Developmental Haemostasis

• Antithrombin: the levels of antithrombin increase with age. Antithrombin levels in newborns are less than 50% of the levels in adults. By six months of age Antithrombin levels increase to adult levels. Antinthrombin is present in various isoforms. There is an increase in the concentration of a specific isoform of Antithrombin, Latent Antithrombin with age.^[5] This form of Antithrombin is known to be associated with thrombosis and hence decreased levels in children may help protect them from spontaneous thrombosis. There is also an increased activity of another form of Antithrombin, Beta Antithrombin in newborns compared to older children and adults.^[6]
• alpha-2-Macroglobulin (A2M): is also a major inhibitor of thrombin. It is present in 2-3 fold higher concentration during childhood, approaching adult levels in late teenage years. It has been shown that a higher proportion of thrombin is inhibited by A2M in children than adults.^[9] This suggests that in children, A2M plays a more important role in thrombin inhibition compared to antithrombin.
• Platelets: are blood cells that once activated, aggregate and form clots. There are age-related differences in platelet number and their activity. They form aggregates with white blood cells and in adults the platelets that are bound to white blood cells are usually activated. In children, these white blood cell-platelet aggregates are increased in children compared to adult levels, however this takes place without a corresponding increase in platelet activation.^[10] Increased white blood cell-platelet aggregates in adults can indicate atherosclerosis, but this is not the case in children.

Reference ranges demonstrate the normal test values for a healthy population. Diseases and disorders are diagnosed when a test value is outside the reference range. Many laboratories compare paediatric results to adult reference ranges or to published paediatric reference ranges that may not be specific for the test used.^[11] This can lead to misdiagnosis or over-diagnosis of blood clotting disorders as many proteins exist at levels during stages of infancy that would be associated with disease in adults. This can lead to unnecessary stress for families and can have significant medical implications for the child (e.g. further testing). The differences in the haemostatic proteins can lead to different interactions with anticoagulant drugs that are used to prevent and treat thrombosis in children.^[12][13] More studies are required to determine the optimal treatment strategies and doses of anticoagulants in children.^{[citation needed]}

The role of developmental haemostasis in normal physiology is still not fully understood. It has been observed that the newborn haemostatic system is protective and contributes to a decreased risk of bleeding or thrombosis compared to adults. The differences may also be due to the role haemostatic proteins play within other physiological systems.^{[citation needed]}