A survey of characteristics and current educational needs of hemophilia treatment centers within Asia Pacific.

BACKGROUND: Poor disease understanding and gaps in expertise regarding hemophilia care have been identified at all levels in Asia Pacific. Continued education for involved healthcare professionals (HCPs) is crucial for improved delivery. OBJECTIVES: To identify training and educational needs of hemophilia HCPs in Asia Pacific. METHODS: Clinicians working at hemophilia treatment centers (HTCs), identified from the World Federation of Hemophilia Directory, were contacted by the Asia Pacific Hemophilia Working Group (APHWG). An electronic survey was sent to 161 centers from 15 countries for which HTC identification was complete to assess HTC characteristics, educational status, and needs. Responses were stratified by national economic capacity. RESULTS: From March 23 to June 6, 2016, clinicians from 58 HTCs completed the survey. Most reported availability of specialists to serve core patient requirements, although availability of trained nurses and geneticists was low in lower-middle income countries (LMICs). Although 98.3% of HTCs had laboratory facilities, 8.8% do not participate in any quality assessment schemes. The most common limitations of current initiatives were infrequency and lack of local language content. Education is currently mostly received via internet, particularly among LMICs and upper-middle income countries (UMICs), though there is strong preference for meetings. Main barriers to receiving education were funding and time constraints. Unique priority topics were musculoskeletal management, quality of life and management by non-hematologists (high-income countries), inhibitor management and research (UMICs), and outcomes assessment (LMICs). CONCLUSION: In Asia Pacific, training programs should be tailored according to unique needs of differing economic capacities and resource settings.

Nijmegen-Bethesda assay to measure factor VIII inhibitors.

Hemophilia A is an inherited bleeding disorder caused by a deficiency of factor VIII coagulant activity (FVIII:C). Patients are treated with infusions of either plasma-derived or recombinant factor VIII. However, some patients develop inhibitory antibodies (inhibitors) to infused factor VIII which render it ineffective. The original Bethesda method was developed to standardize measurement of inhibitors in a factor VIII neutralization assay. One Bethesda unit is defined as that amount of inhibitor that results in 50% residual FVIII:C activity of a defined test mixture. In the Nijmegen modification of the original Bethesda method, the pH and the protein concentration of the test mixture is further standardized. As a result, the FVIII:C in the test mixture is less prone to artifactual deterioration and the test has improved specificity. Even with a standardized procedure a number of factors can affect the performance of the test and it is important for laboratory staff to be aware of their impact on the result outcome.

The unrecognized psychosocial factors contributing to bleeding risk in warfarin therapy.

BACKGROUND AND PURPOSE: Warfarin is an effective drug for the prevention of thromboembolism in the elderly. The major risk for patients taking warfarin is bleeding. We aimed to assess the impact of psychosocial factors, including mood, cognition, social isolation, and health literacy on warfarin instability among community-based elderly patients. METHODS: A case-control study was conducted between March 2008 and June 2009 in a community-based setting. Cases were patients previously stabilized on warfarin who recorded an international normalized ratio≥6.0. Control subjects were patients whose international normalized ratio measurement was maintained within the therapeutic range. Patient interviews investigated potential predisposing factors to elevated International Normalized Ratio levels. RESULTS: A total of 486 patients were interviewed: 157 cases and 329 control subjects, with an approximate mean age of 75 years. Atrial fibrillation was the most common primary indication. Adjusted multivariate logistic regression revealed impaired cognition (OR, 1.9; 95% CI, 1.0 to 3.6), depressed mood (OR, 2.2; 95% CI, 1.2 to 3.9), and inadequate health literacy (OR, 4.0;95% CI, 2.1 to 7.4) were associated with increased risk of an elevated International Normalized Ratio. CONCLUSIONS: This study identified impaired cognition, depressed mood, and inadequate health literacy as risk factors for warfarin instability. These had a similar impact to well-recognized demographic, clinical, and medication-related factors and are prevalent among the elderly. These findings suggest that elderly patients prescribed warfarin should be reviewed regularly for psychosocial deficits.

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.

Age of red blood cells and mortality in the critically ill.

INTRODUCTION: In 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. METHODS: We 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. RESULTS: Compared 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). CONCLUSIONS: In 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.

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.

A consensus statement on the management of pregnancy and delivery in women who are carriers of or have bleeding disorders.

Pregnancy and delivery are critical times for women with bleeding disorders, with mothers, and possibly their affected infants, being exposed to a variety of haemostatic challenges. Management of women with bleeding disorders during pregnancy involves a multidisciplinary team including, but not limited to, an obstetrician, an anaesthetist and a haematologist. This consensus document from the Australian Haemophilia Centre Directors' Organisation (AHCDO) provides practical information for clinicians managing women with bleeding disorders during pregnancy. Included are: the expected physiological response in pregnancy in such women; management of pregnancy, labour and delivery, as well as obstetric anaesthesia issues, postpartum care, and reducing and treating postpartum haemorrhage; and management of infants at risk of a bleeding disorder and of bleeding in neonates. The guidelines were developed after extensive consultation, face-to-face meetings and revisions. The final document represents a consensus opinion of all AHCDO members. Where evidence is lacking, recommendations are based on clinical experience and consensus opinion.

Development and management of systemic lupus erythematosus in an HIV-infected man with hepatitis C and B co-infection following interferon therapy: a case report.

INTRODUCTION: The association of human immunodeficiency virus and immune dysfunction leading to development of autoimmune markers is well described, but human immunodeficiency virus infection is relatively protective for the development of systemic lupus erythematosus. In contrast, development of systemic lupus erythematosus with hepatitis C and with interferon therapy is well described in a number of case reports. We here describe the first case of systemic lupus erythematosus developing in a man infected with human immunodeficiency virus, hepatitis C and hepatitis B co-infection where the onset seems to have been temporally related to interferon therapy. CASE PRESENTATION: We report the occurrence of systemic lupus erythematosus complicating interferon-alpha therapy for hepatitis C in a 47-year-old asplenic male with haemophilia co-infected with human immunodeficiency virus and hepatitis B. He presented with a truncal rash, abdominal pains and headache and later developed grade IV lupus nephritis requiring haemodialysis, mycophenolate mofetil and steroid therapy. We were able to successfully withdraw dialysis and mycophenolate while maintaining stable renal function. CONCLUSION: Interferon-alpha is critical in antiviral immunity against hepatitis C but also acts as a pathogenic mediator for systemic lupus erythematosus, a condition associated with activation of plasmacytoid dendritic cells that are depleted in human immunodeficiency virus infection. The occurrence of auto-antibodies and lupus-like features in the coinfections with hepatitis C require careful assessment. Immunosuppressant therapy for lupus risks exacerbating underlying infections in patients with concurrent human immunodeficiency virus, hepatitis B and C.

Who is responsible for the care of patients treated with warfarin therapy?

OBJECTIVE: To identify potential weaknesses in the system of managing warfarin therapy. DESIGN, PARTICIPANTS AND SETTING: A structured interview-based study of 40 community-dwelling patients taking warfarin and with an international normalised ratio > or = 6.0 and 36 of their treating doctors (35 general practitioners and 1 specialist), conducted between July and November 2007. Patients all received services from and were recruited sequentially by a large, private metropolitan pathology provider in Melbourne. MAIN OUTCOME MEASURES: Patients' demographic, clinical, cognitive and psychosocial characteristics, warfarin knowledge, medication complexity and adherence; and doctors' experience with, approach to and involvement in warfarin management, and their perception of responsibility for warfarin management and patient education. RESULTS: Interviews revealed multiple difficulties, including cognitive dysfunction, possible depression, and medication non-adherence, in 30 of 40 patients. Of 36 doctors interviewed, 12 were unaware of these difficulties in their patients. Five doctors considered they had sole responsibility for their patients' anticoagulation, while 15 confirmed a mutual relationship with the pathology service, and 16 deferred total responsibility to the pathology provider. Only 14/36 doctors reported conducting patient education at commencement of warfarin therapy, with the other 22 stating this was the responsibility of the initiating specialist, pathology service or dispensing pharmacist. CONCLUSIONS: There is a need for improved role clarification in coordinating warfarin management. We propose exploring the possibility of a Warfarin Suitability Score to assist better recognition of patients in whom treatment may be problematic, along with a model of care using practice nurses with GPs to facilitate optimal patient care.

Mis-identification of factor inhibitors by diagnostic haemostasis laboratories: recognition of pitfalls and elucidation of strategies. A follow up to a large multicentre evaluation.

AIMS: We previously reported the ability of diagnostic haemostasis facilities to identify coagulation factor abnormalities and inhibitors, through a large multi-centre study conducted on behalf of the Royal College of Pathologists of Australasia (RCPA) Quality Assurance Program (QAP). In the current report, additional data evaluation aims to (1) help identify the reasons behind the failures in inhibitor identification, (2) highlight the pitfalls in inhibitor testing, and (3) help elucidate some strategies for overcoming these problems and to assist in better identification and characterisation of inhibitors. METHODS: Forty-two laboratories blind tested a set of eight samples for the presence or absence of inhibitors. These included true factor inhibitors (FVIII and FV), and other samples that reflected potential pre-analytical variables (e.g., heparin contamination, serum, EDTA plasma, aged plasma) that might arise and complicate inhibitor detection or lead to false inhibitor identification. RESULTS: There was a wide scatter of inhibitor results, with false positive and false negative inhibitor identification, and mis-identification of inhibitors (e.g., FVIII inhibitor identified where FV inhibitor present). Further analysis of the pattern of reported laboratory results, including routine coagulation testing and factor profiles, allowed some additional interpretative power to provide strategies that will assist laboratories to improve the accuracy of inhibitor identification in the future. CONCLUSIONS: There are currently occasional lapses in factor inhibitor identification, which this report will hopefully help address.

2B or not 2B? Disparate discrimination of functional VWF discordance using different assay panels or methodologies may lead to success or failure in the early identification of type 2B VWD.

Laboratory proficiency in the identification of functional von Willebrand factor (VWF) discordance in type 2B von Willebrand disease (VWD) was assessed by external quality assurance surveys conducted by the RCPA Haematology QAP, and using six different type 2B VWD plasma samples (three historical and three previously unpublished) tested by up to 52 laboratories. For the three most recent samples, functional VWF discordance was either not identified in testing or by interpretation with misidentification as 'normal' or 'type 1 VWD', on average for 25.7% of test occasions when laboratories performed VWF:Ag and VWF:RCo as their primary VWF test panel, but somewhat fewer occasions (10.9%) for laboratories that incorporated VWF:CB as an additional functional VWF assay. VWF assay sub-methodologies also influenced the appropriate identification of samples as potentially type 2 VWD, and VWF functional discordance was more consistently identified when laboratories used (i) automated platelet agglutination for VWF:RCo compared to classical platelet aggregometry, (ii) inhouse VWF:CB assays compared to commercial kit methods, and (iii) automated LIA-based 'VWF:Activity' assays compared to ELISA based assays. We conclude that:(i) laboratories are generally proficient in tests for VWD but interpretative diagnostic errors do occur; (ii) correct diagnosis is more likely when test panels are more comprehensive and include the VWF:CB; (iii) sub-methodology influences the appropriate identification of VWF functional discordance. On the basis of these findings, we provide a series of recommendations to enable the appropriate laboratory identification of VWD, in particular type 2B VWD.

The safety and efficacy of enfuvirtide therapy for HIV infection in patients with hemophilia: a case series.

The treatment of patients with human immunodeficiency virus (HIV) infection and hemophilia involves unique challenges that may be addressed with novel antiretroviral classes. We describe the safety and efficacy of enfuvirtide therapy in 4 patients with severe hemophilia A. Although local skin reactions were common, neither local nor systemic bleeding worsened. Three patients achieved undetectable HIV loads with enfuvirtide salvage regimens.

Massive blood transfusion and trauma resuscitation.

AIMS: To review the massive transfusion practice at a Level I adult Trauma Centre during initial trauma reception and resuscitation. METHODS: All trauma patients presenting to The Alfred Emergency & Trauma Centre and receiving a transfusion of five units or more of packed red blood cells within 4h of presentation over a 26-month period were included in this study. Patient demographics, clinical characteristics, injuries, surgical management and volume of blood transfused were analysed with mortality as the primary endpoint. Initial clinical features and injuries predictive of massive transfusion were also analysed. RESULTS: There were 119 patients who received a transfusion of five units or more of packed red blood cells (PRBCs) within 4h of presentation. The median Injury Severity Score of this group of patients was 34.0 (IQR 26-48) and mortality was 27.7%. The median number of packed red blood cell transfused was 8.0 (IQR 6-14) in the 1st 4h. Initial clinical features and injuries independently associated with a larger volume of blood transfused were initial hypotension, fractures of the pelvis, kidney injuries, initial acidaemia, and thrombocytopaenia. The Injury Severity Score, initial coagulopathy measured by APTT and the presence of head injuries were the independent predictors of mortality. CONCLUSIONS: The volume of blood transfused during trauma resuscitation was not found to be an independent predictor of mortality. Prospective studies into transfusion practice and clinical features of patients during the trauma resuscitation phase requiring massive transfusion are needed to establish evidence-based guidelines for massive transfusion.

Comparison of the pharmacokinetics of two von Willebrand factor concentrates [Biostate and AHF (High Purity)] in people with von Willebrand disorder. A randomised cross-over, multi-centre study.

Plasma-derived factor concentrates are important in the management of von Willebrand disorder (VWD). In our geographic locality, a single viral inactivation step concentrate (AHF [High Purity]), has been replaced with one using a double viral inactivation step (Biostate). The aim of this study was to compare the pharmacokinetics of von Willebrand factor (VWF) and factor VIII (FVIII) after administration of AHF (High Purity) and Biostate. This study was a single-blind, randomised cross-over, multi-centre investigation in twelve people with VWD, comprising four type 3, two type 2B, one type 2M and five type 1 VWD. The subjects received a single infusion of 60 IU/kg ristocetin cofactor activity (VWF:RCo) of either AHF (High Purity) or Biostate, and after a minimum 15-day wash-out period they received the alternative product. Blood samples were collected for up to 48 hours after each dose for assay of FVIII coagulant activity (FVIII:C) and VWF by VWF:RCo, collagen binding capacity (VWF:CB) and antigen (VWF:Ag). As a measure of delivered VWF 'functionality' we calculated the area-under-the-concentration-time-curve (AUC) ratios of VWF:RCo to VWF:Ag and VWF:CB to VWF:Ag. The effect on platelet adhesiveness by PFA-100 closure times (CTs) was measured prior to and 30 minutes post infusion. VWF multimers were also assessed pre and post infusion. Pharmacokinetic parameters after AHF (High Purity) and Biostate were in close agreement for VWF:RCo (confirming dosing equivalence). Parameters for other study markers were also similar, although Biostate tended to yield relatively lower VWF:Ag and higher VWF:CB levels. Although AHF (High Purity) and Biostate resulted in similar levels of high-molecular-weight (HMW) multimers post-infusion, the relative level of HMW to low-molecular-weight (LMW) multimers were determined to be higher following Biostate. The relative levels of functional VWF (i.e. VWF:CB and VWF:RCo) to VWF:Ag were also higher in Biostate compared to AHF (High Purity). With both study products, PFA-100 CTs 30 minutes post infusion showed minor improvement for only some subjects. In conclusion, the pharmacokinetics of FVIII:C and VWF are not significantly different after administration of AHF (High Purity) and Biostate. Study parameters considered as 'in-vitro' markers of VWF 'functionality' or potential clinical efficacy (i.e. VWF:CB and VWF:RCo relative to VWF:Ag, level of HMW VWF relative to LMW-VWF) were determined to be higher for Biostate than AHF (High Purity). PFA-100 CTs did not adequately reflect changes in these VWF parameters. Based on these results, one would expect Biostate to be at least as effective, if not superior to AHF (High Purity) for the treatment of VWD.

AIDS-related plasmablastic lymphoma of the oral cavity associated with an IGH/MYC translocation--treatment with autologous stem-cell transplantation in a patient with severe haemophilia-A.

Plasmablastic lymphoma is an AIDS related lymphoma that continues to have a poor prognosis despite significant advances in the management of HIV and lymphoproliferative diseases. In part this has been due to limited insights into the biology of this disease and the molecular mechanisms of oncogenesis. To date molecular abnormalities have not been described in plasmablastic lymphoma, and its aggressive clinical behaviour has been difficult to understand. We describe the first reported cytogenetic abnormality in plasmablastic lymphoma, an IgH/MYC translocation. It is also the first description of autologous stem cell transplantation in a patient with severe haemophilia A.

Reducing errors in identification of von Willebrand disease: the experience of the royal college of pathologists of australasia quality assurance program.

Regular multilaboratory surveys of laboratories derived primarily from Australia, New Zealand, and Southeast Asia have been conducted during the last 8 years to evaluate testing proficiency in the diagnosis of von Willebrand disease (vWD). We summarize and update the findings of these surveys with a particular emphasis on diagnostic errors and error rates associated with particular tests or test panel limitations. A total of 43 plasma samples have been dispatched to survey participants. These have included 13 normal samples, five type 1 vWD samples, eight type 2 vWD samples (three 2A, three 2B, one 2M, and one 2N), and four type 3 vWD samples. In addition to numerical test results, participant laboratories (currently, n = 49) were asked to provide diagnostic interpretations regarding results, and whether or not vWD was suggested, and if so, a probable subtype. Although laboratories usually provided correct interpretative responses, diagnostic errors occurred in a substantial number of cases. On average, type 1 vWD plasma was misidentified as type 2 vWD in 13.3% of cases, and laboratories performing von Willebrand factor (vWF):ristocetin cofactor activity (RCo) without vWF:collagen-binding activity (CB) were seven times more likely to make such an error compared with those performing vWF:CB. Similarly, type 2 vWD plasma was misidentified as type 1 or type 3 vWD in an average of 20.1% of cases, and laboratories performing vWF:RCo without vWF:CB were three times more likely to make such an error compared with those performing vWF:CB. Finally, normal plasma was misidentified as vWD in an average of 6.7% of cases, and laboratories performing vWF:RCo without vWF:CB were four times more likely to make such an error compared with those performing vWF:CB. We conclude that although laboratories are generally proficient in tests for vWD, diagnostic errors do occur and error rates are substantially reduced when test panels are more comprehensive and include the vWF:CB.

Identification of factor inhibitors by diagnostic haemostasis laboratories: a large multi-centre evaluation.

We have assessed the proficiency of diagnostic haemostasis facilities to correctly identify coagulation factor abnormalities and inhibitors. Forty-two laboratories participating in the external Quality Assurance Program (QAP) conducted by the RCPA agreed to participate and were each sent a set of eight samples (each 3 x 1 ml) for evaluation. They were asked to blind test these samples for the presence or absence of inhibitors, and where identified, to perform further analysis (including specific inhibitor analysis). In order to make the exercise more challenging, in addition to true factor inhibitors, samples were provided that reflected potential pre-analytical variables that might arise and complicate inhibitor detection or lead to false inhibitor identification. In brief, the sample set comprised a true high level factor (F) V inhibitor, a true moderate level FVIII inhibitor (but sample was defibrinogenated), a true lupus anticoagulant (LA), a normal (but slightly aged) plasma sample, a normal serum sample, a normal EDTA sample, an oral anticoagulant/vitamin K deficiency sample, and a gross heparin ( approximately 10 U/ml) contaminated sample. Sixty-three percent of participants correctly identified the true FV inhibitor as such, although the reported range varied greatly [10 to >250 Bethesda units (BU/ml)] and 46% correctly identified the true FVIII inhibitor, despite the complication of the sample presentation, although the reported range also varied (7 to 64 BU/ml). Some laboratories either failed to identify the inhibitor present, or misidentified the inhibitor type. The LA, the oral anticoagulant/vitamin K deficiency, the normal serum sample, and the normal (aged) sample were also correctly identified by most laboratories, as was the absence of specific factor inhibitors in these samples. However, a small subset of laboratories incorrectly identified the presence of specific factor inhibitors in some of these samples. The heparin sample was also correctly identified by most (68%) laboratories. In contrast, the normal EDTA sample was misidentified as a FV and/or FVIII inhibitor by most (68%) laboratories, and only one laboratory correctly identified this as an EDTA sample. Thus, we conclude that although laboratories are able, in most cases, to identify the presence of true factor inhibitors, there is a large variation in identified inhibitor levels and there are also some significant errors in identification (i.e. false negatives and misidentifications). In addition, there is a significant false positive error rate where some laboratories will identify the presence of specific factor inhibitors where no such inhibitor exists (i.e. false positives).