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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.
J Craniomaxillofac Surg ; 47(2): 341-348, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30579746

RESUMO

BACKGROUND: Cranioplasty is a surgical procedure used to treat a bone defect or deformity in the skull. To date, there is little consensus on the standard-of-care for graft materials used in such a procedure. Graft materials must have sufficient mechanical strength to protect the underlying brain as well as the ability to integrate and support new bone growth. Also, the ideal graft material should be individually customized to the contours of the defect to ensure a suitable aesthetic outcome for the patient. PURPOSE: Customized 3D-printed scaffolds comprising of polycaprolactone-ß-tricalcium phosphate (PCL-TCP) have been developed with mechanical properties suitable for cranioplasty. Osteostimulation of PCL-TCP was enhanced through the addition of a bone matrix-mimicking heparan sulphate glycosaminoglycan (HS3) with increased affinity for bone morphogenetic protein-2 (BMP-2). Efficacy of this PCL-TCP/HS3 combination device was assessed in a rat critical-sized calvarial defect model. METHOD: Critical-sized defects (5 mm) were created in both parietal bones of 19 Sprague Dawley rats (Male, 450-550 g). Each cranial defect was randomly assigned to 1 of 4 treatment groups: (1) A control group consisting of PCL-TCP/Fibrin alone (n = 5); (2) PCL-TCP/Fibrin-HSft (30 µg) (n = 6) (HSft is the flow-through during HS3 isolation that has reduced affinity for BMP-2); (3) PCL-TCP/Fibrin-HS3 (5 µg) (n = 6); (4) PCL-TCP/Fibrin-HS3 (30 µg) (n = 6). Scaffold integration and bone formation was evaluated 12-weeks post implantation by µCT and histology. RESULTS: Treatment with PCL-TCP/Fibrin alone (control) resulted in 23.7% ± 1.55% (BV/TV) of the calvarial defect being filled with new bone, a result similar to treatment with PCL-TCP/Fibrin scaffolds containing either HSft or HS3 (5 µg). At increased amounts of HS3 (30 µg), enhanced bone formation was evident (BV/TV = 38.6% ± 9.38%), a result 1.6-fold higher than control. Further assessment by 2D µCT and histology confirmed the presence of enhanced bone formation and scaffold integration with surrounding host bone only when scaffolds contained sufficient bone matrix-mimicking HS3. CONCLUSION: Enhancing the biomimicry of devices using a heparan sulphate with increased affinity to BMP-2 can serve to improve the performance of PCL-TCP scaffolds and provides a suitable treatment for cranioplasty.


Assuntos
Materiais Biomiméticos/uso terapêutico , Fosfatos de Cálcio/uso terapêutico , Heparitina Sulfato/uso terapêutico , Poliésteres/uso terapêutico , Crânio/cirurgia , Tecidos Suporte , Animais , Materiais Biomiméticos/administração & dosagem , Fosfatos de Cálcio/administração & dosagem , Heparitina Sulfato/administração & dosagem , Humanos , Imagem Tridimensional , Masculino , Poliésteres/administração & dosagem , Ratos , Ratos Sprague-Dawley , Crânio/diagnóstico por imagem
4.
Glia ; 67(4): 668-687, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30585359

RESUMO

The lack of endogenous repair following spinal cord injury (SCI) accounts for the frequent permanent deficits for which effective treatments are absent. Previously, we demonstrated that low sulfated modified heparin mimetics (LS-mHeps) attenuate astrocytosis, suggesting they may represent a novel therapeutic approach. mHeps are glycomolecules with structural similarities to resident heparan sulfates (HS), which modulate cell signaling by both sequestering ligands, and acting as cofactors in the formation of ligand-receptor complexes. To explore whether mHeps can affect the myelination and neurite outgrowth necessary for repair after SCI, we created lesioned or demyelinated neural cell co-cultures and exposed them with a panel of mHeps with varying degrees and positions of their sulfate moieties. LS-mHep7 enhanced neurite outgrowth and myelination, whereas highly sulfated mHeps (HS-mHeps) had attenuating effects. LS-mHeps had no effects on myelination or neurite extension in developing, uninjured myelinating cultures, suggesting they might exert their proregenerating effects by modulating or sequestering inhibitory factors secreted after injury. To investigate this, we examined conditioned media from cultures using chemokine arrays and conducted an unbiased proteomics approach by applying TMT-LC/MS to mHep7 affinity purified conditioned media from these cultures. Multiple protein factors reported to play a role in damage or repair mechanisms were identified, including amyloid betaA4. Amyloid beta peptide (1-42) was validated as an important candidate by treating myelination cultures and shown to inhibit myelination. Thus, we propose that LS-mHeps exert multiple beneficial effects on mechanisms supporting enhanced repair, and represent novel candidates as therapeutics for CNS damage.


Assuntos
Doenças do Sistema Nervoso Central/tratamento farmacológico , Doenças do Sistema Nervoso Central/metabolismo , Doenças Desmielinizantes/tratamento farmacológico , Heparitina Sulfato/uso terapêutico , Recuperação de Função Fisiológica/efeitos dos fármacos , Peptídeos beta-Amiloides/metabolismo , Animais , Animais Recém-Nascidos , Antimetabólitos/farmacologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Meios de Cultivo Condicionados/farmacologia , Citocinas/metabolismo , Desoxiuridina/farmacologia , Embrião de Mamíferos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas da Mielina/metabolismo , Glicoproteína Mielina-Oligodendrócito/metabolismo , Neuritos/efeitos dos fármacos , Neuroglia/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Oligodendroglia/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Medula Espinal/citologia
5.
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
6.
Molecules ; 23(11)2018 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-30413079

RESUMO

Beyond anticoagulation, the therapeutic potential of heparin derivatives and heparan sulfate (HS) mimetics (functionally defined HS mimetics) in oncology is related to their ability to bind and modulate the function of a vast array of HS-binding proteins with pivotal roles in cancer growth and progression. The definition of structural/functional determinants and the introduction of chemical modifications enabled heparin derivatives to be identified with greatly reduced or absent anticoagulant activity, but conserved/enhanced anticancer activity. These studies paved the way for the disclosure of structural requirements for the inhibitory effects of HS mimetics on heparanase, selectins, and growth factor receptor signaling, as well as for the limitation of side effects. Actually, HS mimetics affect the tumor biological behavior via a multi-target mechanism of action based on their effects on tumor cells and various components of the tumor microenvironment. Emerging evidence indicates that immunomodulation can participate in the antitumor activity of these agents. Significant ability to enhance the antitumor effects of combination treatments with standard therapies was shown in several tumor models. While the first HS mimetics are undergoing early clinical evaluation, an improved understanding of the molecular contexts favoring the antitumor action in certain malignancies or subgroups is needed to fully exploit their potential.


Assuntos
Materiais Biomiméticos/química , Heparitina Sulfato/química , Neoplasias/metabolismo , Animais , Materiais Biomiméticos/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Progressão da Doença , Glucuronidase/metabolismo , Heparitina Sulfato/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Receptores de Fatores de Crescimento/metabolismo , Selectinas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade
7.
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
8.
Metab Brain Dis ; 33(1): 1-10, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28921412

RESUMO

Sanfilippo disease is one of mucopolysaccharidoses (MPS), a group of lysosomal storage diseases characterized by accumulation of partially degraded glycosaminoglycans (GAGs). It is classified as MPS type III, though it is caused by four different genetic defects, determining subtypes A, B, C and D. In each subtype of MPS III, the primary storage GAG is heparan sulfate (HS), but mutations leading to A, B, C, and D subtypes are located in genes coding for heparan N-sulfatase (the SGSH gene), α-N-acetylglucosaminidase (the NAGLU gene), acetyl-CoA:α-glucosaminide acetyltransferase (the HGSNAT gene), and N-acetylglucosamine-6-sulfatase (the GNS gene), respectively. Neurodegenerative changes in the central nervous system (CNS) are major problems in Sanfilippo disease. They cause severe cognitive disabilities and behavioral disturbances. This is the main reason of a current lack of therapeutic options for MPS III patients, while patients from some other MPS types (I, II, IVA, and VI) can be treated with enzyme replacement therapy or bone marrow or hematopoietic stem cell transplantations. Nevertheless, although no therapy is available for Sanfilippo disease now, recent years did bring important breakthroughs in this aspect, and clinical trials are being conducted with enzyme replacement therapy, gene therapy, and substrate reduction therapy. These recent achievements are summarized and discussed in this review.


Assuntos
Terapia Genética , Transplante de Células-Tronco Hematopoéticas , Heparitina Sulfato/uso terapêutico , Sulfatases/uso terapêutico , Acetilglucosaminidase/genética , Terapia Genética/métodos , Humanos , Mutação/genética
10.
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
11.
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
12.
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
13.
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
14.
Glycoconj J ; 34(3): 299-307, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-27778131

RESUMO

Glycosaminoglycans are integral part of the dynamic extracellular matrix (ECM) network that control crucial biochemical and biomechanical signals required for tissue morphogenesis, differentiation, homeostasis and cancer development. Breast cancer cells communicate with stromal ones to modulate ECM mainly through release of soluble effectors during cancer progression. The intracellular cross-talk between cell surface receptors and estrogen receptors is important for the regulation of breast cancer cell properties and production of ECM molecules. In turn, reorganized ECM-cell surface interface modulates signaling cascades, which regulate almost all aspects of breast cell behavior. Heparan sulfate chains present on cell surface and matrix proteoglycans are involved in regulation of breast cancer functions since they are capable of binding numerous matrix molecules, growth factors and inflammatory mediators thus modulating their signaling. In addition to its anticoagulant activity, there is accumulating evidence highlighting various anticancer activities of heparin and nano-heparin derivatives in numerous types of cancer. Importantly, heparin derivatives significantly reduce breast cancer cell proliferation and metastasis in vitro and in vivo models as well as regulates the expression profile of major ECM macromolecules, providing strong evidence for therapeutic targeting. Nano-formulations of the glycosaminoglycan heparin are possibly novel tools for targeting tumor microenvironment. In this review, the role of heparan sulfate/heparin and its nano-formulations in breast cancer biology are presented and discussed in terms of future pharmacological targeting.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica , Heparina/química , Heparitina Sulfato/uso terapêutico , Animais , Antineoplásicos/química , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Comunicação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citocinas/genética , Citocinas/metabolismo , Matriz Extracelular/química , Matriz Extracelular/metabolismo , Feminino , Heparina/uso terapêutico , Heparitina Sulfato/química , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Ligação Proteica/efeitos dos fármacos , Transdução de Sinais , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo , Células Estromais/patologia
15.
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
16.
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
17.
Rom J Ophthalmol ; 61(1): 2-10, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29450364

RESUMO

The extracellular matrix (ECM) is responsible for many of the cell behavior processes, including cell proliferation and growth, survival, change in cell shape, migration, and differentiation. The most important component of the ECM is heparan sulfate (HS), because it insures the storage of many cell communication proteins, necessary for the continuous and identical renewal of cells and thus for tissue regeneration. Regenerating agents (RGTA®) are bioengineered structural analogues of heparan sulfate glycosaminoglycans that replace the degraded endogenous HS of the ECM. In the ophthalmological field, RGTA® represents an innovative approach for the improvement of the ocular surface wound healing and matrix remodeling and plays a role in controlling and regulating the wound healing process in various ocular diseases.


Assuntos
Materiais Biomiméticos/uso terapêutico , Terapia Baseada em Transplante de Células e Tecidos/métodos , Doenças da Córnea/terapia , Matriz Extracelular/metabolismo , Heparitina Sulfato/uso terapêutico , Cicatrização/fisiologia , Materiais Biomiméticos/química , Doenças da Córnea/metabolismo , Regeneração Tecidual Guiada/métodos , Heparitina Sulfato/química , Humanos , Medicina Regenerativa/métodos , Engenharia Tecidual/métodos
18.
Int J Low Extrem Wounds ; 15(1): 63-7, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26933115

RESUMO

A novel heparan sulfate glycosaminoglycan mimetic product for local application to promote wound healing (CACIPLIQ) has recently become available. It is a biophysical therapeutic product comprising a polysaccharide as an innovative biomaterial to accomplish mechanical tissue engineering and skin regeneration in the site of ulceration. We present a series of 12 patients with type 2 diabetes (4 men and 8 women; age 53-87 years; diabetes duration 8-25 years) having chronic resistance to therapy for foot and lower extremity ulcerations. CACIPLIQ was locally applied twice per week after careful debridement. Complete ulcer healing was accomplished in all patients after a mean treatment duration of 4.92 months (range = 2-12 months). The product was very well tolerated. In conclusion, these results, although preliminary, are encouraging and suggest adequate efficacy and safety of the new product in difficult-to-heal foot and lower extremity ulcerations in type 2 diabetes.


Assuntos
Bandagens , Diabetes Mellitus Tipo 2/complicações , Pé Diabético/complicações , Pé Diabético/tratamento farmacológico , Heparitina Sulfato/uso terapêutico , Úlcera da Perna/complicações , Úlcera da Perna/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Cicatrização
19.
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
20.
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
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