June 11, 2019

Maurizio Zangari, M.D.

Professor
Department of Hematology Oncology
UAMS College of Medicine
Director of Myeloma Bone Disease Research

Research Interest Statement

My research focuses on the clinical and preclinical aspects of bone disease. I first described the bone anabolic properties of proteasome inhibitors in myeloma patients and the effects on the PTH axis. Specifically, I investigated the effect of proteasome inhibition on the PTH axis and parathyroid hormone 1 and 2 receptors.

After establishing a 5GTM1 murine model in C57BL/KaLwRij mice, I tested the function of a proteasome inhibitor through the PTH-PTHR1 axis and found that PTHR1 plays an important role in the antimyeloma effect of proteasome inhibition.  I further studied the essential role of PTH in antimyeloma proteasome activity by testing the effect of PTHR antibodies and the effects of parathyroidectomy. We recently tested the role of alkaline phosphatase in myeloma mouse model and developed compounds that affect the phosphorous metabolism. All this work indicates a close effect of bone metabolic activity on myeloma progression.

I also have an interest in the effects of the chromosomal aberrations that occur during the disease process and how this relates to survival and development of lytic disease in myeloma patients. Collaborating with Jeffrey Sawyer, Ph.D., to discover complex aberrations found in myeloma karyotypes has led to the identification of the mechanism for the amplification of chromosome region 1q21 in myeloma. Since 1q21 is a copy number associated with high-risk myeloma, this could change the way we approach myeloma patients.

My research has also focused on the effect of immunomodulatory drugs and proteasome inhibitors on the coagulation system in myeloma patients, where we found that patients who developed VTE after treatment with lenalidomide and high-dose dexamethasone did not experience shorter time to progression or overall survival.  While researching the role of activated protein C in thrombotic manifestations in patients with myeloma, we found that acquired protein C resistance is the most common, transitory coagulation abnormality associated with VTE in myeloma patients. Furthermore, when the highest VTE risk is present, baseline coagulation tests may be used to identify patients who will benefit from appropriate anticoagulation therapy.

Dr. Zangari is the Principal Investigator for the Following Clinical Trials

  1. Phase 1 Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 701 in Subjects With Multiple Myeloma (Amgen)
  2. Phase 1 First-in-Man, Multicenter, Open-Label, Two Part Dose-Escalation and Cohort Expansion Study of Single-Agent GBR 1342 in Subjects with Previously Treated Multiple Myeloma (Glenmark)
  3. Phase 1B/2A Multicenter, Open-Label, Dose Escalation Study To Determine The Maximum Tolerated Dose, Assess The Safety And Tolerability, Pharmacokinetics And Preliminary Efficacy of CC-220 Monotherapy And In combination With Dexamethasone In Subjects With Relapsed And Refractory Multiple Myeloma
  4. UARK 2006 66 Total Therapy 3B: An Extension of UARK 2003 33 Total Therapy 3 A Phase II Study Incorporating Bone Marrow Microenvironment (ME) Co Targeting Bortezomib into Tandem Melphalan Based Autotransplants with DTPACE for Induction Consolidation and Velcade (bortezomib) Revlimid (lenalidomide) and Dexamethasone (VRD) for Maintenance
  5. UARK 2013-13, Total Therapy 4: Formerly 2008-01 – A Phase III Trial for Low Risk Myeloma Ages 65 and Under: A Trial Enrolling Subjects to Standard Total Therapy 3 (S-TT3)
  6. UARK 2008-03, Total Therapy 6: Phase II Trial for Patients not Qualifying for TT4 AND TT5 Protocols Because of Prior Therapy (No Prior Transplant)
  7. Phase II prospective evaluation of bone remodeling during Ixazomib treatment in relapsed/refractory MM patients

 

Dr. Zangari’s UAMS Collaborators

Frits Van Rhee, M.D., Ph.D.

Sharmilan Thanendrajan, M.D.

Carolina Schinke, M.D.

Donghoon Yoon, Ph.D.

Erming Tian, Ph.D.

Jeffrey Sawyer, Ph.D.

Shmuel Yaccoby, Ph.D.

Joshua Epstein, Ph.D.

Ricky Edmondson, Ph.D.

Stavros Manolagas, M.D.

Charles O’Brien, Ph.D.

Corey Montgomery, M.D.

Richard Nicholas, M.D.

Roy Morello, Ph.D.

 

Dr. Zangari’s External Collaborators

Alexandru Biris, Ph.D, UALR

Shebli Atrash, M.D., Levine Cancer Institute

Larry Suva, Ph.D., Texas A&M University

Gerhard Hildebrandt, M.D., University of Kentucky

Mohamed Salama, M.D., Mayo Clinic

Bum-Jun Kim, Ph.D., Baylor College of Medicine

Josef Prchal, M.D., University of Utah

Faith Davies, M.D., New York University

Gareth Morgan, M.D., Ph.D., New York University

Opportunities for Collaboration

My door is always open to further the world-class, compassionate and innovative care provided to our patients at UAMS. If my experience has taught me anything, it’s that the future is only discovered through the meeting of new ideas with the experience of the past.

You Might Not Know That

In my leisure time, I enjoy tending my garden and sharing fruits and vegetables with friends. I am still slowly running in the soccer field and riding the bike with my son, Alex. I like to spend more time fishing, but I have yet to hook the big catch yet.

Recent Cancer-Related Publications

Bacteremias following autologous stem cell transplantation for multiple myeloma: Risk factors and outcomes. Mohan M, Susanibar-Adaniya S, Buros A, Crescencio JCR, Burgess MJ, Lusardi K, Davies F, Morgan G, Vanrhee F, Zangari M, Schinke C, Thanendrarajan S, Kothari A. Transpl Infect Dis. 2019 Apr;21(2):e13052. doi: 10.1111/tid.13052. Epub 2019 Feb 15

Poor overall survival in hyperhaploid multiple myeloma is defined by double-hit bi-allelic inactivation of TP53. Ashby C, Tytarenko RG, Wang Y, Weinhold N, Johnson SK, Bauer M, Wardell CP, Schinke C, Thanendrarajan S, Zangari M, van Rhee F, Davies FE, Sawyer JR, Morgan GJ, Walker BA. Oncotarget. 2019 Jan 22;10(7):732-737. doi: 10.18632/oncotarget.26589. eCollection 2019 Jan 22.

Combination of flow cytometry and functional imaging for monitoring of residual disease in myeloma. Rasche L, Alapat D, Kumar M, Gershner G, McDonald J, Wardell CP, Samant R, Van Hemert R, Epstein J, Williams AF, Thanendrarajan S, Schinke C, Bauer M, Ashby C, Tytarenko RG, van Rhee F, Walker BA, Zangari M, Barlogie B, Davies FE, Morgan GJ, Weinhold N. Leukemia. 2018 Dec 20. doi: 10.1038/s41375-018-0329-0. [Epub ahead of print]

Mesenchymal stem cells gene signature in high-risk myeloma bone marrow linked to suppression of distinct IGFBP2-expressing small adipocytes. Mehdi SJ, Johnson SK, Epstein J, Zangari M, Qu P, Hoering A, van Rhee F, Schinke C, Thanendrarajan S, Barlogie B, Davies FE, Morgan GJ, Yaccoby S. Br J Haematol. 2019 Feb;184(4):578-593. doi: 10.1111/bjh.15669. Epub 2018 Nov 8.

FRAX is a robust predictor of baseline vertebral fractures in multiple myeloma patients. Atrash S, Dua I, Buros AF, Van Rhee F, Suva LJ, Thanendrarajan S, Schinke C, Davies F, Morgan G, Zangari M. Bone. 2019 Apr;121:134-138. doi: 10.1016/j.bone.2018.09.013. Epub 2018 Sep 19.

Visualizing collagen proteolysis by peptide hybridization: From 3D cell culture to in vivo imaging. Bennink LL, Li Y, Kim B, Shin IJ, San BH, Zangari M, Yoon D, Yu SM. Biomaterials. 2018 Nov;183:67-76. doi: 10.1016/j.biomaterials.2018.08.039. Epub 2018 Aug 22.

The presence of large focal lesions is a strong independent prognostic factor in multiple myeloma. Rasche L, Angtuaco EJ, Alpe TL, Gershner GH, McDonald JE, Samant RS, Kumar M, Van Hemert R, Epstein J, Deshpande S, Tytarenko R, Yaccoby S, Hillengass J, Thanendrarajan S, Schinke C, van Rhee F, Zangari M, Walker BA, Barlogie B, Morgan GJ, Davies FE, Weinhold N. Blood. 2018 Jul 5;132(1):59-66. doi: 10.1182/blood-2018-04-842880. Epub 2018 May 21.

Kinase domain activation through gene rearrangement in multiple myeloma. Morgan GJ, He J, Tytarenko R, Patel P, Stephens OW, Zhong S, Deshpande S, Bauer M, Weinhold N, Schinke C, Rasche L, Bailey M, Ali S, Ross J, Miller VA, Stephens P, Thanendrarajan S, Zangari M, van Rhee F, Mughal T, Davies FE, Walker BA. Leukemia. 2018 Nov;32(11):2435-2444. doi: 10.1038/s41375-018-0108-y. Epub 2018 Mar 23.

Effect of low-dose bortezomib on bone formation in smouldering multiple myeloma. Hildebrandt GC, Berno T, Gurule A, Mohan M, Yoon D, Salama M, Zangari M. Br J Haematol. 2019 Jan;184(2):308-310. doi: 10.1111/bjh.15095. Epub 2018 Mar 24. No abstract available.

Treatment to suppression of focal lesions on positron emission tomography-computed tomography is a therapeutic goal in newly diagnosed multiple myeloma. Davies FE, Rosenthal A, Rasche L, Petty NM, McDonald JE, Ntambi JA, Steward DM, Panozzo SB, van Rhee F, Zangari M, Schinke CD, Thanendrarajan S, Walker B, Weinhold N, Barlogie B, Hoering A, Morgan GJ. Haematologica. 2018 Jun;103(6):1047-1053. doi: 10.3324/haematol.2017.177139. Epub 2018 Mar 22.

The Pattern of Mesenchymal Stem Cell Expression Is an Independent Marker of Outcome in Multiple Myeloma. Schinke C, Qu P, Mehdi SJ, Hoering A, Epstein J, Johnson SK, van Rhee F, Zangari M, Thanendrarajan S, Barlogie B, Davies FE, Yaccoby S, Morgan GJ. Clin Cancer Res. 2018 Jun 15;24(12):2913-2919. doi: 10.1158/1078-0432.CCR-17-2627. Epub 2018 Mar 21.

Surgical thyroparathyroidectomy prevents progression of 5TGM1 murine multiple myeloma in vivo. Zangari M, Yoo H, Shin IJ, Yoon D, Suva LJ. J Bone Oncol. 2018 Feb 23;12:19-22. doi: 10.1016/j.jbo.2018.02.005. eCollection 2018 Sep. Review.

Thymic PTH Increases After Thyroparathyroidectomy in C57BL/KaLwRij Mice. Zangari M, Yoo H, Shin I, Kim B, Edmondson R, Morgan GJ, Suva LJ, Yoon D. Endocrinology. 2018 Apr 1;159(4):1561-1569. doi: 10.1210/en.2017-03083.

Spatial genomic heterogeneity in multiple myeloma revealed by multi-region sequencing. Rasche L, Chavan SS, Stephens OW, Patel PH, Tytarenko R, Ashby C, Bauer M, Stein C, Deshpande S, Wardell C, Buzder T, Molnar G, Zangari M, van Rhee F, Thanendrarajan S, Schinke C, Epstein J, Davies FE, Walker BA, Meissner T, Barlogie B, Morgan GJ, Weinhold N. Nat Commun. 2017 Aug 16;8(1):268. doi: 10.1038/s41467-017-00296-y.

The level of deletion 17p and bi-allelic inactivation of TP53 has a significant impact on clinical outcome in multiple myeloma. Thanendrarajan S, Tian E, Qu P, Mathur P, Schinke C, van Rhee F, Zangari M, Rasche L, Weinhold N, Alapat D, Bellamy W, Ashby C, Mattox S, Epstein J, Yaccoby S, Barlogie B, Hoering A, Bauer M, Walker BA, Davies FE, Morgan GJ. Haematologica. 2017 Sep;102(9):e364-e367. doi: 10.3324/haematol.2017.168872. Epub 2017 May 26. No abstract available.

The prognostic value of the depth of response in multiple myeloma depends on the time of assessment, risk status and molecular subtype. Schinke C, Hoering A, Wang H, Carlton V, Thanandrarajan S, Deshpande S, Patel P, Molnar G, Susanibar S, Mohan M, Mathur P, Radhakrishnan M, Hoque S, Jo Kamimoto J, Grazziutti M, van Rhee F, Zangari M, Insuasti-Beltran G, Alapat D, Post G, Yaccoby S, Epstein J, Rasche L, Johnson S, Moorhead M, Willis T, Barlogie B, Walker B, Weinhold N, Davies FE, Morgan GJ. Haematologica. 2017 Aug;102(8):e313-e316. doi: 10.3324/haematol.2017.165217. Epub 2017 May 18. No abstract available.

Low expression of hexokinase-2 is associated with false-negative FDG-positron emission tomography in multiple myeloma. Rasche L, Angtuaco E, McDonald JE, Buros A, Stein C, Pawlyn C, Thanendrarajan S, Schinke C, Samant R, Yaccoby S, Walker BA, Epstein J, Zangari M, van Rhee F, Meissner T, Goldschmidt H, Hemminki K, Houlston R, Barlogie B, Davies FE, Morgan GJ, Weinhold N. Blood. 2017 Jul 6;130(1):30-34. doi: 10.1182/blood-2017-03-774422. Epub 2017 Apr 21.

Clinical characteristics and prognostic factors in multiple myeloma patients with light chain deposition disease. Mohan M, Buros A, Mathur P, Gokden N, Singh M, Susanibar S, Jo Kamimoto J, Hoque S, Radhakrishnan M, Matin A, Davis C, Grazziutti M, Thanendrarajan S, van Rhee F, Zangari M, Davies F, Morgan G, Epstein J, Barlogie B, Schinke C. Am J Hematol. 2017 Aug;92(8):739-745. doi: 10.1002/ajh.24756. Epub 2017 Jun 1.

Extensive Remineralization of Large Pelvic Lytic Lesions Following Total Therapy Treatment in Patients With Multiple Myeloma. Mohan M, Samant RS, Yoon D, Buros AF, Branca A, Montgomery CO, Nicholas R, Suva LJ, Morello R, Thanendrarajan S, Schinke C, Yaccoby S, van Rhee F, Davies FE, Morgan GJ, Zangari M. J Bone Miner Res. 2017 Jun;32(6):1261-1266. doi: 10.1002/jbmr.3111. Epub 2017 Mar 27.

Bi-allelic inactivation is more prevalent at relapse in multiple myeloma, identifying RB1 as an independent prognostic marker. Chavan SS, He J, Tytarenko R, Deshpande S, Patel P, Bailey M, Stein CK, Stephens O, Weinhold N, Petty N, Steward D, Rasche L, Bauer M, Ashby C, Peterson E, Ali S, Ross J, Miller VA, Stephens P, Thanendrarajan S, Schinke C, Zangari M, van Rhee F, Barlogie B, Mughal TI, Davies FE, Morgan GJ, Walker BA. Blood Cancer J. 2017 Feb 24;7(2):e535. doi: 10.1038/bcj.2017.12.

Adverse Metaphase Cytogenetics Can Be Overcome by Adding Bortezomib and Thalidomide to Fractionated Melphalan Transplants. Jethava YS, Mitchell A, Epstein J, Zangari M, Yaccoby S, Tian E, Waheed S, Khan R, Papanikolaou X, Grazziutti M, Cottler-Fox M, Petty N, Steward D, Panozzo S, Bailey C, Hoering A, Crowley J, Sawyer J, Morgan G, Barlogie B, van Rhee F. Clin Cancer Res. 2017 Jun 1;23(11):2665-2672. doi: 10.1158/1078-0432.CCR-15-2620. Epub 2016 Nov 3.

Hyperhaploidy is a novel high-risk cytogenetic subgroup in multiple myeloma. Sawyer JR, Tian E, Shaughnessy JD Jr, Epstein J, Swanson CM, Stangeby C, Hale CL, Parr L, Lynn M, Sammartino G, Lukacs JL, Stein C, Bailey C, Zangari M, Davies FE, Van Rhee F, Barlogie B, Morgan GJ. Leukemia. 2017 Mar;31(3):637-644. doi: 10.1038/leu.2016.253. Epub 2016 Oct 3.

Assessment of Total Lesion Glycolysis by 18F FDG PET/CT Significantly Improves Prognostic Value of GEP and ISS in Myeloma. McDonald JE, Kessler MM, Gardner MW, Buros AF, Ntambi JA, Waheed S, van Rhee F, Zangari M, Heuck CJ, Petty N, Schinke C, Thanendrarajan S, Mitchell A, Hoering A, Barlogie B, Morgan GJ, Davies FE. Clin Cancer Res. 2017 Apr 15;23(8):1981-1987. doi: 10.1158/1078-0432.CCR-16-0235. Epub 2016 Oct 3.

Dose-dense and less dose-intense total therapy 5 for gene expression profiling-defined high-risk multiple myeloma. Jethava Y, Mitchell A, Zangari M, Waheed S, Schinke C, Thanendrarajan S, Sawyer J, Alapat D, Tian E, Stein C, Khan R, Heuck CJ, Petty N, Avery D, Steward D, Smith R, Bailey C, Epstein J, Yaccoby S, Hoering A, Crowley J, Morgan G, Barlogie B, van Rhee F. Blood Cancer J. 2016 Sep 16;6:e471. doi: 10.1038/bcj.2016.85. No abstract available.

Clonal selection and double-hit events involving tumor suppressor genes underlie relapse in myeloma. Weinhold N, Ashby C, Rasche L, Chavan SS, Stein C, Stephens OW, Tytarenko R, Bauer MA, Meissner T, Deshpande S, Patel PH, Buzder T, Molnar G, Peterson EA, van Rhee F, Zangari M, Thanendrarajan S, Schinke C, Tian E, Epstein J, Barlogie B, Davies FE, Heuck CJ, Walker BA, Morgan GJ. Blood. 2016 Sep 29;128(13):1735-44. doi: 10.1182/blood-2016-06-723007. Epub 2016 Aug 11.

Dose-dense and less dose-intense Total Therapy 5 for gene expression profiling-defined high-risk multiple myeloma. Jethava Y, Mitchell A, Zangari M, Waheed S, Schinke C, Thanendrarajan S, Sawyer J, Alapat D, Tian E, Stein C, Khan R, Heuck CJ, Petty N, Avery D, Steward D, Smith R, Bailey C, Epstein J, Yaccoby S, Hoering A, Crowley J, Morgan G, Barlogie B, van Rhee F. Blood Cancer J. 2016 Jul 29;6(7):e453. doi: 10.1038/bcj.2016.64. Erratum in: Blood Cancer J. 2016 Sep 16;6:e471.

Flow cytometry defined cytoplasmic immunoglobulin index is a major prognostic factor for progression of asymptomatic monoclonal gammopathies to multiple myeloma (subset analysis of SWOG S0120). Papanikolaou X, Rosenthal A, Dhodapkar M, Epstein J, Khan R, van Rhee F, Jethava Y, Waheed S, Zangari M, Hoering A, Crowley J, Alapat D, Davies F, Morgan G, Barlogie B. Blood Cancer J. 2016 Mar 25;6:e410. doi: 10.1038/bcj.2016.19. No abstract available.

The effects of proteasome inhibitors on bone remodeling in multiple myeloma. Zangari M, Suva LJ. Bone. 2016 May;86:131-8. doi: 10.1016/j.bone.2016.02.019. Epub 2016 Mar 3. Review.

Monoclonal antibody therapy in multiple myeloma: where do we stand and where are we going? Thanendrarajan S, Davies FE, Morgan GJ, Schinke C, Mathur P, Heuck CJ, Zangari M, Epstein J, Yaccoby S, Weinhold N, Barlogie B, van Rhee F. Immunotherapy. 2016;8(3):367-84. doi: 10.2217/imt.15.118. Epub 2016 Feb 17. Review.

Clinical value of molecular subtyping multiple myeloma using gene expression profiling. Weinhold N, Heuck CJ, Rosenthal A, Thanendrarajan S, Stein CK, Van Rhee F, Zangari M, Hoering A, Tian E, Davies FE, Barlogie B, Morgan GJ. Leukemia. 2016 Feb;30(2):423-30. doi: 10.1038/leu.2015.309. Epub 2015 Nov 3.

Inhibiting MEK in MAPK pathway-activated myeloma. Heuck CJ, Jethava Y, Khan R, van Rhee F, Zangari M, Chavan S, Robbins K, Miller SE, Matin A, Mohan M, Ali SM, Stephens PJ, Ross JS, Miller VA, Davies F, Barlogie B, Morgan G. Leukemia. 2016 Apr;30(4):976-80. doi: 10.1038/leu.2015.208. Epub 2015 Jul 31. No abstract available.

Four genes predict high risk of progression from smoldering to symptomatic multiple myeloma (SWOG S0120). Khan R, Dhodapkar M, Rosenthal A, Heuck C, Papanikolaou X, Qu P, van Rhee F, Zangari M, Jethava Y, Epstein J, Yaccoby S, Hoering A, Crowley J, Petty N, Bailey C, Morgan G, Barlogie B. Haematologica. 2015 Sep;100(9):1214-21. doi: 10.3324/haematol.2015.124651. Epub 2015 May 28.

Drug resistance in hematologic malignancies: induction mechanisms, genetics, and therapeutics. Zhan F, Zangari M, Qiu L. Biomed Res Int. 2015;2015:384575. doi: 10.1155/2015/384575. Epub 2015 Apr 27. No abstract available.

Evidence of an epigenetic origin for high-risk 1q21 copy number aberrations in multiple myeloma. Sawyer JR, Tian E, Heuck CJ, Johann DJ, Epstein J, Swanson CM, Lukacs JL, Binz RL, Johnson M, Sammartino G, Zangari M, Davies FE, van Rhee F, Morgan GJ, Barlogie B. Blood. 2015 Jun 11;125(24):3756-9. doi: 10.1182/blood-2015-03-632075. Epub 2015 May 5.

The flow cytometry-defined light chain cytoplasmic immunoglobulin index and an associated 12-gene expression signature are independent prognostic factors in multiple myeloma. Papanikolaou X, Alapat D, Rosenthal A, Stein C, Epstein J, Owens R, Yaccoby S, Johnson S, Bailey C, Heuck C, Tian E, Joiner A, van Rhee F, Khan R, Zangari M, Jethava Y, Waheed S, Davies F, Morgan G, Barlogie B. Leukemia. 2015 Aug;29(8):1713-20. doi: 10.1038/leu.2015.65. Epub 2015 Mar 10.

A Phase I Dose-Escalation Study of Antibody BI-505 in Relapsed/Refractory Multiple Myeloma. Hansson M, Gimsing P, Badros A, Niskanen TM, Nahi H, Offner F, Salomo M, Sonesson E, Mau-Sorensen M, Stenberg Y, Sundberg A, Teige I, Van Droogenbroeck J, Wichert S, Zangari M, Frendeus B, Korsgren M, Poelman M, Tricot G. Clin Cancer Res. 2015 Jun 15;21(12):2730-6. doi: 10.1158/1078-0432.CCR-14-3090. Epub 2015 Feb 24.

Impact of a change in antibacterial prophylaxis on bacteremia and hospitalization rates following outpatient autologous peripheral blood stem cell transplantation for multiple myeloma. Kim JH, Goulston C, Zangari M, Tricot G, Boyer MW, Hanson KE. Transpl Infect Dis. 2014 Jun;16(3):421-9. doi: 10.1111/tid.12225. Epub 2014 May 5.

Jumping translocations of 1q12 in multiple myeloma: a novel mechanism for deletion of 17p in cytogenetically defined high-risk disease. Sawyer JR, Tian E, Heuck CJ, Epstein J, Johann DJ, Swanson CM, Lukacs JL, Johnson M, Binz R, Boast A, Sammartino G, Usmani S, Zangari M, Waheed S, van Rhee F, Barlogie B. Blood. 2014 Apr 17;123(16):2504-12. doi: 10.1182/blood-2013-12-546077. Epub 2014 Feb 4.

Parathyroid hormone receptor mediates the anti-myeloma effect of proteasome inhibitors. Zangari M, Berno T, Yang Y, Zeng M, Xu H, Pappas L, Tricot G, Kamalakar A, Yoon D, Suva LJ. Bone. 2014 Apr;61:39-43. doi: 10.1016/j.bone.2013.12.025. Epub 2013 Dec 31.

Could hypoxia increase the prevalence of thrombotic complications in polycythemia vera? Zangari M, Fink L, Tolomelli G, Lee JC, Stein BL, Hickman K, Swierczek S, Kelley TW, Berno T, Moliterno AR, Spivak JL, Gordeuk VR, Prchal JT. Blood Coagul Fibrinolysis. 2013 Apr;24(3):311-6. doi: 10.1097/MBC.0b013e32835bfdb9.