Page 10 - RVC Clinical Connections - Spring 2025

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Page 10 - RVC Clinical Connections - Spring 2025
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RVC RESEARCH    STUDY    VETERINARY SERVICES       RVC.AC.UK
         Internal medicine

        PROGRESSING IMHA TREATMENT THROUGH
        COLLABORATIVE RESEARCH


        Barbara Glanemann, Associate Professor in Small Animal Medicine
        M      ost immune-mediated haemolytic   Case study
               anaemia
                                 treatments
                         (IMHA)
                                            Milo, a three-year-old male entire cocker
               involve suppressing the immune
        system to stop the body from destroying its   spaniel, presented to the Queen Mother
                                            Hospital for  Animals with a 48hrs history
        own red blood cells. Distressing side effects   of lethargy, anorexia and icterus. Being
        of the medications include increased thirst,   only mildly anaemic and thrombocytopenic
        appetite and urination, panting, muscle   with marked hyperbilirubinaemia on initial
        wastage, lethargy and behavioural changes.   presentation to his primary care practice, he
          There  is  consequently  a  major  clinical   was  referred  for  further  management  of  a
        need to understand how dogs can be   possible leptospirosis infection.
        treated  effectively,  while  minimising  the   By the time of admission to the QMHA
        adverse  effects  experienced  in  treatment.   though, Milo had marked anaemia with typical   Erythrophagocytosis on peripheral blood
                                                                                 smear at time of diagnosis
        At the RVC we are attempting to uncover   hallmarks of immune-mediated haemolysis
        new information on how IMHA develops in   (e.g. positive Coombs test, spherocytosis,
        dogs and hoping to identify which treatment   erythrophagocytosis  on  peripheral  blood
        works best for individual dogs. This could   smear, hyperbilirubinaemia).
        have a major impact on the quality of life for   Further investigations were performed to
        dogs with this distressing disease.  rule out any potential underlying causes,
          We have been awarded a grant from the   and after initial transfusion of a matched
        Morris Animal Foundation’s Donor Inspired   red blood cell unit, Milo was subsequently
        Study  programme  to  advance  critical   started on immunosuppressive therapy,
        research into IMHA. The grant will support   consisting of prednisolone and azathioprine.
        the exploration of mechanisms that cause   To  minimise  the  risk  of  thromboembolic
        the disease, using cutting-edge single cell   disease, clopidogrel therapy was also   In vitro haemolysis assay to assess
        RNA  sequencing  approaches,  as  well  as   initiated.                  phagocytic activity of PBMC after exposure to
                                                                                 dexamethasone, ciclosporine, mycophenolate
        evaluating different treatments ex vivo with                             and leflunomide
        the aim of understanding how individual
        dogs respond to different medications that                               Milo’s owner had kindly agreed for his
        are already available in veterinary practice.                           residual blood samples to be used for
          This research is led by myself, in                                    research. From the residual EDTA blood
        collaboration  with  RVC  colleagues  James                             sample at time of admission, we were able
        Swann  (Visiting  Associate  Professor),                                to isolate his peripheral blood mononuclear
        Balazs Szladovits (Associate Professor in                               cells (PBMC) and expose those cells ex
        Clinical Pathology) and Floryne Buishand                                vivo to immunosuppressive drugs used
        (Lecturer in Soft Tissue Surgery).                                      commonly in veterinary medicine prior
          Residual samples will be obtained from                                to evaluating their capacity to lyse red
        dogs presented and diagnosed with IMHA                                  blood cells. Furthermore, we will be able
        at  the  RVC  and  two  collaborating  referral                         to perform single cell RNA sequencing of
        centres – Davis Veterinary Specialists and                              those  PBMC  to  define  the  predominant T
        Dick White Referrals. The findings will help                            cell activation state. By comparing this to
        improve understanding of which genes are   Severe icterus on presentation  data from healthy control PBMC, we hope
        turned on and off – therefore shedding light                            to understand how myeloid cells become
        on  what  is  going  wrong  with  the  patient’s                        hyperactivated to engage in phagocytosis of
        immune system.                                                          erythroid cells in patients with IMHA.
          Comparing results to those from healthy                                Following seven days of hospitalisation
        dogs will help improve knowledge of how                                 Milo’s PCV had stabilised and he was
        and  why  the  immune  system  attacks  red                             discharged for continued therapy at home.
        blood cells and may identify new therapeutic                            Immunosuppressive therapy will be tapered
        targets for drug development.  As we will                               off  gradually  over  the  following  weeks,
        also investigate how those immune cells                                 while careful monitoring for any relapse and
        from dogs with IMHA respond to common                                   adverse treatment effects.
        medications, we can create prediction
        models, which would be available to vets to
        help decide which medication will be most                                      For small animal referrals, please call:
                                                                                     01707 666399
        effective for their individual patient.  Milo’s mucous membranes at discharge    Email:
                                                                                     qmhreception@rvc.ac.uk
        10   Spring 2025
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