Anthea Greenway

Neonatal thrombosis and its treatment

Thromboembolic disease (TE) has been described as the new epidemic of tertiary paediatrics, and no where is this more evident than in the neonatal population. As survival of premature and sick newborns has improved, the frequency of complications associated with intensive supportive therapy and monitoring has increased. Clinically significant thrombosis is emerging as one of the more common complications associated with improved neonatal outcome. The long-term implications of neonatal thrombosis are only just being realised. This systematic review will consider the epidemiology, diagnostic strategies, and outcome for both arterial and venous TE in neonates. The role of inherited thrombophilic abnormalities, and the evidence for anticoagulation therapy will also be considered. The lack of high level evidence in determining optimum therapy is obvious. Further research regarding diagnostic strategies, and optimal therapies is urgently needed.

Vitamin D status of chronically ill or disabled children in Victoria

Objective:  To establish the percentage prevalence of hypovitaminosis D in chronically ill or disabled children in Melbourne, Australia.

Platelet Dysfunction and Increased Bleeding Tendency in McCune-Albright Syndrome

We observed increased bleeding tendency and platelet function abnormalities in 3 boys with McCune-Albright syndrome (MAS). We speculate that platelet dysfunction contributed to excessive blood loss in our patients. This report of platelet dysfunction in MAS highlights the need for assessment of platelet functions in the condition.

Rituximab and protection from vaccine preventable diseases: applying the evidence to pediatric patients

ABSTRACT Introduction: This article analyses and highlights the challenge of immunization and preventing vaccine preventable diseases in pediatric patients on rituximab. Rituximab is a chimeric anti-CD 20 monoclonal antibody that is an immunosuppressant affecting both cellular and humoral immunity. Children and adolescents on rituximab are at increased risk of infection and vaccine preventable diseases, and require additional strategies to optimize and maximize their protection against such illnesses. Areas covered: This article provides a comprehensive MEDLINE and Pubmed review of existing literature regarding vaccine immunogenicity and safety in patients on rituximab, and assists in providing an evidence base to develop immunization guidelines. Of particular note, the use of live-attenuated vaccines and optimum timing of vaccines post rituximab is considered and discussed. Expert commentary: The increasing use of rituximab in a variety of novel areas within pediatrics must be accompanied by informed discussion around mitigating the risks. These include immunosuppression, and potential susceptibility to infection. Optimizing vaccine status by establishing adequate antibody titers prior to commencement remains the best preventative strategy.

Hospitalisations for sickle-cell disease in an Australian paediatric population.

Sickle‐cell disease (SCD) is more prevalent in Australia due to increased migration; however, the Australian paediatric SCD population has not been previously described. This study aimed to identify the demographic features of and quantify the hospital resource utilisation in the SCD population at The Royal Childrens Hospital in Victoria.

Congenital Methemoglobinemia Type II—Clinical Improvement with Short‐Term Methylene Blue Treatment

We report a case of prophylactic management with methylene blue (MB) in an almost 4‐year‐old male with congenital methemoglobinemia type II. He has a CYB5R3 compound heterozygote mutation, causing a cytochrome‐b(5) reductase deficiency. Since the MB treatment regimen has commenced, his methemoglobin level has been significantly lower. He has shown modest behavioral improvements (as assessed on the Achenbach behavior report scales). There have been no iatrogenic side effects. These findings are encouraging for symptomatic improvement with regular prophylactic MB treatment but represent a single case report, which must be interpreted with caution.

Characterization of core clinical phenotypes associated with recurrent proximal 15q25.2 microdeletions.

A recurrent proximal microdeletion at 15q25.2 with an approximate 1.5 megabase smallest region of overlap has recently been reported in seven patients and is proposed to be associated with congenital diaphragmatic hernia (CDH), mild to moderate cognitive deficit, and/or features consistent with Diamond–Blackfan anemia. We report on four further patients and define the core phenotypic features of individuals with this microdeletion to include mild to moderate developmental delay or intellectual disability, postnatal short stature, anemia, and cryptorchidism in males. CDH and structural organ malformations appear to be less frequent associations, as is venous thrombosis. There is no consistent facial dysmorphism. Features novel to our patient group include dextrocardia, obstructive sleep apnea, and cleft lip.

Transfusion service management of sickle-cell disease patients.

The transfusion management of patients with sickle-cell disease (SCD) can be a challenge. These patients can become highly alloimmunized, and their RBC needs are not always predictable. Patients with SCD are often transfused under two conditions: regular, scheduled RBC transfusions to keep the HbS level below a certain threshold to prevent stroke or before surgery, and during emergency crises. From the transfusion medicine perspective, the key is to balance the speed with which a potentially lifesaving transfusion can be provided, with the potential for acute and delayed haemolysis or hyperhaemolysis, and causing future alloimmunization. If these recipients are not exposed to alloantigens, then they will not become alloimmunized; thus, a logical transfusion strategy is to match the donor and recipient for as many antigens as possible – for every RBC transfusion! However, ethnic differences between donors and SCD patients make it difficult to find completely antigen-matched units, and if other donor attributes such as a negative CMV status or HbS negativity is required, the pool of suitable donors is further reduced. And therein lies the blood banker’s conundrum – how can RBC units be provided to patients with SCD quickly and safely? There are no universally recognized standards for the transfusion management of SCD, or the nature of the RBCs provided. Historically in the USA, the protocols for providing RBCs to patients with SCD have been highly variable between centres. In 2003, a College of American Pathologists proficiency testing survey revealed that of the nearly 1200 transfusion service respondents, 63% issued RBCs that were compatible only for the recipient’s ABO and RhD groups. Almost 30% obtained the recipient’s phenotype and issued RBCs that were matched beyond ABO and RhD for the other major antigens in the Rh system and K, as these are the main antigens to which patients with SCD become alloimmunized [1–4]. The remainder obtained the phenotype but did not issue extended matched RBCs. Note that these responses described the local practice when dealing with non-alloimmunized SCD patients and that blood group genotyping was in its infancy at the time the survey was performed. A survey performed in 2004 and 2005 of blood banks that are or were affiliated with comprehensive sickle-cell centres in the USA revealed a higher proportion of centres that obtained an SCD patient’s phenotype before transfusion (81%), and a corresponding percentage of these centres routinely provide phenotypically matched RBCs for their SCD patients (77%), as would be expected. Interestingly, 8% of the transfusion services at these centres of excellence did not have a ‘typical procedure’ for obtaining an RBC phenotype in patients with SCD and 9% did not routinely provide antigen-matched RBCs. Of the centres that did prophylactically match antigens between donor and recipient, the most common were C, E and K. Not surprisingly, the vast majority of the respondents to this survey felt that there was no ‘clear consensus’ on the use of phenotypically matched RBCs or the selection of blood products for SCD patients. A more recent survey in 2010 of centres that participated in an American randomized controlled trial of using RBC transfusion to prevent nosocomial acute chest syndrome found that 83% of the transfusion service respondents provided extended matched RBCs for all transfusions to patients with SCD, while others only provided extended matched RBCs if the patient had become alloimmunized [4]. One centre did not have a consistent policy for providing extended matched RBCs. Interestingly, there was no difference in the antibody prevalence rate between the centres that routinely provided extended matched RBCs for all transfusions and those that did not. Perhaps this was due to the patients with SCD receiving transfusions at other hospitals where routine antigen matching is not practiced, thereby negating the protective effects of antigen matching [3, 5]. Confounding the selection of RBCs and the development of universal SCD transfusion management guidelines, it is currently not known why some SCD patients become alloimmunized while others do not. Although specific genes predisposing to alloimmunization have not (yet?) been found [6], genetic factors have been proposed [7], as well as certain clinical factors that relate to patient’s underlying inflammatory state, such as the presence of acute chest syndrome or vaso-occlusive crisis at the time the patient was transfused [8]. A recent study of 83 patients with SCD revealed high levels of various cytokines in 12 patients, although the 16 7% rate of alloimmunization amongst these patients was not significantly different than the 28 2% rate seen amongst the 71