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CLL Support Association
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Uncontrolled bleeding events with Ibrutinib and in general

Hi all,

On another forum I saw a comment by a patient who wisely advised wearing a bracelet bearing important information that could help medical personnel help a patient with an uncontrolled bleeding event but suggested asking for a Vitamin K shot in the event of a bleed. Bleeding is a concern with patients on Ibrutinib but also many other patients on W&W or taking other therapies if they are also on blood thinning drugs. This is my take on the bleeding issue.

A medical bracelet is a great idea however it should not be assumed that a Vitamin K shot will reverse or stop all bleeding events. Vitamin K will only work if a person is on a vitamin K antagonist blood thinner like Warfarin (Coumadin). The newer blood thinning agents such as Pradaxa (Dabigatran) or Factor Xa blood thinners Xaralto (Rivaroxaban), Eliquis (Apixaban) & Savaysa (Edoxaban) may or may not have their own agents to reverse blood thinning. Pradaxa has a special FDA approved drug Praxbind (Idarucizumab) but the FDA refused to approve the reversal drug AndexXA designed for the 3 Factor Xa drugs.

Platelets are not the only concern regarding potential bleeding events as there are many clotting factors to consider as well. A proper medical work up can predict with considerable accuracy the potential for a patient on Ibrutinib to be wary for bleeding events and some common supplements to avoid such as fish oil or aspirin that might exacerbate or precipitate a bleed. haematologica.org/content/1...

Bottomline, if on a blood thinner, is to beware which drug, if any, has what agent that is approved for reversing uncontrolled bleeding events.


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Please think very carefully about treatment combining ibrutinib and Factor Xa blood thinners, the combo was awful in my case... there is very little data or knowledge in this area...


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Hi Cllcanada, I'm interested in learning more about your experience. My husband will soon begin CLL treatment, likely Ibrutinib. He is on a 10mg Xarelto dosage (recently reduced from standard 20mg dosage). I'm interested in finding the best targeted therapy/blood clot med combo. Thanks, Carol

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Well not everyone is an Imbruvica (ibrutinib) bleeder, just an unfortunate few... ☹️

Warfarin, used to be mentioned with regards to observation with Imbruvica (ibrutinib), but the last drug label revision has removed that... no explanation...

The one advantage perhaps it that Warfarin has a antidote,, vitamin K , but regrettable the new drugs, like Xarelto, do not...

The Ontario monograph still carries a number of warnings..

Patients who require anticoagulant treatment should not start ibrutinib until they are stable on their anticoagulant. Do not use warfarin or other vitamin K antagonists concomitantly with ibrutinib.


My recommendation is to monitor stools and urine for blood and have a stool sample tested in month 3 after taking Imbruvica (ibrutinib), just to check for occult blood.

Any signs of blood see the doctor ASAP. I experienced very mild petechiae that was transient, then blood filled welts, the size of half a golf ball... coupled with bleeds from my urethera, [caused by a ghost UTI infection treated with CIPRO], colon bleeds [turned out to be adenocarcinoma] , A.fib increase... I stopped treatment...

Vigilance is key... and action is imperative.



Thank you Chris. How were your CLL/clot medications adjusted after the significant bleeds you experienced?


20mg of Xarelto...I'm still on it... I was quite early on Imbruvica (ibrutinib) in a community setting... knowledge wasn't too deep...

I was on Xarelto for A.fib prior to Imbruvica (ibrutinib), but it got worse on it...

I'm on Zydelig (idelalisib) currently and have had no issues... at all... only side effect was mild colitis...

Oh and my experience in part, now limits the use of Cipro on Imbruvica (ibrutinib) 🙂 The drug label has been changed


So to clarify, your doc changed targeted therapy due to bleed, correct? Also, my husband is being seen at Stanford in California. Apparently, evidence suggests that 10mg Xarelto is equally effective with less bleed risk. And I think FDA approval is in the works. I don't know if this applies to afib as it does to clotting issues.


A.fib and clotting are quite different...

No I refused ibrutinib treatment... then went on to have a hemicolectomy, watch and wait for about another 9 months then needed treatment and started on Zydelig (idelalisib) and rituxan, which has been fine...

Imbruvica (ibrutinib) effects BTK and TEC gene on platelets... there are a couple of recent papers on it.

A very small number of patients are Imbruvica (ibrutinib) bleeders...

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Thanks for your time. I just looked up 'hemicolectomy'. Sounds like you had a secondary diagnosis on top of CLL. I'm not sure I'm totally following your comments. Do you think is is unusual for a hemonc to recommend ibrutinib to someone using xarelto for clotting disorder? Husband is under care of Stanford CLL guru. I also learned yesterday that he's been experiencing night sweats this week, a first.


I have no knowledge of the use of Xarelto except for my case of A.fib.

Actually adenocarcinoma was my third cancer... I had a Richter's transformation...previously to DLBCL., after FR.

Night sweats don't signal treatment, they are a B symptom which is taken in conjunction with many other things...

Your husband is under the care of a CLL specialist, he is in good hands...



Thanks Chris. I think doc will find night sweats as significant due to the fact that his ALC is HIGH, RBC and platelet counts are low (though recent improvement in platelet count). He's had a few bouts of chills recently, and though he hasn't lost a lot of weight, he seems to have remarkably lost much muscle tone, very thin looking, skin hanging... He's home recovering from hip revision surgery so hard to tell how fatigued he is as he's not active (no weight bearing on leg for 6 weeks, then another 4 weeks added to this). Femur had to be fractured to remove old implant and this needs more healing prior to beginning rehab/PT. Slightly concerned about Richter's.


Night sweats can be caused by other things than CLL... Infection perhaps...

Richter's is fairly specific... rocketing LDH levels, B2 microglobulin etc... increase in node size... usual first step now is a PET scan... followed by a core biopsy.

In my transformation my absolute lymphocyte count [ALC] shot up, but my LDH was high normal...

When do you see your hemaetologist next?



January. I know that Richter's is also pretty rare. He's been dodging bullets since 2011. Pre-op bloodwork for hip replacement led us to discovering a duodenal tumor with high grade dysplasia. Due to location, he ended up having a full whipple surgery. First attempt at whipple discovered a belly full of large lymph nodes. Surgeon sewed him back up and referred to hemonc. CLL diagnosed followed by Whipple and then hip replacement. Bam.Bam.Bam. his choice. He's had two clotting events, overall feeling pretty good. High stress commercial construction projects. Go. Go. Go. Then discovered hip implant was loose. Revision surgery. Then just diagnosed with Barrett's esophagus. His ALC has been as high as 130, doubled about 9 months ago. New testing revealed unmutated IVGH. He was supposed to be released for full weight load and PT on hip but given 4 more weeks on crutches. He's become very thin. Now a few bouts of chills, a few others of sweats. And sleeping a lot. I'm sure the crutches thing is old and he's trying to stay off leg so bone can heal but I wonder about all the sleep.

Well, I guess that was a 'thanks for listening'. :) Carol


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