RESUMO
BACKGROUND: Inborn errors affecting components of the T-cell receptor signaling cascade cause combined immunodeficiency with various degrees of severity. Recently, homozygous variants in LCP2 were reported to cause pediatric onset of severe combined immunodeficiency with neutrophil, platelet, and T- and B-cell defects. OBJECTIVE: We sought to unravel the genetic cause of combined immunodeficiency and early-onset immune dysregulation in a 26-year-old man who presented with specific antibody deficiency, autoimmunity, and inflammatory bowel disease since early childhood. METHODS: The patient was subjected to whole-exome sequencing of genomic DNA and examination of blood neutrophils, platelets, and T and B cells. Expression levels of the Src homology domain 2-containing leukocyte protein of 76 kDa (SLP76) and tonic and ligand-induced PI3K signaling were evaluated by flow-cytometric detection of phosphorylated ribosomal protein S6 in B and T cells. RESULTS: Compound heterozygous missense variants were identified in LCP2, affecting the proline-rich repeat domain of SLP76 (p.P190R and p.R204W). The patient's total B- and T-cell numbers were within the normal range, as was platelet function. However, neutrophil function, numbers of unswitched and class-switched memory B cells, and serum IgA were decreased. Moreover, intracellular SLP76 protein levels were reduced in the patient's B cells, CD4+ and CD8+ T cells, and natural killer cells. Tonic and ligand-induced levels of phosphorylated ribosomal protein S6 and ligand-induced phosphorylated PLCγ1 were decreased in the patient's B cells and CD4+ and CD8+ T cells. CONCLUSIONS: Biallelic variants in LCP2 impair neutrophil function and T-cell and B-cell antigen-receptor signaling and can cause combined immunodeficiency with early-onset immune dysregulation, even in the absence of platelet defects.
Assuntos
Fosfatidilinositol 3-Quinases , Imunodeficiência Combinada Severa , Masculino , Criança , Humanos , Pré-Escolar , Adulto , Fosfatidilinositol 3-Quinases/genética , Linfócitos T CD8-Positivos , Ligantes , Proteína S6 Ribossômica/genética , Transdução de Sinais/genética , Imunodeficiência Combinada Severa/genética , Imunodeficiência Combinada Severa/diagnóstico , MutaçãoRESUMO
Central venous access devices (CVADs) are commonly used in malignancies. We conducted an online, anonymous cross-sectional survey of practice regarding CVAD management in haematology centres among clinicians in Australia and New Zealand. We identified variation in clinical practice regarding CVAD selection, insertion, management and removal. These findings highlight research gaps in CVAD care.
Assuntos
Cateterismo Venoso Central , Cateteres Venosos Centrais , Hematologia , Humanos , Estudos Transversais , Nova Zelândia , AustráliaRESUMO
BACKGROUND: Idiopathic upper extremity deep vein thrombosis (UEDVT) management is controversial and ranges from anticoagulation alone to the addition of further interventions such as thrombolysis and decompressive surgery. OBJECTIVES: The objective of this systematic review was to assess the effects of anticoagulation alone compared to anticoagulation with additional interventions such as thrombolysis or decompressive surgery on the incidence of recurrent UEDVT and post-thrombotic syndrome (PTS) in patients with idiopathic UEDVT (including those associated with the oral contraceptive pill). PATIENTS/METHODS: A systematic search was conducted for studies which focused on acute UEDVT treatment defined as therapies starting within 4 weeks of symptom onset. We limited studies to those that recruited 10 or more subjects and involved at least 6 weeks to 12 months anticoagulation alone or together with additional interventions with at least 6-month follow-up. Primary outcomes were symptomatic recurrent radiologically confirmed UEDVT and PTS. Secondary outcomes were symptomatic venous thromboembolism, bleeding and mortality. RESULTS: We found seven studies which reported recurrent UEDVT rates and five that reported PTS rates. All studies were retrospective or cross-sectional. None compared anticoagulation alone to anticoagulation with additional intervention. Study heterogeneity precluded meta-analysis and risk of bias was moderate to serious. Recurrent UEDVT occurred in 0% to 12% post-anticoagulation alone and 0% to 23% post-additional interventions. PTS rates varied from 4% to 32% without severe PTS. Only limited studies reported on our secondary outcomes. CONCLUSION: There is limited evidence behind idiopathic UEDVT management. Prospective comparative studies in this area are essential.
Assuntos
Trombose Venosa Profunda de Membros Superiores , Anticoagulantes/uso terapêutico , Anticoncepcionais Orais , Estudos Transversais , Feminino , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Trombose Venosa Profunda de Membros Superiores/diagnóstico , Trombose Venosa Profunda de Membros Superiores/epidemiologia , Trombose Venosa Profunda de Membros Superiores/etiologiaRESUMO
Cannula provoked upper extremity superficial vein thrombophlebitis (UESVT) is common. Retrospective audit of 93 consecutive patients, 51% male, median age 57 years (range 20-91), with symptomatic UESVT revealed varied management including symptomatic management (37%), prophylactic (37%) and higher dose anticoagulation (27%). There was 2% (95% confidence interval (CI) 0-7.6) thrombus extension and 1% (95% CI 0-5.9) major bleeding, both limited to cancer. We argue anticoagulation is unnecessary in most UESVT patients.
Assuntos
Cânula , Tromboflebite , Masculino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Estudos Retrospectivos , Extremidade Superior , Tromboflebite/etiologia , Anticoagulantes/efeitos adversosRESUMO
Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare, but serious, syndrome characterised by thrombocytopenia, thrombosis, a markedly raised D-dimer and the presence of anti-platelet factor-4 (PF4) antibodies following COVID-19 adenovirus vector vaccination. VITT occurs at a rate of approximately 2 per 100 000 first-dose vaccinations and appears exceedingly rare following second doses. Our current understanding of VITT pathogenesis is based on the observations that patients with VITT have antibodies that bind to PF4 and have the ability to form immune complexes that induce potent platelet activation. However, the precise mechanisms that lead to pathogenic VITT antibody development remain a source of active investigation. Thrombosis in VITT can manifest in any vascular bed and affect multiple sites simultaneously. While there is a predilection for splanchnic and cerebral venous sinus thrombosis, VITT also commonly presents with deep vein thrombosis and pulmonary embolism. Pillars of management include anticoagulation with a non-heparin anticoagulant, intravenous immunoglobulin and 'rescue' therapies, such as plasma exchange for severe cases. VITT can be associated with a high mortality rate and significant morbidity, but awareness and optimal therapy have significantly improved outcomes in Australia. A number of questions remain unanswered, including why VITT is so rare, reasons for the predilection for thrombosis in unusual sites, how long pathological antibodies persist, and the optimal duration of anticoagulation. This review will provide an overview of the presentation, diagnostic workup and management strategies for patients with VITT.
Assuntos
COVID-19 , Trombocitopenia , Trombose , Vacinas , Anticoagulantes/efeitos adversos , Vacinas contra COVID-19/efeitos adversos , Humanos , Fator Plaquetário 4/efeitos adversos , SARS-CoV-2 , Trombocitopenia/induzido quimicamente , Trombose/induzido quimicamente , Trombose/complicações , Vacinas/efeitos adversosRESUMO
BACKGROUND: Peripherally inserted central catheter (PICC) thrombosis is common. AIMS: To explore the prevalence of symptomatic PICC thrombosis and pulmonary embolism (PE)/deep vein thrombosis (DVT) in cancer and non-cancer cohorts. In active cancer, we assessed the Khorana risk score (KRS) and Michigan risk score (MRS) for predicting PICC thrombosis and modifications to improve discriminative accuracy. METHODS: We reviewed consecutive cancer patients receiving chemotherapy through a PICC inserted April 2017 to July 2018. For each case, we identified a contemporaneous non-cancer control. RESULTS: Among 147 cancer patients, median age 64 years, PICC duration 70 days (range, 2-452), 7% developed PICC thrombosis (95% confidence interval (CI) 3.6-12.2) and 4% (95% CI 2-9) PE/DVT. Among 147 controls, median age 68 years, PICC duration 18.3 days (range, 0.5-210), 0.7% (95% CI 0-4) developed PICC thrombosis and 2% (95% CI 0.4-6) PE/DVT. In our cancer cohort, no KRS < 1 patients developed PICC thrombosis (95% CI 0-11) compared with 9% (95% CI 5-16) in KRS ≥ 1 (P = 0.12). PICC thrombosis occurred in 4.7% (95% CI 1.5-11.7) MRS ≤ 3 compared with 10.9% (95% CI 4.1-22.2) MRS > 3 (P = 0.32). The addition of thrombocytosis, a variable from KRS, to MRS (modified MRS (mMRS)) improved discriminative value for PICC thrombosis (c-statistic MRS 0.63 (95% CI 0.44-0.82), mMRS 0.72 (95% CI 0.58-0.85)). PICC thrombosis occurred in 1.4% (95% CI 0-8.3) mMRS ≤ 3 and 11.8% (95% CI 6.1-21.2) mMRS > 3 (P = 0.02). More patients were categorised as low risk using mMRS ≤ 3 (47%) than KRS < 1 (22%). CONCLUSION: Cancer patients had longer PICC durations and higher PICC thrombosis rates than those without (7% vs 0.7%). mMRS more accurately classified low PICC thrombosis risk than KRS <1(47% vs 22%). Prospective validation of mMRS is warranted.
Assuntos
Cateterismo Venoso Central , Cateterismo Periférico , Neoplasias , Embolia Pulmonar , Trombose Venosa Profunda de Membros Superiores , Idoso , Humanos , Pessoa de Meia-Idade , Cateterismo Venoso Central/efeitos adversos , Cateterismo Periférico/efeitos adversos , Catéteres , Neoplasias/epidemiologia , Neoplasias/terapia , Neoplasias/etiologia , Embolia Pulmonar/etiologia , Fatores de Risco , Trombose Venosa Profunda de Membros Superiores/epidemiologia , Trombose Venosa Profunda de Membros Superiores/etiologiaRESUMO
Upper extremity deep vein thrombosis (UEDVT) has been increasing in incidence due to the escalating use of central venous catheters such as peripherally inserted central catheters. UEDVT can be primary idiopathic or secondary to pacemaker leads, intravascular catheters or cancer. In comparison to conventional venous thromboembolism such as lower limb deep vein thrombosis or pulmonary embolism the risk factors, investigations, and management are not well defined. We review current evidence in primary and secondary UEDVT, highlighting areas in need of further research. We also explore the entity of venous thoracic outlet syndrome, which is said to be a risk factor for recurrent primary UEDVT and is the rationale behind surgical interventions.
Assuntos
Cateteres Venosos Centrais , Trombose Venosa Profunda de Membros Superiores , Tromboembolia Venosa , Trombose Venosa , Humanos , Recidiva Local de Neoplasia , Fatores de Risco , Trombose Venosa Profunda de Membros Superiores/diagnóstico , Trombose Venosa Profunda de Membros Superiores/etiologia , Trombose Venosa Profunda de Membros Superiores/terapia , Trombose Venosa/etiologiaRESUMO
BACKGROUND: Ferric carboxymaltose is increasingly utilised to treat iron deficiency and is usually diluted in saline and administered as an intravenous infusion over 15 min. Although this is highly convenient compared with older formulations, we hypothesised the drug could be administered, safely given as a rapid bolus injection. AIMS: To define the risk of serious adverse events following administration of an undiluted, rapid, high-dose ferric carboxymaltose injection. Secondary aims included all other adverse events, as well as longitudinal effects on haemoglobin, iron stores, phosphate and hepcidin. METHODS: In a single-arm, Phase II study in 121 patients with iron-deficiency anaemia, we administered up to 1000 mg of ferric carboxymaltose as a rapid undiluted bolus injection, and recorded adverse events and collected blood samples over the first hour, and again at 2 and 4 weeks post-treatment. RESULTS: No patient experienced a serious adverse event. Flushing during the injection was common, as was a transient headache in the subsequent weeks. One patient experienced Grade 3 chest tightness, necessitating emergency department assessment but not admission or treatment. Treatment produced an average 12.3 g/L improvement in haemoglobin within 2 weeks, but commonly caused reductions in serum phosphate (although none of these was clinically symptomatic). Parenteral iron caused elevations in hepcidin sustained to 4 weeks post-injection. Patients stated they would be prepared to receive the treatment again. CONCLUSION: Rapid injection of undiluted ferric carboxymaltose is well tolerated and could provide an approach to treat patients in the ambulatory setting.
Assuntos
Anemia Ferropriva , Anemia Ferropriva/tratamento farmacológico , Compostos Férricos/efeitos adversos , Humanos , Ferro , Maltose/efeitos adversos , Maltose/análogos & derivadosRESUMO
Residual perfusion defects (RPD) as detected by lung scintigraphy occur in over 50% of patients with acute pulmonary embolism (PE) treated with vitamin K antagonists but there is lack of data in patients treated with direct oral anticoagulants. The aim of this retrospective study was to estimate the incidence of RPD detected by ventilation perfusion (VQ) scan at 3-6 months in patients with first acute symptomatic PE treated with rivaroxaban compared to warfarin. Consecutive eligible patients treated with rivaroxaban as part of a previous study were identified. The Monash Health Radiology database was used to identify a historical cohort of age matched (± 5 years) patients treated with warfarin. Follow-up VQ scans were classified as normal (no perfusion defect) or abnormal (matched or unmatched perfusion defects) by two independent nuclear medicine physicians blinded to treatment. Any disagreement was resolved by consensus. One hundred and ninety patients with PE (95 in each cohort) were included (mean age 56.8 years; 41.1% males; 54.2% unprovoked). In the overall cohort, 31.1% had RPD with a significantly lower incidence of RPD in rivaroxaban treated patients 23.2% (95% CI 15.8-32.6), compared to warfarin 38.9% (95% CI 29.8-49.0). Treatment with rivaroxaban was associated with a significantly lower incidence of RPD detected by VQ scan at 3-6 months compared to warfarin. This supports recent in-vitro data suggesting an indirect enhancement of fibrinolysis by direct oral Xa inhibitors but requires confirmation in larger studies.
Assuntos
Anticoagulantes/administração & dosagem , Inibidores do Fator Xa/administração & dosagem , Imagem de Perfusão/métodos , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/tratamento farmacológico , Rivaroxabana/administração & dosagem , Varfarina/administração & dosagem , Doença Aguda , Adulto , Idoso , Anticoagulantes/efeitos adversos , Estudos de Coortes , Inibidores do Fator Xa/efeitos adversos , Feminino , Seguimentos , Humanos , Incidência , Pulmão/diagnóstico por imagem , Pulmão/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Cintilografia/métodos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
In trials assessing venous thromboembolism (VTE) treatment, obese patients are under-represented or excluded. The main objective of this article is to examine the safety of weight-based enoxaparin dosing in obesity, as assessed by anti-factor Xa (anti-Xa) activity, bleeding, and recurrence. A 5-year retrospective audit of patients with acute VTE, weighing > 100 kg, prescribed enoxaparin 1 mg/kg twice daily, with an anti-Xa level 2 to 6 hours post-dose. The primary outcome was anti-Xa levels, and the secondary outcomes were bleeding and recurrence. Results were compared with patients weighing < 100 kg (n = 64), and obese patients prescribed doses < 1 mg/kg (n = 28). One-hundred sixty-six patients weighing > 100 kg with VTE were identified, with 64 excluded for not fulfilling criteria. The remaining 102 patients had a median weight of 130 kg (range: 105-222 kg). The median peak anti-Xa level was 0.93 U/mL, with 56% of levels being in the proposed therapeutic range (0.5-1.0 U/mL), 40% > 1.0 U/mL, and 4% < 0.5 U/mL. The median anti-Xa levels and distribution were not significantly different between patients > 100 kg and patients < 100 kg, while obese patients prescribed < 1 mg/kg were more frequently subtherapeutic (21%). Regardless of weight, the majority of patients with moderate renal impairment (eGFR 30-59 mL/min) had an anti-Xa level > 1.0 U/mL (61%). In the obese patients, there was no major bleeding or recurrence within 30 days. In comparison, patients weighing < 100 kg, despite similar peak anti-Xa levels, had higher rates of bleeding and recurrence. This was likely due to their older age and comorbidities, particularly renal impairment and cancer. These data support weight-based dosing of enoxaparin in obesity with no maximum dose, ensuring therapeutic drug levels, with anti-Xa levels suggested in obese patients with clinical risk factors for bleeding.
Assuntos
Anticoagulantes/uso terapêutico , Enoxaparina/uso terapêutico , Obesidade/complicações , Tromboembolia Venosa/tratamento farmacológico , Adulto , Idoso , Anticoagulantes/farmacologia , Enoxaparina/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/patologia , Estudos Retrospectivos , Tromboembolia Venosa/patologia , Adulto JovemRESUMO
The highest risk of adverse events for patients with acute venous thromboembolism (VTE) is during the early anticoagulation period. However, no established model exists for early clinical monitoring of patients treated with non-vitamin K antagonist oral anticoagulants (NOACs). The authors' aim was to evaluate the utility of a nurse-led pathway to minimize adverse events in acute VTE patients starting on rivaroxaban. The rivaroxaban VTE treatment pathway is a prospective cohort study of consecutive patients with objectively confirmed VTE between July 2015 and May 2017. Primary outcome was the proportion of patients identified at major risk of adverse events (bleeding or recurrent VTE). Secondary outcomes were rates of interventions, major or clinically relevant nonmajor bleeding (CRNMB), recurrent VTE, and all-cause mortality at 90 days. Among 304 participants, 5% (n = 15) were identified to be at major and 9% (n = 28) at possible risk for adverse events. Appropriate interventions to prevent harm were required in 40 patients. Rates of major bleeding, CRNMB, recurrence, and all-cause mortality were 0.3% (95% confidence interval [CI]: 0.1-1.8), 7.2% (95% CI: 4.8-10.7), 1.0 (95% CI: 0.3-2.9), and 1.6% (95% CI: 0.7-3.8), respectively. In conclusion, following discharge of acute VTE patients, a nurse-led pathway identified one in seven (14%) patients at major or possible risk of adverse events. Preemptive interventions to reduce harm translated into the low rates of bleeding and recurrence. The authors' experience highlights the feasibility and importance of a structured clinical surveillance pathway for acute VTE patients initiating NOAC therapy.
Assuntos
Procedimentos Clínicos , Relações Enfermeiro-Paciente , Rivaroxabana/uso terapêutico , Tromboembolia Venosa/prevenção & controle , Doença Aguda , Adulto , Idoso , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Feminino , Hemorragia/induzido quimicamente , Hemorragia/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Estudos Prospectivos , Recidiva , Fatores de Risco , Rivaroxabana/efeitos adversosRESUMO
BACKGROUND: To accurately quantify the costs of care for patients with transfusion-dependent thalassemia (TDT), and to evaluate cost-effectiveness of new treatments, data are required on costs of regular red blood cell (RBC) transfusions. However, no previous studies have evaluated the costs of RBC transfusion specifically in chronically transfused patients. METHODS AND MATERIALS: We performed a time-driven activity-based costing (TDABC) study using a health care provider perspective. This was performed over a 1-month period, capturing every step of the transfusion pathway for patients with TDT at a designated provider of specialist thalassemia services in Australia. Detailed process maps were developed to outline treatments and processes directly related to transfusion. For each process map, detailed data collection, including timing of activities, was performed multiple times to account for variation in practice. Costs associated with RBC transfusion were broken down into fixed, process, and RBC procurement costs. RESULTS: The total per-unit cost was US$695.59 (95% confidence interval, US$694.45-US$696.73). Approximately 40% of cost was for procurement of the RBC unit, with process costs accounting for 55%. The single largest contributor to process costs was attributed to iron chelation medication (approximately 80%). In sensitivity analyses, seniority of staff, time to perform processes, and probabilities of different processes occurring did not substantially influence the RBC transfusion cost; however the number of RBC units per transfusion episode did impact the overall cost per RBC unit. CONCLUSIONS: We found significant costs associated with RBC transfusion for TDT, with the product cost contributing less than one-half of the total cost.
Assuntos
Transfusão de Eritrócitos/economia , Custos de Cuidados de Saúde , Talassemia beta/terapia , HumanosRESUMO
INTRODUCTION: Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is the third most common cardiovascular disease and, globally, more than an estimated 10 million people have it yearly. It is a chronic and recurrent disease. The symptoms of VTE are non-specific and the diagnosis should actively be sought once considered. The mainstay of VTE treatment is anticoagulation, with few patients requiring additional intervention. A working group of experts in the area recently completed an evidence-based guideline for the diagnosis and management of DVT and PE on behalf of the Thrombosis and Haemostasis Society of Australia and New Zealand (www.thanz.org.au/resources/thanz-guidelines). MAIN RECOMMENDATIONS: The diagnosis of VTE should be established with imaging; it may be excluded by the use of clinical prediction rules combined with D-dimer testing. Proximal DVT or PE caused by a major surgery or trauma that is no longer present should be treated with anticoagulant therapy for 3 months. Proximal DVT or PE that is unprovoked or associated with a transient risk factor (non-surgical) should be treated with anticoagulant therapy for 3-6 months. Proximal DVT or PE that is recurrent (two or more) and provoked by active cancer or antiphospholipid syndrome should receive extended anticoagulation. Distal DVT caused by a major provoking factor that is no longer present should be treated with anticoagulant therapy for 6 weeks. For patients continuing with extended anticoagulant therapy, either therapeutic or low dose direct oral anticoagulants can be prescribed and is preferred over warfarin in the absence of contraindications. Routine thrombophilia testing is not indicated. Thrombolysis or a suitable alternative is indicated for massive (haemodynamically unstable) PE. CHANGES IN MANAGEMENT AS A RESULT OF THE GUIDELINE: Most patients with acute VTE should be treated with a factor Xa inhibitor and be assessed for extended anticoagulation.
Assuntos
Embolia Pulmonar , Tromboembolia Venosa , Anticoagulantes/uso terapêutico , Austrália , Angiografia por Tomografia Computadorizada , Medicina Baseada em Evidências , Humanos , Nova Zelândia , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/terapia , Recidiva , Fatores de Risco , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/terapia , Varfarina/uso terapêuticoRESUMO
BACKGROUND/AIM: The ADJUST-PE study showed that an age-adjusted D-dimer (AADD) (age years × 10 ng/mL if >50 years) combined with an unlikely pre-test probability (PTP) can increase the proportion of older patients in whom pulmonary embolism (PE) can be safely excluded, but the IL D-dimer HS assay was not assessed. To assess the ability of the IL D-dimer HS assay to exclude PE using the AADD. METHODS: Retrospective analysis of consecutive patients presenting with symptoms of acute PE to one of three Monash Health Emergency Departments (January 2013-January 2014) who had computed tomography pulmonary angiography. In the group with D-dimer, efficiency (proportion of PE excluded based on a combination of unlikely PTP and negative D-dimer) was determined using (i) current laboratory (200 ng/mL), (ii) conventional (230 ng/mL) and (iii) modified (375 ng/mL if age ≥60 years) AADD cut-offs. RESULTS: A total of 176 patients with D-dimers was included (mean age = 58.5 years; 54.0% males; 71.0% age >50 years). Prevalence of PE in the overall, unlikely and likely PTP groups, was 17.0, 13.0 and 24.6% respectively. In the unlikely PTP group (115 patients), efficiency for the current, conventional, modified and AADD cut-offs was 9.6, 24.3, 30.4 and 37.4% respectively. CONCLUSION: The absolute increase in efficiency of an AADD compared to conventional cut-off using the IL D-dimer HS assay is modest (~10%) and requires prospective validation. Modifying our cut-off to 230 ng/mL and systematic implementation of a clinical algorithm, including D-dimer testing and PTP, is likely a more important first step.
Assuntos
Fatores Etários , Serviço Hospitalar de Emergência/estatística & dados numéricos , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/epidemiologia , Adulto , Idoso , Algoritmos , Austrália , Angiografia por Tomografia Computadorizada , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Probabilidade , Curva ROC , Estudos RetrospectivosRESUMO
Pregnancy-associated venous thromboembolism (PAVTE) consists of deep vein thrombosis and pulmonary embolism (PE) occurring during pregnancy or in the postpartum period. This condition is common and is a major source of morbidity in a population which is young and otherwise relatively healthy. Timely diagnosis and treatment are crucial in ensuring satisfactory patient outcomes. Diagnostic strategies for pregnancy-associated PE in particular require careful consideration of maternal and fetal risks. Low-molecular-weight heparins currently form the mainstay of treatment; however, there are uncertainties around optimal dosing of these agents in certain settings (e.g., obesity). This review discusses the diagnosis and suggested treatment of PAVTE.
Assuntos
Heparina de Baixo Peso Molecular/uso terapêutico , Complicações Cardiovasculares na Gravidez , Embolia Pulmonar , Trombose Venosa , Feminino , Humanos , Gravidez , Complicações Cardiovasculares na Gravidez/sangue , Complicações Cardiovasculares na Gravidez/diagnóstico , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Embolia Pulmonar/sangue , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/tratamento farmacológico , Trombose Venosa/sangue , Trombose Venosa/diagnóstico , Trombose Venosa/tratamento farmacológicoAssuntos
Eletrocardiografia , Hipertensão Pulmonar , Embolia Pulmonar , Tomografia Computadorizada por Raios X , Trombose Venosa , Adulto , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Embolia Pulmonar/complicações , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/fisiopatologia , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/etiologia , Trombose Venosa/fisiopatologiaRESUMO
BACKGROUND: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare complication of adenovirus vector-based COVID-19 vaccines. VITT is associated with markedly raised levels of D-dimer; yet, how VITT modulates the fibrinolytic system is unknown. OBJECTIVES: We aimed to compare changes in fibrinolytic activity in plasma from patients with VITT, patients diagnosed with venous thromboembolism (VTE) after vaccination but without VITT (VTE-no VITT), and healthy vaccinated controls. METHODS: Plasma levels of plasmin-antiplasmin (PAP) complexes, plasminogen, and alpha-2-antiplasmin (α2AP) from 10 patients with VITT, 10 patients with VTE-no VITT, and 14 healthy vaccinated controls were evaluated by enzyme-linked immunosorbent assay and/or Western blotting. Fibrinolytic capacity was evaluated by quantitating PAP levels at baseline and after ex vivo plasma stimulation with 50-nM tissue-type plasminogen activator (tPA) or urokinase for 5 minutes. RESULTS: Baseline PAP complex levels in control and VTE-no VITT individuals were similar but were â¼7-fold higher in plasma from patients with VITT (P < .0001). VITT samples also revealed consumption of α2AP and fibrinogenolysis consistent with a hyperfibrinolytic state. Of interest, VITT plasma produced significantly higher PAP levels after ex vivo treatment with tPA, but not urokinase, compared to the other groups, indicative of increased fibrinolytic potential. This was not due to D-dimer as addition of D-dimer to VTE-no VITT plasma failed to potentiate tPA-induced PAP levels. CONCLUSION: A marked hyperfibrinolytic state occurs in patients with VITT, evidenced by marked elevations in PAP, α2AP consumption, and fibrinogenolysis. An unidentified plasma cofactor that selectively potentiates tPA-mediated plasminogen activation also appears to exist in the plasma of patients with VITT.
Assuntos
Antifibrinolíticos , Transtornos da Coagulação Sanguínea , Trombocitopenia , Trombose , Tromboembolia Venosa , Humanos , Antifibrinolíticos/farmacologia , Vacinas contra COVID-19/efeitos adversos , Fibrinolisina/metabolismo , Fibrinólise , Plasminogênio , Ativador de Plasminogênio Tecidual/farmacologia , Ativador de Plasminogênio Tipo Uroquinase/farmacologiaRESUMO
Early induction response assessment with day-21 bone marrow (D21-BM) is commonly performed in patients with FLT3-mutated acute myeloid leukaemia (AML), where detection of residual leukaemia (RL; blasts ≥5%) typically results in the administration of a second induction course. However, whether D21-BM results predict for RL at the end of first induction has not been systematically assessed. This study evaluates the predictive role of D21-BM morphology in detecting RL following first induction. Between August 2018 and March 2022, all patients with FLT3-AML receiving 7+3 plus midostaurin, with D21-BM performed, were identified. Correlation between D21-BM morphology vs D21-BM ancillary flow/molecular results, as well as vs D28-BM end of first induction response, were retrospectively reviewed. Subsequently, D21-BMs were subjected to anonymised morphological re-assessments by independent haematopathologists (total in triplicate per patient). Of nine patients included in this study, three (33%) were designated to have RL at D21-BM, all of whom entered complete remission at D28-BM. Furthermore, only low-level measurable residual disease was detected in all three cases by flow or molecular methods at D21-BM, hence none proceeded to a second induction. Independent re-evaluations of these cases failed to correctly reassign D21-BM responses, yielding a final false positive rate of 33%. In summary, based on morphology alone, D21-BM assessment following 7+3 intensive induction plus midostaurin for FLT3-AML incorrectly designates RL in some patients; thus correlating with associated flow and molecular results is essential before concluding RL following first induction. Where remission status is unclear, repeat D28-BMs should be performed.