Immune-Mediated Thrombocytopenia (ITP) in Dogs • MSPCA-Angell.
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Prednisone for dogs with low platelets
Prednisone for dogs with low platelets
Prednisone for dogs with low platelets -
Although treatment group and treatment-by-time interactions were not significant for AUC, AUC increased significantly over time Figures 1 , 2. This could reflect biological variability, although enhancement of platelet aggregation secondary to prednisone administration cannot be ruled out as a contributor to changes in two of the groups. In our study, blood samples for platelet analysis were collected before the administration of any anesthetic medication and performance of endoscopy, and there was at least a day recovery period before the collection of the next blood sample.
Additionally, the anesthetic protocol used in the related study acepromazine, butorphanol, and isoflurane has been shown to have no significant effect on platelet function 33 — Alternatively, these changes in the AUC on days 14 and 28 could reflect variability in the aggregometer or aggregometric data.
Aspirin irreversibly inhibits platelet function by inhibiting the cyclooxygenase COX enzyme and preventing the conversion of arachidonic acid to biologically active eicosanoids, prostaglandins, and TXA 2 , which are necessary for normal hemostasis TXA 2 primarily is produced by platelets and triggers platelet activation and vasoconstriction Once synthesized, TXA 2 is rapidly converted to stable metabolites, such as dTXB 2 and 2,3-dinor-thromboxane B 2 , that are eliminated in the urine and considered to be reliable markers of systemic TXA 2 production 25 , 26 , About one third of dogs have platelets that are sensitive to the activating effects of thromboxane 39 , Platelet activation through additional pathways and receptors could provide an additional explanation for why there was minimal inhibition of platelet function in our study.
Thromboxane, even if it does not affect all canine platelets, could still stimulate vasoconstriction. As previously discussed, one potential explanation for the differences between studies is differing durations of drug administration. McLewee et al. Dudley et al. Prednisone, similar to aspirin, has anti-inflammatory properties that would inhibit the conversion of arachidonic acid to prostaglandin synthesis, including TXA 2.
Our study did not detect a difference in thromboxane synthesis between the aspirin and prednisone groups, suggesting that both of these medications had an inhibitory effect on thromboxane synthesis. As expected, thromboxane concentrations in both the aspirin and prednisone groups were significantly decreased compared to the placebo group.
The results of our study contrast with results of a prior study in healthy dogs administered the same prednisone dose and using the same assay to measure dTXB 2 It is possible that prednisone causes an initial increase in thromboxane concentration that wanes during chronic administration. It is possible that co-administration of the medications erodes inhibitory effects due to overlapping mechanisms of action.
Although greater when prednisone and aspirin were used concurrently, thromboxane concentrations for both groups still were below pre-treatment concentrations, suggesting that combination therapy retains some anti-thrombotic benefits, such as vasodilation. The aspirin dose used in this study was greater than that used in previous studies 7 , 8 , 18 , This dose was selected because of the potential for consistent inhibition of platelet function However, the risk of gastric ulceration and hemorrhage increases with increases in the aspirin dose 16 , Glucocorticoids also have been shown to cause gastrointestinal hemorrhage and ulceration in healthy dogs 41 — Co-administration of 2 ulcerogenic drugs, aspirin and prednisone, could increase the risk of gastrointestinal hemorrhage.
Concerningly, scores were significantly higher on day 14 for dogs administered combination therapy, although severe lesions also were identified on day 28 and in dogs administered aspirin or prednisone therapy alone. In whole blood aggregometry, dramatic decreases in the hematocrit can have a significant impact on the assessment of platelet function.
A statistically significant decrease in hematocrit was noted on day 28 of this study, although hematocrit remained within the reference interval for all dogs. Gastric lesions could have contributed to this mild decrease in hematocrit, or it could have reflected biological variation.
Regardless of cause, it is unlikely that the change in hematocrit noted in this study was large enough to meaningfully affect the aggregometric results. There were several additional limitations to our study. Our study utilized healthy dogs with no evidence of hypercoagulability. The sample size calculation indicated 6 dogs per group should be adequate to detect main effects, but that calculation was based on data collected using a different methodology and which differed substantially from the results ultimately obtained in this study.
Enrollment of a larger sample size could have yielded different results. Additionally, only one instrument was used to assess platelet function; including multiple measurements of platelet function could have improved the assessment of platelet function. The instrument used in our study was an impedance aggregometer, which analyzes platelet function in fresh whole blood. Optical aggregometry, which uses platelet rich plasma, and flow cytometry might have provided different insights into platelet function.
Furthermore, our study only evaluated two time points during drug administration, limiting comparison to prior work. Another limitation to our study was that three techniques were used to collect urine for urine dTXB 2 quantitation, and it is possible that the lack of consistency in the collection technique could have influenced the dTXB 2 -to-creatinine ratios.
Additionally, blood and urine were collected within 4 h of drug administration, but sample collection was not performed at the exact same time point for each dog. Because aspirin irreversibly inhibits platelet function and therapeutic monitoring was first performed after 14 days of administration, the platelet function should be inhibited, this small difference in timing would be anticipated to have minimal effect on platelet function testing results. Additionally, previous studies in dogs have shown that the change in platelet function when treated with anti-platelet doses of aspirin are gradual, lacking dramatic changes during a short period of time 18 , An additional limitation to our study was the assessment of only 1 thromboprophylactic agent.
Anticoagulants, such as heparin and rivaroxaban, are considered the preferred anti-coagulant therapy in dogs with IMHA 5 , Thus, oral anti-platelet therapy remains 1 of the most affordable, long-term thromboprophylactic therapies and can be an effective thromboprophylactic therapy in dogs with IMHA 5 , Additional studies would be required to assess the effectiveness of anticoagulant and non-aspirin anti-platelet therapies to counteract glucocorticoid-induced hypercoagulability.
Dogs with IMHA are predisposed to developing thromboembolism, and the administration of glucocorticoids might contribute to a hypercoagulable state. Additional studies using a wider array of platelet function testing methodologies in hypercoagulable dogs need to be performed. The datasets generated for this study are available on request to the corresponding author.
The animal study was reviewed and approved by the University of Tennessee, College of Veterinary Medicine Institutional Animal Care and Use Committee protocol number and was in compliance with the requirements of a facility accredited by the American Association for Accreditation of Laboratory Animal Care. AM and JW organized and conducted the experiment. The funders had no involvement in the design or performance of the study, writing of the manuscript, or the decision to submit the manuscript for publication.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Erb HN. Evaluation of prognostic factors, survival rates, and treatment protocols for immune-mediated hemolytic anemia in dogs: cases J Am Vet Med Assoc. Immune-mediated hemolytic anemia: 70 cases J Am Anim Hosp Assoc. Prognostic factors for mortality and thromboembolism in canine immune-mediated hemolytic anemia: a retrospective study of 72 dogs.
Although platelet-bound antibodies can be detected using flow cytometry, this is not commonly done, so diagnosis of ITP is typically presumptive based on the presence of severe thrombocytopenia without another explanation. Recommended diagnostic workup for possible causes of secondary ITP includes testing for tickborne diseases, as well as chest x-rays and abdominal ultrasound to look for evidence of neoplasia. While point-of-care testing such as 4dx is a useful first step in evaluation for tickborne diseases, a broader tick screening can be useful to look for other diseases such as Rocky Mountain spotted fever and Babesiosis.
Screening for Babesia infection should be considered particularly in overrepresented breeds, such as greyhounds and pit bull terriers. Due to the high prevalence of tickborne disease in New England, it is also common practice to administer doxycycline as a part of initial therapy for ITP to cover for the majority of tickborne diseases.
Figure 1: The shaved ventral abdomen of a patient with ITP secondary to administration of trimethoprim-sulfamethoxazole, displaying petechiae and ecchymoses. Platelet count should be monitored after each dose reduction to make sure there is no sign of relapse. Adjunctive immunosuppressive medications, including cyclosporine, mycophenolate, and azathioprine, are also frequently used in an attempt to better control the disease or reduce the corticosteroid requirement.
A surgery to remove the spleen has been advocated in severe cases of ITP which failed to respond to medical treatment. We rarely recommend this surgery in our hospital but this must be discussed with your own veterinarian.
If ITP is severe enough, hospitalisation in a referral hospital may be needed. In a referral hospital access to unusual medications, including human medication may be facilitated e. Risks ITP is considered to be idiopathic or primary when no underlying cause is found. Secondary ITP occurs when an underlying cause is identified which may include: " Rickettsial infections e. Ehrlichia canis, Anaplasma phagocytophilum " Drugs e.
Any breed, sex or age of dog can be affected by ITP. People often worry that the ITP has been triggered by recent vaccination, as this link has been established in humans although is exceedingly rare. In dogs it has not been proven that any vaccination causes ITP, and if it does occur it is also likely to be a rare event.
It is very important to remember that many of the diseases your dog is vaccinated against are far more dangerous and common than the rare side effects associated with vaccination.
If you are concerned about side effects of vaccination in dogs please discuss this with your veterinarian. Prevalence In a study of dogs in the USA, 5. After stabilisation with treatment, the doses are usually slowly tapered down while monitoring closely the platelet value.
Furthermore, duration of hospitalization was reduced in the vincristine group, compared with the prednisone group 5. No adverse effects attributable to vincristine were observed in any dog. Conclusions and clinical relevance: Administration of combined vincristine and prednisone is associated with more rapid increase in platelet numbers and shortened duration of hospitalization in dogs with IMT, compared with use of prednisone alone.
Objective: To evaluate the effect of prednisone alone, compared with a combination of prednisone and vincristine, on platelet counts in bleeding dogs with severe primary immune-mediated thrombocytopenia IMT. Design: Prospective case study. In addition, 12 dogs received a single dose of vincristine 0. Platelet count, transfusion requirement, and outcome were monitored. Dogs in the prednisone group that failed to respond received 1 dose of vincristine on day 7.
A similarly rapid response was observed in dogs that received vincristine on day 7 after treatment with prednisone alone failed. Furthermore, duration of hospitalization was reduced in the vincristine group, compared with the prednisone group 5. No adverse effects attributable to vincristine were observed in any dog. Conclusions and clinical relevance: Administration of combined vincristine and prednisone is associated with more rapid increase in platelet numbers and shortened duration of hospitalization in dogs with IMT, compared with use of prednisone alone.
Early use of vincristine seems warranted in dogs with severe primary IMT. Abstract Objective: To evaluate the effect of prednisone alone, compared with a combination of prednisone and vincristine, on platelet counts in bleeding dogs with severe primary immune-mediated thrombocytopenia IMT. Substances Glucocorticoids Vincristine Prednisone.
Administration of clopidogrel/prednisone increases platelet dysfunction in healthy dogs. Keywords: antiplatelet, corticosteroid, glucocorticoid. The mainstay of treatment for ITP is immunosuppressive corticosteroid therapy, usually given as prednisone starting at 2 mg/kg/day (or 30 mg/m2 for larger-breed. Dogs with immune-mediated thrombocytopenia (ITP) usually present with prednisone alone is not the optimal therapy for lymphoma—dogs with. Procedure—All dogs received immunosuppressive doses of prednisone ( to 2 mg/kg [ to mg/lb] of body weight, PO, q 12 h). In addition. In healthy dogs, sustained aspirin, prednisone, and combination therapy do not inhibit platelet aggregation, and when used as individual. Figure 1: The shaved ventral abdomen of a patient with ITP secondary to administration of trimethoprim-sulfamethoxazole, displaying petechiae and ecchymoses.Objective —To evaluate the effect of prednisone alone, compared with a combination of prednisone and vincristine, on platelet counts in bleeding dogs with severe primary immune-mediated thrombocytopenia IMT. Procedure —All dogs received immunosuppressive doses of prednisone 1. In addition, 12 dogs received a single dose of vincristine 0. Platelet count, transfusion requirement, and outcome were monitored.
Dogs in the prednisone group that failed to respond received 1 dose of vincristine on day 7. A similarly rapid response was observed in dogs that received vincristine on day 7 after treatment with prednisone alone failed. Furthermore, duration of hospitalization was reduced in the vincristine group, compared with the prednisone group 5. No adverse effects attributable to vincristine were observed in any dog.
Conclusions and Clinical Relevance —Administration of combined vincristine and prednisone is associated with more rapid increase in platelet numbers and shortened duration of hospitalization in dogs with IMT, compared with use of prednisone alone. Early use of vincristine seems warranted in dogs with severe primary IMT. J Am Vet Med Assoc ; — Follow the AVMA. Subscribe to newsletters. All rights reserved. Advanced Search Help. Sign in Sign up. Journal of the American Veterinary Medical Association.
Cited By. Pathology in Practice. Authors Kelsey R. Marc Kent. Renee M. Simon R. Authors Trenton C. David Eshar. Dana M. Denise Lin. Sanjeev K. Outcome of performance-based removal and replacement decisions in commercial swine herds. Authors Stephanie C. John Deen. Theriogenology Question of the Month. Authors Maria S. Kara L. David E. Previous Article Next Article. Comparison of platelet count recovery with use of vincristine and prednisone or prednisone alone for treatment for severe immune-mediated thrombocytopenia in dogs.
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