Projects
Each member of the IPTN may propose sub-studies using the Throm-PED registry (IPTN projects). These proposals (study protocol, including additional datasheets for the Throm-PED registry) will be discussed in the general assembly meeting, which will take place at least once a year during the ISTH congress; or in the executive committee meetings. Each approved IPTN project has its own scientific board, which is responsible for the design and execution of the IPTN project. An additional project agreement is necessary to ensure safe data transfer.
Proposals for IPTN projects can be sent to iptn@erasmusmc.nl
The real world use of DOACs in children
At the moment direct oral anticoagulants (DOACs) are in various stages of receiving regulatory approval by the EMA and FDA for use in children. Given the apparent benefits of DOACs compared to warfarin or LMWH (no need for twice daily injections, few diet and drug interactions, and little need for monitoring), it is likely that they will become widely utilized in children. While the trials are providing essential data regarding drug pharmacokinetics and pharmacodynamics in children, as well as some information on safety and efficacy, they were not powered to demonstrate safety and efficacy. Furthermore, and more importantly, patients enrolled in the trials do not represent the clinical heterogeneity of children with thrombosis seen in day to day practice.
Therefore, as these drugs become more widely used in children, it is essential to continue to evaluate their safety and effectiveness in a real world setting, including children with cancer and/or renal insufficiency. Whether or not there is a role for measuring drug specific levels of anticoagulation (e.g. anti-Xa or dilute thrombin time) to monitor specific subgroups of children remains an important question.
The aims of this registry are (1) to describe current practices in the use of DOACS (apixaban, dabigatran, edoxaban and rivaroxaban) in pediatric patients for the treatment of thrombosis; and (2) to obtain efficacy and safety data on real-world use of DOACs in pediatric patients.
PI: Leslie Raffini (Children's Hospital of Philadelphia) and Susanne Holzhauer (Charité-Universitätsmedizin Berlin)
Management of neonatal renal vein thrombosis
Neonatal renal vein thrombosis (nRVT) is a rare condition. The incidence is about 2.2 per 100.000 live births. Little is known about the epidemiology, risk factors, treatment and long-term outcome. nRVT seems to occur more frequently in males compared to females, and the majority of neonatal RVT are unilateral, with a left-sided predominance. The mortality rates are low, but long-term kidney dysfunction is common: kidney atrophy in 71% of neonates, hypertension in 20% and chronic kidney disease requiring replacement therapy in 3%. There is no consensus for the management of nRVT. International guidelines suggest using supportive care only or anticoagulation in neonates with unilateral RVT and thrombolytic therapy in neonates with bilateral RVT causing kidney failure. However, it is not established whether anticoagulation and/or thrombolytic therapy influence the short-term bleeding risk, the thrombus evolution and recurrence risk, long-term sequelae, and/or mortality.
The aims of this study are (1) to generate insights in the epidemiology, and management of nRVT worldwide, and (2) to study risk factors for recurrent VTE and long-term (> 3 months) renal sequelae to define patients at risk, which may benefit from antithrombotic therapy.
PI: Anthony Chan (McMaster Children’s Hospital, Hamilton, Canada)
Management of catheter-related arterial thrombosis
Catheter-related arterial thrombosis (CAT) is increasingly recognized in neonates and children requiring monitoring in intensive care units or during surgery as well as in children with congenital heart disease undergoing cardiac catheterization. CAT may be associated with serious acute signs and symptoms as well with long-term complications such as leg length difference, claudication, and loss of arterial access for future diagnostic and therapeutic interventions. A recent systematic review of the existing literature on pediatric CAT identify instances of heterogeneity in definitions, diagnostic and treatment modalities employed across studies. No evidence-based guidelines are available so far to prefer one treatment approach (such as anticoagulant or antiplatelet drugs) to another.
Overall, there remains a paucity of data from well-designed studies on the incidence, risk factors, optimal diagnosis and treatment modalities, outcomes, and prognostic factors of pediatric CAT.
The aims of this study are (1) to collect information on the current incidence, comorbidity, clinical presentation, radiological modalities of CAT, (2) to evaluate the treatment modalities used for CAT as well the related clinical and radiological outcome and (3) to identify prognostic factors of pediatric CAT.
PI: Mattia Rizzi (Lausanne University Hospital - CHUV, Lausanne, Switzerland)
Adolescent thromboembolism
Adolescents, in addition to neonates, are at greatest risk for thromboembolism (TE) in the pediatric population, in part due to the advances in diagnostic modalities, therapeutic approaches, technologic support, and overall care for illnesses. In addition, adolescents experience several unique health challenges including estrogen therapy in females, autoimmune disorders, trauma risk, sedentary behavior, and anatomic abnormalities, which can pose additional risks for TE. Few studies in adolescents have shown a multi-factorial risk for TE as opposed to the predominant etiology of central lines seen in younger children. This may necessitate tailored evaluation and management approaches for adolescent TE, different from those for younger children, such as greater utilization of direct oral anticoagulants for better compliance and interventional approaches for extremity TE. The findings of this study we hope will enable physicians to better understand the pathophysiology of TE in adolescents and help to develop tailored evaluation, management and preventive strategies for TE in this population.
The aims of this registry are (1) to evaluate the epidemiology, risk factors, diagnosis, treatment and outcome of TE in adolescents; and (2) to evaluate the safety and efficacy of all treatment modalities used in adolescent TE.
PI: Lakshmi Srivaths (University of Texas Health Science Center, Houston, Texas, USA)
PROSPECT: PROSpective evaluation of Pulmonary Embolism in Children sTudy
Despite a significant increase in the incidence of pediatric PE, there are critical knowledge gaps in identifying outcomes and optimal treatment strategies. The development of a valid cohort and determination of PE-specific outcomes is critical for evaluating the epidemiologic features and understanding the disease trajectory of pediatric PE, a hitherto orphan disease with the potential for significant health consequences. The results of this study will enable us to develop specific guidance for treatment recommendations across multiple domains of health of children.
PROSPECT is a prospective multi-center, multi-national observational cohort study using the current framework of the International Pediatric Thrombosis Network (IPTN) and the REDcap Throm-PED registry as a platform for data collection. PROSPECT is a collaborative study between IPTN and the pediatric PE working party with Johns Hopkins All Children’s Hospital acting as the data coordinating and statistical support center.
The aims of this study are 1) Determine the incidence and prognostic factors for early adverse events (at 30 days post-diagnosis) after pediatric PE. 2) To compare the safety (bleeding) and efficacy (recurrent thrombosis) at 2 years of a conventional 12-week duration of anticoagulation to an extended duration of anticoagulation (>13 weeks) after the 1st episode of pediatric PE.
Additionally, there are two exploratory aims: 1) To characterize the frequency and type of functional limitations in patients who develop pediatric PE. 2) Test the feasibility of standardizing pediatric PE specific common data elements (CDE) across thrombosis registries.
This study has received funding from the INVENT -VTE Dragon’s Den competition and a ISTH grant.
PI: Madhvi Rajpurkar,MD, Central Michigan University, Wayne State University, Children’s Hospital of Michigan, Detroit, USA.
Co-PI: C Heleen van Ommen, MD, PhD - Co-I: Neil A Goldenberg, MD, PhD - Co-I: Ernest Amankwah, PhD
Antiphospholipid antibody syndrome (APS)
Antiphospholipid antibody syndrome (APS) is a multi-system, auto-immune, pro-inflammatory condition characterized by thrombotic and obstetric complications. When it debuts with arterial, venous, or microvascular thrombosis, APS is termed thrombotic APS (TAPS). Specific subsets of patients, notably patients < 50 years of age, patients with cerebrovascular events and those with unprovoked thromboembolism have a higher incidence of TAPS. TAPS in patients less than 18 years of age remains understudied and thrombotic complications of pediatric TAPS are often diagnosed and treated as per practices prevalent in adult medicine. However, there are several aspects of pediatric TAPS that are emerging as distinct from adult onset TAPS . These gaps in knowledge about pediatric TAPS merit further, prospective, collaborative investigation.
The aims of this study are (1) To evaluate the epidemiology, diagnosis, treatment and outcomes of thrombotic complications of pediatric TAPS and (2) To evaluate the safety and efficacy of anti-thrombotic treatment modalities employed in pediatric TAPS.
