Haematology Research

Infants and children have a lower incidence of bleeding and blood clotting events than adults. By understanding the balance between bleeding and clotting in healthy children we can improve the quality of care delivered to sick children and develop strategies to prevent thrombosis in children and adults. 

Pioneering research in developmental haemostasis

Our team investigates developmental haemostasis — how the blood’s clotting system matures with age. We are the only research group in Australia, and one of just three globally, conducting this type of research.

Age-associated alterations

There are age-associated alterations in levels of coagulation proteins and their function. We established the only age-specific reference ranges for coagulation proteins in an Australian population that has adopted inpatient care nationally and internationally.

Our researchers’ novel approach has shown:

• Differences in the concentration, structure and function of coagulation proteins with age
• Differences in the platelet phenotype and function in children compared to adults
• Differences in blood clot formation, and structure in children compared to adults
• Concept of “ageing of the plasma proteome”
• Pharmacokinetics, pharmacodynamics and monitoring strategies for currently used and novel anticoagulants in children.

Global leadership and impact

Our researchers have led the development of international clinical guidelines and position papers for the International Society for Thrombosis and Haemostasis, helping to shape best practices in paediatric haematology worldwide.

More information

• Happi kids research project

Our projects

Developmental haemostasis

HAPPI Kids Study

We are aiming to collect blood samples from around 5,000 children between birth and 18 years, so we can establish normative data for age-appropriate reference intervals in haematology, immunology, and biochemistry for the paediatric population for The Royal Children's Hospital and for laboratories throughout the state of Victoria.

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Intranasal Heparin Trial (INHERIT)

This trial is testing Intranasal Heparin to treat early COVID-19 infection.

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Platelet phenotype and function

Platelets are critical in thrombosis and inflammation but have not been studied in children. Our group has recently showed for the first time increased circulating monocyte-platelet aggregates (MPAs) in children and increased responsiveness to platelet agonists. The preliminary data also shows age-specific changes in the platelet proteome and platelet proteins secreted following platelet activation. This study aims to determine the age-specific differences in platelets responsible for differences in platelet function in children compared to adults.

Anticoagulation

Anticoagulants and antithrombotics (heparin, rivaroxaban, warfarin, aspirin)

Because of recent major advances in the surgical and medical management of children with complex diseases, many of these children are now surviving into adulthood. Despite these advances, many children require ong

oing medication to prevent complications such as blood clots and stroke. Anticoagulants, sometimes referred to as ‘blood thinners’, are used to prevent blood clots and stroke. The group’s research has shown that the blood clotting system in children differs significantly from that in adults. Because of these differences, the team has dedicated many years to investigate the effect of different anticoagulants on children.

This research has become even more vital to the development of new anticoagulants. The team’s ongoing research in this area has become crucial to the effective and safe management of anticoagulants in children now and in the future.

Researchers will aim to determine the specific effects of anticoagulants in children and to improve current strategies for monitoring these drugs in children, by studying plasma samples from newborns to adults and anticoagulants in unwell children at the Royal Children’s Hospital.

Heparin mimics

Synthetically produced anticoagulants have the potential to overcome the significant safety issues associated with heparin. This study aims to develop bespoke polymers with suitable anticoagulant profiles for use as replacements for heparin.

Thrombosis and bleeding

Thrombosis – Central Venous Line (CVL)

A CVL is a catheter placed into a large vein in the chest. This study will for the first time document the natural history of asymptomatic central venous line (CVL)-related deep vein thrombosis (DVT) in sick children, allowing appropriate diagnostic and therapeutic strategies to be developed. 

The study will also identify and provide recommendations on the clinical value of routine ultrasound screening of all children with a CVL for a thrombosis by determining the incidence of clinically significant post-thrombotic syndrome (PTS) a year later.

This study will be conducted as a prospective cohort study of 200 children admitted to the Paediatric Intensive Care Unit (PICU), at the Royal Children’s Hospital, Melbourne. The unit admits approximately 1,000 children a year.

Of these, over 40 percent have a CVL placed because of heart surgery and a further 30 percent require a CVL for medication support. This data shows that the recruitment of 200 children with CVLs in one year is feasible and practical in this setting.

Bleeding and clotting outcomes post-Fontan surgery

The Fontan procedure is the last of a series of operations offered to children born with only one pumping heart chamber. Without this procedure, these children would die. However, the procedure comes with long-term risks. Many patients have ongoing medical complications after the procedure, including blood clots, stroke and bleeding.

The team is currently investigating the long-term outcomes of the Australian and New Zealand (ANZ) Fontan population. This study aims to pinpoint the incidence and identify risk factors for blood clots, stroke and bleeding in the ANZ Fontan population and determine which medications are the best at preventing these complications.

ECMO

Extracorporeal Membrane Oxygenation (ECMO) is a form of cardiopulmonary life support that uses a heart-lung machine to provide artificial oxygenation of the blood and systematic perfusion in patients with severe heart and/or lung failure.

Limitations of this therapy include significant complications of bleeding and clotting. This study aims to establish tailored therapy protocols to reduce bleeding and clotting complications for children on ECMO.

Proteomics research

Age-mediated differences

Human blood plasma is a complex biological fluid that interacts with an array of bodily systems. Changes in plasma protein expression or the presence or absence of specific proteins are regularly used in a clinic as a molecular biomarker tool. A large body of literature exists detailing proteomic changes in pathologic contexts, however, little research has been conducted on the quantitation of the plasma proteome in age-specific, healthy subjects, especially in pediatrics.

Our research focuses on studying variations in protein expression across the age spectrum from neonates to adults.

Thrombin generation

Thrombin generation (TG) is a global analysis of haemostasis that, in theory, could monitor thrombosis risk, anticoagulation management, and guide therapy in bleeding disorders.

The current TG methods of care are inadequate because they cannot specifically measure active and free thrombin, relying instead on extrapolation from algorithms.

The team has patented a substrate to measure true active thrombin, which this study will analyse for the suitability of its use in patients.

Funding

Thank you to our supporters.

• National Health and Medical Research Council (NHMRC)
• Medical Research Future Fund (MRFF)
• Royal Children’s Hospital Foundation
• University of Melbourne
• Diagnostica Stago
• Bayer HealthCare
• Astra Zeneca

Collaborations

We collaborate with leading institutions worldwide, including:

International

• McMaster Children’s Hospital, Hamilton, Canada: Prof Anthony Chan (Patent)
• Lake Forest Hospital, Chicago, USA: Dr Rukhmi Bhat
• Karolinska Institute, Stockholm, Sweden: Dr Maria Magnusson
• Medical University of Vienna, Austria: Prof Christoph Male
• Hadassah Medical Centre, Jerusalem, Israel: Dr Shoshana Revel-Vilk
• The Children’s Hospital of Philadelphia, USA: A/Prof Leslie Raffini
• Bern University, Switzerland: Prof Maja Steinlin
• Johns Hopkins All Children’s Hospital: Professor Neil Goldenberg

National

• Department of Cardiac Surgery, Royal Children’s Hospital: Prof Igor Konstantinov
• Department of Psychology, Royal Children’s Hospital: Prof Vicki Anderson
• The University of Western Australia: A/Prof Matthew Linden
• Deakin University: Prof Jeff Craig

Industry collaborations

• Diagnostica Stago
• Bayer
• Bristol Myers Squibb
• Roche Diagnostics
• Takeda
• Astra Zeneca

Featured publications

Coles CA, Jalali S, de Valle K, Manton N, Karlaftis V, Attard C, Galea E, Forbes R, Piers AT, Clark DR, Woodcock IR, Pellicci DG, Houweling PJ. Detailed immune cell profiling of paediatric patient with limb girdle muscular dystrophy R3. J Neurol Sci. 2025 Sep 15;476:123629. doi: 10.1016/j.jns.2025.123629. Epub 2025 Jul 18. PMID: 40737975.

Collett S, Earnest L, Edeling MA, Yap AHY, Carrera Montoya J, Attard C, Di Rago L, Farley A, Ng AP, Monagle P, Torresi J. Adenovirus vectors can infect mouse megakaryocytes - implications for vaccine-induced thrombosis/thrombocytopenia. Res Pract Thromb Haemost. 2025 Jun 2;9(4):102909. doi: 10.1016/j.rpth.2025.102909. PMID: 40657324; PMCID: PMC12246938.

Monagle P, Azzam M, Bercovitz R, Betensky M, Bhat R, Biss T, Branchford B, Brandão LR, Chan AKC, Faustino EVS, Jaffray J, Jones S, Kawtharany H, Kerlin BA, Kucine N, Kumar R, Male C, Pelland-Marcotte MC, Raffini L, Raulji C, Sartain SE, Takemoto CM, Tarango C, van Ommen CH, Velez MC, Vesely SK, Wiernikowski J, Williams S, Wilson HP, Woods G, Zia A, Mustafa RA. American Society of Hematology/International Society on Thrombosis and Haemostasis 2024 updated guidelines for treatment of venous thromboembolism in pediatric patients. Blood Adv. 2025 May 27;9(10):2587-2636. doi: 10.1182/bloodadvances.2024015328. PMID: 40423983; PMCID: PMC12235321.

Hock DH, Caruana NJ, Semcesen LN, Lake NJ, Formosa LE, Amarasekera SSC, Stait T, Tregoning S, Frajman LE, Bournazos AM, Robinson DRL, Ball M, Reljic B, Ryder B, Wallis MJ, Vasudevan A, Beck C, Peters H, Lee J, Tan NB, Freckmann ML; MitoMDT Diagnostic Network for Genomics and Omics; Karlaftis V, Attard C, Monagle P, Samarasinghe A, Brown R, Bi W, Lek M, McFarland R, Taylor RW, Ryan MT, Cooper ST, Stark Z, Christodoulou J, Compton AG, Thorburn DR, Stroud DA. Untargeted proteomics enables ultra-rapid variant prioritisation in mitochondrial and other rare diseases. Genome Med. 2025 May 22;17(1):58. doi: 10.1186/s13073-025-01467-z. PMID: 40400026; PMCID: PMC12096736.

Nekipelov K, Nahain AA, Otto S, Xu Y, Li JP, Letunica N, Collett S, Attard C, Monagle P, Vamvounis G, Tsanaktsidis J, Ferro V, Bendas G. A Novel Series of Synthetic Heparin-Mimetics-Itaconic Acid-Containing Copolymers for Targeting Tumor Cell Coagulability and Metastasis. Macromol Biosci. 2025 Jul;25(7):e2400633. doi: 10.1002/mabi.202400633. Epub 2025 Apr 7. PMID: 40192620; PMCID: PMC12259396.

Cai T, Emery-Corbin SJ, McCafferty C, Van Den Helm S, Letunica N, Attard C, Barton R, Horton S, Bottrell S, Schultz B, MacLaren G, Chiletti R, Best D, Johansen A, Newall F, Butt W, d'Udekem Y, Dagley LF, Yousef JM, Monagle P, Ignjatovic V. Comprehensive Characterization of Surface-Bound Proteins and Measurement of Fibrin Fiber Thickness on Extracorporeal Membrane Oxygenation Circuits Collected From Patients. Pediatr Crit Care Med. 2024 Nov 1;25(11):1017-1025. doi: 10.1097/PCC.0000000000003591. Epub 2024 Aug 13. PMID: 39145643.

Payne RM, Burns KM, Glatz AC, Male C, Donti A, Brandão LR, Balling G, VanderPluym CJ, Bu'Lock F, Kochilas LK, Stiller B, Cnota JF 2nd, Rahkonen O, Khan A, Adorisio R, Stoica S, May L, Burns JC, Saraiva JFK, McHugh KE, Kim JS, Rubio A, Chía-Vazquez NG, Meador MR, Dyme JL, Reedy AM, Ajavon-Hartmann T, Jarugula P, Carlson-Taneja LE, Mills D, Wheaton O, Monagle P. Apixaban for Prevention of Thromboembolism in Pediatric Heart Disease. J Am Coll Cardiol. 2023 Dec 12;82(24):2296-2309. doi: 10.1016/j.jacc.2023.10.010. PMID: 38057072.

Letunica N, McCafferty C, Swaney E, Cai T, Monagle P, Ignjatovic V, Attard C. Proteomic Applications and Considerations: From Research to Patient Care. Methods. Mol Biol. 2023;2628:181-192. doi: 10.1007/978-1-0716-2978-9_12. PMID: 36781786.