundbeck, Italfármaco, Angelini Pharma and Casen Recordati; and declares no support related to the subject of this article.

Clozapine is the most effective antipsychotic for treatment resistant schizophrenia but adverse reactions to clozapine include neutropenia. Patients with COVID-19 infection frequently experience lymphopenia, but not neutropenia.The impact of clozapine treatment in the presence of COVID-19 is unknown

Show 2 cases of neutropenia in patients treated with long-term clozapine during COVID-19 infection.

Subjects: 48 admitted patients to a long-stay psychiatric unit. COVID-19 infection confirmed by positive nasopharyngeal swab for viral ribonucleic acid of SARS-CoV-2. Hematological controls between March and April 2020.

16 patients (33%) treated with clozapine.18 patients (37’5%) had COVID-19 infection, of which 5 (10’4%) were treated with clozapine; 2 presented neutropenia. 1- 56-year-old woman diagnosed with schizophrenia on clozapine since 2009. Begins to have a dry cough and fever with positive COVID-19 swab (day 0). Slight leukopenia without neutropenia was observed on day 1. On day 7, neutropenia was observed with an absolute neutrophil count (ANC) of 1100. We decided to suspend clozapine and to initiate daily hematological controls. The ANC on day 8 was 970. Over the next few days the ANC will progressively improve until neutropenia resolved (day 22). 2- 55-year-old woman who required a transfer to a general hospital because of respiratory complications from COVID-19. She presented significant leukopenia (1’01x 10^3/uL) and neutropenia (ANC 100). Clozapine was not withdrawn. She was treated with granulocyte colony-stimulating factor.

An urgent full blood count will be required to exclude neutropenia with appropriate action. Further research will be needed to clarify the possible relationship between COVID-19, clozapine and neutropenia.

No significant relationships.

Clozapine is among the most effective antipsychotics used for treatment resistant schizophrenia. Adverse reactions to clozapine include neutropenia. Case series report that clozapine-treated patients with COVID-19 have no documented neutropenia.

We sought to investigate the potential adverse effect of coronavirus disease (COVID-19) in patients taking clozapine.

We retrospectively inspected data of 13 consecutive patients on clozapine, admitted to Highgate Mental Health Centre -Camden & Islington NHS Foundation Trust between March and June 2020. Selection was based on their COVID-19 symptoms presentation and/or COVID-19 positive test. We used a linear regression model with COVID status as independent variable and absolute neutrophil count (ANC) as dependent variable to inform about a correlation between COVID-19 status and neutrophil count. STATA was used for statistics.

We collected data on thirteen patients of which nine were male. The median age was of 41.97 years; six subjects were Black, three were Asian and four were White Caucasian. Ten subjects tested positive to COVID-19 and 3 were suspected cases -these latter were excluded from stastical analysis. During COVID-19 infection, neutrophils count (ANC) dropped significantly to 4.215 from a baseline value of 5.337. The beta values of 0.83 shows that ANC declined significantly during COVID-19 infection (p =<.0001, R2 = 95%). In three of thirteen patients, ANC drop was significant and changed the patients’ monitoring status from green to amber and required frequent blood tests.

Clinicians should bear in mind that a significant drop in neutrophils count may occur in COVID-19 -infected patients taking clozapine.

No significant relationships.