Alison Street

Guidelines for the management of hemophilia.

Hemophilia is a rare disorder that is complex to diagnose and to manage. These evidence‐based guidelines offer practical recommendations on the diagnosis and general management of hemophilia, as well as the management of complications including musculoskeletal issues, inhibitors, and transfusion‐transmitted infections. By compiling these guidelines, the World Federation of Hemophilia aims to assist healthcare providers seeking to initiate and/or maintain hemophilia care programs, encourage practice harmonization around the world and, where recommendations lack adequate evidence, stimulate appropriate studies.

Fresh frozen plasma (FFP) use during massive blood transfusion in trauma resuscitation.

INTRODUCTION Recent retrospective studies have found high fresh frozen plasma (FFP) to packed red blood cell (PRBC) ratios during trauma resuscitation to be associated with improved mortality. Whilst this association may be related to a mortality bias present in these studies, there has been an overall tendency towards a 1:1 FFP:PRBC ratio in massive transfusion guidelines worldwide. The aim of this study was to retrospectively review the administration of FFP in patients undergoing massive transfusion during trauma resuscitation, to add to the evidence base for massive transfusion guidelines. MATERIALS AND METHODS Multi-trauma patients who were administered blood transfusions of 5units or more of packed red blood cells (PRBCs) in the first 4h were included in this study. Mortality was the primary endpoint with length of hospital stay, ICU hours and mechanically ventilated hours secondary endpoints. RESULTS There were 331 patients included in this study with a median Injury Severity Score (ISS) of 36 (25-50) and a mortality of 29.9%. There was little change in the ratio of FFP:PRBC transfused per patient from 2005 to 2008. A low FFP:PRBC ratio in the first 4h of resuscitation, older age, low initial GCS and coagulopathy on presentation were significant independent factors associated with mortality. When deaths in the first 24h were excluded, the FFP:PRBC ratio had no association with mortality. DISCUSSION This study has shown increased initial survival in association with higher FFP:PRBC ratios during massive transfusion in a population with a high proportion of blunt injuries. The association is difficult to interpret because of an inherent survival bias. The optimal ratio of FFP:PRBC during massive transfusion may be different to 1:1 and further prospective research is required. There is now an increasing need for well designed randomised controlled trials to determine the best FFP:PRBC ratio for the resuscitation of blunt multi-trauma patients.

MULTIMERIC ANALYSIS OF VON WILLEBRAND FACTOR BY MOLECULAR SIEVING ELECTROPHORESIS IN SODIUM DODECYL SULPHATE AGAROSE GEL

We report the development and optimisation of an agarose gel electrophoretic method for the separation and detection of von Willebrand Factor (vWF) multimers. The method has been specifically developed for use in the clinical evaluation and classification of patients with von Willebrands Disease (vWD) and clearly shows structural multimer abnormalities associated with the bleeding diathesis of this inherited bleeding disorder.

Age of red blood cells and mortality in the critically ill

IntroductionIn critically ill patients, it is uncertain whether exposure to older red blood cells (RBCs) may contribute to mortality. We therefore aimed to evaluate the association between the age of RBCs and outcome in a large unselected cohort of critically ill patients in Australia and New Zealand. We hypothesized that exposure to even a single unit of older RBCs may be associated with an increased risk of death.MethodsWe conducted a prospective, multicenter observational study in 47 ICUs during a 5-week period between August 2008 and September 2008. We included 757 critically ill adult patients receiving at least one unit of RBCs. To test our hypothesis we compared hospital mortality according to quartiles of exposure to maximum age of RBCs without and with adjustment for possible confounding factors.ResultsCompared with other quartiles (mean maximum red cell age 22.7 days; mortality 121/568 (21.3%)), patients treated with exposure to the lowest quartile of oldest RBCs (mean maximum red cell age 7.7 days; hospital mortality 25/189 (13.2%)) had an unadjusted absolute risk reduction in hospital mortality of 8.1% (95% confidence interval = 2.2 to 14.0%). After adjustment for Acute Physiology and Chronic Health Evaluation III score, other blood component transfusions, number of RBC transfusions, pretransfusion hemoglobin concentration, and cardiac surgery, the odds ratio for hospital mortality for patients exposed to the older three quartiles compared with the lowest quartile was 2.01 (95% confidence interval = 1.07 to 3.77).ConclusionsIn critically ill patients, in Australia and New Zealand, exposure to older RBCs is independently associated with an increased risk of death.

The definition of massive transfusion in trauma: a critical variable in examining evidence for resuscitation.

Objectives ‘Massive’ transfusion is a poorly defined inclusion criteria for studies examining the blood and blood product that are used during trauma resuscitation. We aimed to compare the traditional definition of massive transfusion (≥10 units in 24 h) to a more acute definition of at least 5 units in 4 h. Methods Multitrauma patients were subgrouped according to the traditional definition and compared with the acute definition. Demographics, presenting vital signs and blood results, management including transfusion practice and outcomes were retrospectively studied. Associations of transfused fresh frozen plasma:packed red blood cells (PRBC) ratios with mortality were studied. Results There were 927 patients who received PRBCs in the first 24 h, with 314 patients identified using the traditional definition and 303 patients using the acute definition. The patients identified using the traditional definition received 18 (12–29) units of PRBC in 24 h, significantly higher than those identified using the acute definition [15 (9–29) units, P<0.001]. The traditional definition excluded a significant proportion of patients who died in the emergency department. By using the acute definition to select a study sample, there seems to be an increase in mortality with fresh frozen plasma:PRBC ratio of 1 : 1 ratio compared with a 1 : 2 ratio. Conclusion The traditional ‘massive’ transfusion definition not only ‘dilutes’ the potential study samples with a less acute group of patients, but also further excludes patients who die early. This latter group is most likely to be benefitted from any change to resuscitation practice. An acute definition of massive transfusion should be adopted when examining clinical practice during initial trauma resuscitation.

Haemophilia and ageing

Summary.  Men with haemophilia have not only the challenges of living with HIV and/or HCV infection and premature arthritis as complications of their disorder, but they also confront the other ails of ageing. These include genitourinary problems such as prostatic hypertrophy, prostatic cancer and renal stone disease, and arterial disease for which haemophilia is not protective. Progressive arthritis and declining fitness may lead to loss of independence which causes great concern. Associated with the physical aspects of ageing, many patients also suffer from psychological symptoms which may be precipitated by changes in work such as early retirement and altered family dynamics. Many older men with haemophilia may never have consulted primary care physicians because of the rarity and complexity of their disorder. Haemophilia centre staff often assume responsibility for the identification and management of all health problems of their patients. Even when other clinicians are involved, patients require their centres involvement in the investigation and support of many procedures such as coronary artery surgery and urological surgery. This paper addresses falls in the older man with haemophilia, their causes and consequences and cardiovascular problems in particular. Very little literature has been published about these common problems. We need to be aware of the ageing issues in haemophilia and develop ‘wellness’ programs which are directed to the early identification of disease as well as preventative strategies to reduce the physical and psychological impacts of ageing.

Early prediction of acute traumatic coagulopathy

INTRODUCTION The inability to accurately predict acute traumatic coagulopathy (ATC) has been a key factor in the low level of evidence guiding its management. The aim of this study was to develop a tool to accurately identify patients with ATC using pre-hospital variables without the use of pathology or radiological testing. METHODS Retrospective data from the trauma registry on major trauma patients were used to identify variables independently associated with coagulopathy. These variables were clinically evaluated to develop a scoring system to predict ATC, which was prospectively validated in the same setting. RESULTS There were 1680 major trauma patients in the derivation dataset, with 151 patients being coagulopathic. Pre-hospital variables independently associated with ATC were entrapment (OR 1.85; 95% CI: 1.12-3.06), temperature (OR 0.60; 95% CI: 0.60-0.72), systolic blood pressure (OR 0.99; 95% CI: 0.98-0.99), abdominal or pelvic content injury (OR 2.0; 95% CI: 1.27-3.12) and pre-hospital chest decompression (OR 4.99; 2.77-8.99). The COAST score was developed, scoring points for entrapment, temperature <35°C, systolic blood pressure < 100 mm Hg, abdominal or pelvic content injury and chest decompression. Prospectively validated using 1225 major trauma patients, a COAST score of ≥ 3 had a specificity of 96.4% with a sensitivity of 60.0%, with an area under the receiver operating characteristic curve of 0.83 (0.78-0.88). CONCLUSIONS The COAST score accurately identified a group of patients with ATC using pre-hospital observations. This predictive tool can be used to select patients for inclusion into prospective studies examining management options for ATC. Mortality in these patients is high, potentially improving feasibility of outcome studies.

Comprehensive care for haemophilia around the world

Summary.  Comprehensive haemophilia care has been defined as the continuing supervision of all medical and psychosocial factors affecting the person with haemophilia family. Services offered by haemophilia treatment centres (HTCs) adopting the comprehensive care model include establishing prophylaxis and other treatment protocols, development of psychosocial, education and research programme, maintenance of a patient registry, genetic and reference diagnostic services and orchestration and management of a wide variety of multidisciplinary interventions. Most centres practising this model of care are based in developed countries and can meet costs for plentiful treatment products through government or insurance‐company funding. Not all the programmes are dependent on the level of product supply, however, and many have been supported in countries with emerging economies as part of national healthcare systems, particularly in relation to blood management. In this paper we present perspectives from different areas of the world on how to adopt, adapt and achieve economically appropriate models of comprehensive care.

Clinical outcomes and patient satisfaction following total joint replacement in haemophilia--23-year experience in knees, hips and elbows.

Summary.  Joint replacement surgery is an available option for end‐stage haemophilic arthropathy. However, reports with long‐term follow‐up are limited. Moreover, patient satisfaction in this setting has never been measured. We share our institution’s experience with joint arthroplasty in haemophilic arthropathy and report on clinical outcomes and patient satisfaction. Between 1985 and 2007, 65 consecutive joints in 45 patients (mean age: 48.6; range: 22–83) underwent joint replacement surgery. Of these, 40 total knee replacements in 31 patients, 18 total hip replacements in 16 patients and 6 total elbow replacements in 3 patients were included. Average follow‐up was 10.7 years (2.4–24.3). Charts were reviewed retrospectively and patients were asked to return for clinical assessment and completion of questionnaires. According to the Knee Society clinical score, postoperative results were good to excellent in 83% of knees. According to the Harris Hip Score, results were good to excellent in 31% of hips. According to the Mayo Elbow Performance Score, results were good to excellent in 83% of elbows. Complication rates are higher than in the non‐haemophilic population, while prosthesis survival rates are lower. Patient satisfaction with pain relief is higher than satisfaction with functional improvement. For 88% of joints, patients are willing to have the same operation again. This study confirms previous knowledge on the role of total joint arthroplasty in haemophilic arthropathy. Despite high complication rates and modest functional outcomes, the operations are valuable for achieving pain relief. In general, patients find that risks are outweighed by the benefits.

Balance dysfunction in adults with haemophilia

Summary.  The main focus of lower limb physical performance assessment in people with haemophilia (PWH) has usually been on function, muscle strength and joint flexibility. The impact of haemophilic arthropathy on balance and falls risk is relatively under‐explored. The aim of this study was to evaluate balance and related performance in PWH compared with age and gender matched healthy controls. It involved a comprehensive suite of clinical and laboratory measures of static and dynamic balance, mobility, strength, physical activity and falls efficacy completed in 20 PWH (mean age 39.4, 100% male) and 20 controls. Fifty percent of PWH reported falls in the past 12 months. Moderate impairment of balance and related measures were identified in PWH compared with the controls, with an average 35% difference between groups. Significant differences were evident between groups on both clinical and laboratory measures, including measures of dynamic bilateral stance balance [limits of stability measures on the laboratory test, functional reach; (P < 0.001); dynamic single leg balance (Step Test, P < 0.001)], gait and mobility (gait speed, step width and turning measures on the laboratory test, timed up and go test; P < 0.001); muscle strength (timed sit to stand, P = 0.002; quadriceps strength, P < 0.001); and activity level and falls efficacy, (P < 0.004). The dynamic clinical and laboratory measures testing similar domains of balance, gait and mobility had moderate correlations (0.310 < r < 0.531, P < 0.01). Moderate impairments in balance, mobility and related measures were identified in PWH, compared with the control group. Clinicians should include assessments of balance and related measures when reviewing adults with haemophilia.