**2.2 Extracorporeal oxygen membrane oxygenation (ECMO) protocol in children**

ECMO is an equipment used for cardiopulmonary support in children who have severe cardiac and/or pulmonary compromise and do not respond to medications and mechanical ventilatory support. There are two types of ECMO, venovenous (VV) ECMO which mainly support respiratory system while venoarterial (VA) ECMO support both respiratory and cardiac system [17–19]. To maintain the blood flow of ECMO circuit, which is an artificial system with nonbiological surface, the usage of an anticoagulant, mainly unfractionated heparin (UFH), is required to reduce thrombin

## *Protocols for Bleeding and Thrombosis in Pediatric Intensive Care Units DOI: http://dx.doi.org/10.5772/intechopen.104882*

and fibrin formation in the ECMO circuit. The current guideline for ECMO management is recommended by Extracorporeal Life Support Organization (ELSO) registry which is the largest international adult and pediatric database for patients treated with extracorporeal life support (ECLS) [19]. There are four parts of ECMO circuit including a cannula, a pump with console, an oxygenator and a heart exchanger [20].

Monitoring and adjustment of the UFH dosage to balance between bleeding and clotting in patients using ECMO is challenging [21]. Dalton et al. reported the high bleeding complication in children receiving ECMO at 70% including 16% of intracranial bleeding. In contrast, 31% of children required ECMO circuit components changes due to clot and 13% of children developed patient-associated clot [22]. Although the standard dose of UFH for ECMO is the treatment dose of UFH at 20–25 unit/kg/hour, the variation of dose could be increased to 50–60 unit/kg/hour to reach the target ranges of UFH monitoring [23]. The summary of methods for UFH monitoring with the target ranges of each methods is shown in **Table 2**. However, the target ranges can be varied based on the institutional protocol, normal laboratory reference range of each test and the current bleeding conditions of the patients and thrombotic status of both patients and ECMO circuits. Moreover, there is currently no one perfect laboratory test to monitor UFH when the children are receiving ECMO.

Antithrombin (AT) is a natural anticoagulant and the main targeted protein working UFH to inhibit FXa and thrombin [23]. Therefore, the effect of heparin can be decreased by the deficiency of AT or heparin resistance particularly in infants aged less than 6 months when the synthesis of AT is not fully developed [21, 27]. Although the targeted AT level while the patients are receiving ECMO is approximately 70–120% [21, 28], there is no current consensus on that targeted AT level, the dosage, the timing and method of administration even in adult patients [28]. Moreover, the impact of AT supplementation in patients receiving ECMO is less understandable than that in patients with hereditary AT deficiency due to the patient and circuit interaction and their underlying diseases [21]. Furthermore, the widely available source of AT is FFP which is not appropriate source of AT and the AT concentrate, both plasma-derived and recombinant products with various properties of each product, can be accessible only in some countries [21].

In children who have contraindication of using UFH such as heparin-induced thrombocytopenia (HIT) or heparin resistance [21], bivalirudin, an intravenous direct thrombin inhibitor which inhibit both circulating thrombin and clot bound thrombin [29] could be an alternative anticoagulant for children receiving ECMO [23]. The median loading dose of bivalirudin is 0.1–0.125 mg/kg and the maintenance dose between 0.045 and 0.48 (0.125) mg/kg/hour [27, 30] to keep targeted APTT between 45 and 85 sec [23, 27]. However, unlike heparin, no antidote is available for bivalirudin and dose reduction is needed in children with renal disease as the main clearance organs are kidney and liver [23, 27].

## **2.3 Venous thromboembolism (VTE) prophylaxis in children**

The incidence of VTE in children has been increasing during the last two decades in both Western and Asian countries especially in hospitalized children [31–33]. Even though the guideline for VTE thromboprophylaxis is well established in adult population [34, 35], the statement of VTE prophylaxis is not clearly mentioned with the limited available evidences and various details of the study [36–38].

Apart from pediatric patients who have hereditary thrombophilia, the hospitalized children are at risk of development of TE since two of three most common risk factors


### **Table 2.**

*The summary of methods for UFH monitoring with the target ranges of each methods [21, 23–25].*

of VTE in the previous reports, including central venous catheterization (CVC), immobilization more than 72 hours and oral contraceptive pill (OCP), are frequently found in pediatric patients who are admitted in the hospital especially children admitted in PICU [37]. Moreover, the incidence of VTE is more common in neonates and adolescents [39], hence, most VTE prophylaxis study protocols were mainly included children admitted in PICU and adolescents to prevent VTE in risky patients.

Recently Jaffrey et al. reported the new score to assess the risk of VTE development in hospitalized children including Braden Q mobility score, length of stay, CVC, history of congenital heart disease and autoimmune/inflammatory disorders in the

*Protocols for Bleeding and Thrombosis in Pediatric Intensive Care Units DOI: http://dx.doi.org/10.5772/intechopen.104882*

risk assessment model (RAM) in 395 pediatric patients with the area under the curve (AUC) of 0.78 [40].

The methods to prevent VTE in children consist of physical methods e.g. intermittent pneumatic compression (IPC), graduated compression stockings (GCS) and devices and venous foot-pumps (VFPs) and pharmacological methods including oral and parenteral anticoagulants [36]. Even though the physical methods do not put the patients to be at risk of bleeding episodes, those could be applied realistically in larger children who usually weigh more than 40 kg [36]. Pharmacological prophylaxis is suggested for only children who have multiple risk factors of VTE [36] and this method should be balance with the bleeding risk of the patients. Children who require CVC, the heparin-bonded central venous line is suggested if it is available [41] due to no thrombosis was found in the report by.
