RESUMO
INTRODUCTION: Mild haemophilia is a congenital bleeding disorder affecting males. The burden of arthropathy in mild haemophilia has not been comprehensively described. AIM: The aim of this study was to compare the incidence, age at diagnosis and surgery for arthropathy and related hospitalizations between people with mild haemophilia and the general population in Sweden. METHODS: This was a register-based cohort study. Eligible participants were those with mild haemophilia born between 1941 and 2008 and a randomly selected, birthdate and sex-matched comparison group from the general population. Follow-up was from birth (or earliest 1984) until death, emigration or end of the study in 2008. Data on arthropathy were obtained from a national patient register. Negative binomial and competing risk regression and Kaplan-Meier estimate curves were used in the analysis. RESULTS: Overall, 315 people with haemophilia and 1529 people in the comparison group were included. Participants with haemophilia born between 1984 and 2008 had a ninefold (95% CI: 3.3-27.2) and 16-fold (95% CI: 6.7-36.5) increased incidence of arthropathy-related hospital admission and arthropathy diagnosis respectively. None in this cohort underwent surgery. Among participants with haemophilia born prior to 1984, the rates of arthropathy diagnosis and surgery of the index joints (knee, elbow, ankle) were increased twofold (95% CI: 1.0-3.2) and fivefold (95% CI: 1.7-17.8) respectively. CONCLUSION: Our data suggested a higher burden of arthropathy among individuals with mild haemophilia compared to the general population. Further research should investigate the need for targeted joint screening programmes among individuals with mild haemophilia.
Assuntos
Hemofilia A/complicações , Hemofilia B/complicações , Artropatias/etiologia , Estudos de Coortes , Feminino , Hemofilia A/mortalidade , Hemofilia A/patologia , Hemofilia B/mortalidade , Hemofilia B/patologia , Humanos , Masculino , SuéciaRESUMO
INTRODUCTION: People with severe haemophilia A have reportedly impaired health related quality of life (utility) mainly due to recurrent bleeding, arthropathy and treatment burden. AIM: To estimate utilities and evaluate their potential correlates - most importantly the joint status - among people with severe haemophilia A. METHODS: In this cross-sectional study, eligible participants had severe haemophilia A, were aged ≥15, negative for factor VIII inhibitor and included in the KAPPA register of Denmark, Norway and Sweden. Data on demographics, treatment history, haemophilia joint health score, and EQ-5D utility were obtained from the register. We used box plots to present utilities and joint status and ordinary least squares regression to evaluate correlates of utilities. Participants were consecutively enrolled in the KAPPA register between April 2013 and June 2016. RESULTS: Overall, 173 participants with median age of 34 (interquartile range: 25-45) were included. Twelve (6.9%) participants were on episodic treatment while 161 (93.1%) were treated using prophylaxis. Concomitant diseases and positive inhibitor history were reported for 73 (43.2%) and 21 (12.1%) participants, respectively. The highest median utility (1.0) was observed among those aged <29 on prophylaxis and those aged 30-44 who had started prophylaxis by age 3. In the multi-variable regression, joint scores of 16-25 (Coef. -0.18, 95% CI: -0.30, -0.06), 26-35 (Coef. -0.21, 95% CI: -0.36, -0.06) and >35 (Coef. -0.37, 95% CI: -0.52, -0.23) were associated with lower utilities. CONCLUSION: Moderate to severe joint manifestations are associated with reduced utilities among persons with severe haemophilia A.
Assuntos
Hemofilia A/complicações , Artropatias/complicações , Artropatias/prevenção & controle , Qualidade de Vida , Sistema de Registros , Adolescente , Adulto , Pré-Escolar , Estudos Transversais , Feminino , Hemofilia A/epidemiologia , Hemofilia A/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Países Escandinavos e Nórdicos/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Impaired platelet function increases the risk of bleeding complications in cardiac surgery. Reliable assessment of platelet function can improve treatment. We investigated whether thromboelastometry detects clinically significant preoperative, perioperative, and postoperative adenosine diphosphate (ADP)-dependent platelet dysfunction in paediatric cardiac surgery patients. METHODS: Fifty-seven children were included in a single-centre prospective observational study. Clot formation (modified rotational thromboelastometry with heparinase, HEPTEM) and platelet aggregation (multiple electrode aggregometry) were analysed at five time points before, during, and after surgery. The accuracy of thromboelastometric indices of platelet function [maximal clot firmness (MCF) and clot formation time (CFT)] to detect ADP-dependent platelet dysfunction (defined as ADP-induced aggregation ≤30 units) was calculated with receiver operating characteristics analysis, which also identified optimal cut-off levels. Positive and negative predictive values for the identified cut-off levels (CFT≥166 s; MCF≤43 mm) to detect platelet function were determined. RESULTS: The MCF and CFT were highly accurate in predicting platelet dysfunction during cardiopulmonary bypass [CPB; area under the aggregation curve 0.89 (95% confidence interval 0.80-0.97) and 0.86 (0.77-0.96), respectively] but not immediately after CPB [0.64 (0.48-0.79) and 0.67 (0.52-0.82), respectively] or on arrival at the intensive care unit [0.53 (0.37-0.69) and 0.60 (0.44-0.77), respectively]. The positive and negative predictive values were acceptable during CPB (87 and 67%, respectively, for MCF≤43 mm; 80 and 100% for CFT≥166 s) but markedly lower after surgery. CONCLUSION: In paediatric cardiac surgery, thromboelastometry has acceptable ability to detect ADP-dependent platelet dysfunction during, but not after, CPB.
Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Período Perioperatório , Agregação Plaquetária , Testes de Função Plaquetária/métodos , Tromboelastografia/métodos , Difosfato de Adenosina/farmacologia , Área Sob a Curva , Transtornos Plaquetários/sangue , Transtornos Plaquetários/diagnóstico , Ponte Cardiopulmonar , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/diagnóstico , Valor Preditivo dos Testes , Estudos ProspectivosRESUMO
INTRODUCTION: Carriers of severe and moderate haemophilia A and B are expected to have approximately 50% of the normal level of factors VIII and IX. However, due to X chromosome inactivation in early embryonic life, factor levels can vary considerably. This can lead to increased bleeding tendency, which may in turn impact on health-related quality of life (HRQOL). AIM: The aim of this study was to assess HRQOL in carriers of severe and moderate haemophilia with and without increased bleeding tendency. METHODS: One hundred and twenty-four adult carriers and 90 controls were recruited. Bleeding tendency was evaluated using a structured bleeding assessment tool. HRQOL was measured by the short form 36 (SF-36) questionnaire. The SF-36 scores were compared with Swedish normative age-matched data and reported as Z scores. RESULTS: There was no significant difference between the whole groups of carriers and controls in the Z scores of the eight SF-36 domains. The mental component summary (MCS) was lower in carriers, compared with controls (P = 0.048). The subgroup of carriers with an increased bleeding tendency had significantly lower Z scores compared to controls regarding the General Health (P = 0.008), the Social Functioning (P = 0.040) and the Mental Health (P = 0.048) domains. The MCS was significantly lower in this carrier subgroup than in controls (P = 0.033). CONCLUSION: We conclude that the subgroup of carriers of haemophilia with increased bleeding tendency have impaired HRQOL. The SF-36 results indicate that this condition affects mental rather than physical health.
Assuntos
Saúde , Hemofilia A/complicações , Hemofilia A/genética , Hemofilia B/complicações , Hemofilia B/genética , Hemorragia/complicações , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos Transversais , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
INTRODUCTION: Haemophilia is a chronic illness that affects the whole family as the child's reactions to the illness occur in interaction with the parents. Limited research has been conducted on how fathers of children with haemophilia experience their life situation. AIM: The aim of this study was to describe the lived experience of being a father to a child with severe haemophilia. METHOD: Individual, qualitative interviews were conducted with 14 fathers of 17 children with severe Haemophilia A. Data were analysed by means of a phenomenological hermeneutic method, including naïve reading, structural analysis and comprehensive interpretation. RESULTS: The results revealed that the fathers gradually grew into fatherhood through a process that can be explained in the metaphor, 'A tortuous road to a capable fatherhood'. The fathers experienced sorrow, powerlessness, concern and loss of a regular fatherhood after the child's diagnosis. The loss of an envisaged fatherhood emerged as the greatest sorrow of being a father to a child with haemophilia. When home treatment with factor concentrates functioned without the involvement of Health Care Personal (HCP), the fathers' sense of insufficiency decreased. CONCLUSION: A sense of being a capable father was associated with a sense of independence and control of one's life situation. Support from the Haemophilia Treatment Centre (HTC) in the learning process is essential for both parents of a child with severe haemophilia. Awareness of the fathers' struggle to feel capable is also vital while supporting the family in the first years after diagnosis.
Assuntos
Emoções , Pai/psicologia , Hemofilia A , Adulto , Criança , Esperança , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Poder PsicológicoRESUMO
Haemophilia is an X-linked inherited rare bleeding disorder affecting mainly men. The treatment consists of replacement therapy that has been associated with severe side effects, such as blood transmitted viral infections, but has markedly improved over the last decades. The aim of this study was to study family structure over time among Swedish persons with haemophilia (PWH), focusing on children, siblings and marital status. PWH A or B were identified from the haemophilia centres and the national Patient Registry. Each PWH was compared to five age- and gender-matched controls. The national Multi-Generation Registry was used to identify children and siblings. A total of 1365 children with a father suffering from haemophilia A or B and 1938 siblings of the PWH were identified. Having one or more children was significantly less common (P = 0.003) for PWH than for controls. Significantly lower rates of having a child were also found for the subgroups of persons suffering from severe haemophilia and those infected with HIV (P < 0.001). A higher proportion of PWH, with or without HIV and/or viral hepatitis had siblings compared to the controls (P < 0.001). However, the mean number of siblings was significantly lower for persons with severe haemophilia (P = 0.001). The number of marriages and divorces did not differ between PWH and controls. Our data indicate a negative impact of HIV and viral hepatitis on family structure for PWH despite the relatively good access to treatment in Sweden over the last few decades. This was particularly true for those with a severe form of haemophilia.
Assuntos
Família , Hemofilia A/epidemiologia , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Irmãos , Suécia/epidemiologiaRESUMO
BACKGROUND: Platelet deficiency, impaired platelet function, or both increase the risk of bleeding complications. We assessed platelet count and function during and after paediatric cardiac surgery. Secondary aims included the effect of modified ultrafiltration, identification of factors associated with platelet dysfunction, and to assess associations between platelet function and transfusion requirements. METHODS: Fifty-seven patients were included in a prospective observational study. Platelet count and platelet function (multiple-electrode impedance aggregometry) were analysed before and during cardiopulmonary bypass (CPB), after modified ultrafiltration, on arrival at the intensive care unit, and on the first postoperative day. Intraoperative transfusions of blood products were registered. RESULTS: Both platelet count and platelet aggregation were markedly reduced during surgery with the greatest reduction at the end of CPB. On postoperative day 1, platelet count was still reduced by 50%, while platelet aggregation had returned to-or above-preoperative levels. There were only moderate correlations between platelet count and platelet aggregation. Modified ultrafiltration had no significant influence on platelet count or aggregation. Young age, low weight, and long operation time were associated with poor platelet aggregation during surgery, while young age, low weight, high preoperative haemoglobin levels, and low preoperative platelet count were associated with poor aggregation after operation. Patients with impaired platelet function during CPB had markedly increased intraoperative transfusion requirements. CONCLUSIONS: Platelet count and platelet aggregation are markedly reduced during and immediately after paediatric cardiac surgery, especially in neonates. The recovery in aggregation is faster than that in platelet count. Intraoperative platelet dysfunction is associated with increased transfusion requirements.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Contagem de Plaquetas , Testes de Função Plaquetária , Anestesia Geral , Anticoagulantes/uso terapêutico , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Transfusão de Sangue/estatística & dados numéricos , Pré-Escolar , Ponte de Artéria Coronária , Feminino , Humanos , Lactente , Recém-Nascido , Período Intraoperatório , Masculino , Estudos Prospectivos , UltrafiltraçãoRESUMO
Limited research has been conducted on how the female carrier experiences her life with a haemophilic child, and earlier studies are mostly questionnaire-based. No previous qualitative study on the female carrier's situation has been conducted in Sweden. The aim of the study was to describe the lived experience of being a carrier of severe or moderate haemophilia and of being the mother of a haemophilic child. The study was conducted via qualitative interviews and analysed by means of a phenomenological hermeneutic method; a total of 13 haemophilia carriers were interviewed in 2010. Being a carrier of haemophilia and having a haemophilic child was life changing. The women moved from a state of sad, guilty chaos to reconciling themselves with the new situation. Our analysis revealed three acts in which phenomena appeared: the time after diagnosis, the turning point and reconciliation with a changing life. Emerging as crucial to the process of reconciliation with a changing life was a sense of being fully informed and supported. The Haemophilia Treatment Centre (HTC) should create an environment that encourages learning, and the team should invite and encourage the woman's partner to be actively involved in the child's care. Moreover, the results indicate that it would be beneficial to invite female carriers to receive patient education at the HTC before they plan to start a family. During this visit, the woman may gain a greater understanding of her carriership to prepare her for future decisions concerning prenatal diagnosis, for example.
Assuntos
Hemofilia A/psicologia , Hemofilia B/psicologia , Heterozigoto , Mães/psicologia , Adaptação Psicológica , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Culpa , Hemofilia A/genética , Hemofilia B/genética , Humanos , Pessoa de Meia-Idade , Pesquisa Qualitativa , SuéciaRESUMO
Sweden has been a pioneer in the treatment of haemophilia, with the first concentrate available in the 1950s. Treatment has improved over the years to its current state-of-the art. The aim of the current study was to evaluate the long-term outcome of haemophilia in terms of incidence, morbidity and mortality. Patients diagnosed with haemophilia A or B registered at the national haemophilia centres and/or the Patient Registry and born before 2009 and alive in 1968 were enrolled and linked to the Cause of Death-, Migration- and Medical Birth registries. Five age- and sex-matched controls were selected for each patient. A total of 1431 patients with haemophilia A or B were compared with 7150 controls. The 3-year moving average incidence rate per 100,000 population varied between 21 and 36. The hazard ratio for all-cause mortality compared with controls was 2.2, 95% CI: [1.8; 2.7], P < 0.001 for the entire group of patients and 1.7, 95% CI: [1.3; 2.2], P < 0.001 when patients with HIV and/or viral hepatitis were excluded. The corresponding figures for the severe haemophilia subgroup were 6.6, 95% CI: [4.5; 10.0], P < 0.001 and 8.2, 95% CI [3.2; 20.8], P < 0.001 respectively. The most common causes of death were related to malignancies and the haemostatic defect. People with haemophilia were 57% less likely to die from ischaemic heart disease than controls. People with haemophilia in Sweden demonstrate higher mortality over time, independent of HIV and viral hepatitis, despite relatively advantageous access to clotting factor concentrates.
Assuntos
Hemofilia A/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Criança , Pré-Escolar , Estudos de Coortes , Hemofilia A/mortalidade , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/mortalidade , Modelos de Riscos Proporcionais , Sistema de Registros , Fatores de Risco , Suécia/epidemiologia , Adulto JovemRESUMO
Factor VIII Inhibitor Bypassing Activity (FEIBA) can effectively achieve haemostasis in haemophilia patients with inhibitors. Further evaluation of FEIBA in surgical settings is of significant interest considering the relatively limited prospective data published to date. The aim of the study is to evaluate the perioperative efficacy and safety of FEIBA in haemophilia patients with inhibitors. Haemophilia patients with inhibitors who underwent surgical procedures and received FEIBA for perioperative haemostatic control were prospectively enrolled in an open-label, noninterventional, postauthorization study [SURgical interventions with FEIBA (SURF)]. Outcome measures included haemostatic efficacy, safety, FEIBA exposure and blood loss associated with the perioperative use of FEIBA. Thirty-five surgical procedures were performed at 19 centres worldwide in patients with congenital haemophilia A, congenital haemophilia B, or acquired haemophilia A. Haemorrhagic risk was severe in 37.1% (13 of 35) of the procedures, moderate in 25.7% (9 of 35) and mild in 37.1% (13 of 35). One moderate risk surgery was excluded from the efficacy analyses because it did not meet all protocol requirements. Haemostasis was judged to be 'good' or 'excellent' in 91.2% (31 of 34) of surgical procedures and 'fair' in 8.8% (3 of 34). Among the 12 adverse events, three were serious adverse events (SAEs), two of which were unrelated to FEIBA therapy; one SAE, a clot in an arteriovenous fistula, was deemed to be possibly related to therapy. This prospective investigation confirms that FEIBA can be safely and effectively used when performing surgical procedures in haemophilia patients with inhibitors.
Assuntos
Fatores de Coagulação Sanguínea/uso terapêutico , Hemofilia A/tratamento farmacológico , Hemofilia B/tratamento farmacológico , Isoanticorpos/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Perda Sanguínea Cirúrgica , Criança , Pré-Escolar , Fator VIII/imunologia , Fator VIII/metabolismo , Fator VIII/uso terapêutico , Feminino , Hemoglobinas/análise , Hemofilia A/cirurgia , Hemofilia B/cirurgia , Hemostasia Cirúrgica , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória , Sistema de Registros , Adulto JovemRESUMO
In an ongoing health-technology assessment of haemophilia treatment in Sweden, performed by the governmental agency Dental and Pharmaceutical Benefits Agency (TLV; tandvårds-och lakemedelsförmånsverket), the Swedish Council on Health Technology Assessment (SBU; statens beredning för medicinsk utvardering) was called upon to evaluate treatment of haemophilia A and B and von Willebrand's disease (VWD) with clotting factor concentrates. To evaluate the following questions: What are the short-term and long-term effects of different treatment strategies? What methods are available to treat haemophilia patients that have developed inhibitors against factor concentrates? Based on the questions addressed by the project, a systematic database search was conducted in PubMed, NHSEED, Cochrane Library, EMBASE and other relevant databases. The literature search covered all studies in the field published from 1985 up to the spring of 2010. In most instances, the scientific evidence is insufficient for the questions raised in the review. Concentrates of coagulation factors have good haemostatic effects on acute bleeding and surgical intervention in haemophilia A and B and VWD, but conclusions cannot be drawn about possible differences in the effects of different dosing strategies for acute bleeding and surgery. Prophylaxis initiated at a young age can prevent future joint damage in persons with haemophilia. The available treatment options for inhibitors have been insufficiently assessed. The economic consequences of various treatment regimens have been insufficiently analysed. Introduction of national and international registries is important.
Assuntos
Fatores de Coagulação Sanguínea/uso terapêutico , Hemofilia A/tratamento farmacológico , Hemofilia B/tratamento farmacológico , Doenças de von Willebrand/tratamento farmacológico , Fatores de Coagulação Sanguínea/administração & dosagem , Humanos , Artropatias/prevenção & controle , SuéciaAssuntos
Fator VIII/genética , Hemofilia A/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Testes de Coagulação Sanguínea , Códon sem Sentido , Estudos Transversais , DNA/química , DNA/genética , DNA/metabolismo , Fator VIII/análise , Fator VIII/metabolismo , Genótipo , Hemofilia A/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Fenótipo , Análise de Sequência de DNARESUMO
There has been increasing interest in the patient's perspective on outcome of treatment. The Haemophilia Activity List (HAL) has been developed as a disease-specific questionnaire for haemophilia patients and is a validated self-report measure of function developed according to WHO's International Classification of Functioning, Disability and Health. To validate HAL in Sweden. The Dutch and English versions of HAL were translated into Swedish using 'the forward-backward translation' method and merged into a final Swedish version. Validation was performed against the Swedish version of the questionnaires Arthritis Impact Measurement 2 (AIMS 2) and Impact on Participation and Autonomy (IPA). Two hundred and twenty-five patients with severe and moderate forms of haemophilia A and B from three centres were invited to participate in the study. Spearman's rank correlation test was used for validation, and internal consistency of the HAL was calculated with Cronbach's alpha. Eighty-four patients (39%) (18-80 years old) filled out the questionnaires. The internal consistency of the Swedish version of HAL was high, with Cronbach's alpha being 0.98-0.71. Function of the legs had the highest consistency and transportation had the lowest. The correlation was excellent between the HAL sum score and AIMS 2 physical (r = 0.84, P < 0.01), IPA autonomy indoors (r = 0.83, P < 0.01) and autonomy outdoors (r = 0.89, P < 0.01). The Swedish version of HAL has both internal consistency and convergent validity and may complement other functional tests to gather information on the patient's self-perceived ability.
Assuntos
Atividades Cotidianas , Avaliação da Deficiência , Hemofilia A/fisiopatologia , Hemofilia B/fisiopatologia , Inquéritos e Questionários/normas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Adulto JovemAssuntos
Hemofilia A/genética , Hemorragia/genética , Trombina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Adulto JovemRESUMO
To elucidate the possible role of genetic variation in androgen receptor (AR), estrogen receptor alpha (ER alpha), and ER beta on serum androgen levels in premenopausal women, the CAG repeat polymorphism of the AR gene, the TA repeat polymorphism of the ER alpha gene, and the CA repeat polymorphism of the ER beta gene were studied in a population-based cohort of 270 women. Total testosterone, free testosterone, dehydroepiandrosterone sulfate, androstenedione, 17-hydroxyprogesterone, 3 alpha-androstanediol glucuronide, 17 beta-estradiol, LH, FSH, and sex steroid hormone-binding globulin (SHBG) were measured in serum samples obtained in the follicular phase of the menstrual cycle. Women with relatively few CAG repeats in the AR gene, resulting in higher transcriptional activity of the receptor, displayed higher levels of serum androgens, but lower levels of LH, than women with longer CAG repeat sequences. The CA repeat of the ER beta gene also was associated with androgen and SHBG levels; women with relatively short repeat regions hence displayed higher hormone levels and lower SHBG levels than those with many CA repeats. In contrast, the TA repeat of the ER alpha gene was not associated with the levels of any of the hormones measured. Our results suggest that the serum levels of androgens in premenopausal women may be influenced by variants of the AR gene and the ER beta gene, respectively.
Assuntos
Androgênios/sangue , Polimorfismo Genético/fisiologia , Receptores Androgênicos/genética , Receptores de Estrogênio/genética , Adulto , Sequência de Bases/genética , Estudos de Coortes , Receptor beta de Estrogênio , Feminino , Hormônio Foliculoestimulante/sangue , Hormônios Esteroides Gonadais/sangue , Humanos , Hormônio Luteinizante/sangue , Globulina de Ligação a Hormônio Sexual/análise , Repetições de TrinucleotídeosRESUMO
INTRODUCTION: Apixaban is an oral direct factor Xa inhibitor developed for the prophylaxis and treatment of thromboembolic disorders. Laboratory monitoring is not necessary, but the effects on common coagulation reagents and assays constitute clinically valuable information. OBJECTIVES: To investigate the effects of apixaban on commonly used coagulation methods, and to evaluate anti-FXa assays for specific determination of the drug concentration. MATERIALS AND METHODS: Apixaban was added to plasma from healthy subjects in the concentration range 0-1000 µg L(-1) , and analyses were performed with different reagents for activated partial thromboplastin time (APTT), prothrombin time (PT), antithrombin, protein C, and protein S. A lupus anticoagulant assay and an APTT assay with varying phospholipid concentrations were used to study the phospholipid dependence. RESULTS: In general, apixaban showed fewer effects in vitro than have been shown for rivaroxaban, another direct FXa inhibitor. The concentration needed to double the APTT varied between 2200 and 4700 µg L(-1) , and the concentration needed to double the PT varied between 700 and 3900 µg L(-1) . The effects on antithrombin, protein C and protein S assays were dependent on the type of reagent. Apixaban did not cause false-positive lupus anticoagulant results. Chromogenic anti-FXa assays showed linear dose-response curves with apixaban. CONCLUSIONS: Therapeutic concentrations of apixaban variably affect different assay groups, and even different reagents within an assay group. The effects were much smaller than with rivaroxaban. The use of APTT and/or PT assays to screen the anticoagulant activity of apixaban cannot be recommended. A chromogenic anti-FXa assay can be used for reliable measurements of apixaban concentration.
Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Inibidores do Fator Xa/química , Fator Xa/química , Pirazóis/química , Piridonas/química , Administração Oral , Calibragem , Reações Falso-Positivas , Voluntários Saudáveis , Humanos , Coeficiente Internacional Normatizado , Inibidor de Coagulação do Lúpus/química , Morfolinas/química , Tempo de Tromboplastina Parcial , Fosfolipídeos/química , Proteína C/química , Proteína S/química , Tempo de Protrombina , Reprodutibilidade dos Testes , Rivaroxabana , Tiofenos/químicaRESUMO
INTRODUCTION: Rivaroxaban is an oral direct factor Xa inhibitor developed for prophylaxis and treatment of thromboembolic disorders. Laboratory monitoring is not necessary but the dose-dependent effects on common reagents and assay procedures are largely unknown. OBJECTIVES: To investigate the effect of rivaroxaban on commonly used coagulation assays. MATERIALS AND METHODS: Rivaroxaban was added to plasma from healthy subjects in the concentration range 0-1000 µg L(-1) and analyzed using different reagents for activated partial thromboplastin time (APTT), prothrombin time (PT), antithrombin, fibrinogen and activated protein C (APC) resistance assays. RESULTS: At an expected peak concentration of rivaroxaban in clinical use, the APTTs were almost invariably prolonged but at lower concentrations the effect was weak. The concentration needed to double the APTT varied between 389 ± 106 and 617 ± 149 µg L(-1) for different reagents. The PT assays showed a marked degree of difference. In general, the Quick PT type assays were more sensitive compared with the Owren type PT assays. The results from antithrombin assays were dependent on the type of reagent, with the Xa-based assay being sensitive for rivaroxaban with an estimated increase of 0.09 IU mL(-1) per 100 µg L(-1) rivaroxaban. There were only minor effects on fibrinogen assays based on thrombin reagents. The APTT-based assay for APC resistance is affected in a dose-dependent manner whereas an assay based on the activation of coagulation at the prothrombinase level was unaffected. CONCLUSIONS: Different assays, and even different reagents within an assay group, display variable effects by therapeutic concentrations of rivaroxaban.
Assuntos
Anticoagulantes/administração & dosagem , Testes de Coagulação Sanguínea , Coagulação Sanguínea/efeitos dos fármacos , Inibidores do Fator Xa , Morfolinas/administração & dosagem , Tiofenos/administração & dosagem , Resistência à Proteína C Ativada/sangue , Administração Oral , Adulto , Antitrombinas/metabolismo , Relação Dose-Resposta a Droga , Feminino , Fibrinogênio/metabolismo , Humanos , Masculino , Tempo de Tromboplastina Parcial , Valor Preditivo dos Testes , Tempo de Protrombina , Reprodutibilidade dos Testes , RivaroxabanaRESUMO
Raised levels of inflammation markers have been associated with several mental disorders; however, studies regarding the relationship between inflammation or the immune system and various aspects of human behaviour are not numerous. The aim of the present study was to investigate whether an association exists between personality traits and two single nucleotide polymorphisms located in genes that are associated with the innate immune system. The studied population consisted of 42-year-old women recruited from the population registry that had been assessed by means of Karolinska Scales of Personality, a self-reported inventory. The first polymorphism, +1444C>T (rs1130864), is located in the gene coding for C-reactive protein (CRP), a marker of low-grade inflammation. The T-allele has previously been suggested to be linked to raised serum levels of CRP. The second polymorphism, Y402H (1277T>C, rs1061170), is located in the gene coding for complement factor H, an important regulator of the complement system. The C-allele has consistently been associated with age-related macular degeneration. While the +1444T allele was associated with higher scores in the personality traits impulsiveness, monotony avoidance and social desirability, the 1277C polymorphism was associated with higher scores in verbal aggression and lower scores in social desirability. In conclusion, the associations between the personality traits and the studied polymorphisms further support the possible influence of the immune system on mental functions.
Assuntos
Imunidade Inata/genética , Personalidade/genética , Proteína C-Reativa/genética , Proteína C-Reativa/fisiologia , DNA/genética , Análise Mutacional de DNA , Extroversão Psicológica , Feminino , Variação Genética , Genótipo , Humanos , Imunidade Inata/fisiologia , Pessoa de Meia-Idade , Transtornos Neuróticos/genética , Transtornos Neuróticos/psicologia , Personalidade/fisiologia , Testes de Personalidade , Polimorfismo Genético/genética , Transtornos Psicóticos/genética , Transtornos Psicóticos/psicologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Desejabilidade SocialAssuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Ponte de Artéria Coronária/efeitos adversos , Fibrinogênio/uso terapêutico , Técnicas Hemostáticas , Hemorragia Pós-Operatória/prevenção & controle , Idoso , Testes de Coagulação Sanguínea , Transfusão de Sangue , Feminino , Hemostáticos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/sangue , Hemorragia Pós-Operatória/etiologia , Proteínas Recombinantes/uso terapêutico , Suécia , Fatores de Tempo , Resultado do TratamentoRESUMO
The associations were examined in women between personality traits and steroid hormones, particularly androgens, as well as polymorphisms in genes regulating androgen concentration and effects. Women, all 42 years of age and premenopausal (n = 270), were recruited randomly. Conventional "masculine" and "feminine" personality traits were examined by questionnaire and set in relation to psychosocial and socioeconomic conditions, behavior in childhood, hormones, risk factors for disease, and polymorphisms in microsatellites in the CYP aromatase and the androgen receptor gene. The proportions of personality traits considered as being dominated by "masculinity" (M) or "femininity" (F) were 44.9%, respectively 15.0%, the rest consisting of a combination of M and F (33.2%) or "undifferentiated" (6.9%). M characteristics were positively associated with education, sporting, self-confidence, and good adaptation to work situation. M scores correlated with reports of "tomboyism" as girls. There was essentially no difference in hormones or disease risk factors between M and F women. The number of (CAG) repeats in the microsatellite of the transactivating domain of the androgen receptor was 19 (2.3; M and SD). M characteristics were more pronounced in the presence of longer repeat stretches (n > 20). No associations were found with F scores. There were no significant associations to the number of tetranucleotide repeats (TTTA) in the fourth introne of the aromatase gene. It was concluded that a majority of women showed M type of personality traits, associated with normal hormones, somatic health, and a long microsatellite in the transactivating domain of the AR gene.