Prophylactic Anticoagulation for Central Venous Line Insertion in Critically Ill Children

The study population will be divided into two groups:

1. Enoxaparin Group (Anticoagulation Arm):

This group will receive prophylactic anticoagulation with enoxaparin in accordance with institutional guidelines for prophylactic anticoagulation in Pediatric patients.
2. Usual Care Group (Control Arm):

This group will receive standard care without prophylactic anticoagulation.

All patients in this study will be subjected to:

A- Demographic and clinical data Collection:

* Patient demographics: age, sex, body mass index (BMI) and the primary diagnosis.
* CVC characteristics: type of line, number of lumens, catheter size, site and laterality, and date of insertion and removal.
* Thrombotic events: date of thrombus detection, affected blood vessel (confirmed by Doppler ultrasound), and anticoagulation details (type, dose, and duration. (
* Anticoagulant use: agent used (e.g., LMWH), initiation timing and monitoring. B- Full clinical examination will be done including vital signs (HR, RR, BP, temperature) for each child.

C- Investigations will be done including the following:

Laboratory Analysis: CBC, Platelet counts at baseline, day 3-5, for monitoring heparin- related thrombocytopenia, CRP, Electrolytes, Blood culture, Urea, creatinine, ALT, AST and D-dimer level.

Radiological: Ultrasound of catheterized vessel if clinical suspicion of thrombosis; consider scheduled ultrasound on day 7 and 14.

Intervention and Monitoring

Enoxaparin Group (Intervention Arm):

* Children randomized to receive enoxaparin will be administered enoxaparin subcutaneously every 12 hours, with dosing based on age and weight as follows:

1. 0.75mg/kg for children ≤2 months old.
2. 0.5 mg/kg (maximum 30 mg) for children >2 months old.
* Doses will be adjusted for obesity and renal insufficiency as needed.
* The first dose will be given within 24 hours of CVC insertion. The dose will be adjusted to achieve a target anti-Xa level of 0.2-0.5 IU/mL.
* Anti-Xa levels will be measured locally 4-6 hours after every third dose, and dosing will be adjusted accordingly until the target range is reached. Once therapeutic range is achieved, anti-Xa monitoring will be performed weekly.
* Enoxaparin will be discontinued in the event of a clinically significant bleeding episode. It will be resumed 24 hours after correction of any coagulopathy, as confirmed by clinical and laboratory parameters.

Usual Care Group (Control Arm):

Children randomized to usual care will not receive anticoagulation. Standard CVC care procedures will be followed according to PICU protocols.

Monitoring for Thrombosis and Bleeding

1. All children will undergo daily clinical monitoring for signs of bleeding.
2. To evaluate catheter-related thrombosis, ultrasound imaging of the vein proximal and distal to the CVC insertion site.
3. To assess coagulation profile and thrombotic risk, blood samples will be drawn at the following time points:

1. On the day of CVC insertion
2. The day after insertion
3. Day 4 after insertion

• Enoxaparin (Drug): Enoxaparin Group (Intervention Arm): This group will receive prophylactic anticoagulation with enoxaparin in accordance with institutional guidelines for prophylactic anticoagulation in Pediatric patients. * Children randomized to receive enoxaparin will be administered enoxaparin subcutaneously every 12 hours, with dosing based on age and weight as follows: 1. 0.75mg/kg for children ≤2 months old. 2. 0.5 mg/kg (maximum 30 mg) for children >2 months old. Doses will be adjusted for obesity and renal insufficiency as needed. * The first dose will be given within 24 hours of CVC insertion. The dose will be adjusted to achieve a target anti-Xa level of 0.2-0.5 IU/mL. * Anti-Xa levels will be measured locally 4-6 hours after every third dose, and dosing will be adjusted accordingly until the target range is reached. Once therapeutic range is achieved, anti-Xa monitoring will be performed weekly. * Enoxaparin will be discontinued in the event of a clinically significant bleeding episode. I

Primary outcomes

• Incidence of catheter-related venous thrombosis [14 days]: Incidence (%) of catheter-related venous thrombosis within 14 days following central venous catheter placement, diagnosed using duplex ultrasonography. Both symptomatic thrombosis (clinically suspected and confirmed by imaging) and asymptomatic thrombosis (identified by protocol-specified ultrasound screening at Day 7-14) will be included. Outcome adjudication will be performed by an independent blinded committee.

Secondary outcomes

• Incidence of catheter patency [Day 7 and Day 14]: Percentage of participants with a functioning central venous catheter without need for replacement or fibrinolytic therapy at Day 7 and Day 14.
• Percentage of participants who develop catheter-related bloodstream infection, diagnosed according to CDC criteria. [30 days]: Percentage of participants who develop catheter-related bloodstream infection
• Incidence of major bleeding [14 days]: Percentage of participants experiencing major bleeding within 14 days, defined as bleeding causing hemodynamic instability, requiring blood transfusion, surgical intervention, or resulting in intracranial hemorrhage.
• Incidence of minor bleeding [14 days]: Percentage of participants experiencing minor bleeding not fulfilling criteria for major bleeding.
• Catheter removal due to thrombosis [30 days]: Percentage of participants requiring catheter removal because of confirmed catheter-related thrombosis.
• Catheter dwell time [30 days]: Duration of central venous catheter placement measured in days from insertion until catheter removal.
• All-cause in-hospital mortality [During hospitalization (up to 30 days)]: Percentage of participants who die from any cause during hospitalization.

Sex: All, ages: 1 Month to 18 Years

Inclusion Criteria:

* All Children requiring a newly placed central venous line (peripherally inserted central catheter \[PICC\], or non-tunneled central venous catheter) for clinical care.

Exclusion Criteria:

* Known major congenital bleeding diathesis or platelet count <50,000/µL at time of insertion.
* Already on therapeutic anticoagulation for another indication.
* Known heparin allergy or history of heparin-induced thrombocytopenia.
* Use of dialysis catheters (study focuses on standard CVCs/PICCs).

• Hani Hamed Saad, MD, pediatrics, Principal investigator, Faculty of medicine, Menoufia University