FATE

Question 1

What are the three factors described by Virchow’s triad that contribute to thrombosis?

Answer 1

1. Hypercoagulability
2. vascular stasis
3. endothelial injury

Question 2

What percentage of cardiomyopathic cats exhibited hypercoagulability in a study by Stokol et al JVIM 2008?

Answer 2

50%

Question 3

What causes blood stasis in cats?

Answer 3

Reduced blood velocity or turbulent blood flow, often due to vascular or heart valve or chamber anomalies

Question 4

What are some prognostic indicators in hypertrophic cardiomyopathic cats found by Payne et al JVIM 2013?

Answer 4

• Left atrial (LA) size
• decreased LA function
• LA:Ao
• presence of spontaneous echocardiographic contrast (SEC)

Question 5

What is the gender predisposition for thrombosis in cats?

Answer 5

Male cats (66%)

Question 6

What percentage of cats affected by thrombosis have underlying cardiomyopathy?

Answer 6

90%

Question 7

What percentage of cats affected by thrombosis were previously diagnosed with cardiac disease?

Answer 7

< 10%

Question 8

In what % of cats with FATE are both pelvic limbs affected?

Answer 8

75%

Question 9

Two or more of the following:
* Coagulation factor excess (high fibrinogen concentration or factor VIII coagulant activity)
* Inhibitor deficiency (low antithrombin activity)
* Thrombin generation (high thrombin-antithrombin complex and d-dimer concentrations)

Answer 9

What defines hypercoagulability in the context of feline cardiomyopathy?

Question 10

Closure time measured by PFA-100, prothrombin time, activated partial thromboplastin time (aPTT)

Answer 10

Which laboratory tests showed no difference between healthy cats and cardiomyopathic cats?

Question 11

7 to 12 years old

Question 12

Treatment of acute paralysis and pain secondary to the embolism

Answer 12

What are the short-term concerns clinicians need to address in cats with thrombosis?

Question 13

Management of congestive heart failure (CHF) and advanced heart disease

Answer 13

What are the long-term concerns for management in cats with thrombosis?

Question 14

Thrombin generation

Answer 14

Fill in the blank: Hypercoagulability is defined as two or more of the following: coagulation factor excess, inhibitor deficiency, or _______.

Question 15

Increased platelet activation and increased concentration of activated clotting factors

Answer 15

What can make diagnosing endothelial injury difficult in vivo?

Question 16

What is the 5P rule for diagnosing FATE?

Answer 16

Pallor (purple/pale toes)
Polar (cold extremities)
Pulselessness
Paralysis
Pain

Question 17

Name X diagnostic tools to diagnose FATE

Answer 17

• 5P rule
• lack of bleeding when cutting a toe nail
• absence of Doppler flow
• direct US visualization
• infrared thermal imaging (difference of 2.4°C between affected and non-affected limbs; can also be used to assess reperfusion)
• angiography
• glucose/lactate differential between affected and normal limbs

Question 18

What change in glucose and lactate levels of the affected and normal limbs did McMichael et al JVECC 1998 report in their abstract?

Answer 18

Glucose:
affected limb: 2.8 +/- 1.4 mmol/l (50 +/- 25 mg/dl)
central: 10 +/- 4.9 mmol/l (182 +/- 89 mg/dl)

Lactate:
affected limb: 10.7 +/- 2.7 mmol/l (192 +/- 49 mg/dl)
central: 2.1 +/- 0.8 mmol/l (38 +/- 14 mg/dl)

Question 19

What did Guillaumin et al JVECC 2021 report about lactate vs. glucose as a diagnostic marker for diagnosing FATE when comparing affected and normal limbs?

Answer 19

lactate may be a more robust diagnostic tool than glucose, with a mean lactate in the affected limb of 11.3 +/- 3.5 mmol/L compared to 3.4 +/- 1.2 mmol/L in normal limb.

Question 20

What were sensitivity, specificity, PPV and NPV of a difference in 2.4°C between affected and non-affected limbs in cats with FATE when using infrared thermography?

Answer 20

Sensitivity: 85%
Specificity: 100%
PPV: 100%
NPV: 80%

Question 21

What is the survival rate for FATE when treatment is attempted?

Answer 21

27% - 45%

Question 22

What did the BLASTT study (prospective, randomized study) comparing thrombolysis with t-PA to placebo show?

Answer 22

overall STD: 37.5%
–> TPA: 45%
–> placebo: 30%

• statistically significant improvement in limb scores compared with baseline for both groups
• Thrombolysis had no statistically significant effect on 48 h survival
• Lower affected limb lactate was associated with better 48 h survival (OR 1.53)

Complications: AKI (22% vs. 19%) and reperfusion injuries (33% vs. 19%,) - not significant

Question 23

What is a positive prognostic factor in FATE?

Answer 23

Cats with motor function at admission or one limb affected (70% survival to discharge vs. 25% survival to discharge with bilateral pelvic paralysis)

Question 24

What are negative prognostic indicators according to Smith et al JVIM 2003?

Answer 24

• lower rectal temperature
• lower HR
• higher phosphorous levels
• absence of motor function

–> presence of CHF was correlated with a shorter long-term survival

Question 25

What did Borgeat et al JVIM 2014 show regarding nonsurvivor baseline characteristics?

Answer 25

* lower rectal temperature

Question 26

What are 2 medical options for thrombolysis?

Answer 26

* streptokinase * t-PA

Question 27

Name 4 possible complications of thrombolysis?

Answer 27

* Hyperkalemia (similar to no thrombolysis) * AKI (similar to no thrombolysis) * clinical bleeding * coagulation abnormalities

Question 28

How does aspiration mediate its antiplatelet action? What is its half-life in cats compared to dogs?

Answer 28

works on the arachidonic acid pathway --> irreversibly inhibits cyclooxygenase pathways cats: 38hr dogs: 7hr

Question 29

How does clopidogrel mediate its antiplatelet action?

Answer 29

- selectively inhibits ADP-in- duced platelet aggregation - no direct affect on arachidonic acid pathway - requires hepatic biotransformation into active metabolite

Question 30

List some causes of the variable effect of UFH. How can UFH be monitored?

Answer 30

- effects depend on the proportion of heparin molecules large enough to bind thrombin - Larger heparin molecules are cleared from the circulation relatively rapidly (half-life: 30 min) Monitoring: aPTT --> 1.5-2.5 times normal control

Question 31

How does the effect of LMWH compare to UFH?

Answer 31

- reduced anti-IIa activity relative to anti-Xa activity - better predictable pharmacokinetic properties - reduced affinity for binding to plasma proteins or cells compared with UFH --> more predictable dose response relationship + longer half-life

Question 32

What is the recommended monitoring for LMWH?

Answer 32

Anti-factor Xa activity

Question 33

What is the half-life of dalteparin and enoxaparin in cats?

Answer 33

dalteparin: 40-60min enoxaparin: 2.3hr Dalteparin 100 IU/kg SC BID failed to achieve anti-Xa activity in 50% of normal cats + failed to maintain anti-Xa activity beyond 4 hr in the other 50%.

Question 34

What antithrombotic treatments are recommended by the CURATIVE guidelines for FATE?

Answer 34

1. Clopidogrel PO (with loading dose) 2. LMWH (dalteparin 75 IU/kg SQ QID; enoxaparin 0.75-1mg/kg SQ QID) 3. UFH (250 U/kg SQ QID) 4. rivaroxaban 0.5-1 mg/kg/d PO (apixaban is not mentioned in CURATIVE guidelines)

Question 35

What is the CURATIVE recommendation for warfarin?

Answer 35

should not be used because of marked interin- dividual variation coupled with a narrow therapeutic index

Question 36

What is the half-life of apixaban in cats?

Answer 36

8.3hr at 0.2mg/kg PO

Question 37

What % of patients with FATE have concurrent CHF?

Answer 37

44-67%

Question 38

What is the treatment of FATE?

Answer 38

1. treat CHF if present 2. Passive range of motion 3. Analgesia (methadone, fentanyl CRI) 4. Antithrombotics (clopidogrel, rivaroxaban) 5. +/- thrombolytics (t-PA) 6. leg warming

Question 39

What % of patients receiving standard treatment for FATE (without thrombolysis) experiences reperfusion injury or AKI?

Answer 39

reperfusion injury: 50% AKI: 30%

Question 40

What are reported risk factors for developing FATE?

Answer 40

* LA dilation * Sponatenous echocontrast * reduced LA appendage flow velocity * history of FATE

Question 41

What is the cumulative risk of FATE in cats with HCM or HCOM at 1, 5 and 10y compared to normal population according to the REVEAL study by Fox et al JVIM 2018?

Answer 41

HCM: 1y: 3.5% 5y: 9.5% 10y: 11.3% normal: 1y: 0% 5y: 0.4% 10y: 0.7%

Question 42

What did Hickey et al JVIM 2014 identify as risk factor for experiencing FATE later in life?

Answer 42

renal infarcts

Question 43

What is the reported recurrence rate of the FATCAT study by Hogan et al JVC 2015 for cats treated with aspirin or clopidogrel?

Answer 43

aspirin: 75% clopidogrel: 49% time to recurrence of FATE or cardiac death: clopidogrel: 11.5m aspirin: 4.3m

Question 44

What die the SUPERCAT study by Brainard et al JAVMA 2024 show when comparing rivaroxaban to clopidogrel in cats with FATE?

Answer 44

FATE recurrence: clopidogrel: 37% rivaroxaban: 39% median (95% CI) time to ATE recurrence: clopidogrel: 663d rivaroxaban: 513d