Guillaumin J, Gibson RM, Goy-Thollot I, Bonagura JD. Thrombolysis with tissue plasminogen activator (TPA) in feline acute aortic thromboembolism: a retrospective study of 16 cases. J Feline Med Surg. 2018 May 1. PMID:29807505
Feline aortic thromboembolism (FATE) is a relatively common complication of cardiac disease in domestic cats. It occurs when a blood clot dislodges from its origin in the left atrium, travels through the ventricle, and lodges in the distal aorta. This results in a loss of blood flow to one or both hind limbs, resulting in pain, paralysis, and death of the tissues. Treatment of this condition is difficult and usually involves supportive care such as pain management, control of reperfusion injury, anticoagulation, and other supportive care. Studies have reported that up to 90% of cats are euthanized, and only 25-45% survive even with aggressive care.
In humans, ischemic stroke is very similar to FATE in cats. If they are treated with intravenous Tissue Plasminogen Activator (TPA) within 6h of the event, prognosis is significantly improved. TPA is a “clot buster” which breaks down existing blood clots. In cats, this therapy has been attempted, however, it is often not within the directed time span or using protocols that differ greatly from the human standard of care. They also lacked uncreated controls. The purpose of this study was to determine if early, short-term infusion of TPA influences short-term outcomes in cats with FATE. The study was designed as a retrospective case-control trial.
Cats were recruited from two academic hospitals in a 10-year period. Cats were diagnosed with FATE based on having limbs that were pale, cold, lacking pulse, and painful with lack of motor function. Only cats with a first episode of FATE were included, with two or more limbs effected. Cats who were euthanized with only analgesia provided were excluded from the study. Cats were classified as having either received standard of care (SoC) therapy or SoC + TPA. SoC included analgesia, cardiac support, and thromboprophylaxis without thrombolysis. The primary outcome was survival to study discharge, with secondary outcomes 48h survival, clinical improvement, and complications during hospitalization.
16 cats fit the inclusion criteria and received TPA in this time period. These cats had a median estimated time from FATE to admission of 3h (range 0-6h). 38 cats were included in the SoC group, with a median estimated time to admission of 6h (range 0-48h). Physical exam findings, blood pressure, biochemistry, lactate level, echocardiographic parameters, and limb scores were recorded for all patients. Castrated male cats represented the majority of cases, consistent with previous reports.
TPA was administered a median of 1.5h after admission, or 4.5h after the suspected event. All cats received 1mg/kg total dose, though the exact protocol differed somewhat between cats. There was no difference in disease severity or health status at admission between groups.
No significant difference was seen between groups in the length of hospitalization or rate of clinical improvement. More of the TPA cats had clinical improvement within the first 12h, however, this was not significant. No difference was seen in the rate of reperfusion injury or acute kidney injury. Likewise, no difference was seen in survival to discharge, euthanasia rate, spontaneous death rate, or short-term survival rate.
Several issues were present in this study. These included the small sample size, lack of consistent SoC therapy, and variations in TPA protocols. The retrospective nature also presented severe limitations including a lack of blinding or adequate controls.
The authors conclude that there was no evidence of a positive or negative effect of TPA in cats with FATE. This study was very limited by the small number of cats and the retrospective nature- larger, ideally multi-institutional prospective studies are needed to determine more definitively if any effect exists. (MRK)
See also:
Welch KM, Rozanski EA, Freeman LM, et al. Prospective evaluation of tissue plasminogen activator in 11 cats with arterial thromboembolism. J Feline Med Surg2010; 12: 122–128.