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BACKGROUND AND AIMS: The natural history of untreated patients with type 1 Gaucher disease (GD1) is not well documented, and there is controversy over when and how to treat such patients, especially if they are only mildly symptomatic. Treatment of GD1 is inconvenient, very costly, and may result in undesirable side effects. We documented the clinical history of 31 untreated patients with GD1 followed in our clinic for 4-26 (median 15) years. METHODS: This was a retrospective, observational study of the progress of untreated adult patients with GD1 followed by blood tests (haemoglobin, platelet counts, ferritin and chitotriosidase), organ volumes (spleen and liver), bone manifestations (through magnetic resonance imaging and dual X-ray absorptiometry scans) and neurological and quality of life issues. Statistical analyses were performed with the use of the Student paired t test and the modified Wald test for 95% confidence intervals. RESULTS: We found that the above parameters remained stable in most patients over a period of 4-26 (median 15) years. Five patients progressed from normal bone density to osteopenia and two from osteopenia to osteofibrosis; six were peri- or post-menopausal females. The DS-3 was stable over time. Only four of the 31 patients were started on enzyme or substrate reduction therapy. CONCLUSIONS: Our results demonstrate that many patients with GD1, provided with close follow-up by a specialist centre, can be followed for many years without requiring treatment and with no or minimal worsening of their GD1 manifestations.
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Background: Mixed warm/cold autoimmune hemolytic anemia (AIHA) is a rare diagnostic entity with limited therapeutic options. Previous literature has described the diagnostic difficulty in this pathology and the limited response rates to corticosteroids. Furthermore, there is limited evidence regarding the use of rituximab in this condition. Methods: Alongside our case report, we conducted a scoping review of case reports/case series describing mixed AIHA, their treatment, and clinical outcomes since 2000. Inclusion criteria included a confirmed diagnosis of mixed AIHA (confirmed warm antibodies and cold agglutinins based on DAT). Case Summary/Results. We present a case of mixed AIHA in an 83-year-old female presenting with extensive, bilateral pulmonary embolisms and left renal vein thrombosis. The patient underwent extensive workup with no identifiable provoking etiology. Initial treatment involved prednisone therapy was transitioned to rituximab upon diagnosis of mixed AIHA. The patient demonstrated a mixed response with stable hemoglobin and transfusion independence; however, with persistently elevated hemolytic indices following completion of rituximab treatment. Our literature review identified 16 articles; two were excluded for unavailable clinical details. The most commonly associated conditions included autoimmune conditions (n = 5, 26%) and lymphoproliferative disorders (n = 3, 12%). The most common treatment involved corticosteroids; seven studies involved the use of rituximab. Conclusion: Mixed AIHA represents a complex diagnosis and optimal management is not well established. Consistent with our case, recent literature suggests a promising response to rituximab and a limited response to steroid treatment. Given the limited literature, additional studies are required to elucidate optimal management of this unique pathology.
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Anemia , Trombocitopenia , Humanos , Hemólise , Estado Terminal , Trombocitopenia/complicações , Anemia/complicaçõesRESUMO
We report a case of pure white cell aplasia (PWCA) postthymoma resection in a 74-year-old male presenting with a 2-week history of fevers, night sweats, and severe febrile neutropenia. His pure white cell aplasia was treated with intravenous immunoglobulin (IVIg), granulocyte colony-stimulating factor (G-CSF), prednisone, and cyclosporine with a mixed response. He also developed immune thrombocytopenia, which responded well to a short course of eltrombopag. With continued cyclosporine treatment, his platelet counts were stable after stopping eltrombopag. The patient's cyclosporine treatment was complicated by renal failure, resulting in cessation of cyclosporine. His PWCA and immune thrombocytopenia significantly worsened after stopping cyclosporine, and unfortunately, he died from multiorgan failure and sepsis.
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BACKGROUND: Antiphospholipid syndrome (APS) is an acquired thrombophilia disorder with prevalence not completely known in patients with first unprovoked venous thromboembolic events (VTE). Recent data suggest that the management of some APS patients should be different from that of patients with other thrombophilia. Our aim was to estimate the prevalence of APS in a community-based cohort of patients with a first unprovoked VTE. METHODS: We conducted a cross-sectional study analyzing data from our computer assisted oral anticoagulant dosage program. Data of all consecutive patients aged 18 to 50 years who were seen between January 1, 2002 and December 31, 2011 for a first proximal unprovoked VTE were extracted. The prevalence and main features of patients who fulfilled the Sapporo revised criteria for APS were collected. RESULTS AND DISCUSSION: A total of 524 incident patients aged 18 to 50 years were included in the anticoagulation clinic during the study period. Of them, 491 were tested for APS and 44 (9.0%; 95% confidence interval [CI]: 6.7-11.8) fulfilled APS criteria. Of 26 APS women, 8 (30.8%) were on combined oral contraceptive pill at the time of VTE, versus 108 (55.1%) in non-APS women (P = .02). No difference was observed between APS and non-APS patients in terms of gender or type of VTE. The prevalence of APS is high in young patients with a first unprovoked VTE. In the direct oral anticoagulant era, when and how to test for APS is challenging and deserves further investigation.
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Síndrome Antifosfolipídica , Trombofilia , Tromboembolia Venosa , Adolescente , Adulto , Anticoagulantes , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/epidemiologia , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Prevalência , Trombofilia/diagnóstico , Trombofilia/epidemiologia , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/epidemiologia , Adulto JovemRESUMO
Patients with acute spinal cord injury (SCI) have the highest risk of venous thromboembolism (VTE) among hospitalized patients. The incidence of total deep vein thrombosis ranges from 50 to 100% in untreated patients and pulmonary embolism is the third most common cause of mortality in these patients. The pathophysiology of the increased risk of VTE is explained by venous stasis after injury, endothelial vessel wall injury from surgery, and a hypercoagulable state associated with trauma. The current thromboprophylaxis options are limited, with low-molecular-weight heparin (LMWH) being the current standard of care. LMWH is commonly administered for 3 months, during which period the risk of VTE is especially high. Some uncertainty exists regarding the optimal timing to initiate pharmacological thromboprophylaxis and the best regimen of LMWH prophylaxis. High-quality data are currently lacking in thromboprophylaxis in patients with SCI. Many questions in this area remain to be answered, which are described in this narrative review.
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Heparina de Baixo Peso Molecular/uso terapêutico , Traumatismos da Medula Espinal/complicações , Tromboembolia Venosa/prevenção & controle , Trombose Venosa/tratamento farmacológico , Doença Aguda , Anticoagulantes/uso terapêutico , Biomarcadores/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Tromboembolia Venosa/complicações , Tromboembolia Venosa/diagnóstico , Trombose Venosa/complicações , Trombose Venosa/diagnósticoRESUMO
A targeted antidote for reversal of direct factor Xa (FXa) inhibitors is now available for clinical use in the United States, but it is costly and has limited availability. In a systematic review, we evaluated the safety and effectiveness of 4-factor prothrombin complex concentrate (4F-PCC) as an alternative for managing direct FXa inhibitor-related major bleeding. A systematic literature search was conducted using Medline, Embase, and the Cochrane Register of Controlled Trials up to September 2018. No comparative studies were found. Ten case series with 340 patients who received PCC for direct FXa inhibitor-related major bleeding were included. The pooled proportion of patients with effective management of major bleeding was 0.69 (95% confidence interval [CI], 0.61-0.76) in 2 studies using the International Society on Thrombosis and Haemostasis (ISTH) criteria and 0.77 (95% CI, 0.63-0.92) in 8 studies that did not use the ISTH criteria; all-cause mortality was 0.16 (95% CI, 0.07-0.26), and thromboembolism rate was 0.04 (95% CI, 0.01-0.08). On the basis of evidence with very low certainty from single-arm case series, it is difficult to determine whether 4F-PCC in addition to cessation of direct oral FXa inhibitor is more effective than cessation of direct oral FXa inhibitor alone in patients with direct FXa inhibitor-related major bleeding.
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Fatores de Coagulação Sanguínea/uso terapêutico , Inibidores do Fator Xa/efeitos adversos , Hemorragia/etiologia , Hemorragia/terapia , Gerenciamento Clínico , Inibidores do Fator Xa/uso terapêutico , Hemorragia/sangue , Hemorragia/diagnóstico , Humanos , Viés de Publicação , Resultado do TratamentoRESUMO
Anticoagulant therapy is often refrained from out of fear of hemorrhagic complications. The most frequent type of major bleeding is gastrointestinal, but intracranial hemorrhage has the worst prognosis. Management of these complications in patients on anticoagulants should follow the same routines as for nonanticoagulated patients, as described here with the previously mentioned bleeds as examples. In addition, for life-threatening or massive hemorrhages, reversal of the anticoagulant effect is also crucial. Adequate reversal requires information on which anticoagulant the patient has taken and when the last dose was ingested. Laboratory data can be of some help, but not for all anticoagulants in the emergency setting. This is reviewed here for the different types of anticoagulants: vitamin K antagonists, heparins, fondaparinux, thrombin inhibitors and factor Xa inhibitors. Specific antidotes for the latter are becoming available, but supportive care and nonspecific support for hemostasis with antifibrinolytic agents or prothrombin complex concentrates, which are widely available, should be kept in mind.
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Anticoagulantes/efeitos adversos , Antitrombinas/efeitos adversos , Inibidores do Fator Xa/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/terapia , Heparina/efeitos adversos , Vitamina K/antagonistas & inibidores , Anticoagulantes/uso terapêutico , Antitrombinas/uso terapêutico , Gerenciamento Clínico , Inibidores do Fator Xa/uso terapêutico , Heparina/uso terapêutico , HumanosRESUMO
BACKGROUND: Due to a paucity of data on the efficacy and safety of direct oral anticoagulants (DOACs) in patients with a body mass index >40 kg/m2 or a weight >120 kg, the use of DOACs in this group is not recommended. OBJECTIVES: To determine the proportion of obese patients with body weight >120 kg with a peak plasma concentration of DOACs lower than the expected median trough level derived from population pharmacokinetic studies for each DOAC. METHODS: Patients with body weight >120 kg taking DOACs for any indication underwent a peak drug concentration measurement at steady state. RESULTS: 38 patients were included in the analysis. The mean age was 64 ± 11 years, and 30 (79%) were males. The median body weight was 132.5 kg (interquartile range [IQR] 127-146.5). The median peak concentrations (IQR) were 148 ng/mL (138-240), 138 ng/mL (123-156.5), 215 ng/mL (181-249) for apixaban, dabigatran, and rivaroxaban, respectively. Two patients (5%, 95% confidence interval [CI]: 0.5%-18%) had a peak plasma concentration lower than the median trough and eight (21%, 95% CI: 11%-37%) had a peak plasma concentration below the fifth percentile (10th percentile for dabigatran) peak concentration. CONCLUSIONS: Most patients in our study had peak plasma concentration higher than the median trough level for each of the three DOACs. However, 21% had a peak plasma concentration that was below the usual on-therapy range of peak concentration for the corresponding DOAC.
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Venous thromboembolism (VTE) occurs in 10-20%% of patients with cancer and is associated with significant mortality and morbidity in these patients. The current standard of care recommended by international guidelines is to use low-molecular-weight heparin (LMWH) for 6months for the management of cancer-associated thrombosis (CAT), which is based on evidence from randomized controlled trials demonstrating that LMWH significantly reduced the risk of recurrent VTE compared with vitamin K antagonists. However, patients with CAT have a high risk of VTE recurrence of up to 20% despite receiving anticoagulation. Reasons for recurrent VTE may include non-compliance, temporary cessation of therapy due to bleeding or for procedures, inadequate dosing, cancer progression, and the presence of heparin-induced thrombocytopenia. Management of patients with CAT and recurrent VTE is not well defined. Management strategies for recurrent VTE include switching to LMWH if an oral anticoagulant is employed, dose escalation of LMWH, or as a last resort option consider insertion of a vena cava filter. In this review, we discuss the acute, long-term, and extended management of CAT, risk factors for recurrent VTE, and management of recurrent VTE.
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Neoplasias/complicações , Tromboembolia Venosa/tratamento farmacológico , Humanos , Recidiva , Fatores de Risco , Tromboembolia Venosa/patologiaRESUMO
Direct oral factor Xa (FXa) inhibitors are widely used for anticoagulation but a targeted antidote is not available. Four-factor prothrombin complex concentrate (4FPCC) has been shown in observational studies to support hemostasis in most patients with major bleeding related to FXa inhibitors with an acceptable rate of thromboembolic events. However, the effectiveness of 4FPCC for reversal of FXa inhibitors prior to emergency surgery or invasive procedures is unclear. A retrospective chart review was performed in patients that received 4FPCC at Hamilton General Hospital from 2015 to 2017. The primary effectiveness outcome was based on the comment of the surgeon on the adequacy of the hemostasis. If no such comment was documented, the case was discussed with a surgeon specialized in the type of surgery/procedure performed to obtain their best opinion. The principal safety outcome was thromboembolic events including venous thromboembolism, ischemic stroke, systemic embolism or myocardial infarction during 7 days after surgery. A total of 247 patients that had received 4FPCC were initially screened and 21 were on a FXa inhibitor and had emergency surgery/procedure. The mean age was 74 ± 11 years, and 14 (66.7%) were males. Hemostasis was rated as good in most patients (18 of 21, 85.7%). There were no thromboembolic events. The all-cause mortality rate was 28.6%; 2/3 of these patients had an intracranial hemorrhage. Hemostasis was rated as good in most patients with no thromboembolic events observed. Prospective studies assessing the safety and effectiveness of 4FPCC for this indication are needed.
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Fatores de Coagulação Sanguínea/uso terapêutico , Serviços Médicos de Emergência , Inibidores do Fator Xa , Procedimentos Cirúrgicos Operatórios/métodos , Idoso , Idoso de 80 Anos ou mais , Fatores de Coagulação Sanguínea/farmacologia , Feminino , Hemostáticos , Humanos , Hemorragias Intracranianas , Masculino , Pessoa de Meia-Idade , Mortalidade , Estudos Retrospectivos , TromboemboliaRESUMO
Anticoagulant-related nephropathy is an acute kidney injury (AKI) associated with excessive anticoagulation. The nature of the association between excessive anticoagulation with warfarin and AKI and its incidence remain unclear. To evaluate the incidence of AKI in excessively anticoagulated patients taking warfarin and examine potential risk factors. A retrospective chart review was performed in patients on chronic warfarin. The primary outcome was AKI, defined as an acute increase in creatinine of > 26.5 µmol/L within 7-14 days of an international normalized ratio (INR) ≥ 4.0. 292 patients with an INR ≥ 4.0 were included. 101 patients had CKD and 191 did not have CKD. Of the 292 patients with an INR ≥ 4.0, 38 (13%) had an AKI. In univariable analyses, CKD [odds ratio (OR) 2.1, 95% confidence interval (CI) 0.99-4.43] and use of renin-angiotensin system (RAS) blockers and/or diuretics (OR 3.85; 95% CI 1.15-20.15) were significantly associated with the risk of AKI. In a binomial logistic regression model, use of RAS blockers and/or diuretics was the only significant predictor of AKI (OR 3.4; 95% CI 1.02-11.76). Use of RAS blockers and/or diuretics significantly increased the risk of AKI in patients with warfarin-related excessive anticoagulation. Further prospective studies examining the association of high INRs and AKI are needed.
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Injúria Renal Aguda/induzido quimicamente , Varfarina/efeitos adversos , Idoso , Creatinina , Diuréticos/uso terapêutico , Humanos , Incidência , Coeficiente Internacional Normatizado , Pessoa de Meia-Idade , Sistema Renina-Angiotensina/efeitos dos fármacos , Estudos Retrospectivos , Fatores de RiscoRESUMO
Direct oral anticoagulant (DOAC) use is increasing worldwide. However, if not taken or prescribed correctly, DOACs have serious side effects. It is crucial that healthcare providers (HCPs) offer patients accurate information and counselling around DOACs, to optimize safe and effective use. To assess knowledge around oral anticoagulant indication, dosing, storage, and administration, an electronic survey was distributed to HCPs across Canada from June to August 2017, with 18 questions on the practical use of oral anticoagulants. A total of 191 responses were received: 100 from nurse practitioners, 42 from pharmacists, 27 from Hematologists, 5 from Thrombosis specialists, 4 from internists, 9 from residents and fellows, and 2 each from family physicians and registered nurses. Only 51 (26.7%) of the respondents correctly identified all the approved indications for warfarin and 4 DOACs. Only 101 (52.9%) correctly identified that DOACs are not approved for treatment of heparin-induced thrombocytopenia, cerebral sinus venous thrombosis, or mechanical prosthetic valves. 112 (58.6%) felt comfortable or very comfortable prescribing oral anticoagulants. Half of the respondents knew that dabigatran should not be crushed, however only 85 (44.5%) knew that it should not be exposed to moisture. 94 (49%) knew that higher dose rivaroxaban should be taken with food. The results of our study demonstrate that there are important knowledge gaps around HCPs' practical understanding of oral anticoagulants. Future research should focus on educational interventions to improve HCPs' knowledge around indications, dosing, storage, and administration, with the goal of enhancing patient safety.
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Anticoagulantes/administração & dosagem , Armazenamento de Medicamentos/métodos , Pessoal de Saúde/educação , Administração Oral , Anticoagulantes/uso terapêutico , Canadá , Estudos Transversais , Humanos , Inquéritos e QuestionáriosAssuntos
Anticoagulantes/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Coluna Vertebral/cirurgia , Cirurgiões/normas , Trombose/tratamento farmacológico , Canadá , Feminino , Humanos , Masculino , Coluna Vertebral/patologia , Inquéritos e Questionários , Trombose/patologiaRESUMO
We present a case of renal infarction in a 43-year-old female with history of stroke at age 14. She was found to be heterozygous for the prothrombin G20210A gene mutation. Loop monitoring revealed no atrial fibrillation. Transthoracic and transesophageal echocardiograms showed no thrombus. However, there was a small shunt due to an atrial septal defect (ASD). She was treated with warfarin and had device closure of her ASD. This was a suspected case of paradoxical embolism through an ASD leading to renal infarction.
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Background Direct oral anticoagulants are convenient because of their fixed dosing and without laboratory monitoring. There are instructions on avoidance of moisture, no crushing of capsules, and administration with food for some direct oral anticoagulants. Whether patients adhere to this and are prescribed appropriate doses are unknown. Aims To assess direct oral anticoagulant dosing and medication use. Methods Patients ≥18 years old, receiving a direct oral anticoagulant for any diagnosis, were prospectively included. Nurses at our perioperative anticoagulation clinic helped patients complete a 12-item questionnaire. Results Ninety-three consecutive patients were recruited. Forty-nine were on dabigatran, 18 on apixaban, and 26 were on rivaroxaban. Sixty-two patients (67%) received appropriate direct oral anticoagulant dosing and administered the medication correctly. Eighteen patients (19%) administered the direct oral anticoagulant properly but at an inappropriate dose. Thirteen patients (14%) received an appropriate dose but administered the direct oral anticoagulant inappropriately: 10 (11%) removed dabigatran from its packaging before administration (exposing it to moisture); 2 (2%) did not take rivaroxaban with food; and 1 (1%) crushed the dabigatran capsule. Conclusion Our study demonstrates a large variability in how direct oral anticoagulants are dosed, and how patients take them. Improved medication literacy around direct oral anticoagulants is needed. Our study highlights opportunities that nurses have to improve patients' medication literacy.
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Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Prescrições de Medicamentos , Adesão à Medicação/estatística & dados numéricos , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Relações Enfermeiro-Paciente , Educação de Pacientes como Assunto , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
Extended-duration pharmacological thromboprophylaxis, for at least 28 days, is effective for the prevention of symptomatic venous thromboembolism (VTE) in high-risk surgical patients but is of uncertain benefit in hospitalized medical patients. We aimed to evaluate the efficacy and safety of extended-duration thromboprophylaxis in hospitalized medical patients. We conducted a systematic PubMed, Medline and EMBASE literature search until June 2016 and a meta-analysis of randomized controlled trials which compared extended-duration with short-duration thromboprophylaxis in hospitalized medical patients. Four randomized controlled trials comparing extended-duration prophylaxis (24-47 days) with short-duration prophylaxis (6-14 days) in a total of 34,068 acutely ill hospitalized medical patients were included. When compared with short-duration prophylaxis, extended-duration prophylaxis was associated with a decrease in symptomatic proximal or distal deep vein thrombosis (DVT) [relative risk (RR) = 0.52; 95% confidence interval (Cl): 0.35-0.77: p = 0.001; absolute risk reduction (ARR) = 0.32%, number needed to treat (NNT) = 313], and symptomatic non-fatal pulmonary embolism (RR = 0.61; 95% Cl 0.38-0.99: p = 0.04; ARR = 0.16%; NNT = 625), an increase in major bleeding (RR = 2.08; 95% Cl 1.50-2.90: p < 0.0001, absolute risk increase = 0.41%, number needed to harm = 244), and no significant reduction in VTE-related mortality (RR = 0.69; 95% Cl 0.45-1.06: p = 0.09) or all-cause mortality (RR = 1.00; 95% CI 0.89-1.12; p = 0.95). There was heterogeneity for major bleeding due to results from the APEX trial (no difference between betrixaban and enoxaparin). Compared with short-duration thromboprophylaxis, extended-duration treatment reduces the risk for symptomatic DVT and non-fatal pulmonary embolism. Extended treatment with apixaban, enoxaparin and rivaroxaban but not betrixaban increases the risk for major bleeding.
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Pré-Medicação/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Tromboembolia Venosa/prevenção & controle , Doença Aguda , Fibrinolíticos/efeitos adversos , Fibrinolíticos/uso terapêutico , Hemorragia/induzido quimicamente , Hospitalização , Humanos , Fatores de Tempo , Resultado do Tratamento , Tromboembolia Venosa/complicaçõesRESUMO
INTRODUCTION: The true incidence of venous thromboembolism (VTE) in patients with acute spinal cord injury (SCI) is unclear. There are limited data on the risk factors associated with VTE in patients with an acute SCI. METHODS: We performed a retrospective chart review of consecutive adult patients with acute SCI. The primary outcome was incidence of symptomatic deep vein thrombosis (DVT) or pulmonary embolism (PE) within 90days. Secondary outcomes were major bleeding, all-cause mortality, and fatal PE. Step-wise Cox modeling was used to identify risk factors for VTE. RESULTS: A total of 151 patients with acute SCI were included. Median age was 51 (range 17-91years) and 106 (70%) were males. Of the 151 patients, 17 (11%) had symptomatic VTE (9 PEs, 6 lower extremity DVT, 1 upper extremity DVT, and 1 with DVT and PE). In the univariable analyses, male sex and having other sites of injuries along with SCI were significant risk factors. In stepwise Cox modeling, independent risk factors were other sites of injuries (hazard ratio [HR] 6.07, 95% confidence interval [CI] 1.89-19.47, p=0.002), age (HR 1.05 per year, 95% CI 1.02-1.08, p=0.002) and the presence of leg paresis (HR 2.7, 95% CI 0.72-10.54, p=0.14), whereas hypertension appeared to reduce the risk (HR 0.18, 95% CI 0.04-0.78, p=0.02). CONCLUSIONS: Symptomatic VTE is a frequent complication in patients with acute SCI. Age and presence of other sites of injuries along with SCI were independent risk factors for symptomatic VTE.
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Traumatismos da Medula Espinal/complicações , Tromboembolia Venosa/etiologia , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Feminino , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Tromboembolia Venosa/tratamento farmacológico , Adulto JovemRESUMO
Venous thromboembolism (VTE), which constitutes pulmonary embolism and deep vein thrombosis, is a common disorder associated with significant morbidity and mortality. Landmark trials have shown that direct oral anticoagulants (DOACs) are as effective as conventional anticoagulation with vitamin K antagonists (VKA) in prevention of VTE recurrence and associated with less bleeding. This has paved the way for the recently published guidelines to change their recommendations in favor of DOACs in acute and long-term treatment of VTE in patients without cancer. The recommended treatment of VTE in cancer patients remains low-molecular-weight heparin. The initial management of pulmonary embolism (PE) should be directed based on established risk stratification scores. Thrombolysis is an available option for patients with hemodynamically significant PE. Recent data suggests that low-risk patients with acute PE can safely be treated as outpatients if home circumstances are adequate. There is lack of support for use of inferior vena cava filters in patients on anticoagulation. This review describes the acute, long-term, and extended treatment of VTE and recent evidence on the management of sub-segmental PE.
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Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a life-threatening disease in which intracranial hemorrhage (ICH) is the major risk. Although thrombocytopenia, which is caused by maternal antibodies against ß3 integrin and occasionally by maternal antibodies against other platelet antigens, such as glycoprotein GPIbα, has long been assumed to be the cause of bleeding, the mechanism of ICH has not been adequately explored. Utilizing murine models of FNAIT and a high-frequency ultrasound imaging system, we found that ICH only occurred in fetuses and neonates with anti-ß3 integrin-mediated, but not anti-GPIbα-mediated, FNAIT, despite similar thrombocytopenia in both groups. Only anti-ß3 integrin-mediated FNAIT reduced brain and retina vessel density, impaired angiogenic signaling, and increased endothelial cell apoptosis, all of which were abrogated by maternal administration of intravenous immunoglobulin (IVIG). ICH and impairment of retinal angiogenesis were further reproduced in neonates by injection of anti-ß3 integrin, but not anti-GPIbα antisera. Utilizing cultured human endothelial cells, we found that cell proliferation, network formation, and AKT phosphorylation were inhibited only by murine anti-ß3 integrin antisera and human anti-HPA-1a IgG purified from mothers with FNAIT children. Our data suggest that fetal hemostasis is distinct and that impairment of angiogenesis rather than thrombocytopenia likely causes FNAIT-associated ICH. Additionally, our results indicate that maternal IVIG therapy can effectively prevent this devastating disorder.