PracticeUpdate: Haematology & Oncology

ASH 2016 21

PICCs are associated with a greater risk of blood clots in children A n overwhelming number of blood clots happen in patients with peripherally inserted

ErythroMer biosynthetic red blood cells bind oxygen to within 10% of human erythrocytes T he first artificial red blood cells designed to emulate vital functions of natural red blood cells have been developed. If confirmed safe in humans, the nanotechnology-based product could represent an innovative alternative to blood transfusions. Allan Doctor, MD, of Washington University in the US, explained that ErythroMer are designed to be freeze-dried, stored at ambient temperatures, and reconstituted with water when needed. They may be especially valuable on the battlefield and in other situations where donated blood is difficult to obtain or store. Dr Doctor said, “A key goal is to advance field resuscitation of civilian trauma victims in remote settings and soldiers wounded in austere environments without access to timely evacuation. ErythroMer would be a blood substitute that a medic could carry in his or her pack and take out, add water, and inject.” He noted, “No simple, practical means are available to transfuse most trauma victims outside of hospitals. Delays in resuscitation impact outcomes significantly. We hope to push timely, effective care to field settings.” Proof-of-concept studies in mice demonstrated that, like erythrocytes, the artificial cells capture oxygen in the lungs and release it to tissues in a pattern that indistinguishable from that seen in control mice injected with their own blood. In rats, ErythroMer effectively resuscitated animals in shock following acute loss of 40% of their blood volume. The donut-shaped artificial cells are formulated with nanotechnology. They are about one-fiftieth the size of human erythrocytes. A lining encodes a control system that links ErythroMer’s oxygen binding to changes in blood pH, enhancing oxygen acquisition in the lungs and then dispensing oxygen to tissues in greatest need. Tests showed that ErythroMer matches this vital oxygen binding feature of human erythrocytes within 10%, a level probably sufficient to stabilise a bleeding patient until a blood transfusion can be obtained. ErythroMer has overcome key barriers that halted development of previous blood substitutes, including efficacy and blood vessel narrowing. The team’s next steps are to test ErythroMer in larger animals, assess ongoing safety, optimise pharmacokinetics, and ultimately conduct in-human clinical trials. Dr Doctor and colleagues are also pursuing methods for scaling up production. If further testing goes well, they estimate ErythroMer could be ready for use by field medics and emergency responders within 10–12 years.

ranged in age from 6 months to just under 18 years. Sixty-five blood clots were identified during follow-up, 55 of which were in children with PICCs. The median time to developing a blood clot after a PICC was placed was 15 days. The median time to develop a blood clot after a tunnel line was placed was 40 days. Forty-nine percent of central venous catheters were removed before 6 months. The average duration a central venous catheter was in place, including both PICCs and tunnel lines, was 56 days. The data also showed that children with congenital heart disease, who already suffer from abnormal blood circulation, and those with cancer, especially leukaemia, are at greater risk. Multiple-lumen venous lines were also associated with a higher risk of clots. Similarly, blood clots were four times more likely to occur if the child was diagnosed with a central line infection. Infections were significantly more likely with tunnel lines. PICCs are increasingly being used in many paediatric centres, a trend Dr Jaffray said has paralleled a noticeable rise in the number of blood clots seen in children and was the main impetus for her research. The study will continue to accrue patients and additional analyses will show whether the main reason for inserting the line (for example, chemotherapy, prolonged courses of antibiotics, or feeding) plays a role. Dr Jaffray concluded that the findings will help inform the first guidelines on how to use and select central venous lines in children and when anticoagulants might be recommended to prevent blood clots. anticoagulants might be recommended to prevent blood clots. The findings will help inform the first guidelines on how to use and select central venous lines in children and when

central catheters placed compared to tunnel lines. Julie Jaffray, MD, of Children’s Hospital Los Angeles, California, summarised results of a prospective, multicentre comparative study,explaining that inserting a central line into the arm or closer to the heart may affect thrombotic risk. In this first prospective, multicentre paediatric study comparing thrombosis in children with peripherally inserted central catheters (PICCs) versus centrally inserted tunnel lines, 85% of blood clots were in children with a PICC. “We know children with cancer or who are in the paediatric intensive care unit will need a central line, but these lines aren’t perfect,” Dr Jaffray noted. “The important question is, are we choosing the right line for them or are we just putting in the line that’s easier to place?” Part of the draw of PICC lines is that they are much easier to insert. They can be inserted at the bedside with a touch of sedation if needed. For tunnel lines, patients are booked for anaesthesia and a surgeon or interventional radiologist places the tube. This interim analysis was based on 1096 children, who had a total of 1233 central venous catheters placed (67% PICCs and 33% tunnel lines) at four children’s hospitals from 2013 to 2016. Patients

PracticeUpdate Editorial Team

PracticeUpdate Editorial Team

VOL. 2 • NO. 1 • 2017