Unilateral inguinofemoral lymphadenectomy in patients with early-stage vulvar squamous cell carcinoma and a unilateral metastatic sentinel lymph node is safe.

OBJECTIVE: Optimal management of the contralateral groin in patients with early-stage vulvar squamous cell carcinoma (VSCC) and a metastatic unilateral inguinal sentinel lymph node (SN) is unclear. We analyzed patients who participated in GROINSS-V I or II to determine whether treatment of the contralateral groin can safely be omitted in patients with a unilateral metastatic SN. METHODS: We selected the patients with a unilateral metastatic SN from the GROINSS-V I and II databases. We determined the incidence of contralateral additional non-SN metastases in patients with unilateral SN-metastasis who underwent bilateral inguinofemoral lymphadenectomy (IFL). In those who underwent only ipsilateral groin treatment or no further treatment, we determined the incidence of contralateral groin recurrences during follow-up. RESULTS: Of 1912 patients with early-stage VSCC, 366 had a unilateral metastatic SN. Subsequently, 244 had an IFL or no treatment of the contralateral groin. In seven patients (7/244; 2.9% [95% CI: 1.4%-5.8%]) disease was diagnosed in the contralateral groin: five had contralateral non-SN metastasis at IFL and two developed an isolated contralateral groin recurrence after no further treatment. Five of them had a primary tumor ≥30 mm. Bilateral radiotherapy was administered in 122 patients, of whom one (1/122; 0.8% [95% CI: 0.1%-4.5%]) had a contralateral groin recurrence. CONCLUSION: The risk of contralateral lymph node metastases in patients with early-stage VSCC and a unilateral metastatic SN is low. It appears safe to limit groin treatment to unilateral IFL or inguinofemoral radiotherapy in these cases.

2019 IUSTI-Europe guideline for the management of anogenital warts.

This guideline is an update of the 2011 European Guideline for the Management of Anogenital Warts. It is intended to support best practice in the care of patients with anogenital warts by including evidence-based recommendations on diagnosis, treatment, follow-up and advice to patients. It is intended for use by healthcare professionals in sexual healthcare or dermato-venereology clinics in Europe but may be adapted for use in other settings where the management of anogenital warts is undertaken. As a European guideline, recommendations should be adapted according to national circumstances and healthcare systems. Despite the availability of vaccine to prevent HPV types 6 and 11, the cause of >95% anogenital warts, they remain an important and frequent health problem. The previous systematic review of randomized controlled trials for anogenital warts was updated. The changes in the present guideline include the following: Updated background information on the prevalence, natural history and transmission of human papillomavirus (HPV) infection and anogenital warts. Key recommendations for diagnosis and treatment have been graded according to the strength of the recommendation and the quality of supporting evidence. 5-fluorouracil, local interferon and photodynamic therapy have been evaluated and included as potential second-line treatment options. Evidence of the impact of HPV vaccination on the incidence of anogenital warts has been updated.

Patient-centred value framework for haemophilia.

INTRODUCTION: Growing budgetary demands have led to increased scrutiny of healthcare spending for rare diseases, leading to a unified goal within the haemophilia community to define objectively patient-centred value in haemophilia care. AIM: To develop a patient-centred outcomes framework with global applicability for assessing value in haemophilia healthcare. METHODS: An international, multidisciplinary panel of experts convened to identify the range of patient impacts of haemophilia health care and organize these into a three-tiered, patient-centred outcomes framework based on Porter's model for assessing value. RESULTS: In addition to measures common to other chronic diseases (eg survival and quality of life), Tier 1, health status achieved or retained, includes haemophilia-specific outcomes of bleeding frequency, musculoskeletal complications and life-threatening bleeds, as well as measures of function or activity. Tier 2, process of recovery, includes such outcomes as time to initial treatment, time to recovery and time missed at education/work; also included are disutility of care, measured by inhibitor development, pathogen transmission/infections, orthopaedic intervention and difficult venous access. Tier 3, sustainability of health, is measured by bleed avoidance, maintenance of productive lives and good health over time; potential long-term negative consequences include insufficient or inappropriate therapy and age-related complications. The applicability of the outcomes framework for different types of haemophilia healthcare interventions is described. CONCLUSION: Haemophilia health care can affect multiple patient-centred outcomes across diverse patient types and healthcare systems. This framework organizes those outcomes for informing value-based decision making by multiple stakeholders and provides the basis for further refinement and development of a standardized outcomes set.

The changing face of an epidemic: healthy old age with HIV.

The demographics of the HIV epidemic in the UK have changed significantly. Owing to a steady rate of new diagnoses and improved survival, the population of individuals living with HIV continues to increase. HIV is now widely considered to be a chronic condition and HIV-positive individuals are expected to live into old age. Increasing rates of age-related comorbidities challenge HIV care providers to deliver durable viral suppression, ensure long-term adherence to antiretroviral treatment and promote wellbeing into old age. High rates of mental health disorders and social stigma continue to have a negative impact on the quality of life of people living with HIV. Models of care must adapt to this evolving epidemic.

Estimating the potential cost of a high dose immune tolerance induction (ITI) therapy relative to the cost of a combined therapy of a low dose ITI therapy with bypassing agent prophylaxis.

INTRODUCTION: The International Immune Tolerance Study (I-ITI) demonstrated comparable success rates between low (FVIII 50 IU/kg/TIW) and high dose (FVIII 200 IU/kg/day) regimens. While costlier, the high dose ITI regimen achieved shorter time-to-treatment success with fewer bleeding episodes compared to the low dose ITI regimen. Adding bypassing agent prophylaxis (BAP) to a low dose ITI regimen may reduce bleeding while still being less costly than high dose ITI. AIM AND METHODS: An economic model was developed to compare high dose ITI to low dose ITI with BAP. All model inputs were derived from clinical trials. The I-ITI study indicated a median time to negative inhibitor titre of 4.6 and 9.2 months and average number of bleeds/patient of 4.2 and 9.9 for the high and low dose regimens respectively. Based on the BAP trials, aPCC (85 U/kg/TIW) and rFVIIa (90 µg/kg/day) achieved a 62% and 45% reduction in bleeding frequency respectively. Cost analysis was from a US third party payer perspective and limited to drug costs. One-way, two-way and probabilistic sensitivity analyses were performed. RESULTS: Costs of low dose ITI with aPCC prophylaxis until negative inhibitor titre is achieved was 24.0% less compared to high dose ITI. Low dose ITI with rFVIIa prophylaxis cost 46.5% more compared to high dose ITI. Model results were robust in the majority of the sensitivity analyses. CONCLUSION: A low dose ITI regimen with aPCC prophylaxis may be cost saving compared to a high dose ITI regimen with the potential to reduce morbidity by lowering the risk for breakthrough bleeds.

Use of plasma human herpesvirus-8 viral load measurement: evaluation of practice in three UK HIV treatment centres.

A retrospective audit of plasma human herpesvirus-8 (HHV-8) viral load testing was performed in three HIV treatment centres over 24 months. Reasons for testing (360 tests) were: symptoms of systemic inflammatory response syndrome (SIRS) (fever, lymphadenopathy and raised inflammatory markers); monitoring in known HHV-8 pathology other than Kaposi sarcoma (KS); investigation of known/suspected KS, and other/no reason. Of patients with multicentric Castleman disease (MCD), 14/16 (88%) had detectable plasma HHV-8, as did 27/45 (60%) with biopsy proven or clinically confirmed KS, and 6/19 (32%) with lymphoma. Neither of the two patients with MCD and no detectable HHV-8 had SIRS symptoms at the time of the test. There was wide variation between centres in the indications prompting HHV-8 testing, with a more conservative approach resulting in a higher proportion of positive results. Measuring plasma HHV-8 in the absence of SIRS symptoms, established HHV-8 disease monitoring, or confirmed/suspected KS is unlikely to yield detectable HHV-8 thus allowing potential cost savings.

Complications of haemophilia in babies (first two years of life): a report from the Centers for Disease Control and Prevention Universal Data Collection System.

AIM: To describe the prevalence and complications in babies ≤2 years with haemophilia. METHODS: We used a standardized collection tool to obtain consented data on eligible babies aged ≤2 years with haemophilia enrolled in the Centers for Disease Control and Prevention Universal Data Collection System surveillance project at US Hemophilia Treatment Centers (HTCs). RESULTS: Of 547 babies, 82% had haemophilia A, and 70% were diagnosed within one month of birth. Diagnosis was prompted by known maternal carrier status (40%), positive family history (23%), bleeding (35%) and unknown 2%; 81% bled during the first two years. The most common events were bleeding (circumcision, soft tissue, oral bleeding) and head injury. There were 46 episodes of intracranial haemorrhage (ICH) in 37 babies (7%): 18 spontaneous, 14 delivery related, 11 traumatic, 2 procedure related and 1 unknown cause. Of the 176 central venous access devices (CVADs) in 148 (27%) babies, there were 137 ports, 22 surgically inserted central catheters and 20 peripherally inserted central catheters. Ports had the lowest complication rates. Inhibitors occurred in 109 (20%) babies who experienced higher rates of ICH (14% vs. 5%; P = 0.002), CVAD placement (61% vs. 19%; P < 0.001) and CVAD complications (44% vs. 26%; P < 0.001). The most common replacement therapy was recombinant clotting factor concentrates. CONCLUSION: Bleeding events in haemophilic babies ≤2 years were common; no detectable difference in the rates of ICH by the mode of delivery was noted. Neonatal factor exposure did not affect the inhibitor rates. Minor head trauma, soft tissue and oropharyngeal bleeding were the leading indications for treatment.

Rare coagulation disorders: fibrinogen, factor VII and factor XIII.

Rare coagulation disorders (RCDs) include the inherited deficiencies of fibrinogen, factor (F) II, FV, combined FV and VIII, FVII, FX, combined FVII and X, FXI, FXIII and combined congenital deficiency of vitamin K-dependent factors (VKCFDs). Despite their rarity, a deep comprehension of all these disorders is essential to really understand haemostasis. Indeed, even if they share some common features each RCD has some particularity which makes it unique. In this review, we focus on three disorders: fibrinogen, FVII and FXIII.

Pharmacokinetic characterization of recombinant factor XIII (FXIII)-A2 across age groups in patients with FXIII A-subunit congenital deficiency.

Three trials investigated the pharmacokinetics (PK) of recombinant factor XIII (rFXIII) A-subunit. To compare the PK characteristics of rFXIII among trials and different age groups of patients. Dosing with rFXIII 35 IU kg(-1) every 4th week. Blood samples for PK assessments were collected regularly throughout the dosing interval from a total of 68 individual patients with FXIII congenital deficiency. The mean PK parameters were similar across the three age groups, and for the three trials, as well as constant over time based on results from patients participating in both mentor 1 and mentor 2 trials. The geometric mean half-life ranged from 11.6 to 15.0 days, and the trough FXIII activity levels ranged from 0.15 to 0.21 IU mL(-1) . The population PK model identified body weight as a statistically significant covariate influencing clearance (CL) and volume of distribution (Vd ), with a similar increase in both parameters with increased body weight. The half-life was not affected by body weight. Gender (females vs. males) and age category (paediatric vs. adult) did not affect CL. The PK profile of rFXIII, after dosing with 35 IU kg(-1) of rFXIII, was independent of age and comparable between trials and FXIII trough activity levels were constant. Despite rather large individual variation in the maximal FXIII activity levels, all individual mean trough activity levels were above 0.1 IU mL(-1) during the entire duration of the trials. The results support that monthly dosing with 35 IU kg(-1) of rFXIII to patients with FXIII A-subunit deficiency, regardless of age, is adequate for prophylaxis.

Pharmacokinetics and safety of plasma-derived factor XIII concentrate (human) in patients with congenital factor XIII deficiency.

UNLABELLED: Congenital factor XIII (FXIII) deficiency is a rare condition with substantial risk for life-threatening bleeding. Replacement of deficient FXIII with plasma-derived FXIII concentrate is a treatment option. The current 12-week study evaluated the steady-state pharmacokinetic (PK) and safety profile of prophylactic infusions of FXIII concentrate (human) in patients with congenital FXIII deficiency. Patients received FXIII concentrate (human) 40 IU kg(-1) on Days 0, 28, and 56. FXIII levels were assessed before and after each infusion; steady-state PK parameters were assessed up to 28 days after the infusion on Day 56. Treatment effectiveness in maintaining trough FXIII activity levels ≥ 5% over 28 days and safety parameters were also assessed. Fourteen patients received FXIII concentrate (human) and 13 completed the study. Post-infusion, FXIII activity levels increased to within the range found in patients without congenital FXIII deficiency without reaching supra-therapeutic levels. Non-baseline-adjusted trough FXIII activity levels were maintained at or above 10% at all post-baseline visits in all patients. Steady-state PK parameters were baseline-adjusted; maximum FXIII activity was 87.7% at 1.72 h post-infusion, subsequently declining to a minimum of 5.0%. The half-life was 6.6 days. FXIII concentrate (human) was generally well tolerated. Two patients had possibly treatment-related adverse events. There were no reports of thromboembolism, viral transmission, bleeding events or treatment-related hypersensitivity. These findings support use of FXIII concentrate (human) 40 IU kg(-1) every 28 days as an appropriate regimen for routine, long-term prophylaxis in children and adults with congenital FXIII deficiency. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov/ct2/show/NCT00883090.

Efficacy and safety of prophylactic treatment with plasma-derived factor XIII concentrate (human) in patients with congenital factor XIII deficiency.

UNLABELLED: Congenital factor XIII (FXIII) deficiency is an extremely rare, potentially life-threatening bleeding disorder. Routine prophylactic management is recommended for individuals with clinically relevant FXIII deficiency. This prospective, multicentre, open-label study evaluated the long-term efficacy and safety of prophylactic infusions of FXIII concentrate (human) 40 IU kg(-1) in patients with congenital FXIII deficiency. FXIII concentrate (human) was administered every 4 weeks for 12 months. Dosing was adjusted to maintain trough FXIII activity levels of 5-20%. Logistical and ethical constraints precluded use of a placebo control group. Annualized incidence of spontaneous bleeding was compared with historical rates; safety was assessed as a secondary objective. Forty-one patients were enrolled and completed the study. The annualized rate for spontaneous bleeding episodes requiring FXIII treatment was 0.000 episodes per patient-year (95% CI: 0.000; 0.097). The study met its primary endpoint: the upper limit of the 95% CI was substantially below the historical rate of 2.5 bleeding episodes per patient-year. Five spontaneous bleeding episodes (involving three patients; none requiring FXIII treatment) and eight trauma-related bleeding episodes (two requiring FXIII treatment) occurred. Five patients had surgery during the study, only one of whom required FXIII treatment for post-surgical bleeding. Most patients (≥ 85%) had trough FXIII activity levels ≥ 10%. No patient discontinued treatment due to an adverse event. No adverse events related to thromboembolism or viral transmission were reported. Prophylactic treatment with FXIII concentrate (human) was well tolerated and prevented spontaneous bleeding episodes that were serious enough to require treatment with FXIII-containing product. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov/ct2/show/NCT00885742.

Haemophilia Experiences, Results and Opportunities (HERO) study: treatment-related characteristics of the population.

The HERO (Haemophilia Experiences, Results and Opportunities) quantitative surveys collected information on characteristics and perceptions of adult persons with haemophilia (PWH) and parents of children with haemophilia. The aim of this article is to describe the perceptions of PWH and parents on psychosocial aspects related to treatment. Two online surveys (one for PWH, one for parents) were conducted in 10 countries. Among 675 PWH respondents, 77% reported having responsibility for their own care; 72% of 561 parent respondents had the main responsibility for their son. PWH were most commonly treated on demand (45% of 648 adults using factor concentrate), with 32% on regular prophylaxis and 23% treated on demand with short-term prophylaxis (e.g. for sports/physiotherapy). Children were most often treated with prophylaxis (65% of 549 children using factor concentrate), with 26% treated on demand and 8% treated on demand with short-term prophylaxis. Factor was generally used as instructed at home. Some respondents (41% PWH; 30% parents) had difficulties/concerns with factor availability/affordability. PWH reported more bleeds in the last 12 months than parents reporting their son's bleeds (mean 17.8 vs. 8.7). Both PWH and parents generally perceived that overall, their (their son's) haemophilia was well controlled. Results differed by country. The HERO study captured new, patient-based data regarding many facets of life relevant to PWH, including treatment. The information conveyed in this article largely represents new insights regarding perceptions of treatment and provides initial benchmark statistics for further research.

Pharmacokinetics of recombinant factor XIII at steady state in patients with congenital factor XIII A-subunit deficiency.

BACKGROUND: The use of monthly recombinant factor XIII (rFXIII) recently demonstrated favorable safety and efficacy for congenital FXIII A-subunit deficiency patients aged ≥ 6 years (mentor(™) 1 trial), although the pharmacokinetics (PK) were not fully evaluated. OBJECTIVES: To comprehensively evaluate the steady-state PK of rFXIII in patients aged ≥ 6 years with congenital FXIII A-subunit deficiency. PATIENTS/METHODS: mentor(™) 2 is an ongoing, multinational safety and efficacy trial in which patients are receiving monthly rFXIII (35 IU kg(-1) ) for ≥ 52 weeks. For this 28-day PK analysis, blood samples were collected immediately predosing, and 1 h, 2 h, 3, 7, 14, 21, and 28 days postdosing. FXIII activity was measured and PK parameters were calculated using non-compartmental analysis, without prior baseline adjustment. Information regarding adverse events and bleeding was collected at each visit. Antibody assessments were performed predosing and at day 28. RESULTS: PK analysis in 23 patients revealed first-order elimination of rFXIII with a geometric mean half-life of 13.6 days. Mean FXIII activity was > 0.1 IU mL(-1) throughout the 28-day period, with a geometric mean peak activity of 0.87 IU mL(-1) and trough of 0.16 IU mL(-1) . The geometric mean clearance was 0.15 mL h(-1) kg(-1) . No bleeding episodes occurred during the PK session, and no anti-rFXIII antibodies were detected. Peak and trough FXIII activities were constant over time, compared with previous activities (≥ 10 rFXIII doses) in the same patients. CONCLUSIONS: Clearance of rFXIII is unaffected over time, and monthly prophylaxis with 35 IU kg(-1) rFXIII provides FXIII activity > 0.1 IU mL(-1) throughout the dosing interval in patients with congenital FXIII A-subunit deficiency.

Diagnosis of suspected inherited platelet function disorders: results of a worldwide survey.

BACKGROUND: Diagnosis of inherited platelet function disorders (IPFDs) is important for appropriate management and to improve epidemiologic and clinical knowledge. However, there remains a lack of consensus on the diagnostic approach. OBJECTIVES: To gain knowledge on the current practices for the diagnosis of IPFD worldwide. METHODS: A 67-item questionnaire was distributed to the ISTH members and to the members of several national hemostasis and thrombosis societies. RESULTS: A total of 202 laboratories from 37 countries participated in the survey. The most frequent criterion to define patients with a suspected IPFD was a history of mucocutaneous bleeding and no acquired cause, but heterogeneity on the identification criteria was evident. Only 64.5% of respondents performed a direct clinical interview. On average, each laboratory studied 72 patients per year. The most commonly used laboratory equipment were the light-transmission aggregometer, the Platelet Function Analyzer-100, and the flow cytometer. Screening tests were platelet count, peripheral blood smear, light-transmission aggregometry, and Platelet Function Analyzer-100. Second-step tests were flow cytometry, molecular genetic analysis, and electron microscopy. Methodologies varied widely. In total, ~ 14,000 patients were investigated yearly and 60% turned out to not have a defect. Of the remaining 40%, only 8.7% received a diagnosis at a molecular level. CONCLUSIONS: Many laboratories worldwide are involved in the diagnosis of IPFD. A large fraction of the patients studied remain without a diagnosis. A high variability in the diagnostic approaches is evident.

Haemophilia Experiences, Results and Opportunities (HERO) Study: influence of haemophilia on interpersonal relationships as reported by adults with haemophilia and parents of children with haemophilia.

Evidence delineating the effects of haemophilia on interpersonal relationships is sparse and largely outdated, failing to reflect the impact of current treatment strategies. HERO (Haemophilia Experiences, Results and Opportunities) was commenced to garner a more comprehensive understanding of psychosocial issues facing persons with haemophilia (PWH). This article describes the findings of the quantitative HERO survey relating to the influence of haemophilia on interpersonal relationships of adult PWH, and parents/caregivers of children with haemophilia. Separate questionnaires were completed by adult PWH and parents of minor children from 10 countries, including satisfaction with support from partners, family, friends and other social contacts; disclosure of haemophilia and carrier status and family dynamics. A total of 675 PWH and 561 parents completed the survey. Over half of PWH (57%) and parents (84%) were married. Most PWH were satisfied with support from partners (94%), family (90%) and friends (85%), with lower percentages reported among those with inhibitors. Most parents were likewise satisfied with support from partners (88%) and family (83%). Whereas PWH were reticent to disclose their diagnosis beyond family and friends, parents were more likely to share their son's diagnosis, and most were satisfied with the support from their son's peers (74%), teachers (83%) and other adults in supervisory roles (85%). PWH and parents surveyed were satisfied overall with the support they received from partners, family, friends and social contacts. Relationships are affected by haemophilia in various ways, and particularly affected in terms of disease burden, age and social life.

Haemophilia Experiences, Results and Opportunities (HERO) Study: survey methodology and population demographics.

Psychosocial factors have a significant impact on the quality of life of persons with haemophilia (PWH). The Haemophilia Experiences, Results and Opportunities (HERO) initiative was developed to provide a greater understanding of the psychological components which influence the lives of PWH. This article describes the HERO methodology and the characteristics of respondents. Two online surveys (one for adult PWH ≥18 years and one for parents of children <18 years with haemophilia) were developed by an international advisory board and conducted in 10 countries. The surveys included demographic and treatment characteristics, relationships, sexual intimacy, quality of life, barriers to treatment and sources of information. A total of 675 PWH [age, median (range) 36 (18-86 years)] and 561 parents [39 (23-68 years)] completed the survey. PWH/parents reported haemophilia A (74%/76%), B (13%/16%) or with inhibitors (13%/8%). Spontaneous joint bleeding was reported in 76%/52% of PWH/children with haemophilia A, 67%/47% with haemophilia B and 93%/76% with inhibitors. Median number of bleeds (interquartile range) was 7 (2-20) for PWH and 4 (2-10) for children in the past year. Most PWH and children were treated with factor concentrate. PWH reported arthritis (49%) and HIV/HCV infections (18%/43%) related to haemophilia. Most PWH and parent respondents had received formal education (85%/89%) and were employed full- or part-time (60%/72%). HERO is one of the largest multinational studies focused on psychosocial issues in haemophilia, including historical and treatment information that will allow for multivariate analyses of determinants of health in haemophilia.

Enhancing patient safety with an electronic results checking system in a large HIV outpatient service.

OBJECTIVE: To establish whether an automated electronic tracker system for reporting blood results would expedite clinician review of abnormal results in HIV-positive outpatients and to pilot the use of this system in routine clinical practice. SETTING: An outpatient service in central London providing specialist HIV-related care to 3900 HIV positive patients. DESIGN: A comparison of the time taken from sampling to identification and clinician review of abnormal blood results for biochemical tests between the original paper-based checking system and an automated electronic system during a 3-week pilot. RESULTS: Of 513 patients undergoing one or more blood tests, 296 (57%) had one or more biochemical abnormalities identified by electronic checking system. Out of 371 biochemical abnormalities, 307 (82.7%) were identified simultaneously by the paper-based system. Of the 307, 33 (10.7%) were classified as urgent, 130 (42.3%) as non-urgent and 144 (46.9%) as not clinically significant. The median interval between sampling and receipt of results was 1 (interquartile range 1-2) vs 4 days ( interquartile range 3-5), P <0.0001; clinician review 3 (interquartile range 1-4) vs 3 days (interquartile range 3-6), P<0.037; and review of non-urgent abnormalities by the regular clinician 2 (interquartile range 1-4) vs 10 days ( interquartile range 9-12), P=0.136, for electronic and paper-based systems respectively. Seven (11%) of the missing paper-based system results were classified as urgent. The electronic system missed three abnormalities as a result of a software processing error which was subsequently corrected. CONCLUSIONS: The electronic tracker system allows faster identification of biochemical abnormalities and allowed faster review of these results by clinicians. The pilot study allowed for a software error to be identified and corrected before full implementation. The system has since integrated successfully into routine clinical practice.

Newborn screening for severe combined immunodeficiency: an opportunity for intervention.

Severe combined immunodeficiency (SCID) is a potentially fatal disorder characterized by defective T- and B-lymphocyte function. We describe a 34-week female twin who had developed feeding intolerance, perioral cyanosis, abdominal distension and neutropenia at 1 month of age. Despite several evaluations including an 'inconclusive' newborn screening result for SCID, the presence of profound lymphopenia was unappreciated. Eventually a diagnosis of SCID in association with adenosine deaminase deficiency was made. This case serves to emphasize the importance of newborn screening for SCID in the context of careful evaluation of clinical and laboratory findings that may be overlooked and result in a delay in the diagnosis of a potentially life-threatening condition.

Recommendations for the Standardization of Light Transmission Aggregometry: A Consensus of the Working Party from the Platelet Physiology Subcommittee of SSC/ISTH.

Light transmission aggregometry (LTA) is the most common method used to assess platelet function. However, there is no universal standard for its performance. The Platelet Physiology Subcommittee of the Scientific and Standardization Committee (SSC) of the International Society on Thrombosis and Haemostasis formed a working party of experts with the aim of producing a series of consensus recommendations for standardizing LTA. Due to a lack of investigations that directly compared different methodologies to perform LTA studies, there were insufficient data to develop evidence-based guidelines. Therefore, the RAND method was used, which obtains a formal consensus among experts about the appropriateness of health care interventions, particularly when scientific evidence is absent, scarce and/or heterogeneous. Using this approach, each expert scored as "appropriate", "uncertain" or "inappropriate" a series of statements about the practice of LTA, which included pre-analytical variables, blood collection, blood processing, methodological details, choice of agonists and the evaluation and reporting of results. After presentation and public discussion at SSC meetings, the assessments were further refined to produce final consensus recommendations. Before delivering the recommendations, a formal literature review was performed using a series of defined search terms about LTA. Of the 1830 potentially relevant studies identified, only 14 publications were considered to be actually relevant for review. Based upon the additional information, 6 consensus statements were slightly modified. The final statements were presented and discussed at the SSC Meeting in Cairo (2010) and formed the basis of a consensus document, which is the subject of the present report. This article is protected by copyright. All rights reserved.

Surveillance of female patients with inherited bleeding disorders in United States Haemophilia Treatment Centres.

Inherited bleeding disorders are especially problematic for affected girls and women due to the monthly occurrence of menstrual periods and the effects on reproductive health. Although heavy menstrual bleeding (HMB) is the most common manifestation, females with inherited bleeding disorders (FBD) experience other bleeding symptoms throughout the lifespan that can lead to increased morbidity and impairment of daily activities. The purpose of this article is to describe the utility of a female-focused surveillance effort [female Universal Data Collection (UDC) project] in the United States Haemophilia Treatment Centres (HTCs) and to describe the baseline frequency and spectrum of diagnoses and outcomes. All FBD aged 2 years and older receiving care at selected HTCs were eligible for enrollment. Demographic data, diagnoses and historical data regarding bleeding symptoms, treatments, gynaecological abnormalities and obstetrical outcomes were analysed. Analyses represent data collected from 2009 to 2010. The most frequent diagnoses were type 1 von Willebrand's disease (VWD) (195/319; 61.1%), VWD type unknown (49/319; 15.4%) and factor VIII deficiency (40/319; 12.5%). HMB was the most common bleeding symptom (198/253; 78.3%); however, 157 (49.2%) participants reported greater than four symptoms. Oral contraceptives were used most frequently to treat HMB (90/165; 54.5%), followed by desmopressin [1-8 deamino-D-arginine vasopressin (DDAVP)] (56/165; 33.9%). Various pregnancy and childbirth complications were reported, including bleeding during miscarriage (33/43; 76.7%) and postpartum haemorrhage (PPH) (41/109; 37.6%). FBD experience multiple bleeding symptoms and obstetrical-gynaecological morbidity. The female UDC is the first prospective, longitudinal surveillance in the US focusing on FBD and has the potential to further identify complications and reduce adverse outcomes in this population.