Background: The concept of developmental hemostasis has been universally accepted. Plasma concentrations of many coagulation factors in childhood are significantly different from adults for both mean values and ranges of normal. Thus, an understanding of developmental hemostasis and the development of appropriate age-dependent reference ranges are pivotal for prevention, diagnosis, and treatment of hemostatic problems during childhood. However, no data of developmental hemostasis are available in healthy Chinese children.

Methods:

Coagulation data from children aged 0-18 years old receiving minor elective surgery in Chengdu Women and Children's Central Hospital, from Sep. 2017 to Feb. 2019 was collected, and patient medical records were reviewed. Ethical approval was obtained from the parents of all children and the study was approved by the Ethics Review Committee at Chengdu Women and Children's Central Hospital.

To qualify for the study, enrolled subjects had to meet the following criteria: (1) Children aged 0-18 years receiving minor elective surgery.(2) No history of bleeding problems.(3)No family history of bleeding nor thrombosis .(4) No history of heart, lung, liver or kidney diseases, normal physical examination. (5) Normal blood routine test. Normal liver function and kidney function, (6)No history of medication use for at least two weeks prior to specimen collection.(7) The operation gone successfully, and postoperative recovery was well.

Blood samples (3 mL) were obtained by venipuncture into plastic tube containing 3.2% (109 mmol/L) buffered sodium citrate (1 part citrate:9 parts blood). The specimens were centrifuged immediately at 2500 g for 15 min at room temperature to prepare platelet-poor plasma (PPP) for the preoperative coagulation screening tests, consisting of activated partial thromboplastin time (APTT), prothrombin time (PT)), international normalized ratio (INR), thrombin time (TT) and fibrinogen. Activity of coagulation factors VIII, IX, XI, XII,Ⅱ,Ⅴ,Ⅶ,Ⅹ were determined using one-stage clotting methods with respective factor-deficient plasma.

Results: A total of 82 samples were collected, while only 67 met the enrollment criteria. Specimens with inappropriate ratio of blood to anticoagulant, hemolysis or abnormal values of coagulation tests (APTT, PT, TT, fibrinogen) were excluded from analysis.

The total of 67 children (40 Male 27 female), with a median age of 2.0 years (range: 1month -14 years) were divided into three groups according to the age: <1y group 15 cases, 1-5y group 45 cases, and >6y group 7cases.

(1) The values of APTT, PT, TT, and fibrinogen were (36.1±5.2) seconds, (11.1±0.85) seconds, (20.3±1.6) seconds, (2.4±0.89) g/L respectively. No significant differences were found between groups.

(2) In all children ,the activities of factor VIII、IX、XI、XII、vWF、II、V、VII、X were(123.6±48.3)%、(75.9±16.9)%、(95.9±24.3)%、(43.7±16.3)%、(111.3±50.4)%、(90.2±14.0)%、(104.7±21.1)%、(81.6±19.1)%、(93.0±21.8)% respectively. Factor VIII and vWF activities were significantly higher than other factors, while factor XII activities were significantly lower than others.

(3)Mean values of FII:C, FVIII:C, FIX:C, FXI:C were significantly lower in children below <1year old group than those in 1-5y group. No significant difference were seen in FVII:C, FV:C, FX:C, FXII:C, vWF:C among three groups.

Conclusions: Coagulation test is just a simple and easy screening test. Coagulation factor activities changed dynamically with age during childhood, especially the FII:C, FVIII:C, FIX:C and FXI:C. Physiological reference ranges for coagulation factor activities in Chinese children of different ages should be established in order to evaluate the children with congenital or acquired bleeding diseases correctively.

Disclosures

No relevant conflicts of interest to declare.

Author notes

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Asterisk with author names denotes non-ASH members.

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