Ultrasound‐Guided Peripheral Venous Catheter for Automated Erythrocytapheresis in a Paediatric Population Affected by Sickle Cell Disease

ABSTRACT

Introduction

Automated erythrocytapheresis (aEEX) is an effective therapy for severe sickle cell disease (SCD). Its use in paediatrics can be limited by challenges in obtaining reliable venous access.

Methods

We conducted a retrospective, single‐centre study to evaluate the safety and feasibility of ultrasound (US)‐guided peripheral venous catheter (PVC) placement for aEEX compared with central venous catheter (CVC) use in children and adolescents with SCD.

Results

Between May 2018 and July 2025, 99 aEEX procedures using PVC were compared with 44 using CVC in 23 patients (median age: 16.4 years). The most frequent indication was severe disease phenotype (62.9%), defined as recurrent vaso‐occlusive crises and/or splenic sequestration and/or acute chest syndrome despite optimal hydroxyurea therapy. The procedure success rate was 99.0% for PVC and 97.7% for CVC, with median post‐apheresis HbS of 26.5% and 24.0%, respectively. Complications, mostly transient and without clinical impact, occurred in 9.1% of PVC procedures and 6.8% of CVC procedures. No infectious or and thrombotic events were reported.

Conclusions

These findings indicate that aEEX under light sedation with US‐guided PVC placement is a safe, well‐tolerated and effective alternative to CVC in selected paediatric patients with SCD. This approach may expand access to aEEX reducing reliance on CVC and manual exchange procedures.

Trial Registration

The authors have confirmed clinical trial registration is not needed for this submission.

1.

Sickle cell disease (SCD) is the most common haemoglobinopathy worldwide, with a rising global prevalence of 382 cases per 100,000 newborns [1]. SCD is a hereditary chronic haemolytic anaemia characterised by intravascular haemolysis, endothelial dysfunction and an inflammatory cascade leading to ischaemic tissue damage and vaso‐occlusive crises (VOCs), particularly under hypoxic conditions [2]. Erythrocytapheresis (EEX) represents a cornerstone in SCD management, as it improves oxygen delivery, reduces blood viscosity and lowers haemoglobin S (HbS) levels. It is used to treat both acute and chronic complications and to prevent organ damage, including in patients undergoing surgery [3, 4]. Scheduled EEX aims to maintain HbS levels below 30% in patients with severe phenotypes, primarily for stroke prevention, but also in cases of recurrent VOCs, acute chest syndrome, splenic sequestration or priapism [5]. Automated EEX (aEEX), an isovolumic aphaeretic procedure, is more effective than manual exchange (mEEX) in achieving HbS reduction in a single session, prevents iron overload, representing a major advantage in chronic transfusion programmes [6 ^– 8]. However, aEEX requires specialised centres, adequate venous access and careful monitoring, particularly in paediatric patients. The choice of vascular access is therefore critical: double‐lumen central venous catheters (CVCs) provide optimal flow but require complex placement, often with intravenous sedation depending on patient age and compliance and expose to potential complications (thrombosis, infections). In contrast, peripheral venous catheters (PVCs), when feasible, are preferred due to their lower invasiveness. In children, vascular access is further challenged by vessel size, body weight and compliance, often favouring mEEX, especially in urgent settings [9, 10].

Since May 2018, the Paediatric Haematology Centre at IRCCS San Gerardo dei Tintori (Monza) has implemented a multidisciplinary vascular access team (MVAT) specialised in ultrasound (US)‐guided techniques, including haematologists, anaesthesiologists, apheresis physicians and trained nurses. This approach has improved the feasibility of aEEX in children and adolescents with difficult intravenous access (DIVA), previously underwent only mEEX in both, urgent or elective settings.

In this single‐centre retrospective observational study, we included urgent and elective aEEX procedures performed in patients with SCD younger than 21 years between May 2018 and July 2025, with the aim of evaluating the feasibility and effectiveness of US‐guided PVCs compared with CVCs.

All vascular access devices (VADs) were inserted by the MVAT in either outpatient or ward settings. CVCs and midlines were placed under sterile conditions, whereas PVCs were inserted using an aseptic no‐touch technique. All procedures were performed under US guidance (Esaote MyLabSix) following structured vascular assessment (RaCeVa, RaFeVa or RaPeVa). PVCs—either short peripheral catheters (SPCs) or midlines—were the first‐line option, with two catheters placed (one per arm) for each patient, mainly in deep veins of the arm. Following PVC placement, a moderate‐rate isotonic saline infusion was initiated through the withdrawal line to maintain vessel patency. If placement was unsuccessful or clinically indicated (e.g., prolonged intravenous therapy for severe infection), dual‐lumen CVCs were inserted via femoral (FICC), peripheral (PICC) or central (CICC) access using the modified Seldinger technique, with tip confirmation by intracavitary ECG (for PICC and CICC). Catheters were secured according to guidelines and removed after the procedure unless clinically required. Sedation was determined by an anaesthesiologist based on patient age and anxiety. Minimal sedation consisted of oral or intravenous midazolam (0.5 mg/kg/dose, maximum 15 mg and 0.1 mg/kg/dose, maximum 5 mg, respectively), whereas deep sedation (midazolam combined with fentanyl or propofol) was administered when necessary (e.g., after failed placement attempts). All aEEX procedures were performed using the Spectra Optia system.

A total of 143 aEEX procedures were performed in 23 patients with SCD (patient characteristics are summarised in Table S1). Most patients had severe genotypes (SS, 73.9%) and 17 out of 23 had previously received mEEX or top‐up transfusions. Five patients required iron chelation prior to aEEX, whereas none required it thereafter. PVCs were used in 69.2% of procedures and CVCs in 30.8% (Table 1). The median age at first aEEX was 13.0 and 16.4 years at the time of procedures, with a slightly higher age in the PVC group (p = 0.053).

TABLE 1.

AEEX features distributed for PVCs and CVCs.

	Total N = 143	PVC N = 99 (69.2%)	CVC N = 44 (30.8%)	p‐value
aEEX modality, N (%)				0.069
Elective	118 (82.5)	86 (86.9)	32 (72.7)
Urgent	25 (17.5)	13 (13.1)	12 (27.3)
Indication for elective aEEX, N (%)
Severe SCD phenotypea	90 (62.9)	70 (70.7)	20 (45.5)
Pre‐surgery	14 (9.8)	13 (13.1)	1 (2.3)
Pathological TCD	10 (7.0)	2 (2.0)	8 (18.2)
Pre‐HSCT	2 (1.4)	1 (1.0)	1 (2.3)
Severe infections	2 (1.4)	0 (0.0)	2 (4.5)
Indication for urgent indication, N (%)
Severe VOCs	24 (16.8)	12 (12.1)	12 (27.3)
Priapism	1 (0.7)	1 (1.0)	0 (0.0)
Age at aEEX (years), median (Q1–Q3)	16.4 (13.7–18.7)	16.5 (14.2–19.2)	15.6 (10.4–18.1)	0.053
Sedation, N (%)				0.197
Oral midazolam	110 (76.9)	80 (80.8)	30 (68.2)
Intravenous midazolam	17 (11.9)	9 (9.1)	8 (18.2)
Intravenous midazolam combined with fentanyl or propofol	16 (11.2)	10 (10.1)	6 (13.6)
Apheresis procedure, median (Q1–Q3)
Infused volume (mL/kg)	20.8 (18.6–23.5)	20.6 (18.8–23.0)	20.9 (17.5–25.4)	0.667
Exchanged volume (mL)	1270 (1048–1587)	1270 (1056–1583)	1261 (1000–1590)	0.881
Duration (minutes)	76.5 (60.0–87.3)	77.0 (59.0–86.0)	75.0 (65.5–95.5)	0.127
HbS detection (%), median (Q1–Q3)
HbS pre aEEX	60.0 (52.0–69.0)	60.0 (52.0‐69.0)	58.5 (51.5–69.0)	0.671
HbS post aEEX	26.0 (22.0–32.0)	26.5 (23.0–34.0)	24.0 (19.0–29.0)	0.013
HbS drop	33.0 (26.8–39.0)	32.0 (27.0–37.0)	33.5 (25.8–43.3)	0.291
Complications during aEEX, N (%)	12 (8.4)	9 (9.1)	3 (6.8)	0.755
Type of complications, N (%)				0.455
Transient complications, N (%)	10 (7.0)	8 (8.1)	2 (4.5)
Complications leading to procedural failure, N (%)	2 (1.4)	1 (1.0)b	1 (2.3)c
Completed procedures, N (%)	141 (98.6)	98 (99.0)	43 (97.7)	0.522

Note: Q1 = first quartile; Q3 = third quartile.

Abbreviations: aEEX = Automated erythrocytapheresis; HSCT = haemopoietic stem cell transplantation; SCD = sickle cell disease; TCD transcranial doppler; VOCs = vaso‐occlusive crisis.

^a Severe SCD phenotype = defined by recurrent vaso‐occlusive crises and/or splenic sequestration and/or acute chest syndrome despite optimal hydroxyurea therapy.

^b Interrupted aEEX due to unstable PVC.

^c Failed aEEX due to incorrect position of the CVC tip in the vessel during blood exchange (similar HbS pre‐ and post‐procedure).

In our cohort, chronic aEEX was performed mainly for non‐neurological indications, including recurrent VOCs, splenic sequestration or acute chest syndrome; no patients underwent chronic aEEX for primary or secondary stroke prevention. Most procedures (82.5%) were elective, mostly performed in patients with severe phenotypes, whereas severe VOCs represented the main indication in acute settings. SPCs were the most frequently used devices (72%), typically two per procedure (inflow and outflow), predominantly 18‐gauge, whereas 7‐French FICCs were the most common CVCs (Figure 1). Minimal sedation was used in 88.8% of procedures, predominantly via the oral route. Although deep sedation was more frequent with CVCs, no significant difference in distribution was observed. No procedures required operating room support. aEEX proved effective, achieving a median HbS level of 26.0% overall, with comparable results between PVC and CVC groups (26.5% [Q1–Q3: 23.0–34.0] vs. 24.0% [Q1–Q3: 19.0–29.0]; Figure S1A). Although post‐procedure HbS was slightly higher in the PVC group (p = 0.013), this difference was not clinically significant, also considering the slightly lower baseline HbS levels in the CVC group. In addition, HbS reduction was comparable between groups (32.0% vs. 33.5%), confirming similar efficacy (Figure S1B).

FIGURE 1.

The percentages displayed on top of the bars are calculated on the total number of intravenous catheters. The percentages in the SPC column are calculated on the total number of SPCs used. CICC = centrally inserted central catheter; CVC = central venous catheter; FICC = femorally inserted central catheter; PICC = peripherally inserted central catheter; PVC = peripheral venous catheter; SPC = short peripheric catheter.

Procedural success was 98.6%, with only two incomplete procedures due to catheter‐related issues (PVC instability and CVC tip malposition causing recirculation). The overall complication rate was 8.4%, consisting mainly of transient catheter‐related events requiring technical adjustments. These occurred more frequently with PVCs but did not affect procedural outcomes. No complications were observed during sedation, insertion or removal and no infections or thromboses were reported. Procedural duration and exchanged volumes were comparable between groups.

These findings demonstrate that US‐guided PVC use for aEEX is feasible, safe and effective in paediatric SCD, with outcomes comparable to those achieved with CVCs. Vascular access remains a major challenge in SCD, particularly in children, often leading to reliance on central access. The use of central VADs, including dual‐lumen ports and short‐term FICCs, is well established and associated with low procedure‐related risks [11, 12]. PVC was the preferred first‐line approach whenever technically feasible, while the choice to proceed with CVC was individualised according to patient characteristics, vascular feasibility and clinical needs. Therefore, future studies should aim to identify predictors of peripheral access failure and criteria to guide the selection of the most appropriate vascular access strategy. In adult populations, Puntensen et al. [13] reported a large series of aEEX procedures performed using PVCs, demonstrating low rates of access‐related complications and satisfactory performance. In paediatric settings, only a limited number of studies have reported successful use of PVCs for aEEX and chronic transfusion programmes in patients with haemoglobinopathies, including SCD and thalassaemia [10, 14]. Current recommendations favour peripheral access when feasible to minimise risks, as peripheral VADs can provide adequate flow rates (16–18 gauge) for apheresis [15]. Beyond reducing procedural invasiveness, successful use of peripheral venous access may also reduce the risk of catheter‐related bloodstream infections and catheter‐associated thrombosis. This advantage is particularly relevant in patients with SCD, who frequently require repeated vascular access and have an intrinsically increased thrombotic risk. Although no catheter‐related infections or thromboses were observed in our cohort, avoiding central venous access whenever feasible remains an important clinical goal [16, 17]. Moreover, children with chronic conditions may have a lower pain threshold [18]; thus, US guidance can significantly improve procedural tolerance and the overall experience for patients and families. In our cohort, US‐guided access under minimal sedation improved acceptability and comfort, with predominant use of oral sedation even for central catheter placement and no access‐related complications observed.

The implementation of a dedicated multidisciplinary paediatric team played a key role in the progressive increase in aEEX procedures performed via PVCs. Most patients had previously undergone mEEX and some required iron chelation; notably, none required chelation after initiation of chronic aEEX, highlighting a major advantage. Consequently, mEEX use declined and all patients on chronic transfusion programmes are now treated with aEEX, benefiting from stable HbS control, fewer hospital visits and reduced impact on daily life.

However, logistical challenges remain, particularly in coordinating the MVAT and Apheresis Unit, especially outside standard working hours, whereas mEEX can be more readily performed at the bedside.

Strengths of this study include the homogeneous SCD population and the direct comparison between PVCs and CVCs. Procedures showed high success rates and comparable efficacy across access types. Although minor transient complications were more frequent with PVCs, they were clinically insignificant. Limitations include the retrospective design, incomplete procedural data and the relatively older cohort compared with other paediatric series. Although peripheral venous access was successfully achieved in our cohort, the relatively older age of the patients represents an important caveat regarding the generalisability of our findings.

In conclusion, these findings support US‐guided PVC placement as a safe, well‐tolerated and effective strategy to perform aEEX in young patients with SCD, significantly reducing the need for central venous access. In our setting, over the years, the presence of a dedicated multidisciplinary paediatric team with expertise in US‐guided vascular access has enabled broader implementation of aEEX, offering an important therapeutic option for patients with severe SCD phenotypes who were previously limited to repeated mEEX in elective and urgent setting. In conclusion, the use of US‐guided placement of PVCs is a safe and well tolerated procedure to undergo aEEX in SCD children and adolescent and an easy to learn technique to implement. Prospective studies incorporating standardised metrics and patient‐reported outcomes are warranted to further define the role of PVCs in paediatric aEEX.

Author Contributions

Laura Ocello: operative placement of VADs, data collection, analysis, writing – original draft, writing – review and editing. Fabio Pavan: organisation of the MVAT, operative placement of VADs, conceptualisation and review. Giulia M. Ferrari: conceptualisation and review. Fabiola Guerra: data collection and review. Alessandra Moretto: organisation of the MVAT, operative placement of VADs. Elena Tassistro: statistical analysis. Maria G. Valsecchi: statistical analysis. Irene Lepri: data collection. Linda Gregorio: data collection. Alice Passoni: psychological support for patients. Adriana Balduzzi: review. Valentina Baldini: collection of apheresis procedure data and review. Paola Corti: conceptualisation, review of the final manuscript.

Funding

The project is supported (not financially) by the European Reference Network on Rare Hematological Diseases (ERN‐EuroBloodNet)—Project ID No. 10108571. ERN‐EuroBloodNet is partly co‐funded by the European Union within the framework of the Fourth EU Health Programme. This paper has been partially supported by the Italian Ministry of Health, within “Ricerca Corrente Program”.

Ethics Statement

Ethical approval was not required because this retrospective observational study was conducted using exclusively anonymised data collected during routine clinical care, in accordance with local institutional regulations.

Consent

All patients included signed the informed consent for the European RADeep registry.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Supporting Table 1: jha270409‐sup‐0001‐TableS1.docx

Supporting Figure 1: jha270409‐sup‐0001‐FigureS1.docx

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.