Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Reference values for thrombotic markers in children Darintr Sosothikul, Yaowaree Kittikalayawong, Pattramon Aungbamnet, Chatchai Buphachat and Panya Seksarn Thromboembolic events are an increasingly common problem encountered in children. The laboratory diagnosis of thrombotic disorders in children differs from that in adults. To establish the normal reference of natural anticoagulant parameters in children of different age groups, plasma from healthy children between the ages of 2 months and 16 years (n U 127) and adults (n U 30) were assayed for a disintegrin-like and metalloprotease with thrombospondin type 1 domain 13 (ADAMTS-13), von Willebrand factor collagen-binding activity (vWF:CB), tissue factor pathway inhibitor (TFPI), homocyteine and natural anticoagulants. Children were divided into four age groups: less than 1 year, 1–5 years, 6–10 years, and 11–16 years. The reference values for ADAMTS 13, homocysteine, and protein C activity were significantly lower in children of all age groups compared with those in the adults. Similarly, those for protein C antigen, total protein S, free protein S and antithrombin III (AT III) for children less than 1 year were significantly lower than in the adults. On the contrary, TFPI levels were significantly higher in the children for all age groups when compared with the adults. vWF:CB levels were comparable across all groups. There are age-related physiologic differences in ADAMTS-13, TFPI, homocysteine and natural anticoagulants between children and adults. Our data will provide physicians with a useful reference guide in interpreting test results of inhibitors of hemostatic parameters in children suspected of thrombotic disorders. Blood Coagul Fibrinolysis 23:208– 211 ß 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins. Blood Coagulation and Fibrinolysis 2012, 23:208–211 Keywords: children, reference values, thrombosis Hematology and Oncology Division, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand Correspondence to Darintr Sosothikul, MD, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand Tel: +662 256 4949; fax: +662 256 4911; e-mail: dsosothikul@hotmail.com Received 17 May 2011 Revised 18 November 2011 Accepted 7 December 2011 Introduction Thromboemobolic diseases are rare in children [1,2] with incidence rates of 00.05 – 0.07/10 000 children [3,4]. How- ever, of late, incidences of pediatric venous thromboem- bolism have been increasing [5,6]. Increases in thrombotic complications are due to advancements in therapeutic or invasive procedures for the treatment of the patients’ primary illness and heightened awareness of the disorders among the medical staff [7,8]. The most common cause of pediatric venous thromboembolism is the use of indwelling/central venous catheters [9,10] among patients with cancer, congenital heart disease, prematurity, infection, and others [3,7,8,11]. Tests to routinely detect thrombosis in children were initially based on reference values in adults [12]. As it was shown that plasma concentrations of many hemostatic com- ponents in newborns and children of various age groups have different levels compared with adults [13,14], pediatric reference ranges for hemostatic components were finally established in 1997 [14]. These age-appro- priate pediatric reference values have helped physicians to efficiently diagnose thrombosis in children and prevent future posttraumatic syndromes. Even though most of the patients will have spontaneous recovery, these will be major significant consequences to the patients as they grow older, which can affect their quality of life and financially burden the healthcare system. Therefore, these age-dependent reference ranges have helped phys- icians worldwide avoid under or over-diagnosing children with these disorders. Previous reference values of thrombotic markers were determined more than 30 years ago using old procedures and equipment [12,15]. It has been shown that these clinical reference ranges [14] are no longer applicable when current coagulation testing systems have been used [16]. After taking all of these issues into account, we observed that there was an urgent need to obtain up-to- date reference intervals based on our laboratory analyzer and reagents [17,18], to accurately diagnose thrombotic abnormalities in the pediatric population. Hence in 2005, in our pilot project, specimens from a total of 70 children between the ages of 1 and 18 years were measured and reference ranges were established [19]. To confirm the data previously obtained, we decided to expand the study to include a much larger sample size to accurately estab- lish the normal range of natural anticoagulants in Thai children of different age groups. Materials and methods Patients Blood was collected from healthy children between the ages of 2 months and 16 years (n ¼ 127) and adults (n ¼ 30) at the King Chulalongkorn Memorial Hospital, 208 Original article 0957-5235 ß 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI:10.1097/MBC.0b013e328350294a