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Year : 2018  |  Volume : 2  |  Issue : 2  |  Page : 29-34

Low-dose imatinib mesylate causing subdural hematoma in remission phase of chronic myeloid leukemia: A rare phenomenon

Department of Critical Care, Bhagwan Mahavir Medica Superspecialty Hospital, Ranchi, Jharkhand, India

Date of Web Publication21-Nov-2018

Correspondence Address:
Rajesh Kumar Singh
Department of Critical Care, Bhagwan Mahavir Medica Superspecialty Hospital, Ranchi, Jharkhand
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/sccj.sccj_19_18

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Chronic subdural hematoma (SDH) is associated with trauma, antiplatelet therapy, anticoagulant medications, long-term alcohol abuse, arteriovenous malformations, and even postcraniotomy. However, SDH associated with imatinib mesylate (IM) treatment for chronic myeloid leukemia (CML) is rare that too in the remission phase of CML is even rarer. Among the cases of CML in remission phase, the literature review of those with SDH revealed that IM was taken in a dose of 800 mg per day. We report a case of SDH in a 70-year-old gentleman who was in the chronic remission phase of CML and was treated with IM 400 mg per day by hematologist.

Keywords: Chronic myeloid leukemia,chronic remission phase, imatinib mesylate low dose, subdural hematoma

How to cite this article:
Mishra VK, Singh RK, Chaudhuri S, Sinha M. Low-dose imatinib mesylate causing subdural hematoma in remission phase of chronic myeloid leukemia: A rare phenomenon. Saudi Crit Care J 2018;2:29-34

How to cite this URL:
Mishra VK, Singh RK, Chaudhuri S, Sinha M. Low-dose imatinib mesylate causing subdural hematoma in remission phase of chronic myeloid leukemia: A rare phenomenon. Saudi Crit Care J [serial online] 2018 [cited 2022 Dec 4];2:29-34. Available from: https://www.sccj-sa.org/text.asp?2018/2/2/29/245943

  Introduction Top

Chronic subdural hematoma (SDH) is usually seen in scenarios such as posttrauma, antiplatelet, and anticoagulant therapy, thrombocytopenia, any cause of coagulopathy, or even in chronic alcoholics.[1],[2],[3],[4],[5] Chronic SDH rarely occurs in hematological malignancy and even in such cases, is associated more with acute myeloid leukemia. Chronic SDH is rarely associated with chronic myeloid leukemia (CML), and its occurrence in the chronic remission phase of a patient being treated with imatinib mesylate (IM) makes this case extremely unique.[1] Hemorrhage due to IM has been postulated due to platelet dysfunction and a decreased level of α2-plasmin inhibitor.[6]

Literature search revealed very few cases of CML with IM-induced SDH in the chronic remission phase, that too in those on IM 400 mg per day dosing.

  Case Report Top

A 70-year-old male patient with chief complaints of headache, giddiness, and vomiting for the duration of 2 weeks. He was a known hypertensive, diabetic on regular medications. He was also a known case of CML, diagnosed 3 years back and was on in remission period and on maintenance dose of IM [Figure 1] and [Figure 2]. He was admitted to our hospital with heart rate of 76/min, blood pressure 150/70 mmHg, and oxygen saturation 98%. On examination, Glasgow Coma Score was E4M6V5, with pupils bilaterally normal size and reacting to light. There was no focal neurological deficit. Computerized tomography brain revealed right frontotemporal SDH with mass effect [Figure 3]. There was no history of trauma, oral anticoagulants, or antiplatelets intake. Hematological investigation were within normal limits, and coagulation profile was normal [Figure 4] and [Figure 5]. He was on IM 400 mg/day for the past 3 years and was in chronic remission phase of CML with <10% blasts in bone marrow. IM was stopped, burr hole and evacuation of SDH was done under general anesthesia, and the procedure was uneventful. He was eventually discharged and was referred to hematologist for follow-up.
Figure 1: Bone marrow report of the patient proving chronic myeloid leukemia in remission phase with 3% blasts

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Figure 2: Report of patient showing breakpoint cluster region-Abelson oncogene locus gene positive in chronic myeloid leukemia

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Figure 3: Computerized tomography brain of the patient showing right-sided subdural hematoma with midline shift

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Figure 4: Complete blood picture of the patient showing normal platelet count

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Figure 5: Prothrombin time/international normalized ratio report showing normal coagulation profile with no other possible cause of subdural hematoma

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  Discussion Top

CML is a myeloproliferative disorder caused due to reciprocal translocation of chromosome t(9;22) (q34;q11) and is characterized the presence of the Philadelphia chromosome, breakpoint cluster region-Abelson oncogene locus (BCR-ABL) gene, and increase in tyrosine kinase.[7] CML has three phases – chronic remission phase, accelerated phase, and blast crisis phase.[8] Chronic remission phase has <10% peripheral or bone marrow blasts. Accelerated phase has blasts ranging from 10% to 29%, and blast crisis phase has blasts >30%. Our patient was in chronic remission phase with 3% blasts in bone marrow and was on IM 400 mg per day. IM is a tyrosine kinase inhibitor which binds to amino acids of BCR/ABL tyrosine kinase binding site, prevents autophosphorylation, and finally, halts the pathways promoting tumor growth.[1] In the blast phase of CML, the incidence of intracranial bleed is about 5%. The risk of bleed is about 1% in the accelerated phase of CML, whereas it is only around 0.6% in chronic remission phase.[1],[5]

Reports of chronic SDH with IM at doses of 800 mg per day even in chronic remission phase has been reported.[6],[7] The pharmacokinetics of IM in the IRIS study revealed that at doses of 400 mg daily, there was no rise in hemorrhagic complications.[9] However, in our patient, the uniqueness is accentuated by the fact that SDH occurred spontaneously, even with a dose of 400 mg per day in remission phase.

Although there are multiple mechanisms of spontaneous SDH in blast and accelerated phases of CML, the causes of spontaneous SDH in CML patients in chronic remission phase with low-dose IM may be due to a reduction in α2-plasmin inhibitor level. The incidence of hemorrhagic episodes in patients with <60% of normal α2-plasmin inhibitor level has been reported even on 400 mg daily IM doses. We did not have the α2-plasmin inhibitor level available in this patient.[7],[10] When the α2-plasmin inhibitor level decreases to <60% of normal, abnormal fibrinogenolysis can occur, leading to hemorrhage.[11]

In the blast and accelerated phases, the causes of SDH can be due to occlusion of dural vessels by malignant cells, rupture of occluded dural vessels in subdural space, thrombocytopenia, disseminated intravascular coagulation, platelet dysfunction, and necrosis in metastatic deposits.[1]

The patient had normal coagulation profile, only 3% blasts in bone marrow report, normal platelet count, and on low dose 400 mg daily IM. The SDH can only be explained by a reduction in α2-plasmin inhibitor to <60% of normal.

  Conclusion Top

Extreme sagacity must be exercised while dealing with patients of CML on low-dose IM in chronic remission phase even though risk of cerebral hemorrhage is very low, and α2-plasmin inhibitor level must also be monitored.

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.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Raheja A, Satyarthee GD. Spontaneous chronic subdural haematoma development in chronic myeloid leukaemia cases at remission phase under maintenance therapy, management strategy – A series with literature review. Rom Neurosurg 2016;3:432-40.  Back to cited text no. 1
Abdulhamid MM, Li YM, Hall WA. Spontaneous acute subdural hematoma as the initial manifestation of chronic myeloid leukemia. J Neurooncol 2011;101:513-6.  Back to cited text no. 2
Bromberg JE, Vandertop WP, Jansen GH. Recurrent subdural haematoma as the primary and sole manifestation of chronic lymphocytic leukaemia. Br J Neurosurg 1998;12:373-6.  Back to cited text no. 3
Comănescu A, Roşca E, Bota M, Ninulescu G. Chronic subdural hematoma in a patient with acute myeloid leukemia and dural metastatic infiltration. Rom J Morphol Embryol 2008;49:259-62.  Back to cited text no. 4
Druker BJ, Sawyers CL, Capdeville R, Ford JM, Baccarani M, Goldman JM, et al. Chronic myelogenous leukemia. Hematology Am Soc Hematol Educ Program 2001;2001:87-112.  Back to cited text no. 5
Kim MS, Lee DH, Lee YR, Kim DK, Bae SH, Hwang JY, et al. A case of subdural hematoma in patient with chronic myeloid leukemia treated with high-dose imatinib mesylate. Korean J Hematol 2010;45:73-5.  Back to cited text no. 6
Khaladkar SM, Thakkar DK, Jantre MN, Kulkarni VM, Singh A. Chronic subdural haematoma-unusual cause of headache in a patient with chronic myeloid leukaemia treated with high-dose imatinib mesylate: A rare case report with review of literature. Med J Dr DY Patil Univ 2015;8:411-3.  Back to cited text no. 7
Cortes JE, Talpaz M, O'Brien S, Faderl S, Garcia-Manero G, Ferrajoli A, et al. Staging of chronic myeloid leukemia in the imatinib era: An evaluation of the world health organization proposal. Cancer 2006;106:1306-15.  Back to cited text no. 8
Larson RA, Druker BJ, Guilhot F, O'Brien SG, Riviere GJ, Krahnke T, et al. Imatinib pharmacokinetics and its correlation with response and safety in chronic-phase chronic myeloid leukemia: A subanalysis of the IRIS study. Blood 2008;111:4022-8.  Back to cited text no. 9
Matsue K, Aoki T, Odawara J, Kimura S, Yamakura M, Takeuchi M, et al. Haemorrhagic complications associated with reduced alpha2-plasmin inhibitor during imatinib use in a patient with philadelphia chromosome-positive acute lymphoblastic leukaemia. Leuk Res 2009;33:867-9.  Back to cited text no. 10
Okajima K, Kohno I, Tsuruta J, Okabe H, Takatsuki K, Binder BR, et al. Direct evidence for systemic fibrinogenolysis in a patient with metastatic prostatic cancer. Thromb Res 1992;66:717-27.  Back to cited text no. 11


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]


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