Case Presentation: Management of a Patient With Factor Xa-Associated ICH Using Specific Reversal Therapy

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Dr. Seiffge: 
I will skip now to my cases. I brought you a few cases, about Xa inhibitor-associated bleeds. I brought two cases actually. So the first patient was an 86-year-old female patient who had a history of hypertension and atrial fibrillation with a CHADS-Vasc score of 4, HAS-BLED of 1, and was she was taking rivaroxaban 20 mg, and was a patient from our department. On admission, she had NIHSS of 6, Glasgow Coma was 15. So quite minor deficits for a hemorrhage, blood pressure was slightly elevated 157, and with a slightly reduced renal function. The key time metrics that you just heard from Natalie were last time - from last intake of the of rivaroxaban to ICH was 4 hours, so we should be somewhere in the peak area of the drug. So time from onset to admission was 45 minutes, she was very quick in hospital and we measured the anti-Xa activity in our hospital, we get the results within 30 to 1 hour. And she was highly anticoagulated. You see the level was 600 nanograms per mL which is a very high level, peak level, much more than the patient that you've seen in the ANNEXA study.

So what did we do? The case was several years ago, and was during the time where andexanet alfa was not available. So this was the baseline imaging. You see this tiny thalamic bleeds on baseline imaging with an ICH volume of 1 mL, because somebody asked whether there is a minimum volume that we should not reverse, and this patient actually had just 1 mL of bleeding so we gave her a PCC, about 1000 units, 25 units per kg. She was also enrolled in a study. I don't know in which arm she was, whether she had tranexamic acid or not, but she was enrolled in a study. And 12 hours later, we saw this picture, the ICH expanded to 35 mL, she had new intraventricular hemorrhage. And after 24 hours, we performed a second CT scan, and you see 75 nanograms per mL, and now a large intraventricular bleed you already see the ventricles dilating and she deteriorated to a Glasgow Coma Scale of 6, and at day 7, she was dead.  She died unfortunately, so a very poor outcome for somebody who has a lot to lose in the situation.

A different lady 90-year-old a lady that we have treated a few years ago. Also history of hypertension, also atrial fibrillation, a CHADS-Vasc score of 4, HAS-BLED score of 2, she was taking apixaban 2x 5 mg. On admission, she had an NIHSS of 20, so severely disabled actually. She also had she had elevated blood pressure of 160. She had a normal renal function. Her clinic metrics were time from some last intake of apixaban to ICH onset at 3 hours. Time from ICH onset to admission, 90 minutes, so slightly longer than the first patient but still quite early. And she had a calibrated anti-Xa activity of 114, which is after 3 hours with this was renal function probably on the upper slope of going to the peak level.

This was her baseline imaging. She got an MRI at baseline, and you see this bleed with a volume of about 20 mL. She also had some interventricular blood over here. She actually received low-dose andexanet alfa. And this was a follow-up imaging and it's a CT but you can still appreciate I think that the image look quite comparable. So that seems at least visually, there was no hematoma expansion and also, if you measure it with a semi-automated volumetric analysis, you'll see that the volume stayed stable over the time, and she, at 3 months, had a Modified Rankin Score of 3, so she was able to walk with a stick, but she had to need some help as a 90-year-old lady.

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