Diagnosis and Treatment of Immune-Mediated Thrombocytopenia in Dogs

Author: Andréanne Cléroux, DVM, IPSAV, DACVIM (SAIM) (Internal Medicine)

Immune-mediated thrombocytopenia (ITP) is the most common acquired primary hemostatic disorder in dogs, and although less common, is also recognized in cats. It is characterized by immune-mediated destruction of platelets and megakaryocytes. Rapid recognition of the disease and initiation of therapy is critical given that this condition can be life-threatening. ITP is diagnosed as a condition of exclusion and can be classified as primary (idiopathic, non-associative) or secondary (associative). The absence of definitive diagnostic criteria complicates diagnosis, but recently published ACVIM consensus statements (part I, part II)
provide systematic recommendations for diagnosis and treatment.

Diagnosis

ITP typically presents with variable clinical signs, ranging from subclinical thrombocytopenia to life-threatening hemorrhage. Severe thrombocytopenia is common but does not consistently correlate with bleeding severity. Diagnosis begins with confirmation of thrombocytopenia via blood smear evaluation to rule out pseudothrombocytopenia caused by platelet clumping or analyzer error. Testing should be performed to confirm that consumption, sequestration, or bone marrow disease is not the cause of thrombocytopenia. To differentiate primary from secondary ITP a review of the patient’s history is essential, and should include recent vaccinations, drugs, toxins, travel, exposure to fleas, ticks, and other vectors as well as the use of flea/tick/heartworm prevention.

Most evidence suggests that dogs with ITP have more severe thrombocytopenia compared with non-immune causes of thrombocytopenia, but it is important to know that there is overlap between diagnostic groups. A platelet count <20 000/uL supports a diagnosis of ITP in dogs but is insufficient to independently make a diagnosis. In addition to CBC and biochemistry panels and urine testing, additional diagnostic tests should be performed in dogs with suspected ITP, including infectious disease testing (combined serology and PCR), and imaging (thoracic radiographs, abdominal ultrasound) to screen for cancer and look for foci of inflammation or infection. Coagulation testing (activated partial thromboplastin time and prothrombin time) and the measurement of fibrinolysis markers (d-dimer, fibrin degradation products) may be considered to differentiate patients with consumptive and toxic coagulopathies from patients with primary ITP. Measurement of platelet/megakaryocyte-associated antibodies and bone marrow cytology are not routinely recommended and might be reserved for complicated cases.

Treatment

The primary goals of treatment are to achieve a platelet count ≥100,000/μL without bleeding and minimize complications from immunosuppressive therapies. Treatment should be individualized, balancing disease severity with the risks of therapy. Blood transfusions may be required for severe anemia or active hemorrhage.

Immunosuppressive glucocorticoids, such as prednisone or prednisolone, are the cornerstone of treatment and first-line therapy. The use of vincristine and human IV Ig as first-line emergency adjunctive treatments for dogs with ITP and clinically relevant bleeding in conjunction with immunosuppressive doses of glucocorticoids has been evaluated and has been associated with shorter hospitalization time and faster initial platelet count recovery. The use of these drugs is not without potential adverse effects and is typically reserved for dogs experiencing bleeding.

The addition of a second immunosuppressive should be considered in the following circumstances:

• There is no response within 5-7 days of starting glucocorticoids;

• The patient is experiencing severe adverse effects to glucocorticoids;

• There is a relapse during tapering of glucocorticoids after a complete response. Additionally, the early use of a second immunosuppressive drug may be considered in dogs >25kg to allow for more rapid tapering of glucocorticoid dosages and in dogs with severe bleeding because of the anticipated delayed onset of action of secondary drugs. Options include cyclosporine (modified), mycophenolate mofetil, leflunomide, and azathioprine.

The use of proton-pump inhibitors, sucralfate, or other gastroprotectants may be considered in the presence of observed or suspected melena as, although GI bleeding can occur without loss of mucosal integrity in dogs with ITP, it is impossible to exclude with certainty the possibility of GI ulceration, especially in the face of glucocorticoid treatment.

Monitoring

Close monitoring of platelet counts and clinical signs is essential during treatment. Definitions of response include:

• No response: platelet count <30 000/uL or ongoing bleeding after 2 weeks of therapy.

• Partial response: platelet count ≥30 000/uL and <100 000/uL with a >2-fold increase in platelet count from baseline, and the absence of bleeding.

• Complete response: platelet count ≥100 000/uL, without bleeding.

• Full remission: platelet count ≥100 000/uL, without bleeding in the absence of ongoing treatment.

When complete remission is achieved and sustained for a few weeks, the dose of glucocorticoids may be tapered by 20-25% every 2-4 weeks provided platelet count is stable and confirmed immediately before each dosage reduction.

When in full remission, patients may be monitored monthly for 3 months, with subsequent gradual extensions in the assessment interval. Platelet count should be measured before any procedure or vaccination. Additionally, clients should monitor their pets closely for signs of relapse.

Vaccination

For patients that have recovered from ITP associated with vaccination, public health considerations and risk of disease exposure should be weighed against the unknown and presumed risk of relapse of immune-mediated disease. Revaccination may be avoided by monitoring titers. It is unclear whether the same degree of caution is needed in dogs with ITP that was not originally associated with vaccination.

Key points

Veterinarians play a vital role in diagnosing and stabilizing ITP cases. Recognizing severe thrombocytopenia and initiating appropriate diagnostics to exclude secondary causes are critical. Early treatment with glucocorticoids and adjunctive therapies, when indicated, can significantly improve outcomes. Collaboration with specialists is recommended for patients with relevant bleeding, imaging (abdominal ultrasound), as well as refractory or complex cases. For detailed algorithms and further recommendations, refer to the full ACVIM consensus statements on ITP diagnosis and treatment.