Red blood cell transfusion support and management of secondary iron overload in patients with haematological malignancies in the Netherlands: a survey.

BACKGROUND AND OBJECTIVES: Evidence-based guidelines on optimal triggers for red blood cell (RBC) transfusion in patients with haematological malignancies exist, but the evidence is weak. Secondary iron overload is an often overlooked chronic complication of RBC transfusions, and also here, guidelines are either lacking or lack international consensus. Our aim was to evaluate the triggers for RBC transfusion support and management of secondary iron overload among haematologists in the Netherlands. MATERIALS AND METHODS: For this cross-sectional study, all haematologists and haematologists in training in the Netherlands were sent a web-based, 25-question survey including three clinical scenarios. The survey distribution took place between 19 November 2015 and 26 January 2016. RESULTS: Seventy-seven responses were received (24%), well distributed among community and university hospitals. A wide variation in haemoglobin triggers existed: 5·6-9·5 g/dl (median: 8·0 g/dl). Personalization of this trigger was mostly based on (estimated) cardiopulmonary compensation capacity of patients. About 65% of respondents reported two RBC units per transfusion episode (range 1-3). For monitoring secondary iron overload, serum ferritin was most frequently measured (97%), while a value of 1000-1500 µg/l was the most common cut-off to initiate treatment (39%). For 81% of respondents, phlebotomies were the first choice of treatment, although often the haemoglobin level was considered a limiting factor. CONCLUSION: Our results confirm large reported variation in daily practice among haematologists in the Netherlands regarding RBC transfusion support and management of secondary iron overload. Future studies providing better evidence are needed to improve guidelines specific for patients with haematological malignancies.

Patient blood management knowledge and practice among clinicians from seven European university hospitals: a multicentre survey.

BACKGROUND AND OBJECTIVES: The aim of this survey was to evaluate the knowledge about Patient Blood Management (PBM) principles and practices amongst clinicians working in seven European hospitals participating in a European Blood Alliance (EBA) project. MATERIALS AND METHODS: A web-based questionnaire was sent to 4952 clinicians working in medical, surgery and anaesthesiology disciplines. The responses were analysed, and the overall results as well as a comparison between hospitals are presented. RESULTS: A total of 788 responses (16%) were obtained. About 24% of respondents were not aware of a correlation between preoperative anaemia (POA) and perioperative morbidity and mortality. For 22%, treatment of POA was unlikely to favourably influence morbidity and mortality even before surgery with expected blood loss. More than half of clinicians did not routinely treat POA. 29%, when asked which is the best way to treat deficiency anaemia preoperatively, answered that they did not have sufficient knowledge and 5% chose to 'do nothing'. Amongst those who treated POA, 38% proposed red cell transfusion prior to surgery as treatment. Restrictive haemoglobin triggers for red blood cell transfusion, single unit policy and reduction of number and volumes of blood samples for diagnostic purposes were only marginally implemented. CONCLUSION: Overall, the responses indicated poor knowledge about PBM. Processes to diagnose and treat POA were not generally and homogeneously implemented. This survey should provide further impetus to implement programmes to improve knowledge and practice of PBM.

The practice of diagnosing and reporting transfusion-associated circulatory overload: a national survey among physicians and haemovigilance officers.

OBJECTIVES: This study aims at identifying factors that disciplines consider when diagnosing and reporting transfusion-associated circulatory overload ('TACO'). BACKGROUND: TACO is a clinical diagnosis based mainly on subjective factors. Therefore, TACO could be an underreported complication of blood transfusion. METHODS: A survey was conducted among critical care physicians, anaesthesiologists, haematologists, transfusion medicine physicians and haemovigilance officers using case vignettes and a questionnaire. Factors that may affect diagnosing TACO were investigated using conjoint analysis. A positive B-coefficient indicates a positive preference for diagnosing TACO. Participants rated factors influencing reporting TACO on a 0- to 100-point scale. RESULTS: One hundred and seven surveys were returned (62%). Vignettes showed preferences in favour of diagnosing TACO with the onset of symptoms within 2 h [ß 0·4(-0·1-1·0)], positive fluid balance [ß 0·9(0·4-1·5)] and history of renal failure [ß 0·6(0·1-1·2)]. Compared with transfusion of a single unit of red blood cells (RBC), respondents showed a preference for diagnosing TACO following a single unit of solvent/detergent (S/D) plasma or pooled platelet concentrate (PPC) [ß 0·3(-0·2-0·7) resp. 0·5(-0·1-1·2)]. Multiple transfusion (6 RBC + 4 S/D plasma) was a strong preference for diagnosing TACO compared to 1 RBC and 1 S/D plasma [ß 0·3(-0·8-1·3)]. Respondents did not fully take into account new hypertension and tachycardia when reporting TACO [median 70 (IQR 50-80) resp. 60 (IQR 50-80)]. No differences were observed between disciplines involved. CONCLUSION: When diagnosing and reporting TACO, physicians and haemovigilance officers do consider known risk factors for TACO. Reporting could be improved by increasing the awareness of haemodynamic variables in future education programmes.

Pathogen-reduced Ebola virus convalescent plasma: first steps towards standardization of manufacturing and quality control including assessment of Ebola-specific neutralizing antibodies.

BACKGROUND: Ebola virus disease is a public health emergency of international concern, and enormous efforts are being made in the development of vaccines and therapies. Ebola virus convalescent plasma is a promising anti-infective treatment of Ebola virus disease. Therefore, we developed and implemented a pathogen-reduced Ebola virus convalescent plasma concept in accordance with national, European and global regulatory framework. MATERIALS AND METHODS: Ebola virus convalescent plasma manufacture and distribution was managed by a collection centre, two medical centres and an expert group from the European Blood Alliance. Ebola virus convalescent plasma was collected twice with an interval of 61 days from a donor recovering from Ebola virus disease in Germany. After pathogen reduction, the plasma was analysed for Ebola virus-specific immunoglobulin G (IgG) antibodies and its Ebola virus neutralizing activity. RESULTS: Convalescent plasma could be collected without adverse events. Anti-Ebola virus IgG titres and Ebola-specific neutralizing antibodies in convalescent plasma were only slightly reduced after pathogen reduction treatment with S59 amotosalen/UVA. A patient in Italy with Ebola virus disease was treated with convalescent plasma without apparent adverse effects. DISCUSSION: As proof of principle, we describe a concept and practical implementation of pathogen-reduced Ebola virus convalescent plasma manufacture, quality control and its clinical application to an Ebola virus disease patient.

Patient Blood Management in Europe: surveys on top indications for red blood cell use and Patient Blood Management organization and activities in seven European university hospitals.

BACKGROUND AND OBJECTIVES: Patient Blood Management (PBM) in Europe is a working group of the European Blood Alliance with the initial objective to identify the starting position of the participating hospitals regarding PBM for benchmarking purposes, and to derive good practices in PBM from the experience and expertise in the participating teams with the further aim of implementing and strengthening these practices in the participating hospitals. METHODS: We conducted two surveys in seven university hospitals in Europe: Survey on top indications for red blood cell use regarding usage of red blood cells during 1 week and Survey on PBM organization and activities. RESULTS: A total of 3320 units of red blood cells were transfused in 1 week at the seven hospitals. Overall, 61% of red cell units were transfused to medical patients and 36% to surgical patients, although there was much variation between hospitals. The organization and activities of PBM in the seven hospitals were variable, but there was a common focus on optimizing the treatment of bleeding patients, monitoring the use of blood components and treatment of preoperative anaemia. CONCLUSION: Although the seven hospitals provide a similar range of clinical services, there was variation in transfusion rates between them. Further, there was variable implementation of PBM activities and monitoring of transfusion practice. These findings provide a baseline to develop joint action plans to further implement and strengthen PBM across a number of hospitals in Europe.

Treatment of postoperative bleeding after fondaparinux with rFVIIa and tranexamic acid.

Treatment of a haemorrhagic shock after just a single dose of fondaparinux in an orthopaedic patient with reduced renal clearance is presented. Since all routine haemostatic parameters were nearly normal, single doses of rFVIIa (90 microg/kg) and of tranexamic acid (15 mg/kg) were administered to improve thrombin generation and reduce fibrinolysis. This case is the first showing the effectiveness of combining single doses of rFVIIa and tranexamic acid in controlling severe postoperative bleeding after fondaparinux.

Early infections in adults undergoing matched related and matched unrelated/mismatched donor stem cell transplantation: a comparison of incidence.

We compared the incidence of early infectious complications between matched related (MR) and matched unrelated/mismatched (MU/MM) allogeneic stem cell transplant (allo-SCT) recipients in a single centre over a 6-year period in 214 consecutive adult patients. Early infections were defined as occurring from hospital admission for SCT until discharge. One hundred and fifty-nine patients received an allograft from MR donors and 55 patients received MU/MM allo-SCT. One hundred and eight of 214 patients had 147 episodes of fever. Ninety-three episodes (63%) were due to clinically or microbiologically documented infections and 54 episodes (37%) to fever not related to infection. Patients undergoing MU/MM transplantation tended to have more documented infections compared to recipients of MR allo-SCT (P = 0.06). Significantly more MU/MM transplant recipients had breakthrough infections with Herpes simplex virus type 1 (HSV-1, P = 0.003), and more CMV reactivation (P = 0.015). The mortality rate in all patients during hospitalisation post-SCT was 6.3% in MR and 18.2% in MU/MM allo-SCT recipients (P = 0.009). Early mortality was associated with infection in 70% of the patients, with a similar distribution between MR and MU/MM transplant recipients. However, MU/MM transplant recipients had significantly more early deaths due to toxic causes (P < 0.001). We conclude that early post-transplant MU/MM transplant recipients tend to have more documented infections, and have significantly more breakthrough infections with HSV-1 and more CMV reactivation. MU/MM transplant recipients are at higher risk of early mortality, especially due to toxic causes.

Infectious gastro-enteritis: an uncommon cause of diarrhoea in adult allogeneic and autologous stem cell transplant recipients.

The incidence and aetiology of acute diarrhoea in 60 adult allogeneic or autologous stem cell transplant (SCT) recipients was determined in a prospective study. Stool specimens were obtained prior to SCT and on days +20, +40, +60 and +100 post transplant. Microbiological evaluation was performed for pathogenic bacteria, fungi, parasites and viruses. Forty-seven patients were evaluable of whom 31 had a total of 48 acute diarrhoeal episodes. Diarrhoea occurred in 79% of allogeneic and 47% of autologous SCT recipients (P < 0.05). Intestinal infections were found in three of 48 (6%) diarrhoeal episodes. Clostridium difficile with positive toxin was cultured twice and one stool specimen was positive for cryptosporidium. Intestinal pathogens were identified in 13 out of 172 stool specimens from asymptomatic patients and included: rotavirus (4), adenovirus (3), C. difficile, toxin positive (2), and others (4). Graft-versus-host disease was confirmed by biopsy in two of 36 episodes of diarrhoea in allogeneic patients, and in three patients a relationship between reactivation of cytomegalovirus and diarrhoea was suspected. In 40 of 48 (83%) episodes of diarrhoea no clear aetiology could be found.

Piperacillin/tazobactam therapy for diabetic foot infection.

In this study, 29 patients were hospitalized with a diabetic foot infection and were treated with piperacillin/tazobactam. Of these 23 patients who were evaluated for efficacy of treatment, 22 patients improved or were clinically cured. In seven patients (30%), there was persistence of one of the baseline pathogens. Adverse events were reported in 15 patients (58%), three of which were serious. Piperacillin/tazobactam may be useful as monotherapy in diabetic foot infection giving an adequate clinical response and the level of side effects equivalent to those of other broad-spectrum antibiotics.

[Villous adenoma of Vater's papilla; a therapeutic dilemma]. / Het villeuze adenoom van de papil van Vater; een therapeutisch dilemma.

After a cholecystectomy in 1980, local excision of a villous adenoma of the ampulla of Vater was performed in 1983 in a 69-year-old female; this had to be repeated in 1990 because of recurrence. In case of a tumour of this kind, pancreaticoduodenectomy should be considered because of the relatively high risk of recurrence or malignant degeneration. After a radical local excision regular duodenal endoscopy and if possible endoscopic ultrasonography should be performed.

[Diagnostic and pharmaco-therapeutic options in acute severe blood loss]. / Diagnostische en farmacotherapeutische opties bij acuut ernstig bloedverlies.

In patients with excessive blood loss, coagulation is compromised by hypothermia, metabolic acidosis due to impaired tissue perfusion, loss of coagulation factors and platelets while their consumption is increased, and by massive infusion with plasma expanders. Currently available laboratory tests are insufficiently reliable and too time-consuming to enable the evaluation of the effect of pharmaco-therapeutic interventions during severe blood loss. Several haemostatic drugs appear to be effective in the treatment of blood loss after elective surgery, but have been insufficiently investigated in patients with severe bleeding. A rational transfusion policy entailing the use of sufficient amounts of plasma is necessary in the treatment of patients with severe bleeding.

Long-term infectious complications and their relation to treatment duration in catheter-related Staphylococcus aureus bacteremia.

The optimal duration of treatment for catheter-related Staphylococcus aureus bacteremia is not known. Short courses (< or = 2 weeks) of therapy should be viewed with caution because essential data on late complications, such as osteomyelitis and metastatic abscesses, are lacking. This study represents a retrospective analysis of the data from 49 adult patients hospitalised in the period 1994-1996 (mean age, 57 years; range, 20-90 years; 47% male) and from whom Staphylococcus aureus was cultured concomitantly from peripheral blood and catheter segments. Forty-six venous catheters, two arterial catheters, and one unknown type of catheter were used. Forty-four patients were treated with effective anti-Staphylococcus aureus antibiotics. Twenty patients had a favourable outcome, defined as no complication and no death during 1 year of follow-up, 24 patients had complications, 14 patients died due to attributable mortality, and 5 other patients died of an underlying disease without showing signs or symptoms of a complication. Patients were categorised according to the duration of treatment. There were small differences between a shorter (1-14 days) and a longer (>14 days) course of antibiotics with regard to favourable outcome (41% vs. 33%), complications (48% vs. 53%), attributable death (31% vs. 20%), and death due to underlying disease (41% vs. 33%), respectively. The rates of complications and death were high, but a definite conclusion cannot be drawn because the study was underpowered. More randomised trials are needed, but, until the results of such trials are available, the duration of therapy should not be shortened to less than 14 days.

Applicability of a real-time quantitative PCR assay for diagnosis of respiratory syncytial virus infection in immunocompromised adults.

Respiratory syncytial virus (RSV) accounts for the majority of respiratory virus infections, producing high mortality rates in immunocompromised patients with hematologic malignancies. The available methods for the rapid detection of RSV by antigen detection or PCR either lack sensitivity, require complex laboratory manipulation, or have not been evaluated in this patient population. To assess the applicability of a TaqMan-based real-time PCR technique for the detection of RSV A and B in immunocompromised adults, we developed a rapid, sensitive detection method that simultaneously detects RSV A and B and can be applied in routine diagnostics. The specificity of the assay was assessed using a panel of reference strains of other respiratory viruses and RSV. Electron microscopy-counted stocks of RSV A and B were used to develop a quantitative PCR format. Eleven copies of viral RNA could be detected for RSV A strain Long, and 14 copies could be detected for RSV B strain 9320, corresponding to 50% tissue culture infective doses of 0.86 and 0.34, respectively. The assay was evaluated on 411 combined nose and throat swabs derived from immunocompromised adults with or without signs of respiratory tract infection. The diagnostic efficacy of the TaqMan PCR determined on the clinical samples showed that this real-time PCR technique was substantially more sensitive than the combination of conventional viral culture and shell vial culture. None of the clinical specimens derived from patients without signs of respiratory illness were found to be positive for RSV by real-time TaqMan PCR.