Antithrombotic Therapy in Patients with Malignant Lymphoproliferative Disorders Treated with Ibrutinib

EI Emelina, GE Gendlin, IG Nikitin

NI Pirogov Russian National Research Medical University, 1 Ostrovityanova str., Moscow, Russian Federation, 117997

For correspondence: Elena Ivanovna Emelina, MD, PhD, 1 Ostrovityanova str., Moscow, Russian Federation, 117997; e-mail:

For citation: Emelina EI, Gendlin GE, Nikitin IG. Antithrombotic Therapy in Patients with Malignant Lymphoproliferative Disorders Treated with Ibrutinib. Clinical oncohematology. 2019;12(4):449–60 (In Russ).

DOI: 10.21320/2500-2139-2019-12-4-449-460


Background. Antithrombotic therapy in chronic lymphocytic leukemia (CLL) patients is challenging, as this category of patients is initially characterized by high risk of hemorrhagic complications. The use of ibrutinib influencing the platelet function constitutes an additional bleeding risk. A crucial task consists in risk minimization of both hemorrhagic complications and thrombosis while sticking to ibrutinib treatment.

Aim. To assess the feasibility of antithrombotic therapy in CLL patients receiving ibrutinib and having indications for this therapy, as well as the use of dual antiplatelet and dual antithrombotic therapies.

Materials & Methods. The trial included 197 patients with CLL (n = 190), mantle cell lymphoma (n = 5), and Waldenstrom macroglobulinemia (n = 2) aged 32 to 91 years (median 66 years). The number of female patients was 70, aged 39 to 83 years (median 64 years) and the number of male patients was 127, aged 32 to 91 years (median 66 years). The patients were at different stages of ibrutinib treatment within 5 to 56 months. In this work methods of nonparametric statistics were used. All data are shown in the form of median and interquartile range or absolute numbers and percentages.

Results. Antithrombotic therapy during ibrutinib administration was used in 29 (14,7 %) patients. The new oral anticoagulants (NOAC) had to be prescribed to 26 patients with atrial fibrillation (AF). Dual antiplatelet therapy was used in 3 patients who underwent percutaneous coronary intervention with subsequent revascularization. In 2 patients with AF who underwent coronary stenting the dual antithrombotic therapy instead of the triple one was administered according to the management algorithm for patients with high risk of hemorrhagic complications. In 6 patients out of those who had AF and received NOAC the drug was withdrawn because of thrombocytopenia. Hemorrhagic manifestations which were the reason of NOAC withdrawal were observed in 1 female patient in the form of gross hematuria recurring when anticoagulant treatment was switched to the minimal effective doses and also when the administered anticoagulant was replaced with another one used in the minimal dose effective for stroke prevention in patients with AF. Hemorrhagic manifestations which were the reason of anticoagulant dose reduction emerged in 4 patients, and 3 patients required another anticoagulant for the same reason. In 5 patients there was no need to change the anticoagulant treatment. In 10 NOAC recipients no hemorrhagic syndrome was observed. None of 5 patients receiving dual antithrombotic therapy showed hemorrhagic complications within 3 to 14 months. The incidence of them in women is more than twice as high as in men.

Conclusion. Hemorrhagic manifestations in patients receiving ibrutinib and antithrombotic therapy were not life threatening and, in most cases, did not require drug withdrawal. Thrombocytopenia was the main reason for NOAC withdrawal. A thorough follow-up of patients receiving ibrutinib and antithrombotic therapy allows for timely correction of it if necessary. It involves dose reduction, anticoagulant replacement, and in rare cases the withdrawal of antithrombotic therapy with subsequent consideration of the feasibility of its resumption. As a rule, the need for different variants of antithrombotic therapy is not an obstacle to either assignment or continuation of antineoplastic treatment with ibrutinib.

Keywords: ibrutinib, chronic lymphocytic leukemia, antithrombotic therapy, dual antiplatelet therapy, atrial fibrillation, coronary stenting on ibrutinib therapy, new oral anticoagulants, rivaroxaban, dabigatran, apixaban.

Received: February 25, 2019

Accepted: July 31, 2019

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