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BACKGROUND: Patients with hereditary antithrombin deficiency (HAD) have an increased risk of venous thromboembolism (VTE). ATHN 12: HAD Pilot Project established a registry to collect data on patients with HAD to inform current practice and serve as a platform to design a multicenter global registry for patients with HAD. METHODS: The HAD registry was designed in 2020 to identify 100 patients with HAD receiving care at ATHN-affiliated centers. Demographics, type of HAD, thrombotic events, risk factors, anticoagulants, and AT concentrate administration were recorded. RESULTS: Ninety-four (94) patients were included; 65% were females; 51% had type 1 HAD. Mean age at diagnosis was 26 years (SD18); 61% had VTE: 55% deep vein thrombosis and 27% pulmonary embolisms. Eight patients had arterial thrombosis. Recurrent thrombosis occurred in 58.6% patients: (44.8%) despite anticoagulation. The main risk factor for thrombosis in females was estrogen. Direct oral anticoagulants were prescribed in 30%, heparin in 34%, and warfarin in 32%. There were 139 pregnancies. Low molecular weight heparin was administered in 33% and AT concentrate in 19% and 11% prior and post-delivery, respectively. Twelve patients developed thrombosis in pregnancy. Seventy-nine patients underwent 239 surgeries or procedures, mainly gastrointestinal and vascular, respectively. Overall, 35% participants received AT concentrate without adverse events. CONCLUSIONS: In ATHN 12, VTE was the predominant manifestation, frequently recurrent. There was a trend towards using DOACs. LMWH was administered in one-third of pregnancies and AT concentrate in one-fifth without adverse events. These data should encourage prospective studies to optimize the management of these patients.
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Hemophilia is a rare genetic bleeding disorder historically associated with high morbidity and mortality. Some individuals with hemophilia suffer associated chronic joint disease, chronic pain, and other physical and mental health challenges. In the last 50 years, a better understanding of the pathophysiology of the disease has resulted in extraordinary therapeutic advances leading to enhanced quality of life and increased life expectancy. We present an illustrated review of the evolution of hemophilia treatment from the development of non-factor therapies to gene therapy.
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INTRODUCTION: Gastrointestinal (GI) bleeding events (BEs) in von Willebrand disease (VWD) are difficult to diagnose and often recurrent. Limited data from clinical trials has led to lack of consensus on treatment options. AIM: Describe current treatments and outcomes for GI BEs in people with VWD. METHODS: This retrospective, observational, multicentre chart review study was conducted from January 2018 through December 2019 and included patients with inherited VWD with ≥1 GI BE in the preceding 5 years. Baseline characteristics, number and aetiology of BEs, associated GI-specific morbidities/lesions, treatment and outcomes were analysed descriptively. RESULTS: Sixty bleeds were reported in 20 patients with type 1 (20%), type 2 (50%) and type 3 (30%) VWD. During the 5-year study period, 31 (52%) BEs had one identified or suspected cause; multiple causes were reported in 11 (18%). Most GI BEs (72%) were treated with a combination of von Willebrand factor (VWF), antifibrinolytics and/or other haemostatic or non-haemostatic treatments. Time to resolution did not differ by VWF treatment use; however, BEs treated with non-VWF treatments tended to resolve later. In patients with GI-specific morbidities/lesions, 84% resolved with first-line treatment; time to resolution tended to be longer than in patients without such morbidities/lesions. Thirteen BEs occurred in patients receiving prophylaxis and 47 in patients receiving on-demand treatment; 18 BEs resulted in a switch to prophylaxis after bleed resolution. CONCLUSIONS: This study confirms the unmet need for the management of recurrent GI BEs in people with VWD and the need for prospective data, especially on prophylaxis.
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Hemorragia Gastrointestinal , Doenças de von Willebrand , Humanos , Doenças de von Willebrand/complicações , Estudos Retrospectivos , Hemorragia Gastrointestinal/etiologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Idoso , Criança , Fator de von Willebrand/uso terapêutico , Pré-EscolarRESUMO
ABSTRACT: We assessed the feasibility to estimate illness burden in adults with SCD, investigated factors associated with health-related quality of life (HRQoL), and estimated societal burden. We recruited 32 participants and collected data on fatigue, HRQoL, and work productivity and activity impairment via patient survey. Health care utilization was abstracted for the 12 months before enrollment using medical chart review. Mean age was 36.7 years; 84.4% of participants had hemoglobin SS or Sßthal0 disease, and 81.3% reported chronic pain (experiencing pain on ≥3 days per week in the past 6 months). Mean EQ-5D-3L visual analogue scale score was 63.4 and the index score was 0.79. The mean fatigue score was 57.9. Higher fatigue score was correlated with lower EQ-5D index score (correlation coefficient r = -0.35; P = .049) and Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) scores, including pain (r = -0.47; P = .006), sleep (r = -0.38; P = .03), and emotion scores (r = -0.79; P < .0001). The number of hospitalizations was negatively correlated with HRQoL (all P < .05). Patients who reported chronic pain had significantly lower mean ASCQ-Me sleep scores (48.3 vs 57.1; P = .04) and EQ-5D index scores (0.72 vs 0.89; P = .002) than those without chronic pain. Mean estimated annual per person costs were $51 779 (median, $36 366) for total costs, $7619 ($0) for indirect costs (estimated from lost earnings of participants), and $44 160 ($31 873) for medical costs. Fatigue, SCD complications, hospitalization, and chronic pain negatively affected HRQoL. This sample experienced a high economic burden, largely from outpatient doctor visits.
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Anemia Falciforme , Efeitos Psicossociais da Doença , Qualidade de Vida , Humanos , Anemia Falciforme/complicações , Anemia Falciforme/economia , Adulto , Projetos Piloto , Masculino , Feminino , Pessoa de Meia-Idade , Fadiga/etiologiaRESUMO
This paper is a call to action for research and discussion on data visualization education. As visualization evolves and spreads through our professional and personal lives, we need to understand how to support and empower a broad and diverse community of learners in visualization. Data Visualization is a diverse and dynamic discipline that combines knowledge from different fields, is tailored to suit diverse audiences and contexts, and frequently incorporates tacit knowledge. This complex nature leads to a series of interrelated challenges for data visualization education. Driven by a lack of consolidated knowledge, overview, and orientation for visualization education, the 21 authors of this paper-educators and researchers in data visualization-identify and describe 19 challenges informed by our collective practical experience. We organize these challenges around seven themes People, Goals & Assessment, Environment, Motivation, Methods, Materials, and Change. Across these themes, we formulate 43 research questions to address these challenges. As part of our call to action, we then conclude with 5 cross-cutting opportunities and respective action items: embrace DIVERSITY+INCLUSION, build COMMUNITIES, conduct RESEARCH, act AGILE, and relish RESPONSIBILITY. We aim to inspire researchers, educators and learners to drive visualization education forward and discuss why, how, who and where we educate, as we learn to use visualization to address challenges across many scales and many domains in a rapidly changing world: viseducationchallenges.github.io.
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INTRODUCTION: VWD diagnosis is challenging requiring multiple VWF activity tests using many individual assays. We have developed an ELISA-based VWF Multiplex Activity Assay (VWF-MAA) to address this concern; however, the ability of the VWF-MAA to discriminate between type 1 VWD, variant VWD, and normal subjects has not been evaluated. AIM: To evaluate the VWF-MAA and its ability to differentiate between type 1 VWD, variant VWD and normal subjects in individuals undergoing an initial laboratory evaluation for bleeding. METHODS: A total of 177 plasma samples from the Zimmerman Program: Comparative Effectiveness in the Diagnosis of VWD were evaluated from 11 centres across the US and Canada. The VWF-MAA was compared to Versiti Blood Research Institute (VBRI) and Local Center (LC) assigned VWD diagnosis. RESULTS: Overall, 129/177 (72.9%) were correctly assigned as normal (non-VWD), type 1, or variant VWD compared to the VBRI assigned diagnosis. VWF-MAA assigned non-VWD accurately in 29/57 (50.9%) samples, and type 1 VWD accurately in 93/110 (84.6%) samples. Considering LC diagnosis where there was agreement with VWF-MAA and not VBRI diagnosis, type 1 VWD was accurate in 105/110 (95.5%) samples. Bland-Altman analysis demonstrated good correlation between laboratory methods. VWD, types 2A, 2B, 1C VWD were also assigned by the VWF-MAA. CONCLUSIONS: We demonstrate that the VWF-MAA has utility in differentiating type 1 VWD, variant VWD and normal subjects in individuals undergoing an initial laboratory evaluation for bleeding.
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Doença de von Willebrand Tipo 1 , Doença de von Willebrand Tipo 2 , Doenças de von Willebrand , Humanos , Fator de von Willebrand/análise , Doença de von Willebrand Tipo 1/diagnóstico , Doenças de von Willebrand/diagnóstico , Hemorragia , Canadá , Doença de von Willebrand Tipo 2/diagnósticoRESUMO
INTRODUCTION: In recent years, there has been increased focus on individualizing treatment for persons with hemophilia including pharmacokinetic-guided (PK) dosing. AIMS: In this retrospective study clinical outcomes before and after PK-guided prophylaxis were examined. MATERIALS AND METHODS: Eight Haemophilia Treatment Centres from the United States participated in the study and included 132 patients classified into two cohorts: those undergoing a PK-assessment for product switch (switchers) or to optimize treatment (non-switchers). Subset analyses for the two most common products and patients with dosing per prescription label were included for annual bleeding rates (ABR), mean weekly consumption outcomes, and annualized cost of prophylaxis. RESULTS: The most common products before and after index date were octocog alfa, rurioctocog alfa pegol, and efmoroctocog alfa. Seventy-four (56%) patients were identified as switchers and 58 (44%) patients were classified as non-switchers. The majority of patients (78.0%) experienced either a decrease in ABR post-index or maintained 0 ABR during pre- and post-index time periods, with similar proportions identified in both switchers (77.0%) and non-switchers (79.3%) populations. Non-switchers were identified as having no significant change in cost of therapy, while switchers experienced increased cost of therapy driven by higher price of extended half-life products. Within subset analyses, patients receiving rurioctocog alfa pegol and efmoroctocog alfa had mean ABR under 1 after index date. CONCLUSION: PK-guided prophylaxis has the potential to improve clinical outcomes without increase in cost of therapy for patients maintaining product and can aid in maintaining effective protection against bleeds in those switching product.
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Hemofilia A , Humanos , Hemofilia A/tratamento farmacológico , Estudos Retrospectivos , Fator VIII/farmacologia , Hemorragia/prevenção & controle , Meia-Vida , PacientesRESUMO
INTRODUCTION: People with haemophilia rely on specialists for their care, yet the specific dosing regimens of treatments prescribed by these specialists have not been widely studied. AIM: The objective of this study is to describe trends in clinician prescribing practices for the management of haemophilia in the United States (US). METHODS: We administered surveys to members of the Hemostasis and Thrombosis Research Society via paper surveys at its in-person annual symposia in 1999 and 2015, and an online survey in 2021. The surveys collected information on haemophilia treatments including factor dosing, inhibitor therapy and gene therapy. RESULTS: Clinicians treating haemophilia for more than 50% of their practice time have increased from 37.5% of respondents in 1999 to 46.3% in 2021. Clinicians prescribing factor concentrates at >40 units/kg for routine bleeding events increased from 0% in 1999 to 29.3% in 2021 in haemophilia A (HA) and from 22.5% to 87.8% in haemophilia B (HB). In 2021, the clinicians reported prescribing emicizumab to treat HA patients (>89.5% paediatric, >85.7% adult) with or without inhibitors at least some of the time. Approximately 78.0% of respondents reported that they expected to recommend gene therapy at least some of time. CONCLUSION: These data indicate changing trends in prescribing practices among US haemophilia specialists during the past 22 years. Preference for high doses of factor (>40 units/kg) has increased during this period. Emicizumab prophylaxis has been prescribed for patients with and without HA inhibitors. Clinicians expect gene therapy to have value for some haemophilia patients.
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Anticorpos Biespecíficos , Hemofilia A , Hemofilia B , Adulto , Humanos , Criança , Hemofilia A/tratamento farmacológico , Hemofilia B/tratamento farmacológico , Hemorragia/tratamento farmacológico , Anticorpos Biespecíficos/uso terapêutico , Fator VIII/uso terapêuticoRESUMO
OBJECTIVE: We assessed sociodemographic and clinical characteristics associated with depression and anxiety in individuals with Von Willebrand disease (VWD) aged ≥12 years. METHODS: The study collected data on patients' sociodemographic, joint problems and health-related quality of life (HRQoL) using EQ-5D-3L, 8-item patient health questionnaire for depression and 7-item Generalized Anxiety Disorder Questionnaire from participants in seven geographically diverse US haemophilia treatment centres. RESULTS: Analyses included 77 participants. The rates of depression and anxiety were 63.6% and 58.3%, respectively. Persons with low VWF displayed higher rates of depression (86.7%) or anxiety (69.2%) compared to those with VWD (58.1%, p = .04 for depression, and 55.9%, p = .38 for anxiety). Logistic regression analyses demonstrated that having joint problems (odds ratio [OR] = 6.3, confidence interval [CI] = 2.0-20.1) was the most important variable associated with depression, followed by being single, divorced, widowed, or separated in adult participants or parents of participants age < 18 years (OR = 7.0, CI = 1.7-29.0. The most important variable associated with anxiety was being single or lacking a partner (OR = 10.8, CI = 2.5-47.5), followed by age 12-17 years old (OR = 6.7, CI = 1.6-26.9), or having worse health compared to 3-months ago (OR = 12.3, CI = 1.3-116.2). Mean covariates adjusted EQ visual analogue scale score was significantly lower among persons with depression (68.77 ± 3.15 vs. 77.58 ± 4.24, p = .03) than those without depression. CONCLUSIONS: Our study revealed concerning levels of depression and anxiety in this VWD sample. Lack of social support was determined an important factor associated with depression and anxiety in this sample. Mental health screening is critical in VWD clinical evaluation and care.
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Doenças de von Willebrand , Adulto , Humanos , Criança , Adolescente , Doenças de von Willebrand/complicações , Doenças de von Willebrand/epidemiologia , Doenças de von Willebrand/diagnóstico , Fator de von Willebrand/análise , Depressão/complicações , Depressão/epidemiologia , Qualidade de Vida , Ansiedade/complicações , Ansiedade/epidemiologia , Transtornos de Ansiedade/complicações , Transtornos de Ansiedade/epidemiologiaRESUMO
Von Willebrand disease (VWD) is an inherited bleeding disorder caused by quantitative or qualitative deficiencies in von Willebrand factor (VWF). People with VWD may experience excessive, recurrent or prolonged bleeding, particularly during menstruation, childbirth, surgery or following trauma. However, many VWD patients are undiagnosed, and therefore inadequately treated. Reasons for the underdiagnosis of VWD include its relatively mild symptoms, complex diagnosis, lack of awareness among non-specialist healthcare providers and the general population, and a lack of prioritisation of disorders disproportionately affecting females. The vwdtest.com platform was launched as part of a global initiative to raise awareness and improve diagnosis of VWD. Besides providing VWD-specific educational resources, the website includes an online bleeding self-assessment tool and offers diagnostic support for individuals, and their providers, who have a score suggestive of a bleeding disorder. vwdtest.com helps to address these unmet needs, especially in regions with limited access to educational and diagnostic resources.
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Transtornos Hemorrágicos , Doenças de von Willebrand , Feminino , Humanos , Doenças de von Willebrand/diagnóstico , Doenças de von Willebrand/terapia , Doenças de von Willebrand/complicações , Fator de von Willebrand , Hemorragia/diagnóstico , Hemorragia/etiologia , Hemorragia/terapiaRESUMO
Hereditary antithrombin deficiency (ATD) is a rare autosomal dominant condition (estimated prevalence 1:500-1:5000). Most ATD patients have AT activity levels 40-60% of normal. We present treatments for venous thromboembolism (VTE) in five cases of hereditary ATD. Four patients had a family history of ATD, and one had a de novo mutation. The majority of patients had a VTE while on prophylactic anticoagulation. AT concentrate augmentation was added in these cases to treat the VTE and for prophylaxis against further episodes. Two patients had significant bleeding events, one had permanent physical sequelae. Two of the patients were pregnant. VTE is a common cause of morbidity and mortality during pregnancy. Although low molecular weight heparins are the drugs of choice during pregnancy, this treatment was inadequate in one patient (developed VTE on therapy). These cases emphasize the need to screen for ATD in young patients (<55 years) presenting with VTE. AT augmentation therapy may be necessary in patients inadequately treated with conventional anticoagulants. Careful monitoring and individualized care are needed in ATD patients, especially those with demonstrated bleeding tendencies.
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BACKGROUND: FVIII replacement is standard treatment for hemophilia A without inhibitors, but non-factor therapies, such as emicizumab, are changing the treatment landscape. We explore the ramifications of switching treatment. METHODS: Pharmacy database data (July 2017-May 2020) from patients with hemophilia A without inhibitors who switched to rurioctocog alfa pegol or emicizumab prophylaxis after ≥6 months' prophylaxis with another FVIII product were analyzed for total mean weekly consumption, dosing frequency, product wastage, and ABR. RESULTS: Post-switch mean weekly consumption of prophylactic rurioctocog alfa pegol and emicizumab were 6224 IU/kg and 109 mg, respectively. Dosing schedules for emicizumab were primarily weekly (48.2%) and every 2 weeks (40.0%). Most patients in the rurioctocog alfa pegol cohort received treatment twice-weekly (83.3%). Mean product wastage of emicizumab (8.4%) was significantly higher versus rurioctocog alfa pegol (-0.3%; P < 0.001). Mean annualized emicizumab and rurioctocog alfa pegol wastage during prophylaxis was 330.82 mg and -974.80 IU, respectively. ABR change was not significantly different (P = 0.527) for patients switching to emicizumab (-1.05) or rurioctocog alfa pegol (-1.53). CONCLUSIONS: Bleed rates were similar for patients receiving prophylaxis with emicizumab or rurioctocog alfa pegol after switching from prophylaxis with another FVIII. However, wastage associated with dispensing inaccuracies was greater with emicizumab.
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Anticorpos Biespecíficos , Hemofilia A , Humanos , Hemofilia A/complicações , Hemofilia A/tratamento farmacológico , Fator VIII/uso terapêutico , Anticorpos Biespecíficos/efeitos adversosRESUMO
We report on an ongoing collaboration between epidemiological modellers and visualization researchers by documenting and reflecting upon knowledge constructs-a series of ideas, approaches and methods taken from existing visualization research and practice-deployed and developed to support modelling of the COVID-19 pandemic. Structured independent commentary on these efforts is synthesized through iterative reflection to develop: evidence of the effectiveness and value of visualization in this context; open problems upon which the research communities may focus; guidance for future activity of this type and recommendations to safeguard the achievements and promote, advance, secure and prepare for future collaborations of this kind. In describing and comparing a series of related projects that were undertaken in unprecedented conditions, our hope is that this unique report, and its rich interactive supplementary materials, will guide the scientific community in embracing visualization in its observation, analysis and modelling of data as well as in disseminating findings. Equally we hope to encourage the visualization community to engage with impactful science in addressing its emerging data challenges. If we are successful, this showcase of activity may stimulate mutually beneficial engagement between communities with complementary expertise to address problems of significance in epidemiology and beyond. See https://ramp-vis.github.io/RAMPVIS-PhilTransA-Supplement/. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'.
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COVID-19 , Pandemias , COVID-19/epidemiologia , HumanosRESUMO
INTRODUCTION: The sixth Åland Islands Conference on von Willebrand disease (VWD) on the Åland Islands, Finland, was held from 20 to 22 September 2018. AIM: The meeting brought together experts in the field of VWD from around the world to share the latest advances and knowledge in VWD. RESULTS AND DISCUSSION: The topics covered both clinical aspects of disease management, and biochemical and laboratory insights into the disease. The clinical topics discussed included epidemiology, diagnosis and treatment of VWD in different countries, management of children with VWD, bleeding control during surgery, specific considerations for the management of type 3 VWD and bleeding control in women with VWD. Current approaches to the management of acquired von Willebrand syndrome were also discussed. Despite significant advances in the understanding and therapeutic options for VWD, there remain many challenges to be overcome in order to optimise patient care. In comparison with haemophilia A, there are very few registries of VWD patients, which would be a valuable source of data on the condition and its management. VWD is still underdiagnosed, and many patients suffer recurrent or severe bleeding that could be prevented. Awareness of VWD among healthcare practitioners, including non-haematologists, should be improved to allow timely diagnosis and intervention. Diagnosis remains challenging, and the development of fast, simple assays may help to facilitate accurate and rapid diagnosis of VWD.
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Doença de von Willebrand Tipo 3 , Doenças de von Willebrand , Criança , Congressos como Assunto , Feminino , Finlândia , Hemorragia , Humanos , Sistema de Registros , Doenças de von Willebrand/complicações , Doenças de von Willebrand/diagnóstico , Doenças de von Willebrand/tratamento farmacológico , Fator de von Willebrand/uso terapêuticoRESUMO
INTRODUCTION: GOAL-Hem is a novel, haemophilia-specific, patient-centred outcome measure (PCOM) based on goal attainment scaling, allowing people with haemophilia (PwH) to set and monitor the attainment of individualized goals for treatment. AIM: To provide a thorough overview of the creation, validation, and development of GOAL-Hem. METHODS: Clinician workshops were held to develop a haemophilia-specific goal menu. Qualitative data from semistructured interviews with PwH and their caregivers guided further revisions to the goal menu (i.e., goal domains and descriptors). A feasibility study was performed including a 12-week, prospective, noninterventional evaluation involving clinicians and PwH at four US haemophilia treatment centres. Finally, the Patient Voice Study gathered feedback from PwH and their caregivers via an online survey, interviews, and a focus group. RESULTS: The feasibility study validated GOAL-Hem with successful outcomes in construct/content validity and responsiveness, including a large effect in patient- and clinician-rated goal attainments. The Patient Voice Study led to significant refinement of GOAL-Hem goals and descriptors, resulting in a more straightforward and relatable menu for PwH and their caregivers. Overall, GOAL-Hem captured qualitative data in areas important to PwH and employed quantitative methods to evaluate meaningful changes in those areas. The individualized tool was well equipped to handle the complex and chronic nature of haemophilia and was endorsed by PwH, their caregivers, and clinicians. CONCLUSION: The GOAL-Hem development journey may serve as a roadmap for other PCOMs in a variety of settings, including clinical studies, haemophilia treatment centres for care planning, and as a tool to gather real-world evidence.
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Hemofilia A , Tomada de Decisão Compartilhada , Objetivos , Hemofilia A/terapia , Humanos , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Extremely premature neonates have increased risk for bleeding, perhaps the most devastating version of which being intraventricular hemorrhage (IVH). Limited data are available for coagulation parameters in this vulnerable population. OBJECTIVES: We conducted a prospective cohort study characterizing coagulation laboratory parameters in extremely premature neonates 23-30 weeks gestational age (GA) and determined coagulation parameters and clinical risk factors associated with IVH. PATIENTS/METHODS: One hundred twenty neonates 23-30 weeks GA were enrolled, and umbilical cord blood samples were obtained and processed at the time of birth. Coagulation parameters including prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), and activity assays for factors II, VII, IX, X, XIII, and XIII subunit A antigen were performed by standard methods. Clinical risk factors were analyzed for association with IVH. RESULTS: Of the enrolled neonates, 29 (24.2%) experienced IVH. Persistent pulmonary hypertension (PPHN) independently predicted IVH risk with odds ratio (OR) 5.3 (95% confidence interval [CI] 1.1-24.3), P = .0338; and chronic lung disease (CLD) approached significance with OR 2.3 (95% CI 0.9-5.5), P = .0659. Coagulation parameters were evaluated for association with IVH, and there was no significant difference among coagulation tests in neonates with or without IVH or per GA. Reduced factor XIII subunit A showed significant association with death, P = .003. CONCLUSIONS: We present a large, prospective study of laboratory coagulation parameters in extremely premature neonates, including factor X, factor XIII, and factor XIII subunit A not previously described in this population. These findings may impact clinical practice and should encourage additional study in this vulnerable population.
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Coagulação Sanguínea , Hemorragia Cerebral , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/etiologia , Idade Gestacional , Humanos , Recém-Nascido , Estudos Prospectivos , Fatores de RiscoRESUMO
Background and objective Acquired hemophilia A (AHA) is an uncommon autoimmune bleeding disorder caused by the formation of neutralizing antibodies against endogenous factor VIII (FVIII). Delays between the onset of symptoms and the correct diagnosis of the condition lead to poor outcomes and a higher mortality rate. In this study, we aimed to analyze the impact of delays in diagnosis on AHA patients. Methods We conducted a retrospective study at a single hospital system between March 1, 2010, and January 17, 2017, which included six patients meeting the criteria for AHA diagnosis. Results Initial analysis revealed a median age of 79.5 years and a median time to diagnosis from the onset of bleeding of 14 days. Among the six patients, three had cancer (bladder, renal, and prostate) and three had unknown etiologies. One of the patients died prior to the initiation of a bypassing agent. The remaining five patients received recombinant FVIIa (NovoSeven®, Novo Nordisk, Bagsværd, Denmark), and two of those five required a second-line bypassing agent, recombinant porcine sequence FVIII (Obizur®, Takeda Pharmaceutical, Tokyo, Japan) for refractory bleeding. All five patients achieved hemostasis; however, three died within a year, and none of the patients survived for five years. Four of these five patients died directly from bleeding complications. Conclusions Based on our study findings and review of the literature, we propose an algorithm to potentially aid in the early diagnosis and treatment of AHA in emergency and non-specialized settings.
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Heparin-induced skin necrosis (HISN) is a rare complication of heparin anticoagulation. The condition occurs in various situations, including in heparin-naive and exposed individuals, in areas local or distant from the heparin injection site, and with or without frank thrombocytopenia. We present a case in which a patient treated for a pulmonary embolism with therapeutic unfractionated heparin (UFH) develops this adverse event. Symptoms were reversed with cessation of UFH and transition to bivalirudin without surgical debridement. The patient initially had anti-PF4 antibodies present but subsequent testing showed borderline antibodies and a negative serotonin release assay. After starting bivalirudin, the patient was later switched to fondaparinux without further consequences. This case illustrates the pathogenesis of HISN and provides an example of inconsistently abnormal laboratory values. Additionally, it provides two novel exposures the mRNA-1273 vaccine and the immune checkpoint inhibitor pembrolizumab that, to our knowledge, have not been previously reported.