Brian Branchford, MD

I am a physician scientist building an academic career in basic-translational research in non-malignant hematology, with a focus on pediatric thrombosis. The overall goal of my research is to define the role of platelet activation in thromboinflammation as a means to identify biomarkers for risk stratification, as well as potential novel approaches to thrombosis treatment or prevention.  As a research fellow and junior faculty hematologist, I studied basic/translational aspects of the mechanisms that determine platelet activation using a variety of in vitro functional assays and relevant animal models. I studied the role of the GAS6/MERTK signaling pathway in platelet activation responses and thrombus formation using pharmacologic antagonists and transgenic murine models.

I have recently studied differential expression of inflammatory cytokines and platelet activation signaling proteins from our pediatric thrombosis samples compared to healthy controls. We continue to investigate the role of inflammation-triggered platelet activation in thrombosis. My clinical research data and patient care experiences demonstrate a clear role of inflammation as a risk factor for pediatric thrombosis, while my basic science experience involved functional platelet activation assays and murine thrombosis models.  My next quest is to understand the mechanism behind inflammatory triggers of GAS6/MERTK-related platelet activation and subsequent thrombosis. My ultimate hope is that these findings can then be translated back to patient care through implementation of new anti-inflammatory thromboprophylaxis strategies. Recent advances in our understanding of the cross-talk between inflammatory mediators and the hemostatic system, as well as development of the ischemia-reperfusion injury animal model have revolutionized the field of thromboinflammation. New opportunities exist to understand the complex interplay of these systems in diseases like VTE in which the disruption of a normal physiologic process can lead to pathology. The main goal of my research is to integrate the approaches used to study platelet activation and thrombus formation with those used to study inflammation and inflammatory mediators, as well as the integration of multiple pathways in a final common disease process.

• NIH 1 K08 HL146941-01A, The Role of Inflammation in Platelet Activation and Thrombosis (2020-2025). The goal of this project is to investigate the signaling mechaisms underlying platelet activation and thrombosis in the context of inflammation.

Stephanie Springborn
Senior Research Technologist

1. Flood V, Gill J, Morateck P, Christopherson P, Friedman K, Haberichter S, Branchford BR, Hoffman, R, Abshire T, DiPaola J, Hoots K, Leissinger C, Lusher J, Ragni M, Shapiro A, Montgomery R. VWF exon 28 polymorphisms associated with decreased VWF:RCo/VWF:Ag ratios.  Blood.  2010: 116(2): 280-286. PMID 20231421
2. Goldenberg N, Branchford B, Wang M, Durham J, Ray C, Manco-Johnson M. Percutaneous Mechanical and Pharmacomechanical Thrombolysis for Occlusive Deep Venous Thrombosis of the Proximal Limb in Adolescents: Findings from an Institution-Based Prospective Inception Cohort Study of Pediatric Venous Thromboembolism. J Vasc Interv Radiol 2011; 22:121–132. PMID 21216157
3. Cooper L, Moore C, Branchford B, Greffe B, Capocelli K, Kuder A, Mehta I, Mourani P. Successful pulmonary artery embolectomy in a patient with a saddle Wilms tumor embolus.  Pediatr Blood & Cancer. 2012; 58(5):806-9. PMID 21681933
4. Branchford BR, Mourani P, Bajaj L, Manco-Johnson M, Wang M, Goldenberg N. Risk Factors for the Development of In-Hospital Venous Thromboembolism in Children: A Case-Control Study Employing Diagnostic Validation. Haematologica. 2012; 97(4):509-15. PMID 22104422
5. Branchford BR, Gibson E, Manco-Johnson M, Goldenberg N.  Sensitivity of discharge diagnosis ICD-9 codes for pediatric venous thromboembolism is greater than specificity, but still suboptimal for clinical research. Thromb Res. 2012; 129(5):662-3. PMID 22104422
6. Liang X, Branchford B, Greffe B, McGavran L, Carstens B, Meltesen L, Albano E, Quinones R, Cook B, Graham DK. Alk-Positive Extranodal Anaplastic Large Cell Lymphoma with Concurrent MYC Rearrangement in a Pediatric Patient. J Pediatr Hematol Oncol. 2013; 35(5):e209-13, PMID  23619105
7. Flood VH, Friedman KD, Gill JC, Haberichter SL, Christopherson PA, Branchford BR, Hoffman RG, Abshire TC, Dunn AL, Di Paola JA, Hoots WK, Brown DL, Leissinger C, Lusher JM, Ragni MV, Shapiro AD, Montgomery RR. No increase in bleeding identified in type 1 VWD subjects with D1472H Sequence Variation. Blood. 2013; 121(18)3742-4. PMID 23520336
8. Zhang W, McIver A, Stashko MA, DeRyckere D, Branchford BR, Hunter D, Kireev D, Miley MJ, Norris-Drouin J, Stewart WM, Lee M, Sather S, Zhou Y, Di Paola JA, Machius M, Janzen WP, Earp HS, Graham DK, Frye SV, Wang X. Discovery of Mer-specific tyrosine kinase inhibitors for the treatment and prevention of thrombosis. J Med Chem. 2013; 56(23): 9693-700. PMID 23520336
9. Branchford BR, Ruegg K, Vilalobos-Menuey, Jacobson L, Di Paola J, Manco-Johnson M. FVIII/VWF ratio is not a reliable predictor of VWD in children. Pediatr Blood Cancer. 2014;61(5): 936-9 PMID 24281894
10. Atchison CM, Arlikar S,  Amankwah E,  Ayala I, Barrett L, Branchford BR, Streiff M, Takemoto C, Goldenberg NA. Development of a New Risk Score for Hospital-Associated Venous Thromboembolism in Non-Critically-Ill Children: Findings from a Large Single-Institutional Case-Control Study.  J. Pediatr. 2014; 165(4): 793-8. PMID 25064163
11. Amankwah E,  Atchison CM, Arlikar S,  Ayala I, Barrett L, Branchford BR, Streiff M, Takemoto C, Goldenberg NA. Risk Factors for Hospital-Associated Venous Thromboembolism in the Neonatal Intensive Care Unit. Thrombosis Research. 2014; 134(2):305-9. PMID 24953982
12. Arlikar SJ, Atchison CM, Amankwah EK, Ayala IA, Barrett LA, Branchford BR, Streiff M, Takemoto CM, Goldenberg NA.  Development of a new risk score for hospital-associated venous thromboembolism in critically-ill children not undergoing cardiothoracic surgery. Thrombosis Research. 2015; 136(4): 717-22. PMID 25979250
13. Mahajerin A, Branchford BR,  Amankwah EK, Raffini L, Chalmers E, van Ommen CH, Goldenberg NA. Hospital-associated venous thromboembolism in pediatrics: a systematic review and meta-analysis of risk factors and risk assessment models.  Haematologica. 2015; 100(8): 1045-50. PMID 26001789
14. Dittmar M, Smith N, Warren B, Clark B, Wathen B, Hammett K, Reiter P, Hilden J, Goldenberg NA, Branchford B. Improved sensitivity and specificity of pediatric hospital-acquired venous thromboembolism case identification by radiographic designation. Thrombosis Research. 2017; 154: 93-95. PMID 2845607
15. Maloney JP, Branchford BR, Brodsky GL, Cosmic MS, Calabrese DW, Aquilante CL, Maloney KW, Gonzalez JR, Zhang W, Morequ KL, Wiggings KL, Smith NL, Broeckel U, Di Paola J. The ENTPD1 promoter polymorphism 860A>G (rs3814159) is associated with increased gene transcription, protein expression, CD39/NTPDase1 enzymatic activity, and thromboembolism risk. FASEB J. 2017. PMID 28302652
16. Kastelowitz N, Tamura R, Onasoga A, Stalker T, White O, Brown P, Brodsky G, Brass L, Branchford B, Di Paola J, Yin H. Peptides derived from MARCKS block coagulation complex assembly on phosphatidylserine. Sci Rep 2017 Jun 27;7(1): 4275. PMID: 28655899; PMCID: PMC5487340
17. Knight-Perry J, Branchford BR, Thornhill D, Martiniano SL, Sagel SD, Wang M. Venous Thromboembolism in Children with Cystic Fibrosis: Retrospective Incidence and Intrapopulation Risk Factors. Thromb Res. 2017 Oct; 158:161-166.  PMID: 28934665
18. Atchison, CM, Amankwah E, Wilhelm J, Arlikar S, Branchford BR, Stock A, Streiff M, Takemoto C, Ayala I, Everett A, Stapleton G, Jacobs J, Goldenberg NA. Risk Factors for Hospital-Associated Venous Thromboembolism in Critically-Ill Children Following Cardiothoracic Surgery or Therapeutic Cardiac Catheterisation. Cardiol in Young. 2017 Nov 8;1-9. PMID: 29115202
19. Branchford BR, Mahajerin A, Raffini L, Chalmers E, van Ommen CH, Chan AKC, Goldenberg NA; Recommendations for standardized risk factor definitions in pediatric hospital-acquired venous thromboembolism to inform future prevention trials: Communication from the Subcommittee on Pediatric/Neonatal Hemostasis and Thrombosis of the International Society of Thrombosis and Hemostasis. J Thromb Haemost. 2017 Nov; 15(11):2274-2278. PMID: 29027741
20. Jaffray J, Mahajerin A, Young G, Goldenberg N, Ji L, Sposto R, Stillings A, Krava E, Branchford B. A multi-institutional registry of pediatric hospital acquired thrombosis cases: The Children’s Hospital-Acquired Thrombosis (CHAT) Project. Thromb Res. 2018 Jan;161:6-72. PMID: 29207321
21. Newall F, Branchford B, Male C. Anticoagulant prophylaxis and therapy in children: current challenges and emerging issues. J Throm Haemost. 2018 Feb; 16(2): 196-208. PMID: 29316202
22. Branchford BR, Betensky M, Goldenberg NA. Pediatric issues in thrombosis and hemostasis: The how and why of venous thromboembolism risk stratification in hospitalized children. Thromb Res. 2018 Dec; 172:190-193. PMID: 29472108
23. Branchford BR, Stalker TJ, Law L, Acevedo G, Sather S, Brzezinski C, Wilson KM, Minson K, Lee-Sherick AB, Davizon-Castillo  P, Ng C, Zhang W, Neeves KB, Lentz SR, Wang X, Frye SV, Earp HS, DeRyckere D, Brass LF, Graham DK, Di Paola JA. The small molecule MERTK inhibitor UNC2025 decreases platelet activation and prevents thrombosis. J Thromb Haemost. 2018 Feb;16(2): 352-363. PMID: 29045015
24. *Commentary in J Thromb Haemost: Cosemans JMEM. At the MERcy of platelet primers. J Thromb Haemost. 2018 Feb;16(2): 349-351.
25. Law L, Graham D, Di Paola J, Branchford BR. GAS6/TAM pathway signaling in hemostasis and thrombosis. Front Med 2018 May 9; 5:137. PMID: 29868590. PMCID: PMC5954114
26. Branchford BR and Carpenter, S. The role of inflammation in venous thrombosis. Front Pediatr. 2018 May 23;6: 142. PMID: 29876337. PMCID: 5974100
27. Lyren A, Coffey M, Shepherd M, Lashutka N, Muething S, the SPS Leadership Group. We will not compete on safety: How children’s hospitals have come together to hasten harm reduction. Jt. Comm J Qual Patient Saf. 2018 Jul;44(7):377-388. PMID: 30008350
28. Stoffman JM, Andersson NG, Branchford B, Batt K, D’Orion R, Escuriola Ettingshausen C, Hart DP, Jiminez-Yuste V, Kavakli K, Nogami K, Ramirez C, Wu R. Common themes and challenges in hemophilia care: A multinational perspective. Hematology. 2019; 24(1): 39-48. PMID: 30073913
29. Heizer JW, Shardt TQ, Murphy ME, Branchford BR. Unfractionated heparin dosing requirements in the presence of inflammation during the first six months of life. Thromb Res. 2019 May; 177:17-22. PMID: 30844684
30. Majtan T , Park I, Cox A, Branchford BR, di Paola J, Bublil E, Kraus JP. Behavior, body composition, and vascular phenotype of homocystinuric mice on methionine restricted diet or enzyme replacement therapy. FASEB J. 2019 Nov; 33(11): 12477-12486. PMID: 31450979
31. Padhye K, El-Hawary R, Price V, Stevens S, Branchford B, Kulkarni K.  Development of a perioperative venous thromboembolism prophylaxis algorithm for pediatric orthopedic surgical patients. Pediatr Hematol Oncol. 2019 Dec; 23:1-10. PMID: 31868065
32. Mahajerin A, Jaffray J, Branchford B, Stilings A, Krava E, Young G, Goldenberg N, Faustino V. Comparative validation study of risk assessment models for pediatric hospital-acquired venous thromboembolism. J Thromb Haemost. 2019 Dec. PMID: 31808292
33. Goldenberg NA, Branchford BR. Commentary: Phase 3 pediatric anticoagulant era. Blood. 2020 Feb; 135(7):459-60
34. *Commentary on Brandao LR, et al. Safety of dabigatran etexilate for the secondary prevention of venous thromboembolism in children. Blood. 2019 Dec 5: 135(7): 491-504. PMID:31805182
35. Perez Botero J, Lee K, Branchford BR, Bray PF, Freson K, Lambert MP, Luo M, Mohan S, Ross JE, Bergmeier W, Di Paola J; Glanzmann Thrombasthenia: genetic basis and clinical correlates. ClinGen Platelet Disorder Variant Curation Expert Panel. Haematologica. 2020 Mar 5. PMID: 32139434
36. Loi M, Branchford B, Kim J, Self C, Nuss R. COVID-19 Anticoagulation Recommendations in Children. Pediatr Blood Cancer. 2020.
37. MacNevin W, Padhye K, Price V, El-Hawary R, Branchford BR, Stevens S, Kulkarni K. Validation of a Perioperative Venous Thromboembolism Risk Screeening Tool for Pediatric Orthopedic Surgical Patients. [Submitted to Thrombosis and Haemostasis April 2020.]
38. Park I, Johnson LK, Haefner K, Cox A, Branchford BR, Cavasin M, di Paola J, Bublil E and Majtan T. Hypermethioninemia leads to increased mortality and coagulopathy in a transgenic I278T mouse model of homocystinuria. [Submitted to J Thromb Haemost April 2020]
39. Hart DP; Branchford BR; Hendry S; Ledniczky R; Sidonio RF; Négrier C; Kim M; Rice M; Minshall M; Arcé C; Prince S; Kelleher M; Lee S. Optimizing language for effective communication of gene therapy concepts with hemophilia patients: A qualitative study. [Submitted to Orphanet J Rare Dis May 2020]
40. Ng CJ, Spomer N, Shearer R, LeBlanc A, Funk S, Manco-Johnson M, Branchford B, Warren B, Buckner TW, Moyer G, Wang M, Gibson E, Mashburn C. Improvements in Communication and Coordination of Care in a Hemophilia Treatment Center. [Submitted to J Healthc Qual June 2020]
41. Branchford BR, Jones WL, Ramos CR, Moore EE, Hansen K, Coleman JR, Kelher M, Neeves KB; Silliman CC, Banerjee A, di Paola J. Apolipoprotein A-I, elevated in trauma patients, inhibits platelet activation and decreases clot strength. [Submitted to Arterioscler Thromb Vasc Biol June 2020]
42. Jaffray J, Branchford B, Goldenberg N, Malvar J, Croteau SE, Silvey M, Fargo JH, Cooper JD, Bakeer N, Sposto R, Ji L, Zakai NA, Faustino EVS, Stillings A, Krava E, Young G, Mahajerin A. Development of  a Risk Model for Pediatric Hospital-Acquired Thrombosis: A Report from the CHAT Consortium. [Submitted to J. Pediatr June 2020]
43. van Ommen CH, Albisetti M, Bhatt M, Bonduel M, Branchford B, Chalmers E, Chan A, Holzhauer S, Monagle P, Nowak-Gottl U, Revel-Vilk, Sirachainan, Male C for the Subcommittee on Pediatric and Neonatal Hemostasis and Thrombosis. International Pediatric Thrombosis Network to advance pediatric thrombosis research: communication from the Neonatal and Pediatric SSC of the ISTH. [Submitted to J Thromb Haemost July 2020]

Invited Reviews and Editorials

1. Branchford BR, Di Paola J. Making a diagnosis of von Willebrand Disease. American Society of Hematology Education Program Book, 2012; 2012:161-7.  PMID: 23233576
2. Branchford BR, Monahan PE, Di Paola J. New developments in treatment of pediatric hemophilia and bleeding disorders. Curr Opin Pediatr. 2013; 25(1):23-30. PMID: 23274430
3. Branchford B. Clinical and financial impact of HACs: a commentary on clinical and financial costs of hospital-acquired conditions. Transl Pediatr. 2015; 4(4):331-3. PMID 26835397
4. Branchford BR, Ng CJ, Neeves KB, Di Paola J. Microfluidic technology as an emerging clinical tool to evaluate thrombosis and hemostasis. Thrombosis Research. 2015; 136(1): 13-9. PMID: 26014643
5. Branchford BR, Jaffray J, Mahajerin A. Editorial: Pediatric Venous Thromboembolism.  Front Pediatr. 2018; 6: 269. PMID: 30320050. PMCID: PMC6170657