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1.
Thromb Res ; 180: 70-73, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31229923

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Heparin is widely used to prevent clotting of the extracorporeal circuit during haemodialysis (HD). Heparin-induced thrombocytopenia (HIT) is a potentially devastating immune mediated adverse drug reaction caused by the emergence of antibodies that activate platelets in the presence of heparin, leading to a pro-thrombotic state. Danaparoid is an alternative anticoagulant used in patients on HD with HIT but its dosing recommendations in obese patients on HD are relatively scarce. CASE SUMMARY: We report a case of a 48-year-old morbidly obese patient who received weight-based dosing of danaparoid for HD with monitoring of anti-Xa activity. However, despite the patient's anti-Xa level being within the therapeutic range at various time points, the circuit lines kept clotting during HD. WHAT IS NEW AND CONCLUSION: The report provides evidence that the manufacturer's recommendations on dosing danaparoid based on body weight may lead to sub-optimal therapeutic benefit and highlight the need for higher than recommended weight-based dosing in obese individuals on dialysis.


Assuntos
Anticoagulantes/uso terapêutico , Sulfatos de Condroitina/uso terapêutico , Dermatan Sulfato/uso terapêutico , Heparina/efeitos adversos , Heparitina Sulfato/uso terapêutico , Obesidade Mórbida/complicações , Diálise Renal , Trombocitopenia/induzido quimicamente , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Sulfatos de Condroitina/administração & dosagem , Dermatan Sulfato/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Heparina/administração & dosagem , Heparina/uso terapêutico , Heparitina Sulfato/administração & dosagem , Humanos , Diálise Renal/efeitos adversos , Diálise Renal/métodos , Trombocitopenia/complicações , Trombose/complicações , Trombose/prevenção & controle
2.
Prog Mol Biol Transl Sci ; 163: 55-74, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31030761

RESUMO

Heparin is the first glycosaminoglycan ever identified. All the heparin-like glycosaminoglycans that are also isolated from animal tissues or any polysaccharides that mimic the biological activities of heparin are called heparinoids. Heparin is the mostly sulfated glycosaminoglycan made by mast cells and an essential anticoagulant drug in modern medicine. Heparin inhibits both thrombin generation and thrombin activity, releases tissue factor pathway inhibitor, and possesses anti-inflammatory, anti-viral, anti-angiogenesis, anti-neoplastic, and anti-metastatic properties though high affinity interactions with a variety of proteins in the blood circulation. The multi-pharmacological effects of heparin are both sequence- and sulfation degree dependent. Less sulfated heparinoids have been indicated to have more physiological functions than heparin. Since the anticoagulant heparin is associated with severe side effects, such as bleeding and heparin-induced thrombocytopenia and thrombosis, it is expected that the less sulfated heparinoids might serve as alternative drugs for patients who cannot use heparin. The crude heparin isolated from animal tissues contains ~50% heparin and ~50% less sulfated heparinoids. Indeed, the less sulfated waste heparinoids 1 during heparin production is chemically degraded and developed into the clinical drug Danaparoid and the more sulfated waste heparinoids 2 during heparin production is chemically degraded and developed into the clinical drug Sulodexide. Moreover, clinical studies indicate that Danaparoid and Sulodexide have the expected pharmacological activities. We will provide an update on the chemical characteristics and clinical use of the heparinoids Danaparoid and Sulodexide. In addition, the potential clinical applications of Danaparoid and Sulodexide in other therapeutic area will also be discussed.


Assuntos
Sulfatos de Condroitina/uso terapêutico , Dermatan Sulfato/uso terapêutico , Glicosaminoglicanos/uso terapêutico , Heparinoides/uso terapêutico , Heparitina Sulfato/uso terapêutico , Sulfatos de Condroitina/química , Ensaios Clínicos como Assunto , Dermatan Sulfato/química , Glicosaminoglicanos/química , Heparina de Baixo Peso Molecular/uso terapêutico , Heparinoides/química , Heparitina Sulfato/química , Humanos
3.
Blood Adv ; 2(22): 3360-3392, 2018 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-30482768

RESUMO

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction mediated by platelet-activating antibodies that target complexes of platelet factor 4 and heparin. Patients are at markedly increased risk of thromboembolism. OBJECTIVE: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in their decisions about diagnosis and management of HIT. METHODS: ASH formed a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations, which were subject to public comment. RESULTS: The panel agreed on 33 recommendations. The recommendations address screening of asymptomatic patients for HIT, diagnosis and initial management of patients with suspected HIT, treatment of acute HIT, and special situations in patients with acute HIT or a history of HIT, including cardiovascular surgery, percutaneous cardiovascular intervention, renal replacement therapy, and venous thromboembolism prophylaxis. CONCLUSIONS: Strong recommendations include use of the 4Ts score rather than a gestalt approach for estimating the pretest probability of HIT and avoidance of HIT laboratory testing and empiric treatment of HIT in patients with a low-probability 4Ts score. Conditional recommendations include the choice among non-heparin anticoagulants (argatroban, bivalirudin, danaparoid, fondaparinux, direct oral anticoagulants) for treatment of acute HIT.


Assuntos
Anticoagulantes/efeitos adversos , Heparina/efeitos adversos , Trombocitopenia/patologia , Tromboembolia Venosa/tratamento farmacológico , Administração Oral , Anticoagulantes/uso terapêutico , Procedimentos Cirúrgicos Cardiovasculares , Sulfatos de Condroitina/uso terapêutico , Dermatan Sulfato/uso terapêutico , Medicina Baseada em Evidências , Fondaparinux/uso terapêutico , Heparina/uso terapêutico , Heparitina Sulfato/uso terapêutico , Hirudinas , Humanos , Fragmentos de Peptídeos/uso terapêutico , Ácidos Pipecólicos/uso terapêutico , Contagem de Plaquetas , Proteínas Recombinantes/uso terapêutico , Terapia de Substituição Renal , Trombocitopenia/induzido quimicamente , Tromboembolia Venosa/diagnóstico
4.
Postgrad Med J ; 94(1114): 453-457, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30126928

RESUMO

Heparin-induced thrombocytopaenia (HIT) is a severe and potentially life-threatening adverse drug reaction. Patients become extremely hypercoagulable, and this can lead to life-threatening and limb-threatening thrombosis with a mortality of 5%-10%. HIT is an antibody-mediated process in which platelet activation occurs. Diagnosis requires a high index of suspicion along with a scoring system and laboratory testing. Patients suspected of having HIT must not receive any further heparin or low-molecular weight heparin and must be started on an alternative anticoagulant such as argatroban or danaparoid. Fondaparinux may also be considered but is not licenced for this indication.


Assuntos
Anticoagulantes/efeitos adversos , Heparina/efeitos adversos , Trombocitopenia/induzido quimicamente , Anticoagulantes/uso terapêutico , Sulfatos de Condroitina/uso terapêutico , Dermatan Sulfato/uso terapêutico , Fondaparinux , Heparina/uso terapêutico , Heparitina Sulfato/uso terapêutico , Humanos , Ácidos Pipecólicos/uso terapêutico , Polissacarídeos/uso terapêutico , Trombocitopenia/mortalidade
5.
Int J Mol Sci ; 19(6)2018 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-29882770

RESUMO

Oral mucositis is the most frequently occurring early side effect of head-and-neck cancer radiotherapy. Systemic dermatan sulfate (DS) treatment revealed a significant radioprotective potential in a preclinical model of oral mucositis. This study was initiated to elucidate the mechanistic effects of DS in the same model. Irradiation comprised daily fractionated irradiation (5 × 3 Gy/week) over two weeks, either alone (IR) or in combination with daily dermatan sulfate treatment of 4 mg/kg (IR + DS). Groups of mice (n = 5) were sacrificed every second day over the course of 14 days in both experimental arms, their tongues excised and evaluated. The response to irradiation with and without DS was analyzed on a morphological (cell numbers, epithelial thickness) as well as on a functional (proliferation and expression of inflammation, hypoxia and epithelial junction markers) level. The mucoprotective activity of DS can be attributed to a combination of various effects, comprising increased expression of epithelial junctions, reduced inflammation and reduced hypoxia. No DS-mediated effect on proliferation was observed. DS demonstrated a significant mucositis-ameliorating activity and could provide a promising strategy for mucositis treatment, based on targeting specific, radiation-induced, mucositis-associated signaling without stimulating proliferation.


Assuntos
Dermatan Sulfato/uso terapêutico , Neoplasias de Cabeça e Pescoço/radioterapia , Protetores contra Radiação/uso terapêutico , Radioterapia/efeitos adversos , Estomatite/tratamento farmacológico , Estomatite/etiologia , Animais , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Hipóxia/tratamento farmacológico , Hipóxia/etiologia , Hipóxia/patologia , Inflamação/tratamento farmacológico , Inflamação/etiologia , Inflamação/patologia , Junções Intercelulares/efeitos dos fármacos , Junções Intercelulares/patologia , Camundongos , Estomatite/patologia
7.
Pediatr Transplant ; 22(2)2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29239087

RESUMO

In SCT, death from transplant-related complications is the major obstacle hindering improvement of transplant outcomes, and proper supportive care is essential to reduce TRM. The transplant outcomes of 210 pediatric patients with malignant and non-malignant disorders who consecutively underwent SCT in our institution from 2000 to 2013 were analyzed. The transplant years were divided into three periods: A (2000-2004), B (2005-2008), and C (2009-2013), and an improvement in 5-year OS and a decrease in 5-year TRM were observed over these time periods; that is, OS was 61.5%, 60.3%, and 79.5% (P = .062), and TRM was 19.9%, 7.9%, and 0.0% (P < .001) in periods A, B, and C, respectively. On multivariate analysis, the prognostic factor for TRM for all patients was administration of danaparoid (HR = 0.109, 95% CI = 0.033-0.363, P < .001), and for patients with hematological malignancies in allogeneic SCT, the prognostic factors were danaparoid (HR = 0.046, 95% CI = 0.006-0.326, P = .002) and advanced disease at SCT (HR = 4.802, 95% CI = 1.734-13.30, P = .003). A reduction in TRM after SCT was observed over the time periods, and supportive care with danaparoid was found to be significantly effective in reducing TRM in SCT for children.


Assuntos
Anticoagulantes/uso terapêutico , Sulfatos de Condroitina/uso terapêutico , Dermatan Sulfato/uso terapêutico , Heparitina Sulfato/uso terapêutico , Transplante de Células-Tronco/mortalidade , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Prognóstico , Estudos Retrospectivos , Transplante de Células-Tronco/efeitos adversos , Análise de Sobrevida
8.
J Am Coll Cardiol ; 70(21): 2636-2648, 2017 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-29169470

RESUMO

BACKGROUND: Life-threatening heparin-induced thrombocytopenia (HIT) is treated with the alternative nonheparin anticoagulants argatroban, lepirudin, or danaparoid. Frequently, the pentasaccharide fondaparinux is used off-label. OBJECTIVES: The authors sought to investigate the safety and efficacy of the different anticoagulants for treating HIT. METHODS: In a national, multicenter registry study, hospitalized patients who were diagnosed with HIT, an at least intermediate clinical HIT-risk (4Ts score ≥4 points), and received treatment with ≥1 dose of the aforementioned anticoagulants were included. Main outcome measures were the incidences of HIT-specific complications (thromboembolic venous/arterial events, amputations, recurrent/persistent thrombocytopenia, skin lesions) and bleedings. RESULTS: Of 195 patients, 46 (23.6%), 4 (2.1%), 61 (31.3%), and 84 (43.1%) had been treated first-line with argatroban, lepirudin, danaparoid, and fondaparinux, respectively. The composite endpoint of HIT-specific complications (thromboembolic events, amputation, skin necrosis) occurred in 11.7% of patients treated with approved alternative anticoagulation and in 0.0% of fondaparinux-treated patients. The all-cause in-hospital mortality rates were 14.4% during approved alternative anticoagulation and 0.0% during fondaparinux treatment. Bleeding complications occurred in alternatively anticoagulated patients and in fondaparinux-treated patients in 6.3% and 4.8%, respectively. Post hoc analysis of clinical and laboratory features confirmed "true" HIT in at least 74 of 195 (38.0%) patients; 35 of 74 (47.3%) were treated with fondaparinux. CONCLUSIONS: Fondaparinux is effective and safe in suspected acute HIT; no HIT-specific complications occurred in the fondaparinux-treated patients, even among those with a high clinical HIT probability. Further data from randomized controlled trials are urgently needed because lepirudin was recalled from the market; danaparoid access has been limited and is not approved in the United States; and argatroban is contraindicated in patients with impaired liver function, and activated partial thromboplastin time confounding may interfere with monitoring. (Retrospective Registry of Patients With Acute Heparin-induced Thrombocytopenia Type II; NCT01304238).


Assuntos
Anticoagulantes/uso terapêutico , Inibidores do Fator Xa/uso terapêutico , Heparina/química , Polissacarídeos/uso terapêutico , Trombocitopenia/tratamento farmacológico , Sulfatos de Condroitina/uso terapêutico , Dermatan Sulfato/uso terapêutico , Feminino , Fondaparinux , Hemorragia/induzido quimicamente , Heparitina Sulfato/uso terapêutico , Hirudinas , Mortalidade Hospitalar , Hospitalização , Humanos , Masculino , Necrose , Uso Off-Label , Tempo de Tromboplastina Parcial , Segurança do Paciente , Ácidos Pipecólicos/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Sistema de Registros , Estudos Retrospectivos , Tromboembolia/induzido quimicamente , Resultado do Tratamento
9.
BMC Gastroenterol ; 17(1): 112, 2017 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-29070023

RESUMO

BACKGROUND: Portal vein thrombosis (PVT) is a serious complication in liver cirrhosis with portal hypertension. We examined the treatment, recurrence and prognosis of PVT in cirrhotic patients. METHODS: The study subjects were all 90 cirrhotic patients with PVT treated with danaparoid sodium (DS) at our department between July 2007 and September 2016. The mean age was 68 years and mean Child-Pugh score was 7. All patients received 2500 U/day of DS for 2 weeks, and repeated in those who developed PVT recurrence after the initial therapy. RESULTS: Complete response was noted in 49% (n = 44), partial response (shrinkage ≥70%) in 33% (n = 30), and no change (shrinkage <70%) in 18% (n = 16) of the patients after the initial course of treatment. DS treatment neither caused adverse events, particularly bleeding or thrombocytopenia, nor induced significant changes in serum albumin, total bilirubin, prothrombin time, and residual liver function. Re-treatment was required in 44 patients who showed PVT recurrence and 61% of these responded to the treatment. The cumulative recurrence rates at 1 and 2 posttreatment years were 26 and 30%, respectively. The recurrence rates were significantly lower in patients with acute type, compared to the chronic type (p = 0.0141). The cumulative survival rates at 1 and 3 years after treatment (including maintenance therapy with warfarin) were 83 and 60%, respectively, and were significantly higher in patients with acute type than chronic type (p = 0.0053). CONCLUSION: We can expect prognostic improvement of liver cirrhosis by warfarin following two-week DS therapy for the treatment of PVT in patients with liver cirrhosis safety and effectiveness. An early diagnosis of PVT along with the evaluation of the volume of PVT on CT and an early intervention would contribute to the higher efficacy of the treatment.


Assuntos
Anticoagulantes/uso terapêutico , Sulfatos de Condroitina/uso terapêutico , Dermatan Sulfato/uso terapêutico , Heparitina Sulfato/uso terapêutico , Cirrose Hepática/complicações , Veia Porta , Trombose Venosa/tratamento farmacológico , Trombose Venosa/etiologia , Varfarina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Feminino , Humanos , Hipertensão Portal/complicações , Masculino , Pessoa de Meia-Idade , Recidiva , Taxa de Sobrevida , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Trombose Venosa/sangue , Trombose Venosa/diagnóstico por imagem
10.
Blood Coagul Fibrinolysis ; 28(2): 193-197, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27100305

RESUMO

Clinical suspicion of immune heparin-induced thrombocytopenia (HIT) requires cessation of heparin and initiation of an alternative anticoagulant. The platelet count will subsequently recover. This case report describes the clinical course of a patient after a cardiovascular surgery. HIT was clinically and biologically confirmed. Unexpectedly, the platelet count did not recover despite the arrest of heparin. Danaparoid was initiated, and thrombocytopenia persisted. Danaparoid cross-reactivity was suspected, and laboratory assay was performed. Results were misinterpreted because no comparative buffer control was performed to ensure that the platelet aggregation was caused by danaparoid. Moreover, plasma/serum must be diluted to demonstrate this effect. Danaparoid cross-reactivity was incorrectly concluded, and the patient was switched to bivalirudin. The severe thrombocytopenia persisted. Plasmapheresis was started, and platelet count finally increased. The clinical course suggested a delayed-onset HIT. This case report illustrates the need for appropriate testing to differentiate drug cross-reactivity from delayed-onset HIT.


Assuntos
Anticoagulantes/uso terapêutico , Sulfatos de Condroitina/uso terapêutico , Dermatan Sulfato/uso terapêutico , Heparina/efeitos adversos , Heparitina Sulfato/uso terapêutico , Trombocitopenia/induzido quimicamente , Anticoagulantes/administração & dosagem , Sulfatos de Condroitina/administração & dosagem , Dermatan Sulfato/administração & dosagem , Heparitina Sulfato/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade
11.
Ann Thorac Surg ; 103(1): e9-e10, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28007287

RESUMO

Management of heparin-induced thrombocytopenia (HIT) entails cessation of heparin and initiation of a nonheparin parenteral anticoagulant such as danaparoid. Danaparoid cross-reactivity with HIT antibodies is an uncommon complication of treatment of HIT. We report the case of confirmed HIT and in vivo cross-reactivity with danaparoid, complicating severe sepsis due to an infectious endocarditis treated by cardiac surgery.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Sulfatos de Condroitina/imunologia , Dermatan Sulfato/imunologia , Doenças das Valvas Cardíacas/cirurgia , Heparina/imunologia , Heparitina Sulfato/imunologia , Trombocitopenia/complicações , Anticoagulantes/imunologia , Anticoagulantes/uso terapêutico , Sulfatos de Condroitina/uso terapêutico , Reações Cruzadas , Dermatan Sulfato/uso terapêutico , Heparina/efeitos adversos , Heparitina Sulfato/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Trombocitopenia/imunologia
12.
Med Klin Intensivmed Notfmed ; 112(4): 334-346, 2017 May.
Artigo em Alemão | MEDLINE | ID: mdl-28005139

RESUMO

BACKGROUND: In the context of inpatient and increasingly ambulatory thrombosis prophylaxis, heparins have been recognised as standard therapy for decades. In addition to the therapeutic benefit, therapy with heparins also entails the risk of undesirable side effects, such as bleeding and thrombocytopenia. Heparin-induced thrombocytopenia (HIT II) is deemed a serious side effect. AIM: In the following work, HIT II is subjected to a medico-economic consideration (treatment, pharmaceuticals, subsequent costs due to possible complications) and, with regard to a possible HIT II prophylaxis, aspects of increasingly respected patient safety are also considered. METHODS: In the context of a literature search the active ingredients argatroban and danaparoid, which are approved for HIT II treatment, were evaluated. RESULTS: HIT II - especially in combination with thromboembolic complications - represents a medical-economic burden for the hospital. Although this is only an orientation guide, it shows that HIT II syndrome is not adequately cost-covered by the G­DRG system. An early thrombosis prophylaxis with argatroban/danaparoid for HIT II risk patients should therefore be taken into account for medical-related as well as patient safety-relevant aspects. According to experience, the pharmaceutical supply for these medically needed products (anticoagulants) should be ensured for reasons of patient safety. CONCLUSION: The risk of an immunological response to heparin therapy is known. Within the context of increased patient safety, thrombosis prophylaxis should be issued with a risk-adjusted prophylaxis.


Assuntos
Heparina/efeitos adversos , Heparina/economia , Hospitalização/economia , Trombocitopenia/induzido quimicamente , Trombocitopenia/economia , Trombose/economia , Trombose/prevenção & controle , Sulfatos de Condroitina/efeitos adversos , Sulfatos de Condroitina/uso terapêutico , Custos e Análise de Custo , Dermatan Sulfato/efeitos adversos , Dermatan Sulfato/uso terapêutico , Alemanha , Hemorragia/sangue , Hemorragia/induzido quimicamente , Hemorragia/economia , Heparina/uso terapêutico , Heparitina Sulfato/efeitos adversos , Heparitina Sulfato/uso terapêutico , Humanos , Ácidos Pipecólicos/efeitos adversos , Ácidos Pipecólicos/uso terapêutico , Fatores de Risco , Trombocitopenia/tratamento farmacológico , Trombose/sangue , Resultado do Tratamento
13.
J Stroke Cerebrovasc Dis ; 25(4): 825-30, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26796053

RESUMO

BACKGROUND: Ischemic stroke patients subtyped as of undetermined cause (SUC) usually outnumber those with determined cause subtypes. Etiological stroke classifications may lead to neglect of parallel, noncausative findings. Atherosclerosis progresses over decades and is associated with high morbidity and mortality in young stroke patients in long-term follow-up studies. We compared the prevalence of carotid atherosclerosis in all TOAST subtypes among young patients with acute ischemic stroke. METHODS: We investigated 150 patients aged 15-60 years with documented acute ischemic stroke, and 84 controls free of cardiovascular disease. Stroke etiology was classified according to TOAST criteria. Carotid intima-media thickness (cIMT) measurements were obtained from 12 standardized multiangle measurements in the common carotid artery, carotid bifurcation, and internal carotid artery. RESULTS: The causes of stroke were 5.3% large-artery atherosclerosis (LAA), 26.7% cardioembolism, 21.3% small-artery occlusion (SAO), 10% stroke of other determined cause, and 36.7% stroke of undetermined cause (SUC). cIMT was increased in patients with LAA (1.56 mm, P = .002), SAO (1.11 mm, P = .006), and SUC (1.10 mm, P = .004) compared to controls (cIMT 0.86 mm). Segmental cIMT distribution differed across stroke subtypes, age groups, and sexes. CONCLUSIONS: Atherosclerotic disease is prevalent in the majority of young and middle-aged ischemic stroke patients, requiring determined investigation and aggressive treatment of modifiable risk factors.


Assuntos
Doenças das Artérias Carótidas/tratamento farmacológico , Doenças das Artérias Carótidas/etiologia , Sulfatos de Condroitina/uso terapêutico , Dermatan Sulfato/uso terapêutico , Fibrinolíticos/uso terapêutico , Heparitina Sulfato/uso terapêutico , Acidente Vascular Cerebral/complicações , Adolescente , Adulto , Fatores Etários , Doenças das Artérias Carótidas/epidemiologia , Espessura Intima-Media Carotídea , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neuroimagem , Noruega/epidemiologia , Acidente Vascular Cerebral/classificação , Acidente Vascular Cerebral/diagnóstico por imagem , Adulto Jovem
14.
J Stroke Cerebrovasc Dis ; 25(4): 831-4, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26778600

RESUMO

BACKGROUND: Mood disorders are frequent after stroke and are associated with poorer quality of life. Previous studies have reported conflicting results as to stroke subtype in the incidence of poststroke mood disorders. We explored the relationship between subcortical ischemic stroke subtype (lacunar) and presence of such symptoms at 1 year after stroke. METHODS: Anonymized data were accessed from the Virtual International Stroke Trials Archive. Stroke subtypes were classified according to the Trial of Org 10172 in Acute Stroke Treatment classification. Depression and anxiety symptoms were assessed using Hospital Anxiety and Depression Scale. We investigated independent predictors of depression and anxiety symptoms using a logistic regression model. RESULTS: Data were available for 2160 patients. Almost one fifth of the patients developed both anxiety and depression at 1-year follow-up. After adjusting for confounders, the lacunar subtype was least associated with both anxiety (odds ratio [OR] = .61; 95% confidence interval [CI] = .46-.80) and depression symptoms (OR = .71; CI = .55-.93) versus other stroke subtypes. CONCLUSIONS: Lacunar strokes have a weaker association with presence of anxiety and depression symptoms compared with other subtypes.


Assuntos
Ansiedade/etiologia , Depressão/etiologia , Acidente Vascular Cerebral Lacunar/etiologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/psicologia , Idoso , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Sulfatos de Condroitina/uso terapêutico , Depressão/diagnóstico , Depressão/epidemiologia , Dermatan Sulfato/uso terapêutico , Feminino , Fibrinolíticos/uso terapêutico , Seguimentos , Heparitina Sulfato/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Neuroimagem , Escalas de Graduação Psiquiátrica , Qualidade de Vida , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral Lacunar/diagnóstico por imagem , Acidente Vascular Cerebral Lacunar/epidemiologia
15.
Cytotherapy ; 17(10): 1447-64, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26349001

RESUMO

BACKGROUND AIMS: Dermatan sulfate (DS), an anticoagulant and antithrombotic glycosaminoglycan, also has anti-inflammatory activity. In this study, we investigated the effect of DS treatment in the presence or absence of bone marrow mononuclear cells (MNCs) or endothelial progenitor cells (EPCs) in the vascular response to carotid artery lesion in C57BL6 mice. METHODS: Thrombus formation, the expression of adhesion molecules and factors involved in vascular remodeling, inflammation or vascular tone were analyzed by histologic examination, Western blotting and enzyme-linked immunoassay 1 and 3 days after vascular injury. RESULTS: DS injections prevented thrombus formation and decreased P-selectin expression after 3 days of the injury. DS treatment also increased plasma SDF-1 levels but failed to rescue endothelial nitric oxide synthase (eNOS) expression, which is responsible for vascular tone. Treatment with MNCs alone failed to prevent thrombus formation 1 day after injury and increased intercellular adhesion molecule-1 expression, likely because of the inflammatory nature of these cells. Treatment with EPCs with DS was the most efficient among all therapies studied. Dual administration of EPCs and DS promoted an increase in the expression of adhesion molecules and, at the same time, induced a higher expression of eNOS at the injury site. Furthermore, it stimulated an elevated number of EPCs to migrate and adhere to the vascular wall. DISCUSSION: Simultaneous treatment with EPCs and DS increased the expression of adhesion molecules, prevented thrombosis, rescued the expression of eNOS and increased migration of EPCs to the site of injury, thereby affecting thrombus remodeling and inflammation and can be involved in vessel hemostasis.


Assuntos
Lesões das Artérias Carótidas/terapia , Dermatan Sulfato/uso terapêutico , Células Progenitoras Endoteliais/transplante , Fibrinolíticos/uso terapêutico , Trombose/prevenção & controle , Remodelação Vascular/fisiologia , Animais , Anti-Inflamatórios/farmacologia , Células da Medula Óssea/citologia , Artérias Carótidas/efeitos dos fármacos , Artérias Carótidas/patologia , Lesões das Artérias Carótidas/tratamento farmacológico , Lesões das Artérias Carótidas/cirurgia , Adesão Celular/fisiologia , Moléculas de Adesão Celular/metabolismo , Movimento Celular/fisiologia , Células Cultivadas , Quimiocina CXCL12/biossíntese , Terapia Combinada , Molécula 1 de Adesão Intercelular/biossíntese , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo III/biossíntese , Selectina-P/biossíntese
17.
Cochrane Database Syst Rev ; (6): CD008562, 2015 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-26107113

RESUMO

BACKGROUND: Disseminated intravascular coagulation (DIC) is an acquired syndrome characterized by systemic intravascular activation of coagulation, leading to deposition of fibrin in the bloodstream. It may occur in patients with acute and chronic leukemia and is particularly associated with acute promyelocytic leukemia (a subtype of acute myeloid leukemia). OBJECTIVES: To assess the clinical benefits and harms of any pharmacological intervention for treating DIC in patients with acute or chronic leukemia. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2015, Issue 05), MEDLINE (1946 to 7 May 2015), LILACS (1982 to 7 May 2015) and African Index Medicus (7 May 2015). There was no language restrictions. We sought additional randomized controlled trials (RCTs) from the World Health Organization International Clinical Trials Registry Platform and the reference lists of primary studies identified. SELECTION CRITERIA: RCTs assessing the clinical benefits and harms of interventions for treating DIC in patients with acute and chronic leukemia. DATA COLLECTION AND ANALYSIS: Two review authors independently performed trial selection, 'Risk of bias' assessment and data extraction. Primary outcomes were overall mortality, in-hospital mortality from any cause (15-day and 30-day) and adverse events. MAIN RESULTS: In this Cochrane Review update we did not include any new RCT compared with the first review version. Accordingly, four RCTs (388 participants) met the inclusion criteria. These trials evaluated the human activated protein C, recombinant human soluble thrombomodulin, tranexamic acid and dermatan sulphate. Included trials reported data on mortality and bleeding. The studies were conducted in Japan, Italy and the Netherlands. We classified the included trials as: 1) including patients with or without leukemia which did not report data for the leukemia subgroup (366 participants); and 2) only including patients with leukemia (22 participants). Overall, the risk of bias of the included trials was high, since the trial authors did not provide a detailed description about trial design and execution.According to the GRADE recommendations, we judged the overall quality of the body of evidence for all prefixed outcomes as 'very low', due to methodological limitations and very small sample size.One trial, including 10 participants with leukemia and comparing dermatan sulphate with heparin, reported no deaths during trial treatment.In terms of bleeding data, we were unable to pool results from two studies that were only conducted with leukemia patients due to the inconsistency in the measurement and reporting of this outcome. One trial, including 12 participants with leukemia, found very low quality evidence that tranexamic acid can reduce the cumulative hemorrhagic score in participants compared with those assigned to placebo (P = 0.0015, very low quality evidence). On the contrary, there is no evidence that dermatan sulphate compared with placebo reduces new events of hemorrhagic diathesis (1/5 (20%) versus 2/5 (40%); RR 0.50; 95% CI 0.06 to 3.91; P = 0.51, very low quality evidence).No thromboembolic complications were reported in either trial that included patients with leukemia only (very low quality evidence). The safety profile was inconclusive.The included trials did not assess overall mortality, resolution of respiratory failure, renal failure or shock. AUTHORS' CONCLUSIONS: Due to a lack of new RCTs, our conclusions in this Cochrane Review update are the same as the previous review version. We included four RCTs which reported mortality and bleeding data. It is not possible to determine whether human activated protein C, recombinant human soluble thrombomodulin, tranexamic acid and dermatan sulphate are effective or harmful for patients presenting with DIC related to acute or chronic leukemia. The quality of the evidence was low to very low. Therefore, prescription of these interventions for treating DIC in patients with acute and chronic leukemia can neither be supported nor rejected, unless new evidence from a large high-quality trial alters this conclusion.


Assuntos
Anticoagulantes/uso terapêutico , Coagulação Intravascular Disseminada/tratamento farmacológico , Leucemia/complicações , Doença Aguda , Doença Crônica , Dermatan Sulfato/uso terapêutico , Humanos , Leucemia/sangue , Proteína C/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Trombomodulina/uso terapêutico , Ácido Tranexâmico/uso terapêutico
19.
Blood Purif ; 38(2): 127-30, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25412655

RESUMO

PURPOSE: Early clinical signs of heparin induced thrombocytopenia (HIT) are nonspecific and include a sudden drop in the number of platelets as well as formation of arterial and venous thromboses. Regional citrate anticoagulation (RCA) is increasingly used as a very effective modality to prevent filter clotting during renal replacement therapy (RRT). We report the first case where repeated premature filter clotting despite RCA indicated a manifestation of HIT. MATERIALS AND METHODS: A 71-year old woman admitted to the ICU for a compartment syndrome of the leg developed septic shock with acute kidney injury requiring continuous veno-venous hemodialysis (CVVHD). Because of unexpected and repeated premature filter clotting during CVVHD using RCA, HIT was suspected. RESULTS: The diagnosis of HIT was confirmed by the presence of IgG antibodies against heparin and platelet factor (PF) 4 complexes and six points in the 4T score. Discontinuation of heparin administration and initiation of systemic anticoagulation with danaparoid sodium resulted in the normalization of platelet count and hemofilter lifetime. CONCLUSION: RCA does not seem to be sufficient to prevent hemofilter clotting during HIT. Thus, in case of repeated premature filter clotting despite RCA, one should suspect HIT and prompt diagnostic workup as well as a switch to alternative anticoagulation.


Assuntos
Sulfatos de Condroitina/uso terapêutico , Dermatan Sulfato/uso terapêutico , Heparina/efeitos adversos , Heparitina Sulfato/uso terapêutico , Diálise Renal/instrumentação , Trombocitopenia/induzido quimicamente , Lesão Renal Aguda/sangue , Lesão Renal Aguda/complicações , Lesão Renal Aguda/fisiopatologia , Lesão Renal Aguda/terapia , Idoso , Anticoagulantes/uso terapêutico , Citratos/uso terapêutico , Falha de Equipamento , Feminino , Heparina/administração & dosagem , Humanos , Imunoglobulina G/sangue , Fator Plaquetário 4/sangue , Choque Séptico/sangue , Choque Séptico/complicações , Choque Séptico/fisiopatologia , Choque Séptico/terapia , Trombocitopenia/tratamento farmacológico , Trombocitopenia/fisiopatologia , Trombose/induzido quimicamente , Trombose/tratamento farmacológico , Trombose/fisiopatologia
20.
J Am Coll Surg ; 219(5): 865-74, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25256370

RESUMO

BACKGROUND: Decreased antithrombin III (ATIII) activity and large splenic vein diameter (SVD) are risk factors for portal vein thrombosis (PVT) after splenectomy in liver cirrhosis with portal hypertension. Antithrombin III concentrates can prevent PVT. This study was designed to stratify risks for PVT after splenectomy in cirrhotic patients and to develop prophylactic protocols for PVT. STUDY DESIGN: In 53 patients (testing cohort), the cutoff level of preoperative ATIII activity (≤60%) was evaluated for administration of ATIII concentrates. Antithrombin III activity and SVD were re-evaluated as criteria for prophylaxis of PVT. In 57 patients (validation cohort), the risk stratification of PVT and prophylactic protocols were validated. RESULTS: In the testing cohort, 10 (19%) of 53 patients had PVT. Risk level of PVT was stratified and prophylactic protocols were developed. Patients at low risk (ATIII activity ≥70% and SVD <10 mm) were not treated; those at high risk (ATIII activity <70% or SVD ≥10 mm) received ATIII concentrates (1,500 U/day) for 3 days; and those at highest risk (SVD ≥15 mm) received ATIII concentrates for 3 days, followed by danaparoid sodium (2,500 U/day) for 14 days and warfarin. In the validation cohort, 0 of 14 low-risk and 2 of 32 high-risk patients had PVT. Although 8 of 11 patients at highest risk had temporary PVT, it disappeared within 3 months postoperatively. Finally, only 2 (3.5%) of 57 patients had PVT. CONCLUSIONS: Risk stratification of PVT after splenectomy and prophylaxis with ATIII concentrates and danaparoid sodium dramatically reduced the incidence of PVT.


Assuntos
Fibrinolíticos/uso terapêutico , Hipertensão Portal/complicações , Cirrose Hepática/cirurgia , Veia Porta , Complicações Pós-Operatórias/prevenção & controle , Esplenectomia , Trombose Venosa/prevenção & controle , Adulto , Idoso , Anticoagulantes/uso terapêutico , Antitrombina III/uso terapêutico , Sulfatos de Condroitina/uso terapêutico , Protocolos Clínicos , Técnicas de Apoio para a Decisão , Dermatan Sulfato/uso terapêutico , Quimioterapia Combinada , Feminino , Heparitina Sulfato/uso terapêutico , Humanos , Laparoscopia , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Curva ROC , Medição de Risco , Fatores de Risco , Esplenectomia/métodos , Trombose Venosa/etiologia , Varfarina/uso terapêutico
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