Fetal/neonatal alloimmune thrombocytopenia: a systematic review of impact of HLA-DRB3*01:01 on fetal/neonatal outcome.

The most common, severe cases of fetal and neonatal alloimmune thrombocytopenia among whites are caused by antibodies against human platelet antigen 1a (HPA-1a). The aims of this systematic review and meta-analysis are to determine the association between maternal HLA-DRB3*01:01 and: (1) HPA-1a-alloimmunization and (2) neonatal outcome in children born of HPA-1a-immunized women. A systematic literature search identified 4 prospective and 8 retrospective studies. Data were combined across studies to estimate pooled odds ratios (ORs) and the associated 95% confidence intervals (CIs). The population represented by the prospective studies was more than 150 000. In the prospective studies, there were 64 severely thrombocytopenic newborns (platelet count <50 × 109/L) of whom 3 had intracranial hemorrhage. The mothers of all 64 children were HLA-DRB3*01:01+. The number of severely thrombocytopenic children born of HPA-1a-alloimmunized women in the retrospective studies was 214; 205 of whom were born of HLA-DRB3*01:01+ women. For HLA-DRB3*01:01- women, the OR (95% CI) for alloimmunization was 0.05 (0.00-0.60), and for severe neonatal thrombocytopenia 0.08 (0.02-0.37). This meta-analysis demonstrates that the risk of alloimmunization and of having a child with severe thrombocytopenia are both very low for HPA-1a- women who are HLA-DRB3*01:01-.

Contemporary management of neonatal alloimmune thrombocytopenia: good outcomes in the intravenous immunoglobulin era: results from the Australian neonatal alloimmune thrombocytopenia registry.

OBJECTIVE: To describe the natural history, antenatal and postnatal therapy, and clinical outcomes of Australian patients with fetomaternal/neonatal alloimmune thrombocytopenia (NAIT) recorded in the Australian NAIT registry. METHODS: Analysis of registry data of Australian mothers treated antenatally for NAIT and any fetus/newborn with thrombocytopenia (TCP) and maternal human platelet antigen (HPA) antibodies. RESULTS: Ninety four potential cases (91 pregnancies; three twin pregnancies) were registered between December 2004 and September 2015 with 76 confirmed or treated as NAIT. NAIT was frequently unanticipated (44 cases, 58%), whilst 32 cases (42%) were anticipated due to personal or family history. In 70/76 cases, the diagnosis of NAIT was made based on HPA antibody results; anti-HPA-1a was most commonly detected (58/70, 82%), followed by anti-HPA-5b (5/70, 7%). Intracranial haemorrhage (ICH) was detected in seven cases (9%). Maternal antenatal therapy resulted in improved clinical outcomes. For antenatally treated cases, whilst 10/29 (34%) neonates had severe TCP, only one ICH was detected. CONCLUSIONS: This study provides data on contemporary "real world" management of Australian mothers and babies with NAIT. Antenatal IVIG therapy was associated with better neonatal outcomes. Maternal side-effects and treatment costs were substantial.

Antenatal immunoglobulin for fetal red blood cell alloimmunization.

BACKGROUND: Red blood cell alloimmunization in pregnancy can lead to fetal anaemia with potentially disastrous consequences. Traditional management involves the use of intrauterine transfusion, which is associated with significant procedure-related risks. An alternative treatment that has been trialled is the use of immunoglobulin administered intravenously to the mother. OBJECTIVES: The objective of this review was to assess the efficacy and safety of the use of intravenous immunoglobulin antenatally to women with severe fetal red blood cell alloimmunization. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group trials register (19 December 2012), and reference lists of articles. SELECTION CRITERIA: Randomized trials assessing the antenatal use of intravenous immunoglobulin administered at any dose, frequency or duration with a control group (using any other, or no treatment) in the management of fetal red blood cell alloimmunization. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the available evidence. MAIN RESULTS: There are no included studies. AUTHORS' CONCLUSIONS: No information is available from randomized trials to indicate whether the antenatal use of intravenous immunoglobulin is effective in the management of fetal red blood cell alloimmunization. Several case series suggest a beneficial role in delaying the onset of fetal anaemia requiring invasive intrauterine transfusion.

Diagnosis and management of iron deficiency anaemia: a clinical update.

Iron deficiency anaemia (IDA) remains prevalent in Australia and worldwide, especially among high-risk groups. IDA may be effectively diagnosed in most cases by full blood examination and serum ferritin level. Serum iron levels should not be used to diagnose iron deficiency. Although iron deficiency may be due to physiological demands in growing children, adolescents and pregnant women, the underlying cause(s) should be sought. Patients without a clear physiological explanation for iron deficiency (especially men and postmenopausal women) should be evaluated by gastroscopy/colonoscopy to exclude a source of gastrointestinal bleeding, particularly a malignant lesion. Patients with IDA should be assessed for coeliac disease. Oral iron therapy, in appropriate doses and for a sufficient duration, is an effective first-line strategy for most patients. In selected patients for whom intravenous (IV) iron therapy is indicated, current formulations can be safely administered in outpatient treatment centres and are relatively inexpensive. Red cell transfusion is inappropriate therapy for IDA unless an immediate increase in oxygen delivery is required, such as when the patient is experiencing end-organ compromise (eg, angina pectoris or cardiac failure), or IDA is complicated by serious, acute ongoing bleeding. Consensus methods for administration of available IV iron products are needed to improve the utilisation of these formulations in Australia and reduce inappropriate transfusion. New-generation IV products, supported by high-quality evidence of safety and efficacy, may facilitate rapid administration of higher doses of iron, and may make it easier to integrate IV iron replacement into routine care.

An audit of transfusion of red blood cell units in pediatric anesthesia.

BACKGROUND: Patients undergoing surgery are an important user of red blood cells (RBC). Increasingly, medical staff and patients wish to know the likelihood of RBC transfusion for appropriate resource allocation and to inform preoperative discussions regarding risk. Although some adult data are available, little is known about RBC use in children. AIM: The aim of this study was to describe RBC use in the perioperative period in a large pediatric hospital. METHODS: Over a 2-year period the hospital operating theatre database and trauma registry was merged with the blood bank database to identify episodes where RBC units were transfused in association with anesthesia. Incidence of transfusion of RBC units associated with particular procedures was then calculated. RESULTS: A total of 21 441 patients underwent 32 511 anesthetics from January 1, 2006 to December 31, 2007, and 9838 units of RBC were released from the hospital blood bank of which 4070 (41%) were transfused in the perioperative period. Cardiac surgery was the greatest user of RBC units (2359 units). Acute major trauma accounted for only 159 units. Overall 6.3% of anesthetics were associated with a RBC transfusion. The procedures with the greatest frequency of RBC transfusion were cardiac surgery on bypass (79%), cardiac off bypass (55%), liver transplant (87%) and cranioplasty (61%). CONCLUSION: In a tertiary pediatric hospital surgery accounts for a substantial proportion of total RBC use, with particular procedures accounting for the majority of transfusions.

Hereditary hyperferritinemia-cataract syndrome: prevalence, lens morphology, spectrum of mutations, and clinical presentations.

OBJECTIVES: To provide a comprehensive description of the clinical presentations, cataract morphology, and molecular basis of hereditary hyperferritinemia-cataract syndrome (HHCS) in 4 Australian pedigrees and to estimate its prevalence. METHODS: All known cases of HHCS in southeastern Australia were ascertained. Family members provided a medical history and underwent physical examination, lens photography, and venipuncture for measurement of serum ferritin levels and DNA extraction. Sequence analysis of the iron-responsive element of the ferritin light chain on chromosome 19q13.3-qter was performed. RESULTS: We investigated 26 affected individuals from 5 Australian pedigrees. Two pedigrees with HHCS ascertained independently were subsequently found to form 1 large kindred carrying the mutation A40G. The minimum estimated prevalence of HHCS is 1/200000. One pedigree had the mutation G32C. Among 2 smaller pedigrees studied, one carried a novel mutation (C39A), and the other was identified through the 2-year-old propositus with cataract but no positive family history. The latter case was shown to be due to a de novo mutation (G32U). All cataracts were highly distinctive in morphology, consisting of slowly progressive flecks, vacuoles, and distinctive crystalline deposits scattered predominantly in the lens cortex but also in the nucleus. Eight of 18 affected individuals examined have required cataract extraction to date. No other identified clinical manifestations of HHCS were delineated. CONCLUSIONS: Cataract morphology in HHCS is highly distinctive. Longitudinal observation demonstrated slow progression of the cataracts. This study highlights that, although HHCS is an autosomal dominant condition, the diagnosis should be considered even in sporadic cataract of typical morphology. Furthermore, individuals with unexplained hyperferritinemia should be referred for ophthalmological assessment, as the cataract may be asymptomatic but lead to a correct diagnosis of HHCS. Clinical Relevance Progressive cataracts of highly distinctive morphology are an important feature of HHCS. Evaluation for this type of cataract may be of diagnostic value in patients with unexplained hyperferritinemia. Hereditary hyperferritinemia-cataract syndrome can be a cause of cataracts in pediatric patients even in the absence of any positive family history.

Utilization of preoperative autologous blood donation in elective surgery.

BACKGROUND: The aim of the present paper was to review the pattern of collection and transfusion of autologous red cells for elective surgical procedures METHODS: Data on requests for preoperative autologous donation of blood were obtained from the Australian Red Cross Blood Service, Victoria and the Royal Melbourne Hospital for the calendar year 1998. The following information was collected: patient age, sex, surgery type, number of autologous units requested and collected and, if relevant, reasons for not achieving the requested collection. Transfusion of autologous units and any additional homologous units was confirmed from records at the blood banks of the Royal Melbourne Hospital and Melbourne Pathology (the pathology provider performing cross-matching for the majority of autologous units collected by Australian Red Cross Blood Service, Victoria). RESULTS: Over 12 months, 2803 units of autologous blood were requested and 2282 units collected from 1301 patients. The most common reason for failure to collect the number of units requested was insufficient time between referral and surgery. Of the autologous units collected, 73% were transfused giving a collection to transfusion ratio of 1.4. Sixty-eight per cent of patients received their autologous units only, 10% received both autologous and homologous units, while 22% were not transfused. For the majority of procedures, patients using preoperative autologous donation of blood had higher transfusion rates than those who did not use this. CONCLUSIONS: Ninety per cent of patients undergoing preoperative autologous donation of blood successfully avoided homologous blood exposure. However, preoperative autologous donation of blood is both wasteful and increases the incidence of transfusion in surgical procedures.

Use of red blood cell transfusions in surgery.

BACKGROUND: Limited blood supplies necessitate the rational use of blood products. The aim of the present study was to provide a basis for audits of red cell usage in surgery by benchmarking common practice. Application of the data to the construction of a maximum surgical blood order schedule may be relevant for centres that perform a serological crossmatch or who collect autologous units. METHODS: Data on surgical procedures identified by Commonwealth Medical Benefits Schedule item numbers, were collected retrospectively from theatre and blood bank records at the Royal Melbourne and Melbourne Private hospitals from May 1997 to April 1998. The percentage of procedures for which red cells were transfused, and the mean, median and range of units transfused for procedures with >/= 30% transfusion likelihood were identified. RESULTS: Over 12 months, 266 surgical procedure codes were itemized >/= 10 times each, contributing 12 300 data entries. Only 38 procedures demonstrated an incidence of transfusion of at least 30%. Most frequently transfused procedures included spinal fusion, total hip replacement, mandible/maxilla resection, prostatectomy and bladder excision. CONCLUSION: The number of common surgical procedures in which there is a 30% or greater likelihood that red cell transfusions will be given is limited. This benchmarking of common red cell usage is a first step in the process of determination of transfusion appropriateness.