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The primary objective of this study is to investigate whether tranexamic acid (TXA) reduces perioperative blood loss and transfusion requirement in infants undergoing craniosynostosis surgery.
Blood loss during pediatric craniosynostosis surgery can be significant and this may be exacerbated by a dilutional coagulopathy. Multimodal blood conservation strategies may limit allogeneic transfusions, although RCTs are few and limited. It is essential to investigate these techniques to determine their potential to reduce allogeneic blood transfusions and their associated cost and morbidity.
Tranexamic acid (TXA) is a synthetic antifibrinolytic drug that competitively inhibits the lysine binding sites of plasminogen, plasmin, and tissue plasminogen activator. The result is inhibition of fibrinolysis and clot degradation.
Recent studies in adults undergoing cardiac surgery demonstrated that people with different genotypes for the plasminogen activator inhibitor-1 (PAI-1) gene may have varying degrees of bleeding. PAI-1 inhibits the transformation of plasminogen to plasmin thereby decreasing plasmin-induced fibrinolysis. Thus, PAI-1 promotes clot stability and the PAI-1 polymorphism will affect the degree of bleeding and response to TXA during craniosynostosis surgery.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Low Dose | Experimental | TXA 10mg/kg bolus before incision and 5 mg/kg infusion until skin closure |
|
| High Dose | Experimental | TXA 100 mg/kg bolus before incision and 10 mg/kg infusion until skin closure |
|
| Placebo | Placebo Comparator | Normal saline 10 ml before skin incision and infusion according to weight until skin closure |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tranexamic Acid | Drug | 10 mg/kg bolus with a 5 mg/kg/h infusion |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Blood Loss | Blood loss will be carefully measured in sponges, suction cannisters, cell saver systems, and in the plastic pockets of surgical drapes. | Prior and Post Surgery |
| Measure | Description | Time Frame |
|---|---|---|
| Plasminogen Activator Inhibitor-1 (PAI-1) Polymorphism - Samples | PAI-1 promotes clot stability and the PAI-1 polymorphism will affect the degree of bleeding and response to TXA during craniosynostosis surgery | Sample will be drawn immediately after induction and prior to administration of study drug |
| Thromboelastography (TEG)Sample |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Tara Der, MD | The Hospital for Sick Children | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Hospital for Sick Children | Toronto | Ontario | Canada |
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| ID | Term |
|---|---|
| D003398 | Craniosynostoses |
| D006470 | Hemorrhage |
| ID | Term |
|---|---|
| D013580 | Synostosis |
| D004413 | Dysostoses |
| D001848 | Bone Diseases, Developmental |
| D001847 | Bone Diseases |
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| ID | Term |
|---|---|
| D014148 | Tranexamic Acid |
| ID | Term |
|---|---|
| D003509 | Cyclohexanecarboxylic Acids |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
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| Tranexamic Acid |
| Drug |
100 mg/kg bolus with a 10 mg/kg/h infusion |
|
| Saline Placebo | Drug |
|
TEG monitors coagulation of blood samples in vitro to produce a complete picture of clot formation, strength and dissolution (i.e. fibrinolysis) |
| Baseline, immediately after bolus dose of TXA is infused |
| D009140 |
| Musculoskeletal Diseases |
| D019465 | Craniofacial Abnormalities |
| D009139 | Musculoskeletal Abnormalities |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |