Apixaban-induced hepatoxicity: Meet Amanda(12)

Amanda is an 81-year-old woman with a history of high blood pressure (hypertension) which has been managed with 25mg of atenolol (medication used to treat hypertension) daily.

She came into A&E with heart palpitations and shortness of breath and had been experiencing these symptoms for 3 years but only sought help now.

Her ECG presented an irregular heartbeat, whereas Amanda’s ECG from 2 years ago presented normal rhythm and she has no history of irregular heartbeats.

Treatment was then initiated which included rate control, increased dosage of atenolol (from 25mg to 50mg), and 5mg of apixaban two times per day. This treatment aimed to prevent possible strokes.

Amanda was discharged 24 hours after hospitalisation.

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Signs and symptoms of liver toxicity (hepatotoxicity)

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Two days after Amanda was discharged, she returned to A&E with new symptoms which include:

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Primary symptoms:

• Abdominal pain

• Shortness of breath

• Generalised weakness

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Other Symptoms:

• Bloating

• Vomiting

• Nausea

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Her diet and appetite had remained the same and no diarrhoea had occurred in those two days.

With the symptoms pointing towards the direction of possible abnormalities in the abdominal area, the signs the doctors found pointed towards possible problems with the liver in specific.

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Sign 1)

Mild Scleral Icterus – the yellowing of the sclera (the white area of the eye)

• This usually indicates increased levels of bilirubin

Bilirubin: is an orange-yellow pigment produced by the liver when it breaks down red blood cells.

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Sign 2)

Moderate right upper quadrant tenderness (the right upper quadrant is the upper right side of your abdomen and that is where the liver is located)

Everything else was normal but all signs and symptoms pointed towards problems within her liver.

 

How can Apixaban be Toxic to the liver?

Apixaban-induced liver injury is not very common, and even if a case is presented it is usually mild and treatable. It is suggested that patients with prior liver injury may be at a higher risk of apixaban-induced hepatotoxicity. In Amanda’s case, it is a more moderate case of hepatoxicity, and this may because of her age and/or her pre-existing health conditions. Liver injury from apixaban may be due to the production of a toxic or immunogenic as a by-product of apixaban(9). 

Lab results concluded that Amanda’s liver enzymes had increased since Day 0 of her hospital admission. Below is Amanda’s values of bilirubin and enzyme levels from day 0 to day 7:

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Figure 1(12): A graphs showing the values of liver enzyme levels.

The top graph shows the levels of bilirubin from day 0 to 7.

The bottom graph shows the rise and drop in the values of the liver enzymes: ALT (amino alaninetransferase), AST (aspartate aminotransferase), and ALP (alkaline phosphatase) from day 0 to 7.

Apixaban was initiated on day 0 and discontinued on day 3. 

 

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Increased levels of bilirubin indicates that Amanda’s liver wasn’t functioning properly, which allowed doctors to conclude that this was a rare case of Apixaban-induced liver injury. As Amanda had been using atenolol for such a long period, an increased dosage would have not been able to affect the condition of her liver so the only culprit would be apixaban(9). 

Treatment and Follow-up

It was concluded that Apixaban was the culprit for the elevated liver enzymes. Doctors discontinued the use of apixaban and started Amanda on a new treatment which included alternative anti-coagulants such as Heparin, Warfarin, and the continued use of Atenolol.

After 24 hours of discontinuation of apixaban, the liver enzyme levels (ALT, AST, and ALP) started to decline as well as the bilirubin level (as seen in Figure 1). Amanda’s symptoms gradually improved, and she was discharged after 5 days. Doctors had a few follow-ups on Amanda, and each follow-up concluded that she was clinically stable, and her liver returned to normal after the discontinuation of apixaban. 

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The take-home message is that;

 

Apixaban-induced liver injuries are rare and doctor will try to give you the anticoagulant that suits your treatment plan best. However, if you feel like you have any of Amanda’s symptoms please contact 111 or in a severe case please call 999 immediately. 

Drug-induced liver injuries are treatable if spotted early.
 

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