[Haemophilia and dental procedures; a complex combination]. / Hemofilie en tandheelkundige behandelingen; een complexe combinatie.

A 28-year-old patient with severe haemophilia A presented to the emergency department with significant and painful swelling of the left cheek, an extensive haematoma extending from the left ear to the anterior thoracic region, an intraoral haematoma over the soft palate with deviation of the uvula to the right, and complaints of shortness of breath when lying down. Three days prior, his dentist had performed a restoration of the 36 molar under local anaesthesia. Due to pain, the general practitioner had administered an intramuscular injection of a non-steroidal anti-inflammatory drug (NSAID) two days post-procedure. The patient was admitted for treatment with coagulation factors and pain management. Dental procedures and local anaesthesia in patients with a severe coagulation disorder require specific preparatory measures, such as administration of coagulation factors. Collaboration and consultation with a patient's haematologist or haemophilia treatment centre are essential requirements for safe dental care.

Evaluation of the role of the GPIb-IX-V receptor complex in development of the platelet storage lesion.

BACKGROUND AND OBJECTIVES: In mice, loss of sialic acid resulting in shedding of glycoprotein (GP) Ibα and GPV has been linked to platelet survival. The aim of this study was to determine whether loss of sialic acid and the GPIb-IX-V complex contributes to development of the platelet storage lesion (PSL) in human platelet concentrates (PCs). MATERIALS AND METHODS: PCs (stored in plasma (with or without Mirasol treatment); PAS-C or PAS-E) were stored at room temperature. Flow cytometry was used to monitor membrane expression of the GPIb-IX-V complex, CD62P, surface glycans and PS exposure. The functionality of stored platelets was determined employing aggregometry and ristocetin-induced VWF binding. RESULTS: Storage time of PCs in blood banks is limited to 7 days. During this time period, a minor but gradually increasing subpopulation of GPIbα-negative platelets was observed. Also, ristocetin-induced VWF binding was impaired in a small population of platelets. Mean surface expression of GPIbα and GPV remained stable until day 9, whereas CD62P expression increased; also a rapid decrease in ADP-induced aggregation was observed for PAS-C, PAS-E and Mirasol-treated PCs. Upon prolonged storage (>9 days), a slow decline in surface expression of GPIbα and GPV was observed; no major changes were observed in surface sialylation with the exception of Mirasol-treated platelets. CONCLUSION: In a small population of stored platelets, changes in GPIbα occur from day 2 onwards. Loss of sialic acid and subsequent shedding of GPIbα and GPV is not an early event during the development of the PSL.

Prediction of escape red blood cell transfusion in expectantly managed women with acute anaemia after postpartum haemorrhage.

OBJECTIVE: To determine clinical predictors of escape red blood cell (RBC) transfusion in postpartum anaemic women, initially managed expectantly, and the additional predictive value of health-related quality of life (HRQoL) measures. DESIGN: Secondary analysis of women after postpartum haemorrhage, either randomly allocated to, or opting for expectant management. SETTING: Thirty-seven hospitals in the Netherlands. POPULATION: A total of 261 randomised and 362 nonrandomised women. METHODS: We developed prediction models to assess the need for RBC transfusion: one using clinical variables (model 1), and one extended with scores on the HRQoL-measures Multidimensional Fatigue Inventory (MFI) and EuroQol-5D (model 2). Model performance was assessed by discrimination and calibration. Models were internally validated with bootstrapping techniques to correct for overfitting. MAIN OUTCOME MEASURES: Escape RBC transfusion. RESULTS: Seventy-five women (12%) received escape RBC transfusion. Independent predictors of escape RBC transfusion (model 1) were primiparity, multiple pregnancy, total blood loss during delivery and haemoglobin concentration postpartum. Maternal age, body mass index, ethnicity, education, medical indication of pregnancy, mode of delivery, preterm delivery, placental removal, perineal laceration, Apgar score and breastfeeding intention had no predictive value. Addition of HRQoL-scores (model 2), significantly improved the model's discriminative ability: c-statistics of model 1 and 2 were 0.65 (95% CI 0.58-0.72) and 0.72 (95% CI 0.65-0.79), respectively. The calibration of both models was good. CONCLUSIONS: In postpartum anaemic women, several clinical variables predict the need for escape RBC transfusion. Adding HRQoL-scores improves model performance. After external validation, the extended model may be an important tool for counselling and decision making in clinical practice.

Cost-effectiveness of red blood cell transfusion vs. non-intervention in women with acute anaemia after postpartum haemorrhage.

BACKGROUND: Red blood cell (RBC) transfusion is frequently used to treat women with acute anaemia after postpartum haemorrhage. We aimed to assess the economic consequences of red blood cell transfusion compared to non-intervention in these women. METHODS: A trial-based cost-effectiveness analysis was performed alongside the Well-Being of Obstetric patients on Minimal Blood transfusions (WOMB) trial. Women with acute anaemia [Hb 4·8-7·9 g/dl (3·0-4·9 mm)] after postpartum haemorrhage, without severe anaemic symptoms, were randomly allocated to RBC transfusion or non-intervention. Primary outcome of the trial was physical fatigue (Multidimensional Fatigue Inventory, scale 4-20; 20 represents maximal fatigue). Total costs per arm were calculated using a hospital perspective with a 6 weeks time horizon. RESULTS: Per woman, mean costs in the RBC transfusion arm (n = 258) were €1957 compared to €1708 in the non-intervention arm (n = 261; P = 0·024). The 13% difference in costs between study arms predominantly originated from costs of RBC units, as costs of RBC units were six times higher in the RBC transfusion arm. RBC transfusion led to a small improvement in physical fatigue of 0·58 points per day; thus, the costs to improve the physical fatigue score with one point would be €431. CONCLUSION: In women with acute anaemia after postpartum haemorrhage (PPH), RBC transfusion is on average €249 more expensive per woman than non-intervention, with only a small gain in HRQoL after RBC transfusion. Taking both clinical and economic consequences into account, implementation of a non-intervention policy seems justified.

Transfusion policy after severe postpartum haemorrhage: a randomised non-inferiority trial.

OBJECTIVE: To assess the effect of red blood cell (RBC) transfusion on quality of life in acutely anaemic women after postpartum haemorrhage. DESIGN: Randomised non-inferiority trial. SETTING: Thirty-seven Dutch university and general hospitals. POPULATION: Women with acute anaemia (haemoglobin 4.8-7.9 g/dl [3.0-4.9 mmol/l] 12-24 hours postpartum) without severe anaemic symptoms or severe comorbidities. METHODS: Women were allocated to RBC transfusion or non-intervention. MAIN OUTCOME MEASURES: Primary outcome was physical fatigue 3 days postpartum (Multidimensional Fatigue Inventory, scale 4-20; 20 represents maximal fatigue). Non-inferiority was demonstrated if the physical fatigue difference between study arms was maximal 1.3. Secondary outcomes were health-related quality of life and physical complications. Health-related quality of life questionnaires were completed at five time-points until 6 weeks postpartum. RESULTS: In all, 521 women were randomised to non-intervention (n = 262) or RBC transfusion (n = 259). Mean physical fatigue score at day 3 postpartum, adjusted for baseline and mode of delivery, was 0.8 lower in the RBC transfusion arm (95% confidence interval: 0.1-1.5, P = 0.02) and at 1 week postpartum was 1.06 lower (95% confidence interval: 0.3-1.8, P = 0.01). A median of two RBC units was transfused in the RBC transfusion arm. In the non-intervention arm, 33 women received RBC transfusion, mainly because of anaemic symptoms. Physical complications were comparable. CONCLUSIONS: Statistically, non-inferiority could not be demonstrated as the confidence interval crossed the non-inferiority boundary. Nevertheless, with only a small difference in physical fatigue and no differences in secondary outcomes, implementation of restrictive management seems clinically justified.

Diagnosing and treating antiphospholipid syndrome: a consensus paper.

INTRODUCTION: The antiphospholipid syndrome (APS) is defined by the occurrence of venous and/or arterial thrombosis and/or pregnancy-related morbidity, combined with the presence of antiphospholipid antibodies (aPL) and/or a lupus anticoagulant (LAC). Large, controlled, intervention trials in APS are limited. This paper aims to provide clinicians with an expert consensus on the management of APS. METHODS: Relevant papers were identified by literature search. Statements on diagnostics and treatment were extracted. During two consensus meetings, statements were discussed, followed by a Delphi procedure. Subsequently, a final paper was written. RESULTS: Diagnosis of APS includes the combination of thrombotic events and presence of aPL. Risk stratification on an individual base remains challenging. 'Triple positive' patients have highest risk of recurrent thrombosis. aPL titres > 99th percentile should be considered positive. No gold standard exists for aPL testing; guidance on assay characteristics as formulated by the International Society on Thrombosis and Haemostasis should be followed. Treatment with vitamin K-antagonists (VKA) with INR 2.0-3.0 is first-line treatment for a first or recurrent APS-related venous thrombotic event. Patients with first arterial thrombosis should be treated with clopidogrel or VKA with target INR 2.0-3.0. Treatment with direct oral anticoagulants is not recommended. Patients with catastrophic APS, recurrent thrombotic events or recurrent pregnancy morbidity should be referred to an expert centre. CONCLUSION: This consensus paper fills the gap between evidence-based medicine and daily clinical practice for the care of APS patients.

Longitudinal growth during the first years of life: what is normal?

The anthropometric data of a longitudinal growth study on healthy infants, followed from birth until the age of 4 years and performed during 1995-1999 in The Netherlands, were used to analyze the general growth patterns in terms of height, weight and head circumference, based on z-scores, during the first 4 years of life. The well-known phenomenon where each infant or child tends to decelerate or accelerate its growth velocity depending on its starting position on the reference curve is obvious in this study too. This phenomenon, known as the regression to the mean, is a strong phenomenon especially during the first year. Regression to the mean is calculated for the different age groups as factor. With the given alpha, it is possible to estimate the individual expectation of growth.

[Multicentre clinical study into the optimal blood transfusion policy in patients with postpartum haemorrhage: the 'Wellbeing of obstetric patients on minimal blood transfusions' (WOMB) study]. / Een klinisch multicentrisch onderzoek naar het optimale bloedtransfusiebeleid bij patiënten met een fluxus post partum: de 'Wellbeing of obstetric patients on minimal blood transfusions' (WOMB)-studie.

Postpartum haemorrhage is a common and potentially serious complication of delivery. In clinical obstetrics, exact measurement of blood loss is often difficult. Red blood cell (RBC) transfusion is the most important intervention to treat the complications of this sustained blood loss. Despite the introduction of various new guidelines, the triggers for transfusion still vary widely between clinicians. Therefore, a prospective randomised multicentre trial, the 'Wellbeing of obstetric patients on minimal blood transfusions' (WOMB) study, was developed. This study assesses the effect of RBC transfusion on the health-related quality of life (HRQoL) of the mother after delivery. Patients with a haemoglobin (Hb) level between 3.0 and 4.9 mmol/l and a blood loss of at least 1000 ml or a decrease of > 1.2 mmol/l in the Hb level are randomly assigned to receive RBC transfusion or not. A total of 400 patients will be included. Primary outcome is physical fatigue. The total follow-up period is 6 weeks. Currently, the study is ongoing in 10 hospitals in the Netherlands. The goal of this study is to develop a new transfusion policy based on Hb-levels as well as HRQoL criteria.

Postpartum hemorrhage and transfusion of blood and blood components.

UNLABELLED: Postpartum hemorrhage (PPH) is one of the top 5 causes of maternal mortality in developed and developing countries. The incidence of PPH is 40% after vaginal delivery and 30% after cesarean section. Criteria for PPH are based on the amount of blood loss. In clinical obstetrics, exact measurement of blood loss is often difficult. The most important treatment of PPH is red blood cell (RBC) transfusion. In the past few years, increasing concern has arisen about this treatment. Despite the introduction of several new guidelines, transfusion criteria still vary widely between clinicians. The decision whether to prescribe RBC transfusion is mostly based on postpartum hemoglobin (Hb) values. RBC transfusion should be aimed to reduce morbidity and especially to improve health-related quality of life (HRQoL). In this review, etiology, epidemiology, treatment, and prevention of postpartum hemorrhage are described. Special attention is given to the role of RBC transfusion in the treatment of PPH and the effects of RBC transfusion on HRQoL. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to summarize the new guidelines related to transfusion criteria, explain the importance of reducing morbidity related to improving quality of life issues, and list infectious and noninfectious complications of a red blood cell transfusion.

Feasibility of a restrictive red-cell transfusion policy for patients treated with intensive chemotherapy for acute myeloid leukaemia.

Red-cell transfusions are required for symptomatic treatment of severe anaemia caused by intensive chemotherapy. Concerns about the transfusion-related complications, such as infections (e.g. the very low risk of human immunodeficiency virus (HIV)/hepatitis C virus (HCV) transmission and the risk of postoperative infections), haemolytic transfusion reaction, immunological effects and the costs, prompt a reevaluation of the transfusion practice. Retrospective analysis of prospectively collected data on 84 patients with acute myeloid leukaemia (AML), who were treated with combination chemotherapy between June 1, 1997 and December 7, 2001, was performed. The use of red-cell transfusions with a restrictive transfusion policy (haemoglobin = 7.2-8.8 g dL(-1), dependent on age and symptoms, n = 38) was compared with a more liberal transfusion trigger (haemoglobin = 9.6 g dL(-1), n = 46). The number of units transfused was recorded. Signs and symptoms of anaemia, chemotherapy-related effects and complications were investigated for both transfusion policies. The more restrictive transfusion policy led to a significant decrease of 11% of red blood cell (RBC) transfusions in patients with AML. No significant differences were found in the incidence of infections, number of platelet units transfused, bleeding complications, cardiac symptoms or response to chemotherapy. The more restrictive transfusion policy was feasible in this clinical setting, and it might be concluded that a restrictive transfusion policy is safe in supporting clinical patients treated with intensive chemotherapy for AML.

Quality of life measurement in patients with transfusion-dependent myelodysplastic syndromes.

The myelodysplastic syndromes (MDS) are clonal disorders characterized by dysplasia in at least two myeloid cell lines. Fatigue is one of the most significant symptoms. MDS patients are treated with blood transfusions to improve their health-related quality of life (HRQoL). A cross-sectional pilot study was performed for psychometric evaluation of three internationally established HRQoL measures in MDS patients, and for investigation of the association between the severity of chronic anaemia and HRQoL. Fifty consecutive MDS patients completed the Short Form 36, the Multidimensional Fatigue Inventory and the EuroQoL-5D Visual Analogue Scale. Hb level was measured during the same visit. Psychometric analysis focused on feasibility, construct validity and reliability. The questionnaires showed a high feasibility, reliability and validity. MDS patients had worse HRQoL scores than the age- and sex-matched general population. We found a positive correlation between haemoglobin (Hb) level and HRQoL. This study provides insights into the suitability of established HRQoL measures for the evaluation of interventions in MDS patients. Hb value and HRQoL are complementary variables for evaluation of the severity of chronic anaemia in patients with MDS.