ACVIM consensus statements provide a practical framework for the diagnosis and treatment of immune-mediated thrombocytopenia
Journal citation

LeVine, D.N., Kidd, L., Garden, et al. 2024
ACVIM consensus statement on the diagnosis of immune thrombocytopenia in dogs and cats.
Journal of Veterinary Internal Medicine 38(4), 1958-1981
Full text available

LeVine, D.N., Goggs, R., Kohn, B., et al. 2024
ACVIM consensus statement on the treatment of immune thrombocytopenia in dogs and cats.
Journal of Veterinary Internal Medicine 38(4), 1982-2007
Full text available

Publication date

July-August 2024

Type of study

Design: Review/consensus statement
Setting: Cornell University, US
Animals: 287/288 scientific papers reviewed

Background
  • Immune-mediated thrombocytopenia (ITP) is the most common acquired primary haemostatic disorder in dogs. It is seen less commonly in cats.
  • ITP is characterised by an immune-mediated destruction of platelets, leading to severe thrombocytopenia and increased bleeding risk
  • Diagnosis is challenging due to the lack of definitive diagnostic criteria and variability in clinical presentation
  • The management of ITP in veterinary medicine has been varied due to a lack of evidence-based guidelines, particularly beyond the initial use of glucocorticoids
Aims
  • The primary aim is to develop comprehensive, evidence-based guidelines for the diagnosis and treatment of ITP in dogs and cats. This includes the identification of key diagnostic steps and the evaluation of important comorbidities associated with secondary ITP. There is a focus on creating a systematic approach to treatment, incorporating both traditional and emerging therapies, while also identifying areas that require further research.
Methods
  • A systematic literature review was conducted, involving 287 articles regarding diagnosis and 288 articles regarding treatment
  • A panel of experts aimed to address multiple Population Evaluation/Exposure Comparison Outcome (PECO) format questions
  • Evidence evaluators summarised findings and developed guidelines, which were then refined through a Delphi survey process to reach consensus
  • Diagnostic algorithms for ITP were created and underwent multiple rounds of revision by specialist panel members
Results

ITP DIAGNOSIS: Key Updates from the 2024 ACVIM Consensus Statement

General Principles

  • ITP remains a diagnosis of exclusion; there is no single diagnostic test
  • Diagnosis should follow structured algorithms based on platelet count, clinical context and exclusion of other causes
Platelet Count & Indices

  • Platelet count <100 × 109/l must be confirmed on blood smear before proceeding
  • Counts <20 × 109/l support ITP but are not diagnostic alone
  • Low platelet count should be interpreted critically in the context of allowable errors of up to 25%
  • Reticulated platelets may support an immune-mediated process but cannot distinguish primary vs secondary ITP
  • MPV, plateletcrit and IPF are not recommended for routine diagnosis or prognosis
Bone Marrow Examination

  • Not routinely recommended for diagnosis or prognosis
  • Consider only if unexplained cytopenias exist
  • No bone marrow pattern is specific for ITP
Platelet-associated antibodies

  • The presence of platelet surface–associated immunoglobulin (PSAIG) supports an immune component but is not diagnostic for ITP
  • Not recommended routinely due to poor specificity
  • May help monitor relapse if serial testing is available
Coagulation Testing

  • Routine coagulation tests (aPTT, PT) are recommended in both dogs and cats with thrombocytopenia
  • A full laboratory coagulation panel to include fibrin degradation products (FDP) and D-dimer should be considered
Bleeding Severity Scoring

  • A bleeding severity score (e.g., DOGiBAT) is available and recommended in dogs and correlates better with transfusion need and hospital stay than platelet count alone
CBC & Biochemistry

  • Should be performed in all suspected ITP cases
  • Anaemia and elevated BUN may be associated with worse outcomes
Diagnostic Certainty Levels for Primary ITP were established

  • Six tiers: Possible, Possible with immunologic evidence, Probable, Probable with immunologic evidence, Diagnostic, Diagnostic with immunologic evidence
Diagnostic Certainty Levels for Secondary ITP were established

  • Only three tiers are suggested to reflect the challenge of isolating immune-mediated platelet destruction when other potential causes of thrombocytopenia exist: Possible, Probable, Probable with immunologic evidence

ITP TREATMENT: Key Updates from the 2024 ACVIM Consensus Statement

Defining treatment response

  • Definitions of response to ITP treatment and the recommended treatment goal were established
  • No response (NR): Platelet count <30 × 109/l or ongoing bleeding at least 2 weeks after initiating treatment
  • Partial response (PR): Platelet count ≥30 × 109/l and <100 × 109/l, combined with a >2‐fold increase in platelet count from diagnosis, and the absence of bleeding
  • Complete response (CR): Platelet count ≥100 × 109/l, without bleeding
  • Full remission: Platelet count ≥100 × 109/l, without bleeding in the absence of ongoing treatment
  • Recommended treatment goal: Platelet count ≥100 × 109/l with no evidence of bleeding
First-line treatment

  • Glucocorticoids remain the foundation of ITP treatment in both dogs and cats and should be initiated when ITP is strongly suspected
  • Typical: Prednisolone or prednisone
Adjunctive First-line Options

Vincristine (dogs only)

  • There is moderately strong evidence that a single i/v administration of vincristine to dogs with pITP and clinically relevant bleeding, in conjunction with immunosuppressive dosages of glucocorticoids, accelerates initial platelet count recovery and shortens hospitalisation time
  • Avoid or use with caution in ABCB1 (MDR1) mutation breeds
  • In cats with pITP, vincristine is NOT recommended until more evidence becomes available

hIVIg (Human IV Immunoglobulin)

  • Accelerates platelet recovery and shortens hospitalisation time in dogs, compared with glucocorticoids alone, but is more expensive and less accessible than vincristine
  • Preferred over vincristine in dogs with MDR1 mutations or prior vincristine failure
  • May be considered in cats with significant bleeding or refractory pITP; no feline-specific data exist, but panel consensus favours hIVIg over vincristine as an emergency adjunct in this species
Second-line Immunosuppressants

  • Options in dogs: azathioprine, modified cyclosporine, MMF, leflunomide
  • Options in cats: modified cyclosporine or chlorambucil (not azathioprine)
  • There is insufficient evidence to determine whether using a second-line immunosuppressive drug alongside glucocorticoids improves outcomes compared to glucocorticoids alone in dogs and cats

Suggested only if:

  • No response within 5‐7 days of starting glucocorticoids
  • Relapse during steroid taper
  • Severe bleeding or steroid adverse effects
Individualised Treatment

  • Tailor treatment to disease severity
  • Consider adjuncts in patients with GI, CNS or pulmonary haemorrhage
  • Bleeding severity scores (e.g. DOGiBAT) may help individualise therapy in dogs but still require further validation
Markers of disease severity

  • The presence of GI bleeding, specifically melena, and central nervous system or pulmonary haemorrhage
  • High BUN and anaemia necessitating transfusion
Platelet & RBC Transfusions

  • Not recommended routinely
  • Can be used for life-threatening bleeding
  • The average platelet count increase is small and transient
Thrombopoietin Receptor Agonists (e.g. Romiplostim)

  • May be considered in dogs in refractory cases
  • Not yet supported for routine use
  • Not recommended in cats until evidence is available
Not Routinely Recommended in dogs and cats

  • Splenectomy (consider only in refractory cases)
  • Therapeutic plasma exchange (TPE)
  • hIVIg or vincristine as sole agents
  • Antithrombotics, unless concurrent prothrombotic risk factors exist
  • Gastroprotectants, unless GI bleeding is suspected
Relapse Management

  • Reassess diagnosis, investigate for new triggers
  • If relapse occurs during taper, reinstitute prior doses or full induction
  • Future tapers should be more gradual
  • Lifelong treatment may be necessary in some cases
Monitoring

  • Hospitalise if platelet counts <40-50 x 109/l. Monitor with physical examination and CBC every 2–3 days
  • Outpatient care if platelet counts >40-50 x 109/l. Recheck every 1-2 weeks during taper
  • Monitor liver, renal function and for adverse effects throughout
Vaccination

  • There is very limited data in dogs and no data in cats regarding the association between vaccination and ITP disease relapse
  • In dogs and cats with pITP, the risk:benefit of vaccination should be individually assessed
  • If vaccination is necessary, administer only one vaccine per visit and only when immunosuppressive treatment has been stopped or reduced to anti-inflammatory doses; consider monitoring platelet counts at 2 and 5 weeks post-vaccination.
Supportive therapies

  • Cage rest and minimal handling to prevent trauma
  • Anxiolytic medications as needed
  • Avoid nasal cannulae and nasal feeding tubes unless unavoidable
  • Avoid s/c or i/m injections
  • Avoid anticoagulant and antiplatelet drugs when platelet numbers are severely depleted
  • Restrict exercise, soft food and no hard chew toys
Tapering glucocorticoid doses

  • Reduce dose by approximately 25% every 2–4 weeks if platelets are stable (check before each reduction)
  • A faster taper may be used if the starting dose is high
  • Taper by reducing dose or frequency
  • Continue for several months, adjusting based on side effects, concurrent drugs or disease
  • Extend duration if relapse has occurred
Conclusions and clinical relevance

Conclusions

  • The diagnostic consensus statement concludes that ITP diagnosis remains complex and relies heavily on the exclusion of other causes of thrombocytopenia. It emphasises the need for a systematic approach, incorporating clinical evaluation, diagnostic testing and the consideration of comorbidities.
  • The treatment consensus statement advocates for the use of glucocorticoids as the first line of treatment, with vincristine or hIVIG as adjunctive therapies in severe cases. The cautious addition of second-line immunosuppressive agents should be considered when necessary.
  • The statement identifies significant gaps in the current evidence base, particularly regarding the efficacy of second-line treatments and the management of relapses

Clinical Relevance

  • These guidelines provide clinicians with a structured approach to diagnosing and treating ITP, using clinical algorithms, helping to differentiate it from other causes of thrombocytopenia. Treatment frameworks aim to standardise case management and improve patient outcomes.
  • The inclusion of comorbidity screening in the diagnostic process is crucial for identifying secondary ITP and guiding treatment decisions
Reported limitations
  • Reported limitations include the variability in available evidence, particularly the reliance on retrospective data for the assessment of platelet levels and assessment of disease severity
  • There is a lack of high-quality, prospective, controlled studies, particularly regarding second-line immunosuppressive medications, long-term management and treatment of relapses
  • In addition, an inherent difficulty in diagnosing ITP is its heterogeneous nature, which complicates the development of definitive diagnostic criteria
VETbytes critical appraisal

Strengths

  • Comprehensive Review: The study utilised a large body of literature, incorporating a wide range of studies to develop evidence-based guidelines
  • Structured Consensus Process: The use of the Delphi survey process ensured that the guidelines were refined and validated by a panel of experts, enhancing their reliability
  • Practical Diagnostic and Treatment Algorithms: The development of algorithms provides a practical tool for clinicians, helping to streamline the diagnostic process and improve case management

Weaknesses

  • Reliance on Retrospective Data: Many of the studies included in the review were retrospective, which limits the strength of the evidence and the ability to draw definitive conclusions
  • Limited Prospective Studies: The lack of prospective studies in the literature review highlights the need for further research to validate the guidelines and improve the accuracy of ITP diagnosis
  • Diagnostic Complexity: Despite the development of guidelines, the diagnosis of ITP remains challenging due to its heterogeneous nature, which may lead to variability in clinical practice
  • Potential Bias: The reliance on expert opinion, particularly for non-PICO questions, introduces the potential for bias in the recommendations
  • Generalisation Challenges: The variability in ITP presentation and treatment responses may limit the applicability of the guidelines to all clinical scenarios, requiring clinicians to adapt recommendations to individual cases

Critical Appraisal Summary

  • This consensus statement provides a valuable framework for the diagnosis and treatment of immune-mediated thrombocytopenia in dogs and cats. The systematic approach and expert validation add credibility to the guidelines, although the reliance on retrospective data and the inherent complexity of ITP diagnosis are notable limitations.
  • Future research should focus on addressing these limitations through prospective studies, therefore refining the diagnostic criteria and treatment guidelines, particularly in the areas of second-line therapies and relapse management
Related content

See Thrombocytopenia for updates relating to this paper