Feline arterial thromboembolism (FATE): 10 points and a paper

Theory refresher

I came across the paper below on feline arterial thromboembolism (FATE) and thought I would share some of its findings.

However before doing that, here are ten pieces of information about this condition based on current knowledge:

1. Although not identified in all cases, the majority of FATE cats have cardiomyopathy, often hypertrophic cardiomyopathy, which most commonly includes left atrial enlargement and is often advanced by the time of presentation.
2. Thrombi usually form in the left atrium, become dislodged, and then cause occlusion at a distal systemic site. The aortic trifurcation (saddle thromboembolism, aortic thromboembolism) is the most common site; this is the site where the terminal abdominal aorta divides into the external iliac arteries supplying the pelvic limbs and the source of the main arterial supply to the tail.
3. (Per-)acute onset of clinical signs that in general depend on: the site at which the embolus lodges; whether complete or only partial obstruction occurs; the duration of obstruction; the extent and diameter of any collateral circulation.
4. Pain and distress may be a feature but are not present in all cases and likely reflect the severity and stage of pathology in terms of limb ischaemia.
5. Pelvic limb examination in distal aortic TE – findings can vary between limbs:
• Unilateral or bilateral absence of femoral and therefore dorsal pedal pulse Paws are usually colder than the thoracic ones.
• Digital pads may be pale or have blue/purple-looking blood visible with absent refill
• Quicks may appear purple in colour
• Severe neurological abnormalities of the pelvic limbs and tail may be present, including absence of pain sensation; perineal reflex may be absent
• Muscles may be swollen and painful on palpation, or pain sensation may be completely absent
6. Hypothermia is relatively common in cats with distal aortic TE and may be associated with a poorer prognosis.
7. Diagnosis is usually straightforward based on physical examination findings; absence of pulse can be confirmed using a Doppler ultrasound device. Other tests such as cutting a claw or demonstrating pelvic-thoracic limb venous lactate differential are rarely necessary (in my experience) and the patient’s welfare and comfort must be prioritised at all times – must not stress the patient just to get test results for your personal interest!
8. If euthanasia is not being performed, treatment considerations include:
• Analgesia
• Symptomatic/supportive/nursing care
• Thromboprophylaxis
• Treatment for heart failure and heart disease
9. Based on current evidence, thrombolytic agents available at the time of writing should not be used for feline ATE. While drugs such as aspirin, clopidogrel or heparin may help to prevent clot formation and expansion – may! – they do not cause clot dissolution – I think people sometimes misunderstand this.
10. There remains a dearth of good quality clinical evidence for a beneficial effect of thromboprophylaxis but it is recommended based on a perceived positive risk-benefit assessment. Dual anti-platelet therapy with aspirin and clopidogrel (if patient is compliant enough!) is probably most reasonable based on current information. Recently, clopidogrel was reported to increase time to ATE recurrence or cardiac death compared with aspirin in a prospective, randomized, multicentre, clinical trial of cats with a prior history of ATE*.

  

(*Hogan D, Fox P, Jacob K, et al. Analysis of the Feline arterial thromboembolism: Clopidogrel vs. aspirin trial (Fat Cat). In: Proceedings of the ACVIM Forum; June 13–15, 2013; Seattle, WA (abstract))

 

NB. Cats with arterial, including distal aortic, thromboembolism present with a spectrum of severity both in terms of the compromise resulting from the thrombus and the severity of their heart disease. While euthanasia is the most reasonable recommendation for the more severe cases, cats that are less severely affected can be stabilised and return home to enjoy a reasonable quality of life for potentially a period of months if not one-to-two years. Clearly these cats require lifelong medication for their heart disease and for thromboprophylaxis and they remain at constant risk for recurrence. Whether or not treatment is reasonable therefore depends on the individual patient – including carer’s wishes obviously; the challenge is to not subject hopeless cases to unnecessary suffering by persevering while at the same time not immediately euthanising all FATE cats given the spectrum of presentation seen.

Paper

Borgeat K, Wright J, Garrod O, et al. Arterial Thromboembolism in 250 Cats in General Practice: 2004–2012. J Vet Int Med 2014. 28(1):102-108.

Aim/Hypothesis: “Cats with ATE presented to general practice (GP) veterinary clinics have been under-represented in the literature. We aimed to analyze the patient characteristics and outcome in a population of cats managed in GP and to estimate the prevalence of ATE in cats in the United Kingdom (UK) GP. We hypothesized that cats with ATE presenting to GP were likely to be euthanized at presentation without any attempt to treat the disease, but that survival times >1 year were possible for some cats.”

Materials/Methods snippets:

Two large practices and 1 emergency only, out-of-hours, clinic took part in the study; all in southern England, UK.

Retrospective medical record review of cases seen over 98-month period from January 1, 2004 to March 1, 2012

 

Inclusion/exclusion:

 

Included if had typical clinical signs of limb ATE

Excluded if:

• Atypical signs
• Dead on arrival
• Clinical signs suggestive of non-limb ATE
• Diagnosis made post-mortem
• Referred to specialist referral centre for treatment

 

Mortality was defined as either spontaneous death or euthanasia and analysed at different time points:

• Within 24 hours of presentation
• After 24 hours of presentation but before 7 days after presentation
• After 7 days of presentation

 

Main results of interest:

250 cats were diagnosed with ATE; prevalence ~0.3%

Analgesia was administered to all cats not euthanised at presentation (97/250)*

 

(* This implies to me that cats that were euthanised did not receive analgesia. My preference and recommendation is where there is any doubt about discomfort, to administer a fast-acting pure full mu-agonist opioid as soon as possible even if euthanasia is then performed. Firstly owners cannot and should not be rushed into decision-making about euthanasia and it does not seem kind to me to leave the patient in pain in the interim period. Secondly analgesia can improve compliance and distress during intravenous catheter placement for euthanasia.)

Euthanasia was performed at presentation in 153/ 250 (61.2%) cats.

24-hour survival:

Of those cats for which treatment other than euthanasia was attempted, an additional 22/97 (22.7%) cats were euthanised and 7/97 (7.2%) cats died before 24 hours after presentation.

In all, 68/ 250 (27.2%) cats survived for 24 hours after presentation.

 

Mean rectal temperature was lower in non-survivors (36°C [32.0–39.2] versus 37.8°C [33.1– 41.5], P < .001).

“In cats surviving 24 hours in which treatment was attempted, lower rectal temperature at presentation was significantly associated with mortality between 24 hours and 7 days after presentation. This finding remained significant after multivariable analysis that accounted for the effect of other measured variables.”

 

7-day survival:

Of cats that survived 24 hours after presentation: 38/68 (55.9%) were dead <7 days after presentation, 32/38 were euthanised (47% of 24-hour survivors), and 6/38 died (8.8% of 24-hour survivors).
In the univariable analysis, cats with ≥2 limbs affected by ATE were less likely to survive to ≥7 days but this was not an independent predictor of mortality.
Median survival times of all 30 cats surviving 7 days after presentation was 94 days after they were presented.

Another study reported that the presence of congestive heart failure at presentations was associated with a significantly lower median survival time. But this study here did not have enough cats in this category to justify statistical evaluation.

 

Median hospitalisation time for the 30 cats alive ≥7 days was 2 days (range 0–7 days).

Median time from presentation to recurrence was 118 days (range 7–2,614 days).

 

1-year survival:

By 1 year after presentation, 6/30 (20%) cats alive at ≥7 days were still alive. For these cats, median survival time (MST) was 94 days (95% CI, 42–164 days; range 7–2,614).

Similar numbers of patients were euthanised after discharge as a result of CHF and ATE recurrence.

 

“The devastating nature of ATE and CHF in cats is illustrated by the observation that all cats alive at 7 days after presentation died or were euthanized because of cardiac disease or factors relating to ATE.”

 

“Overall, the most common cause of death was euthanasia, performed in 229/250 (91.6%) cats. Spontaneous death occurred in 16/97 (16.5%) cats that were not euthanized at presentation.”

“Unfortunately, data contained in the clinical records from multiple GP centers over a long period, which is based on the experience and opinion of individuals, are likely to be highly variable among clinicians and over time. There is no way of standardizing the data in a retrospective study. There were a large number of missing data points attributable to minimal investigation in patients that were likely to be unstable and poorly tolerant because of stress and pain in a population in which financial restrictions were likely to be common. A prospective study to evaluate outcome in cats treated for ATE, performed in a standardized manner in ≥1 center, should eliminate most of this variation and thus improve reliability and the strength of evidence.”

Below is the authors’ final paragraph with some commentary from me:

“In summary, the estimated prevalence of ATE in cats presented to GP over the 98-month period studied was 0.3%.” So I guess this is an interesting epidemiological finding and gives us some sense of the size of this problem.

“As we hypothesized, cats with ATE presented to GP were likely to be euthanized with no attempt to treat.”

“Approximately, half of cats surviving the initial 24 hours after presentation [68/ 250 (27.2%) cats survived for 24 hours after presentation] survived for 7 days.” To be honest I am not sure this information is of much value. It is interesting sure but I personally don’t think that surviving the initial 24 hours or indeed for 7 days means much here. Ultimately we want these cats to be going home to have a reasonable quality of life for a reasonable period of time and their quality of life was probably not reasonable for at least some of these short survival periods.

“One-fifth of cats alive at ≥7 days survived for 1 year after presentation, confirming that long-term survival is possible in a small proportion of cases.” To remind you: by 1 year after presentation, 6/30 (20%) cats alive at ≥7 days were still alive. For these cats, median survival time (MST) was 94 days (95% CI, 42–164 days; range 7–2,614). So 6 of the initial 250 diagnosed cats survived for 1 year and the data shows the ranges. For sure for some of these cases you can argue that survival was for a reasonable period – whatever ‘reasonable’ means – but this number is smaller still than 6/250. What we could really do with is one or more likely a cluster of factors that are well evidenced that clinicians could use when first presented with an FATE cat to be able to make some sort of reasonable prognostication for survival with a reasonable quality of life for a defined period that is accepted by the majority of people as being reasonable. Unfortunately “We could not identify any significant predictors of mortality after 7 days in this population.”

And a final comment which does not just apply to this study but all veterinary studies looking at survival is that this is always going to be influenced by the option of euthanasia; as we know, this can be a complex and multifactorial decision that depends on the perceptions and beliefs of the pet’s carer, their financial circumstances, their lifestyle and so on, but also their relationship with their veterinary surgeon/practice and the level and nature of advice given. Survival is clearly a primary outcome of major importance but unlike in human medicine, pure medical survival is impossible to assess in pets. Survival in veterinary patients refers to not just medical survival but also not meeting criteria in all their forms that trigger euthanasia.