Skip to main content
Public beta This website is in public beta – please give your feedback.
Pharmacogenomics

Presentation: Patient due to start clozapine and with a clinical suspicion of ACKR1/DARC-associated neutropenia

Clozapine is prescribed for treatment-resistant schizophrenia. To receive clozapine, a patient’s neutrophil count must remain above a minimum threshold. Some patients present with naturally low neutrophil counts without increased infection risk. These patients may be unnecessarily prevented from receiving clozapine.

Example clinical scenario

A patient is due to start clozapine, and an initial blood test reveals an absolute neutrophil count (ANC) of 1.7 × 109/L, which is below the minimum ANC threshold to begin clozapine treatment (>2.0 × 109/L). It is possible that the patient has ACKR1/DARC-associated neutropenia (ADAN; formerly, benign ethnic neutropenia), which normally allows for safe initiation of clozapine with reduced ANC thresholds.

When to consider genomic testing

  • Patients who present with a low ANC may have ADAN, which is a benign neutropenia not associated with increased infection risk.
  • ADAN is strongly associated with a homozygous variant in ACKR1 (c.-67T>C, rs2814778), which is known as the Duffy-null genotype.
  • There are many causes of a low ANC, and consultation with a haematologist is essential to determine whether a patient has ADAN and to rule out any other possible causes of neutropenia.
  • Indicators that a patient may have the ACKR1 variant and ADAN include:
    • African or Middle Eastern ethnicity;
    • persistently low ANCs, observed over multiple blood level measurements; and/or
    • no history of recurrent infections or other significant physical illness.

What do you need to do?

  • Genomic testing for the ACKR1 variant is not currently available via the National Genomic Test Directory, although it can be ordered locally by some haematology clinics. It is recommended to check whether this test is locally available.
  • If you suspect ADAN in a patient taking clozapine, consider a genomic test for the ACKR1 variant, if available locally.
  • If the test is available locally, use an EDTA sample tube (typically purple-topped) for blood extraction.
  • If the patient is homozygous for the ACKR1 variant, initiate a consultation with a haematologist to determine whether the patient has ADAN and to rule out any other possible causes of neutropenia.
  • If the haematologist diagnoses ADAN, inform the patient’s clozapine monitoring service so that revised full blood count (FBC) and ANC thresholds for ADAN can be applied. This should allow for the patient to receive clozapine.
  • If the haematologist concludes that the patient does not have ADAN, continue to apply normal FBC and ANC thresholds for clozapine monitoring, as per standard protocol, and continue to investigate the cause of neutropenia.
  • If the patient is not homozygous for the ACKR1 variant but has an ANC consistently below the normal range, either in isolation or as part of a more general FBC anomaly, initiate a consultation with a haematologist to investigate the cause of neutropenia.
  • Information about patient eligibility and test indications were correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

Resources

For clinicians

References:

For patients

↑ Back to top
  • Last reviewed: 09/01/2025
  • Next review due: 09/01/2026
  • Authors: Professor Elvira Bramon, Dr Stephen Murtough
  • Reviewers: Olubanké Dzahini, Dr John McDermott, Dr Sara Stuart-Smith