In today's VETgirl online veterinary continuing education blog, we discuss treatment for immune-mediated thrombocytopenia (ITP) in dogs. Have you treated a patient with primary ITP? Did you use steroids alone, or did you try combination therapy with vincristine or human intravenous immunoglobulin (hIVIG)? Well, while treatment with immunosuppressive doses of glucocorticoids is the initial treatment of choice, and most patients will have platelet recovery within 1-15 days of starting treatment, adding treatment with vincristine or hIVIG has been shown to shorten platelet recovery time. In some peer-reviewed, scientific veterinary prospective studies, dogs with severe ITP treated with prednisone alone versus prednisone and vincristine, or prednisone alone versus prednisone and hIVIG, both combination therapies resulted in faster increases in platelet numbers and shorter durations of hospitalization. To date, though, there haven’t been any studies looking at the efficacy of vincristine versus hIVIG as adjunctive treatments. This is important because hIVIG is much more expensive, and giving it to your patient is more time consuming and challenging that giving vincristine.
So Balog et al out of Purdue University and University of Georgia wanted to look at platelet recovery time, duration of hospitalization, transfusion requirements, adverse effects and long-term outcome in dogs with severe ITP treated with either vincristine or hIVIG in addition to standard therapy with glucocorticoids. They defined severe ITP as a platelet count < 16,000/uL and no potential causes of secondary ITP. In this prospective, randomized study of client-owned dogs with primary ITP, they enrolled 25 dogs into the study, but 5 ended up being excluded, so a total of 10 dogs were randomly assigned to each group. All of the dogs were treated with glucocorticoids (e.g., prednisone at 1.5-2 mg/kg PO Q12 or dexamethasone 0.2-0.3 mg/kg SQ or IV q24); they were then randomized to receive either hIVIG (0.5 g/kg IV as a CRI over 6-12 hours) or vincristine (0.02 mg/kg IV bolus). There were no differences in age, sex, weight, initial platelet count, BUN or other clinicopathologic data between the two groups. Presenting complaints included petechiae/ecchymoses (8 dogs), melena (6), oral bleeding (6), lethargy (4), cutaneous bleeding (3), decreased appetite (3), epistaxis (2), hematemesis (2), hematochezia (2), hematuria (1), vomiting (1), diarrhea (1), coughing (1) and acute blindness due to hyphema (1).
On admission, the median platelet count for all dogs was 1000/uL (range 0-16,000/uL). 11 dogs were also anemic on admission. The median platelet recovery time was 2.5 days for both groups, with a median hospitalization time of 5 days for the hIVIG group and 4 days for the vincristine group of dogs. 7/10 (70%) of dogs in the hIVIG group and 10/10 (100%) dogs in the vincristine group survived to discharge. Overall, the mean cost of treatment was significantly higher in the hIVIG group ($4108) as compared to the vincristine group ($2426) (P<0.001), which may be due to the cost of hIVIG. 7/10 (70%) of the dogs in the hIVIG group and 6/10 (60%) of the dogs in the vincristine group received transfusions; transfusion requirements were not significantly different between groups. Rescue protocol was initiated in this study if there was no improvement or change in the platelet count after 7 days, of which patients were given the alternative study drug and azathioprine (2 mg/kg PO q24) - this was necessary in 2 dogs that were in the hIVIG group. Both of these dogs survived to discharge. At follow up 6 months later, 52.6% (10/19) of the dogs had died (7/9 from hIVIG group and 3/10 from the vincristine group). At 1 year follow up, 11 dogs had died (e.g., 7/9 from hIVIG group, and 4/10 from the vincristine group).
So, what can we take away from this VETgirl podcast? This study suggests that in dogs with severe ITP, there is no difference in outcome when they are treated with either hIVIG or vincristine as an adjunctive treatment in addition to glucocorticoids. Since vincristine is less expensive, more readily available and easier to administer, it should be used as first line therapy with glucocorticoids for the management of severe ITP. While this study was a small prospective, it was well, and the power to detect a difference among the groups was small, which might be why we didn’t see statistically significant differences in survival to discharge or 1-year survival. However, when looking at the long term outcome in these dogs (1 year out), it's depressing - make sure to educate your pet owners on the poor long term outcome with severe ITP! In conclusion, when treating a dog with severe ITP and trying to decide between vincristine and hIVIG as an adjunctive treatment, vincristine is recommended because in addition to being just as effective, it is easier to give, less expensive and more readily available.
1. Balog K, Huang AA, Sum SO et al. A prospective randomized clinical trial of vincristine versus human intravenous immunoglobulin for acute adjunctive management of presumptive primary immune-mediated thrombocytopenia in dogs. J Vet Int Med 2013;27(3):536-541.
ITP: immune-mediated thrombocytopenia
hIVIG: human intravenous immunoglobulin