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2633 Thrombolytic Therapy for Venous Thromboembolism in the Pediatric Population: A Systematic Review and Meta-Analysis

Program: Oral and Poster Abstracts
Session: 332. Thrombosis and Anticoagulation: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Research, Clinical Research
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Hassan Kawtharany1*, Muayad Azzam, MD2*, Paul Monagle, MD, BS, MSc, FRACP, FRCPA, MB3, Rachel S. Bercovitz, MD, MS4, Aseel Alkhader, MD1*, Qais Hamarsha, MD1*, Hadi Khaled Abou Zeid, MD5*, Razan Mansour, MD6*, Carine Tabak7*, Payal Patel, MD8*, Sarah Lamat Baghdadi7*, Marisol Betensky, MD, MPH9, Rukhmi Bhat, MD, MS10, Tina Biss11*, Brian R. Branchford, MD12, Leonardo R. Brandao, MD, MSc13, Anthony K C Chan14, E. Vincent Faustino, MD15*, Julie Jaffray, MD, MS16, Sophie Jones, PhD17*, Bryce A. Kerlin, MD18, Nicole Kucine, MD, MS19, Riten Kumar, MD, MSc20, Christoph Male, MD21*, Marie-Claude Pelland-Marcotte, MD, PhD22, Leslie Raffini, MD23, Chittalsinh M Raulji, MBBS24, Sarah E Sartain, MD25, Clifford M. Takemoto, MD26, Cristina Tarango, MD27, Heleen Van Ommen, MD, PhD28*, Maria C Velez, MD29*, Sara Vesely, PhD30, John Wiernikowski, PharmD31*, Suzan Williams, MD32*, Hope P. Wilson, M.D.33, Gary Woods, MD34, Ayesha Zia, MD, MSc35 and Reem A Mustafa, MD, PhD, MPH36*

1Evidence-Based Practice and Impact Center, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS
2Evidence-Based Practice and Impact Center, Department of Internal Medicine, University of Kansas Medical Center, Overland Park, KS
3Royal Children's Hospital Murdoch Children's Research Institute, Victoria, AUS
4Northwestern University Feinberg School of Medicine, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL
5University of Balamand, Balamand, Lebanon
6Internal Medicine, The University of Kansas Medical Center, Kansas City, KS
7University of Kansas School of Medicine, Kansas City, KS
8Emergency Medicine-Critical Care Medicine, Emory University, Atlantq, GA
9Johns Hopkins All Children's Hospital, St. Petersburg, FL
10Northwestern University Feinberg School of Medicine, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL
11The Newcastle upon Tyne Hospitals NHS Trust, Newcastle Upon Tyne, ENG, United Kingdom
12Versiti Medical Sciences Institute, Wauwatosa, WI
13Division of Haematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
14McMaster Children’s Hospital, McMaster University, Hamilton, ON, Canada
15Yale School of Medicine, New Haven, CT
16Rady Children's Hospital San Diego, San Diego, CA
17Murdoch Children’s Research Institute Melbourne, University of Melbourne, Melbourne, AUS
18Abigail Wexner Research Institute @ Nationwide Children's Hospital, Center For Clinical & Translational Research, Columbus, OH
19Weill Cornell Medical College, New York, NY
20Dana Farber/Boston Children's Cancer and Blood Disorders Center/Department of Pediatrics, Boston Children's Hospital, Boston
21Medical University of Vienna, Vienna, AUT
22Division of Hematology-Oncology, Department of Pediatrics, CHU de Quebec, Centre Mere-Enfant Soleil, Quebec, QC, Canada
23Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
24Children's Specialty Physicians, Omaha, NE
25Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine/Texas Children's Hospital, Houston, TX
26Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN
27Cincinnati Children's Hospital Medical Center, Cincinnati, OH
28Department of Pediatric Hematology, Erasmus Medical Center Sophia Children's Hospital, Rotterdam, NLD
29Department of Pediatrics, Division of Hematology-Oncology, Louisiana State University Health Sciences Center School of Medicine, New Orleans, LA
30The Univ. of OK Health Sciences Ctr., Oklahoma City, OK
31McMaster Children's Hospital, Hamilton, ON, CAN
32Hospital for Sick Children, Toronto, ON, Canada
33University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL
34Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Children's Healthcare of Atlanta, Atlanta, GA
35Dept. of Pediatrics; Division of Hematology-Oncology, UT Southwestern Medical Center, Dallas, TX
36Division of Nephrology and Hypertension, Department of Internal Medicine, University of Kansas Medical Centre, Kansas City, KS

Introduction: VTE in pediatric patients is usually managed with anticoagulation (AC), however, thrombolytic therapy may be necessary to rapidly restore venous patency in cases of life- or limb-threatening VTEs. The available evidence on the benefits and outcomes of thrombolysis in pediatric VTE is limited. We performed a systematic review and meta-analysis of the literature to evaluate the outcomes of thrombolytic therapy in pediatric patients with VTE.

Methods: As part of the American Society of Hematology/International Society on Thrombosis and Haemostasis guidelines on the management of VTE, we searched the published literature in PubMed, Embase, and The Cochrane Central Register of Controlled Trials, from inception till February 2024. Two reviewers independently screened the studies to assess their eligibility using Covidence systematic review software (Australia). A study was included if it addressed thrombolytic therapy outcomes in pediatric patients (<21 years old) with VTE. We statistically pooled estimates using Review Manager (5.4) using a random effect model. Reviewers assessed the risk of bias using Risk of Bias in Non-randomized Studies - of Interventions (ROBINS-I) tool and assessed the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.

Results: After screening 8925 references, we found a total of 9 eligible studies: 2 for submassive pulmonary embolism (PE) (n=31), 3 for massive PE (n=35), and 5 for deep vein thrombosis (DVT, n=108). When comparing thrombolytic therapy to standard AC in patients with submassive PE, thrombolytic therapy might decrease the risk of progression from submassive to massive PE with an absolute risk (95% confidence interval [CI]) of 40 fewer per 1,000 (from 106 fewer to 892 more). Thrombolysis has no effect on the rates of thrombus resolution with an absolute risk (95% CI) of 0 per 1,000 (from 360 fewer to 560 more). There were no events of chronic pulmonary hypertension or bleeding in either group. Out of 19 patients, there was one death in the standard AC group compared to 0 out of 14 in the thrombolysis group. In patients with massive PE, thrombolytic therapy may decrease mortality rates with an absolute risk (95% CI) of 60 fewer per 1,000 (from 290 fewer to 425 more) and may increase the risk of thrombosis recurrence with an absolute risk (95% CI) of 228 more per 1000 (from 86 fewer to 1000 more). Bleeding was not estimable with 1 event out of 7 patients in the thrombolysis group versus no bleeding on 1 patient in the standard AC group.

In patients with DVT, when compared to standard AC, thrombolytic therapy has little to no effect on mortality, recurrence of thrombosis, and major bleeding with an absolute risk (95% CI) of 3 fewer per 1,000 (from 76 fewer to 346 more), 3 fewer per 1,000 (from 76 fewer to 346 more), and 22 fewer per 1,000 (from 82 fewer to 444 more), respectively. For CRNMB, 1 event out of 42 occurred in the AC group. Thrombolytic therapy might increase the rate of thrombus resolution, and risk of PTS when compared to standard AC, with an absolute risk (95% CI) of 200 more per 1,000 (from 7 fewer to 469 more), and 333 more per 1,000 (from 88 fewer to 1,000 more), respectively.

The certainty of evidence for all estimates is very low due to concerns related to risk of bias and imprecision because of the small number of patients.

Conclusion: The certainty of the evidence is very low (very small sample size and high risk of bias) which limits our ability to make definitive conclusions on the benefits and short-term and long-term outcomes of thrombolysis in children.

Disclosures: Betensky: Aziyo: Honoraria; Abbot: Honoraria; Zoll: Honoraria; Boston Scientific: Honoraria; NHLBI K23: Research Funding. Branchford: Novo Nordisk: Honoraria; Kedrion: Honoraria, Research Funding. Brandao: AstraZeneca: Other: Ad board meeting on andexanet alfa (Feb. and Jun. 2023/ISTH – Montreal/QC, Canada; Pfizer/Bristol Myers Squibb: Research Funding. Chan: Novo Nordisk: Consultancy, Honoraria, Other: clinical trials, Research Funding; Daiichi: Other: clinical trials, Research Funding; Pfizer: Honoraria, Other: clinical trials, Research Funding; Sanofi: Consultancy, Honoraria, Other: clinical trials, Research Funding; Sobi: Other: clinical trials, Research Funding; Takeda: Consultancy, Honoraria, Other: clinical trials, Research Funding; Roche: Consultancy; Octapharma: Honoraria; Attwill: Patents & Royalties: holds a patent; CIHR: Research Funding; Canadian Hemophilia Society: Research Funding; C17: Research Funding; Bayer: Consultancy, Honoraria, Other: clinical trials, Research Funding. Kerlin: Aurinia: Research Funding. Kucine: Protagonist Therapeutics: Consultancy; PharmaEssentia: Consultancy; AOP Health: Other: Conference Presenter. Raulji: Abbvie: Current holder of stock options in a privately-held company; Vertex Pharmaceuticals: Current holder of stock options in a privately-held company. Sartain: Alexion Discovery Partnerships: Research Funding. Takemoto: Merck: Consultancy, Honoraria; Novartis: Other: DSMB; Pfizer: Research Funding; Novo Nordisk: Research Funding. Tarango: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Wilson: Octapharma: Consultancy. Zia: Star Therapeutics: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; COR2ED GmbH: Membership on an entity's Board of Directors or advisory committees; Hema Biologics: Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH