OC 54.4 - Multinational Cohort Analysis of Intracranial Hemorrhage Outcomes in Patients with Brain Tumors Receiving Anticoagulation (ABC Study)

Tuesday, June 27, 2023

11:30 – 11:45 ET

Room: 511

Session Available As: On-Demand

Presenting Author(s)

Avi Leader, MD (he/him/his)

Hematologist
Institute of Hematology, Rabin Medical Center, Petah Tikva
Petah Tikva, HaMerkaz, Israel

Co-Author(s)

EH

Eva N. Hamulyák

Resident Internal Medicine
Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Amsterdam, Noord-Holland, Netherlands
Tzu-Fei Wang, MD, MPH (she/her/hers)

Associate professor
Department of Medicine, University of Ottawa at The Ottawa Hospital and Ottawa Hospital Research Institute, Ottawa, ON, Canada
Ottawa, Ontario, Canada
Lisa Baumann Kreuziger, MD, MS (she/her/hers)

Investigator
Versiti Blood Research Institute, Versiti, Milwaukee, WI, USA
Milwaukee, Wisconsin, United States
BC

Brian J. Carney

Medical Director of Apheresis Services
Division of Hematology and Hematologic Malignancies, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, USA
Boston, Massachusetts, United States
AH

Ann Hoeben

Medical Oncologist
Division of Medical Oncology, Department of Internal Medicine, GROW-School of Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, The Netherlands
Maastricht, Limburg, Netherlands
B�

Berna C. Özdemir

Senior Physician
Department of Medical Oncology, Inselspital Bern, Bern University Hospital, University of Bern, Switzerland
Bern, Bern, Switzerland
RC

Rosana D. Cordova Serrano

Resident
Hematology Department, Instituto Nacional de Cancerología, Mexico City, Mexico
Mexico City, Coahuila de Zaragoza, Mexico
Kristen Sanfilippo, MD, MPHS (she/her/hers)

Associate Professor of Medicine
Washington Univesrity, United States
SR

Shira Rozenblatt

Radiologist
Department of Radiology, Rabin Medical Center, Petah Tikva, Israel
Petah Tikva, HaMerkaz, Israel
LB

Ludo F. M. Beenen

Radiologist
Department of Radiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Amsterdam, Noord-Holland, Netherlands
SY

Shlomit Yust-Katz

Head of Neurooncology Unit
Neurooncology Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel
Petah Tikva, HaMerkaz, Israel
EH

Erez Halperin

Hematology Fellow
Institute of Hematology, Rabin Medical Center, Petah Tikva and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Petah Tikva, HaMerkaz, Israel
AA

Ariela Arad

Hematologist
Hematology Department, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
Jerusalem, Yerushalayim, Israel
AL

Aharon Lubetsky

Director, Thrombosis and Hemostasis Unit
National Hemophilia Center and Thrombosis & Hemostasis Institute, Sheba Medical Center, Israel. Sackler Faculty of Medicine, Tel Aviv University, Israel.
Ramat Gan, HaMerkaz, Israel
Marc Carrier, MD

MD, MSc
Ottawa Hospital Research Institute, Ottawa, ON, Canada
Ottawa, Ontario, Canada
BM

Benjamin Massat

Resident Internal Medicine
Versiti, Medical College of Wisconsin, Milwaukee, WI, USA
Milwaukee, Wisconsin, United States
HB

Harry R. Büller

MD
Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Amsterdam, Noord-Holland, Netherlands
Galia Spectre, MD PhD

Head of Thrombosis and Haemosasis Unit, Department of Hematology
Institute of Hematology, Rabin Medical Center, Petah Tikva
Petah Tikva, HaMerkaz, Israel
Jeffrey I. Zwicker, MD

Chief of the Hematology Service
Department of Medicine, Hematology Service, Memorial Sloan Kettering Cancer Center, New York City, NY
New York, New York, United States

Background: The comparative safety of direct oral anticoagulants (DOACs) versus low molecular weight heparin (LMWH) in brain cancer patients is not established.

Aims: To determine the incidence of intracranial hemorrhage (ICH) in patients with primary and metastatic brain tumors receiving DOACs or LMWH.

Methods: A multinational retrospective cohort study in 12 hospitals included adults with active primary or metastatic brain tumors receiving therapeutic-dose DOACs or LMWH for any indication or duration. The primary outcome was spontaneous ICH based on imaging reports. The 12-month cumulative incidence of the primary outcome and hazard ratios (HR) between the DOAC and LMWH groups were calculated with death as competing risk.

Results: The cohort (n=748) included 240 patients with primary brain tumors (62 DOAC, 178 LMWH) and 508 with brain metastases (203 DOAC, 305 LMWH). Patient characteristics are shown in Tables 1 and 2.

In patients with primary brain tumors, the 12-month cumulative incidence of spontaneous ICH was 8.3% (95% CI 3.0%-17.1%) with DOAC and 13.0% (95% CI 8.4%-18.6%) with LMWH (HR 0.62; 95% CI 0.24-1.64). Death within 30 days post-ICH occurred in 4 (6.5%) and 7 (3.9%) patients with DOAC and LMWH, respectively.

In patients with brain metastases, the 12-month cumulative incidence of spontaneous ICH was 11.7% (95% CI 7.5%-16.8%) with DOAC and 7.9% (95% CI 5.1%-11.5%) with LMWH (HR 1.52; 95% CI 0.84-2.75). Death within 30 days post-ICH occurred in 4 (2.0%) and 5 (1.6%) patients with DOAC and LMWH, respectively.

Conclusion(s): In this study of primary and metastatic brain cancer patients, there was no statistically-significant difference in ICH between DOAC and LMWH. There is potential bias both towards higher (older, more chronic kidney disease) and lower bleeding risk (less recent neurosurgery, less newly-initiated anticoagulation, more cranial irradiation) in the DOAC group. ICH rates are high, warranting further research.

Learning Objectives:

Describe the incidence of intracranial hemorrhage among patients with primary brain cancer or brain metastases receiving anticoagulation
Discuss the risk of intracranial hemorrhage with direct oral anticoagulants compared to low molecular weight heparin among patients with primary brain cancer or brain metastases
List the predictors of intracranial hemorrhage among patients with primary brain cancer or brain metastases receiving anticoagulation