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Year : 2021  |  Volume : 5  |  Issue : 4  |  Page : 71-72

Ibrutinib platelet dysfunction induced intracranial hemorrhage management with activated factor VII and transfusion of platelets

1 Department of Critical Care, Regions Hospital, Saint Paul, MN, USA
2 Department of Critical Care, Latinamerican Council of Neurocritical Care; Center of Biomedical Research, Universidad de Cartagena, Cartagena; Department of Critical Care, Critical Care Unit, Centro Policlinico del Olaya; Department of Critical Care, Colombian Clinical Research Group in Neurocritical Care, Bogota, Colombia

Date of Submission20-Jul-2021
Date of Acceptance08-Aug-2021
Date of Web Publication29-Nov-2021

Correspondence Address:
Luis Rafael Moscote-Salazar
Center of Biomedical Research, Universidad de Cartagena, Cartagena
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/sccj.sccj_24_21

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How to cite this article:
Janjua T, Moscote-Salazar LR. Ibrutinib platelet dysfunction induced intracranial hemorrhage management with activated factor VII and transfusion of platelets. Saudi Crit Care J 2021;5:71-2

How to cite this URL:
Janjua T, Moscote-Salazar LR. Ibrutinib platelet dysfunction induced intracranial hemorrhage management with activated factor VII and transfusion of platelets. Saudi Crit Care J [serial online] 2021 [cited 2022 Oct 2];5:71-2. Available from: https://www.sccj-sa.org/text.asp?2021/5/4/71/331514

Ibrutinib is an oral irreversible inhibitor of Burton's tyrosine kinase. This agent is used for the treatment of refractory chronic lymphocytic leukemia (CLL).[1],[2] Serious side effects are associated with the use of this agent to treat CLL, one of these is intracranial hemorrhage.[3] Patients using concurrent antiplatelet or anticoagulants have a higher incidence of intracranial hemorrhage (ICH). The acute management is complicated with normal platelets counts and coagulation studies. Here, we share a brief synopsis of management in a patient with ibrutinib platelet dysfunction (IPD) induced subdural hemorrhage.

A 65-year-old male right-handed patient who was on ibrutinib for CLL presented with loss of consciousness secondary to acute right-sided subdural hematoma (SDH). The right pupil was dilated and fixed. The patient was intubated in the field and brought to the hospital. A computed tomography (CT) of head without contrast demonstrated a right temporal SDH with effacement of the right ventricle and local mass effects [Figure 1]a. He was taken emergently to the operating room (OR) where he had a right craniotomy and evacuation of SDH [Figure 1]b. Unfortunately, the patient follow-up CT of head the next morning showed reoccurrence of SDH [Figure 1]c and he developed dilated and fixed right-sided pupil. At this point, it was clear that oozing was due to IPD. Rescue therapy with activated factor VII (aFVII) 2 mg intravenous given followed by 2 units of fresh platelets. He was taken back to the OR where right-sided decompressive hemicraniectomy was done with clot evacuation. Postsurgery showed a stable surgical site with no more hemorrhage [Figure 1]d. The patient was diagnosed with CLL 5 years before SDH presentation. After multiple treatment failures, he was placed on ibrutinib 3 months before SDH. He started treatment with ibrutinib due to an increase in his WBC counts, night sweats, lymphadenopathy, and splenomegaly. The patient stayed in the neurocritical care unit without any further hemorrhage. Due to his underlying CLL, he required multiple platelet transfusions to keep the count above 100 K.
Figure 1: Computed tomography scans of head showing pre- and postsurgical course. (a) Presentation computed tomography with right-sided acute subdural hematoma and shift. (b) Postoperative image, (c) Next day computed tomography showing reoccurrence of subdural hematoma with shift, (d) Right-sided hemicraniectomy and clot evacuation

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The management of spontaneous SDH due to coagulopathy is a challenging task in neurocritical care. Most of these coagulopathies are related to anticoagulation and predictably corrected. Some coagulopathies are complex and rapid testing is normal like IPD. Platelet function assay (PFA) in this patient was normal twice. PFA measured through PFA-100™ can be abnormal and might be test used in these patients.[4] Tests may show prolonged epinephrine closure time, lower levels of von Willebrand factor activity, and factor VIII.[4] The mainstay of ICH in the acute phase is the transfusion of platelets,[5] even if the numbers are above 100 k. We used global procoagulant aFVII to help with reduced further hemorrhage while platelet transfusion was arranged. It is not clear if aFVII played any role as the patient was taken to the OR while receiving platelet transfusion.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Advani RH, Buggy JJ, Sharman JP, Smith SM, Boyd TE, Grant B, et al. Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. J Clin Oncol 2013;31:88-94.  Back to cited text no. 1
O'Brien S, Furman RR, Coutre SE, Sharman JP, Burger JA, Blum KA, et al. Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: An open-label, multicentre, phase 1b/2 trial. Lancet Oncol 2014;15:48-58.  Back to cited text no. 2
Martín-Moro F, García-Cosío M, Marquet-Palomanes J, López-Gutiérrez M, Pian-Arias H, López-Jiménez FJ. Intracranial hemorrhage as presentation of chronic lymphocytic leukemia successfully treated with ibrutinib. Ann Hematol 2021. [doi: 10.1007/s00277-021-04393-3]. [Epub, ahead of Print].  Back to cited text no. 3
Lipsky AH, Farooqui MZ, Tian X, Martyr S, Cullinane AM, Nghiem K, et al. Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib. Haematologica 2015;100:1571-8.  Back to cited text no. 4
Seiter K, Stiefel MF, Barrientos J, Shaikh A, Ahmed N, Baskind P, et al. Successful treatment of ibrutinib-associated central nervous system hemorrhage with platelet transfusion support. Stem Cell Investig 2016;3:27.  Back to cited text no. 5


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