Oral haematomas as the major presenting sign of primary immune thrombocytopenia in a cat

Abstract

Case summary

An unowned, entire male domestic shorthair cat was surrendered to a rescue centre. On physical examination, poor body condition (score 3/9) and pigmented mass lesions on the lateral aspects of the upper gingivae were noted. The oral lesions were identified as haematomas only after examination under sedation. A diagnosis of probable primary immune thrombocytopenia (pITP) was made based on profound thrombocytopenia, rapid response to glucocorticoid therapy and the absence of identified triggers for secondary immune thrombocytopenia. The patient was treated with glucocorticoids and remained in remission 18 months from diagnosis.

Relevance and novel information

pITP is infrequently reported in cats and oral haematomas have not previously been documented as a presenting clinical sign. This case report serves to raise awareness of feline ITP and highlights the availability of evidence-based diagnostic and therapeutic guidelines that were published after the case was treated. While pITP can be refractory to treatment and can be associated with treatment-related morbidity, this case report demonstrates that an acceptable outcome can be achieved, albeit with a requirement for long-term treatment and regular monitoring.

Introduction

Primary (spontaneous, non-associative) immune-mediated thrombocytopenia (pITP) results from immune-mediated platelet destruction without an underlying trigger, whereas secondary (associative) ITP (sITP) is triggered by another disease. ¹ Cats are much less commonly affected by ITP than dogs, and most feline cases are sITP. Clinical signs of ITP in cats vary from asymptomatic through surface bleeding to life-threatening haemorrhage.^{2 –7} The diagnosis of pITP in cats is one of exclusion. An American College of Veterinary Internal Medicine (ACVIM) consensus statement arising from a comprehensive evidence review provides guidelines for the diagnosis of ITP with four degrees of certainty: ‘possible’, ‘probable’, ‘diagnostic’ and ‘diagnostic with immunological confirmation’. ¹ We describe a case of ITP with an unusual presentation, where the findings of the partial clinical investigation support a diagnosis of ‘probable’ pITP, and where a satisfactory outcome was achieved with ongoing treatment.

Case description

An unowned, free-roaming, young adult, entire male domestic shorthair cat was presented to a shelter. The finder reported seeing blood around the cat’s mouth. On admission, black material on the teeth was noted and the patient was in poor body condition (score 3/9, body weight 4 kg). A modified live vaccine against feline herpesvirus-1, feline panleukopenia virus and feline calicivirus (Felocell 3; Zoetis) and parasite control (niclosamide/oxibendazole, Ascaten; AlfaMedic, and selamectin, Revolution; Zoetis) were administered.

The cat underwent a 4-day holding period, during which no abnormalities were noted. After the holding period (day 1), pigmented plaque and mass-like lesions were identified on the left and right upper gingivae, respectively, and the breath was malodorous on clinical examination. No other major abnormalities were noted. Serology for feline immunodeficiency virus (FIV) antibody and feline leukaemia virus (FeLV) antigen (SNAP FIV/FeLV Combo; IDEXX) was negative. Oral examination under sedation and castration were scheduled for the next day.Under sedation, the right-sided oral lesion appeared to have reduced in size (Figure 1a). The larger lesion, a dark-coloured mass (approximately 1.5 × 0.5 cm in size) with a broad base on the lateral aspect of the left upper gingiva (Figure 1b,c), had a glistening surface and a firm to spongy texture, consistent with a haematoma. A third lesion, a linear ecchymosis, was identified on the left ventral aspect of the tongue (Figure 1d). Low-grade bleeding was detected at the gingival margins. Extensive bruising was noted over the cephalic venepuncture site that had been used previously for retrovirus testing. No petechiae or other bruising was identified. Clinical findings were considered most consistent with a primary coagulopathy (thrombocytopenia and/or thrombocytopathy) or a secondary coagulopathy with consumptive thrombocytopenia.Diagnostic samples were taken, as outlined below, before treatment with vitamin K₁ (1 mg/kg SC q12h, Phytomenadione; Konakion MM) in case of anticoagulant rodenticide intoxication, doxycycline (5 mg/kg PO q12h) for infectious causes of a primary coagulopathy and dexamethasone (0.2 mg/kg SC q24h) for ITP. Castration was delayed and the cat was recovered.

Figure 1

Oral examination under sedation showing oral lesions in a cat diagnosed with primary immune thrombocytopenia. (a) A haematoma on the right upper gingiva that had regressed in size over 24 h. (b,c) Ventral and lateral views of a haematoma on the left upper gingiva. (c) Dark material on the teeth and bloody fluid around the haematoma likely result from gingival bleeding. (d) A linear ecchymosis on the ventral surface of the tongue

Regenerative anaemia (haematocrit 18.2%, reticulocyte count 128,600/µl, reference interval [RI] 3000–50,000) and apparent thrombocytopenia (0/µl, RI 151,000–600,000) were identified using an automated haematology analyser. On evaluation of a peripheral blood smear (Figure 2), platelets were absent, including at the tail of the smear, confirming the severity of the thrombocytopenia. Moderate polychromasia and anisocytosis supported a regenerative response, and no red cell inclusions or epicellular parasites were identified. Activated partial thromboplastin time and prothrombin time were within the RI at 102 s (RI 60–115) and 16 s (RI 13–22), respectively, ruling out abnormalities of intrinsic and extrinsic coagulation pathways. Biochemistry results were unremarkable, except for mildly elevated globulins (5.2 g/dl, RI 2.8–5.1, albumin: globulin ratio 0.6).

Figure 2

Peripheral blood smear from the cat on day 1, stained with Diff Quik (RAL Diagnostics), magnification × 40. No platelets were seen at the feathered edge or in the body of the smear. Moderate erythrocyte polychromasia and anisocytosis are consistent with a regenerative response

The oral haematomas, gingival oozing and moderate regenerative anaemia were attributed to severe thrombocytopenia. ITP was considered the most likely diagnosis at this stage, given the severity of the thrombocytopenia, and investigations continued. A manual platelet count was performed at each evaluation. Blood collected before treatment was submitted for Coombs testing (Antech Asia Vet) and for molecular infectious disease testing for Anaplasma species, Ehrlichia species, Babesia gibsonii, Mycoplasma haemofelis and Candidatus Mycoplasma haemominutum (CityU Veterinary Diagnostic Laboratory). In addition, whole-blood DNA was extracted and a pan-Babesia PCR targeting mitochondrial cytochrome b and a Babeisa hongkongensis-specific PCR targeting 18S rRNA were performed in the authors’ laboratory, as described previously. ⁸ Retrovirus serology was repeated. All tests returned negative results. Imaging, urine culture and faecal flotation/centrifugation were not performed because of financial limitations.

After 3 days of dexamethasone treatment, the platelet count had normalised (194,000/µl), the haematocrit had increased (25%) and the oral haematomas had resolved. Treatment was changed to prednisolone (2 mg/kg PO q24h). Seven days after starting treatment, the haematocrit was 35% and the platelet count was 350,000/µl (Figure 3). Prednisolone was tapered to 1.25 mg/kg q24h and the platelet count remained stable.

Figure 3

Graph showing the platelet count (left vertical axis) and daily prednisolone dose (right vertical axis) for the patient over time (horizontal axis). All platelet counts were confirmed on a blood film. Triangles denote the dates of vaccination. The circle represents the date of castration. The yellow area on the graph represents the platelet reference interval

On day 31, the platelet count was 295,000/µl and the haematocrit was 42.9%, while the patient remained on prednisolone at 1.25 mg/kg q24h. A second vaccination was administered (Felocell 3; Zoetis). A platelet count 24 h later was low (85,000/µl). Prednisolone was increased to 1.7 mg/kg q24h on day 34 because thrombocytopenia persisted (102,000 /µl, manually confirmed). The platelet count was normal (295,000/µl) on day 46. The platelet count remained within the normal range and prednisolone was successfully tapered, then discontinued over 10 days. The cat was clinically normal before castration on day 154 and the result of a manual platelet count was recorded as ‘normal’. The surgery and postoperative recovery were uneventful.

On day 164, active gingival bleeding and petechiae/ecchymoses on the pinnae were noted. The cat remained bright and alert. The platelet count was 0/µl but the cat was not anaemic (haematocrit 42.9%). Treatment was recommenced at the same doses of dexamethasone then oral prednisolone 2 days later (platelet count 107,000/µl, haematocrit 38.5%). By day 178, the bruising had resolved and the platelet count had normalised (475,000/µl). The platelet count and prednisolone dose over the period before rehoming are shown in Figure 3. When the patient was rehomed on day 277, the platelet count was normal (327,000/µl) and the cat was being treated with prednisolone (1 mg/kg q24h).

Discussion

Primary ITP is a diagnosis of exclusion. ¹ In this case, the combination of profound thrombocytopenia at diagnosis, rapid response to glucocorticoids and an apparent absence of comorbidities based on a thorough physical examination and testing as outlined supports a diagnosis of probable pITP. Evidence for comorbidities that trigger sITP in cats is limited. The 2024 ACVIM consensus statement on the diagnosis of ITP found limited support for neoplastic, drug and inflammatory triggers, and no evidence for infectious, toxic or vaccine associations in cats. ¹ In dogs, infectious triggers, particularly vector-borne diseases, are associated with sITP. This free-roaming cat with an unknown prophylaxis history likely had a high risk of ectoparasite exposure. In Hong Kong, information on vector-borne diseases is emerging.^8,9 The prevalence of Babesia species detection in cats is low. ⁸ B gibsoni was associated with sITP in a cat in Hong Kong. ¹⁰ Anaplasma phagocytophilum has been documented in cats with thrombocytopenia, but was not identified infecting cats in Hong Kong. ⁹ Ehrlichia canis triggers thrombocytopenia in dogs but there is limited evidence that cats are similarly affected. ¹¹ Retroviruses are inconsistently linked to thrombocytopenia in cats.^2,12 Hong Kong’s free-roaming cats are commonly infected with FIV (15.4%) but FeLV detection is rare. ¹³

There was no temporal association between vaccination or administration of medications and thrombocytopenia in this case, since bleeding from the mouth was noted before admission. The dark material covering the teeth, likely from low-grade gingival bleeding, was not identified as such until examination under sedation. A negative Coombs test, as in this case, does not rule out immune-mediated disease associated with Evans syndrome. The mechanisms of ITP are heterogeneous and include antibody-independent platelet destruction. Platelet-bound antibodies have been detected in some cats with ITP but are not validated sufficiently to add diagnostic value. ¹⁴ Collectively, these results support a diagnosis of probable pITP. At the discretion of the attending clinician, imaging and additional diagnostics to screen for underlying neoplasia, infection or inflammatory foci are recommended. ¹ The absence of a history before admission and financial limitations on additional investigations meant that a trigger could not be completely ruled out in this case.

The decision to repeat the administration of a modified live vaccine against feline herpesvirus-1, feline panleukopenia virus and feline calicivirus in this patient is worthy of further discussion. Vaccination could have been delayed on the basis that it might trigger immune-mediated disease. In addition, vaccination may be ineffective or revert to virulence in the face of glucocorticoid treatment. ¹⁵ However, in a high-throughput shelter facility, vaccination using a modified live product was prioritised because of the high risk of life-threatening diseases, such as panleukopenia

Oral haematomas have not been described previously in ITP in cats, to our knowledge. Their appearance as pigmented plaques was unusual. They were identified as haematomas during examination under sedation when rapid regression in size, spongy texture and concurrent gingival bleeding were appreciated. Spontaneous bleeding in cats can occur at platelet counts of 50,000/µl or less but, remarkably, patients can remain asymptomatic despite severe thrombocytopenia. Clinical signs reported in feline pITP previously include hyphaema, intermittent haematuria, petechiae and pulmonary haemorrhage.^4–7

Immunosuppressive doses of glucocorticoids are the first-line treatment for feline ITP. ¹⁶ Success has been achieved with prednisolone or dexamethasone but long-term use carries risks such as diabetes mellitus.^4,6,7 Evidence on which to base alternative treatments in cats is sparse, but recent summaries will be useful for practitioners managing feline ITP.^16,17 The addition of cyclosporin or chlorambucil could be considered ¹⁶ but such combinations carry additional risks. For example, cyclosporine alone or in combination with glucocorticoids has been associated with toxoplasmosis, ¹⁸ while the long-term use of chlorambucil can be associated with thrombocytopenia. ¹⁶

This case remains clinically normal on treatment with prednisolone 1.5 years from diagnosis. Monitoring of urine glucose for early detection of diabetes and regular check-ups including manual platelet counts are advised.

Conclusions

The presentation of pITP in cats is highly variable and clinicians should maintain an index of suspicion for this uncommon diagnosis. A satisfactory outcome can be achieved with immunosuppressive doses of prednisolone in some cases; however, ongoing treatment and monitoring may be required. Identification of the minimal effective dose and use of every-other-day dosing are important to minimise side effects.