As trombofilias na perda gestacional de repetição: uma revisão de prevalência e condutas / Thrombophilias in recurrent pregnancy loss: a review of prevalence and conduct

Objetivo: Discutir o papel das trombofilias na perda gestacional de repetição, com foco em prevalência/associação dessas patologias com perdas de repetição e seu tratamento, por meio de resultados de ensaios clínicos, revisões sistemáticas e metanálises. Métodos: Trata-se de uma revisão não sistemática de artigos publi- cados nas bases eletrônicas PubMed, Cochrane e SciELO nos últimos cinco anos, utilizando os seguintes descritores: "recurrent pregnancy loss", "recurrent abortion", "habitual abortion", "thrombophilia", "antiphospholipid syndrome" e "treatment". Resultados: A maioria dos estudos relatou forte associação entre os anticorpos antifosfolípides específicos e a síndrome do anticorpo antifosfolípide com perda gestacional de repetição. Mulheres portadoras da mutação do fator V de Leiden, mutação do gene da protrombina e deficiência de proteína S apresentaram alto risco de perda gestacional de repetição em uma grande revisão sistemática. Estudos recentes demonstraram taxas de prevalência das trombofilias hereditárias e da síndrome do anticorpo antifosfolípide, em mulheres com perda gestacional de repetição, semelhantes às da população em geral. Os estudos atuais endossam o uso da heparina associada à aspirina em mulheres com síndrome do anticorpo antifosfolípide, com aumento da taxa de nascidos vivos, mas sem diferença em re- lação às complicações obstétricas. Conclusão: Apesar de novos estudos demons- trarem que a prevalência das trombofilias hereditárias e adquiridas em mulheres com perda gestacional de repetição é semelhante à da população em geral, reco- menda-se a pesquisa rotineira de síndrome do anticorpo antifosfolípide nessas pacientes. O uso de aspirina em baixas doses associada à heparina é a intervenção farmacológica de primeira linha para a prevenção de perda gestacional de repeti- ção em pacientes com síndrome do anticorpo antifosfolípide.

Objective: To discuss the role of thrombophilias in recurrent pregnancy loss, focu- sing on the prevalence/association of these pathologies with recurrent abortion and treatment, through results of clinical trials, systematic reviews and meta-analyses. Methods: This is a non-systematic review of articles published in electronic databa- ses PubMed, Cochrane, SciELO in the last five years, using the following descriptors: "recurrent pregnancy loss", "recurrent abortion", "habitual abortion", "thrombophilia", "antiphospholipid syndrome", and "treatment". Results: Most studies have reported a strong association between specific antiphospholipid antibodies and antiphospho- lipid antibody syndrome with recurrent pregnancy loss. Women carrying the factor V Leiden mutation, prothrombin gene mutation, and protein S deficiency were shown to be at high risk of recurrent pregnancy loss in a large systematic review. Recent studies have shown prevalence rates of hereditary thrombophilias and antiphospholipid antibody syndrome, in women with re- current pregnancy loss, similar to those of the general po- pulation. Current studies endorse the use of heparin plus aspirin in women with antiphospholipid antibody syndrome, with an increase in live birth rate, but with no difference in obstetric complications. Conclusion: Although new studies demonstrate that the prevalence of hereditary and acquired thrombophilias in women with recurrent pregnancy loss is si- milar to that of the general population, routine investigation of antiphospholipid antibody syndrome in these patients is recommended. The use of low-dose aspirin plus heparin is the first-line pharmacological intervention for the prevention of recurrent pregnancy loss in patients with antiphospholipid antibody syndrome.

Safety and efficacy of regional citrate anticoagulation in continuous blood purification treatment of patients with multiple organ dysfunction syndrome

The aim of this study was to discuss the safety and efficacy of regional citrate anticoagulation (RCA) on continuous blood purification (CBP) during the treatment of multiple organ dysfunction syndrome (MODS). Thirty-five patients with MODS were divided into two groups: the local citrate anticoagulation (RCA) group, and the heparin-free blood purification (hfBP) group. The MODS severity was assessed according to Marshall's MODS score criteria. Blood coagulation indicators, blood pressure, filter lifespan, filter replacement frequency, anticoagulation indicators, and main metabolic and electrolyte indicators were analyzed and compared between RCA and hfBP groups. RCA resulted in lower blood pressure than hfBP. The filter efficacy in RCA treatment was longer than in the hfBP group. The blood clearance of creatine, blood urea nitrogen and uric acid was better in the RCA group. RCA also led to higher pH than hfBP. Neither treatment resulted in severe bleeding events. In addition, MODS score was positively correlated with prothrombin time and activated partial thromboplastin time but negatively correlated with platelet concentration. RCA is a safer and more effective method in CBP treatment; however, it could also lead to low blood pressure and blood alkalosis.

Doppler velocimetry in fetal rats exposed to enoxaparin and unfractionated heparin (UFH) during pregnancy

Abstract Purpose: To evaluate the effects of enoxaparin and unfractionated heparin (UFH) administered in prophylactic and therapeutic doses on fetal vessels in healthy pregnant Wistar rats, according to Doppler velocimetry measurements. Methods: Fifty animals were assigned to one of five groups: controls (saline), prophylactic and therapeutic enoxaparin (1 and 2 mg/kg/day, respectively), and prophylactic and therapeutic UFH (72 and 400 UI/kg/day, respectively). Uterine horns were examined by ultrasound for identification of live fetuses. A sample of these fetuses underwent Doppler velocimetry. Spectral curves, peak systolic velocity (PSV), pulsatility index (PI), and resistance index (RI) of the middle cerebral artery, ductus venosus, and umbilical artery were investigated. Differences were considered statistically significant when p<0.05. Results: No significant differences in PSV, PI, or RI values were observed among the groups. Conclusion: Doppler velocimetry measurements revealed no significant effects of enoxaparin or unfractionated heparin on fetal vessels in pregnant Wistar rats.

Solução salina versus solução de heparina na perviedade do cateter venoso periférico na terapia venosa intermitente: revisão sistemática / Saline solution versus heparin in the patency of the venous peripheral catheter in the intermittent venous therapy: a systematic review

O uso do cateter venoso periférico intermitente em pacientes hospitalizados pode lhes trazer grandes benefícios, proporcionando maior liberdade com a higiene pessoal, alimentação, deambulação, além melhorias para a equipe de enfermagem com redução das rotinas diárias. No entanto, obstrução do cateter é algo que vem na contramão de uma assistência adequada, causando desconforto para o paciente e aumento do trabalho de enfermagem. Para evitar tal evento e garantir a perviedade do cateter intravascular, deve-se realizar o flushing com solução salina ou solução de heparina, após a administração de medicamentos ou em horários programados de acordo com o protocolo interno das instituições de saúde. Nesse contexto, surge o questionamento de qual é a melhor solução para manter a perviedade do cateter venoso periférico intermitente. Este estudo trata-se de uma revisão sistemática da literatura, com o objetivo de avaliar a efetividade do uso da solução salina comparada à solução de heparina na manutenção da perviedade dos cateteres venosos periféricos. Foi realizada a busca nas bases de dados eletrônicas Cinahl, Cochrane Central, Embase, Lilacs, Pubmed e Web of Science. Das 372 referências identificadas, 12 estudos foram selecionados após a análise de título e resumo para serem lidos na íntegra, sendo que 04 constituíram a amostra final. A extração e análise dos dados foram realizadas por dois revisores independentes e as divergências entre eles foram solucionadas por um terceiro revisor. Os 04 estudos foram publicados no período de 1995 a 2015. Ao todo, foram investigados 975 dispositivos endovenosos mantidos com uma das soluções estudadas em 420 participantes. Os estudos testaram a solução de heparina em dosagens que variaram de 10UI/mL a 100UI/mL versus a solução salina e investigaram as complicações relacionadas ao cateter venoso periférico em uso intermitente, sendo uma delas a obstrução do cateter a qual denominamos como ausência e/ou diminuição da perviedade do cateter venoso, que pode ser evitada com o flushing de forma adequada. As intervenções foram testadas em diferentes populações e não foram concordantes em suas conclusões; dois estudos recomendaram a solução de heparina, um estudo, a solução salina, e um recomenda o uso das duas soluções. Os quatro estudos discutem que as duas soluções são seguras e eficazes para a manutenção da perviedade do cateter venoso periférico. Porém, os autores afirmam que o tamanho da amostra não é suficiente para generalizar os resultados para todos os pacientes hospitalizados. Assim, essa revisão sistemática sugere a necessidade de que novos ensaios clínicos randomizados sejam realizados e que as instituições de saúde devem fomentar as investigações clínicas para validar uma assistência de enfermagem alicerçada em práticas seguras e de qualidade

The using of intermittent peripheral venous catheter in a hospitalized patient can bring to them important benefits, providing more freedom concerning to the personal hygiene, feeding, ambulation, and a lot of another improvements for the nursing team, reducing the daily routines. However, catheter obstruction it is something that disturb an appropriate assistence, provoking discomfort to the patient and increasing the need of job of the nursing team. To avoid this fact and to ensure the patency of the intervascular catheter, must to do the flushing process with saline solution or hepamin, after the application of drugs or in pre established time according to the protocol of procedure of the health institutions. In this regard, it emerges the questioning about what is the best solution to keep the patency of the intermittent peripheral venous catheter. This research is a systematic review about the litetature on this subject, and it aims to evaluate the effectiveness of the using of the saline solution in comparison to the heparin in the maintenance of the patency of the peripheral venous catheter. It has been done a research in the electronic databases Cinahl, Cochrane Central, Embase, Lilacs, Pubmed and Web of Science. An amount of 372 references was identified, but just 12 research were selected after the analysis of their titles and abstracts to be fully read. In the end, 04 of them were picked as definitive samples.The data collect and the anlysis were done by two independent reviewers, and the divergences between them were solved by a third reviewer. The 04 research were publicized in the 1995 to 2015 period. Altogheter, were searched 975 intravenous devices, keeping them with one of the studied solutions in 420 patients. Th estudies tried the heparin in dosages that vary from 10UI/mL to 100UI/mL versus the saline solution and investigated the complications related to the peripheral venous catheter in a intermittent using. One of these complications was the catheter obstruction, wich were designated as lack or the decrease of the patency of the venous catheter, that can be avoided with an appropriate flushing process. The interventions were tried in different populations, and they were not concordant in their conclusions. Two research recommended the heparin, one, the saline solution, and one of them recommend to use both. The four research affirm that the heparin and the saline solution are safety and effective for the maintenance of the patency of the peripheral venous catheter. However, the authors say point out that the quantity of the simple is not enough to to generalize the results regarding to all hospitalized patients. Thus, this systematic review suggest the necessity of new randomized clinical testings. In addition, the health institutions must promote clinical research in order to validate a solid nursing assistance based on safety and appropriated practices

Protocolo de prevenção de tromboembolismo venoso em cirurgia plástica: resultados em 2759 pacientes no Instituto Ivo Pitanguy / Venous thromboemboembolism prevention protocol in plastic surgery: results in 2759 patients at the Ivo Pitanguy Institute

Introdução: A embolia pulmonar é a causa de morte mais previsível em pacientes hospitalizados, sendo isso ainda mais prevalente em pacientes cirúrgicos. 200.000 novos casos ocorrem anualmente, com início súbito e geralmente levando à morte nas primeiras 2 horas. Prevenir é, portanto, mais efetivo que tratar a doença estabelecida. Esse estudo objetiva demonstrar a importância e segurança do protocolo de prevenção do tromboembolismo venoso. Métodos: Conduzimos um estudo retrospectivo no período de maio de 2009 a maio de 2011, quando 2759 pacientes foram submetidos à cirurgia plástica no Instituto Ivo Pitanguy. Todos os pacientes foram submetidos ao protocolo de prevenção e avaliados quanto aos fatores de risco para tromboembolismo venoso. A soma desses fatores gerou um escore que determinou a conduta profilática a ser adotada. Resultados: Houve três casos de tromboembolismo venoso (0,1%), sendo 1 de TEP e 2 de TVP. A quimioprofilaxia com enoxaparina administrada aos 3 pacientes de acordo com o protocolo de prevenção. Nossas taxas permaneceram abaixo das encontradas na literatura, com diferença estatisticamente significativa nos numero total de casos (p < 0,0001). Houve 34 casos de hematoma (1,2%), sendo 55,9% em pacientes submetidos à quimioprofilaxia e 44,1% em pacientes que usaram apenas o dispositivo de compressão pneumática intermitente apenas. As taxas totais de hematoma também permaneceram abaixo das encontradas na literatura, também com diferença estatisticamente significativa (p < 0,001). Conclusão: O protocolo de prevenção do tromboembolismo venoso do Instituto Ivo Pitanguy se provou seguro e importante na prevenção dos casos de TEV, com taxas de hematoma abaixo do descrito na literatura.

Introduction: Pulmonary embolism is the most predictable cause of death in hospitalized patients, even more in surgical patients. 200.000 new cases occur annually, with sudden onset and generally leading to death in the first 2 hours. Preventing is most effective than treating stablished disease. This study aims to show the importance and safety of the venous thromboembolism prevention protocol. Methods: We conducted a retrospective study in the period between May 2009 and May 2011 at The Ivo Pitanguy Institute, where 2759 patients underwent plastic surgery (aesthetic and reconstructive). All patients were assessed for predisposing and exposing risk factors for venous thromboembolism and the sum of those factors generated a score determining the prophylactic procedure to be adopted according to the protocol. Results: There were three cases of venous thromboembolism (0.1%): one case of pulmonary embolism and two cases of deep venous thrombosis. Chemoprophylaxis with heparin was administered in the three patients according to the venous thromboembolism prevention protocol. Our rates remained below those found in the literature, with a statistically significant difference in total cases (p < 0.0001). There were 34 cases of hematoma (1.2%): 55.9% in patients submitted to pharmacological prophylaxis with heparin and 44,1% in patients who used sequential compression devices only. The total rates of hematoma also remained below those found in the literature with a statistically significant difference (p < 0,001). Conclusion: The venous thromboembolism prevention protocol of the Ivo Pitanguy Institute proved to be important and safe, preventing the occurrence of venous thromboembolism cases with low rates of hematoma.

Evaluation of Cellular Proliferative Activity in Patients with Oral Lichen Planus and Hepatitis C through AgNOR Method

The objective of this study was to evaluate the cellular proliferative potential of oral lichen planus (OLP) lesions from patients without hepatitis C virus (HCV) by means of AgNOR method, as well as the cellular proliferative potential of the normal oral mucosa from patients with HCV, treated or untreated by interferon and ribavirin. A cross-sectional study was developed to investigate four groups: 10 HCV+ patients without clinical signs of OLP who had never been treated for HCV infection - Group 1; 10 HCV+ patients that were under interferon and ribavirin treatment - Group 2; 15 patients with reticular OLP lesions histopathologically confirmed, without HCV - Group 3; and 15 blood donors without HCV infection and no clinical signs of OLP GROUP 4 Control Group. The cytological material of all groups was collected by the liquid-based cytology technique. Then, the sedimented material from each patient was filled with the Nucleolar Organizer Regions impregnation by silver method (AgNOR). The count of NORs was performed on 100 epithelial cell nuclei per patient using the Image Tool(tm) software. The Tukey HSD test was used to compare the median value of NORs among the groups and showed that the oral mucosa of HCV+ patients previously treated with anti-HCV drugs (GROUP 2), presented a higher average number of NORs in relation to others (p<0.05). The anti-HCV treatment may be related to increased cell proliferation of oral mucosa, indicating a possible relationship between OLP and HCV+ patients treated with interferon and ribavirin.

O propósito deste estudo foi avaliar o potencial proliferativo celular das lesões de líquen plano bucal (LPB) de pacientes sem vírus da hepatite C (VHC) por meio do método AgNOR, comparando-o ao potencial proliferativo celular da mucosa bucal normal de portadores de VHC, tratados ou não com interferon e ribavirina. Um estudo transversal foi realizado para investigar 4 grupos: 10 pacientes VHC+ sem sinais clínicos de LPB que nunca haviam sido tratados para a infecção por VHC - Grupo 1; 10 pacientes VHC+ que estavam sob tratamento com interferon e ribavirina - Grupo 2; 15 pacientes com LPB reticular histopatologicamente confirmado, sem VHC - Grupo 3; e 15 doadores de sangue sem infecção por VHC e sem sinais clínicos de LPB (Grupo 4 - Grupo de Controle). O material celular de todos os grupos foi coletado pela técnica da citologia em base líquida. Então, o material sedimentado de cada paciente foi submetido ao método da impregnação das regiões organizadoras nucleolares pela prata (AgNOR). A contagem das NORs foi realizada em 100 núcleos celulares epiteliais por paciente por meio do programa Image Tool(r). O teste Tukey HSD foi utilizado para comparar o valor médio de NORs entre os grupos e mostrou que a mucosa bucal dos pacientes VHC+ previamente tratados com fármacos anti-VHC (Grupo 2) apresentou maior número médio de NORs por núcleo em relação aos outros (p<0,05). O tratamento anti-VHC pode estar relacionado ao aumento da atividade proliferativa celular da mucosa bucal, aventando uma possível relação entre LPB e pacientes VHC+ tratados com interferon e ribavirina.

Static body postural misalignment in individuals with temporomandibular disorders: a systematic review

BACKGROUND: The association between body postural changes and temporomandibular disorders (TMD) has been widely discussed in the literature, however, there is little evidence to support this association. OBJECTIVES: The aim of the present study was to conduct a systematic review to assess the evidence concerning the association between static body postural misalignment and TMD. METHOD: A search was conducted in the PubMed/Medline, Embase, Lilacs, Scielo, Cochrane, and Scopus databases including studies published in English between 1950 and March 2012. Cross-sectional, cohort, case control, and survey studies that assessed body posture in TMD patients were selected. Two reviewers performed each step independently. A methodological checklist was used to evaluate the quality of the selected articles. RESULTS: Twenty studies were analyzed for their methodological quality. Only one study was classified as a moderate quality study and two were classified as strong quality studies. Among all studies considered, only 12 included craniocervical postural assessment, 2 included assessment of craniocervical and shoulder postures,, and 6 included global assessment of body posture. CONCLUSION: There is strong evidence of craniocervical postural changes in myogenous TMD, moderate evidence of cervical postural misalignment in arthrogenous TMD, and no evidence of absence of craniocervical postural misalignment in mixed TMD patients or of global body postural misalignment in patients with TMD. It is important to note the poor methodological quality of the studies, particularly those regarding global body postural misalignment in TMD patients. .

Heparin modulates the expression of genes encoding pro and anti-apoptotic proteins in endothelial cells exposed to intestinal ischemia and reperfusion in rats

PURPOSE: To investigate if expression of genes encoding pro and anti-apoptotic proteins in the rat enteric endothelial cells stimulated by intestinal ischemia followed by reperfusion (IR) can be modified by treatment with heparin (HP). METHODS: Eighteen adult Wistar rats were divided in three groups: sham group submitted to laparotomy only (SG), ischemia followed by reperfusion group (IRG); ischemia followed by reperfusion plus pretreatment with HP 100 mg.kg-1 (IRG+HP). Ischemia was performed by clamping of the superior mesenteric artery. After 60 min of ischemia, metal clamps were removed for reperfusion for 120 min. Gene expression of encoding pro (Casp1, Casp6, Casp3, Cflar, Fas and Pgl) and anti-apoptotic (Bcl2, Bcl2l1 and Naip2) proteins in rat enteric endothelial cells was evaluated by PCR microarray method. RESULTS: Compared to rat endothelial cells of SG, the expression of pro-apoptotic genes was up-regulated in IRG while anti-apoptotic genes were down-regulated. In contrast, the expression of anti-apoptotic genes in IRG+HP was up-regulated while pro-apoptotic genes was down-regulated compared to SG. CONCLUSION: The attenuation by heparin of intestinal ischemia-reperfusion previously demonstrated in rodents could be related with ability of this drug to stimulate and reduce gene expression of encoding anti and pro-apoptotic proteins, respectively. .

Selección de variantes de virus dengue sensibles a la heparina en células BHK-21 / Selection of heparin-sensitive dengue virus variants in BHK-21 cells

Estudios previos han demostrado que la adaptación de diversos virus a crecer en líneas celulares de vertebrados, conduce a la selección de variantes virales que unen al heparán sulfato (HS) con alta afinidad. En el presente trabajo se determinó la susceptibilidad de cepas del virus dengue (DENV) a la heparina hipersulfatada un análogo al HS, después de pases seriados en células BHK-21. A aislados de campo de los cuatro serotipos de DENV, se les realizaron ocho pases seriados en células BHK-21. La adaptación de los DENV al cultivo celular seleccionó variantes virales con una aumentada capacidad replicativa en células BHK-21 y una incrementada susceptibilidad a la heparina, en relación a las respectivas cepas no adaptadas, obteniéndose una inhibición de la infectividad más significativa en DENV-2 y DENV-4. Las cepas de DENV adaptadas presentaron cambios en la secuencia de aminoácidos de la proteína de envoltura (E), en particular una substitución K204R para DENV-1, N67K para DENV-2, K308R y V452A para DENV-3 y E327G para DENV-4. Estas sustituciones implicaron ganancia de residuos básicos que incrementaron la carga neta positiva de la proteína. Los resultados sugieren, que la adaptación de cepas de DENV a células BHK-21 selecciona variantes virales sensibles a la heparina y que la efectividad de este compuesto varía dependiendo de la cepa viral. Además sugieren que el HS puede jugar un papel importante en la infectividad de las cepas de DENV adaptadas al cultivo celular, a diferencia de los aislados de DENV no adaptados.

Several studies have shown that adaptation of various viruses to grow in certain cell lines of vertebrates, leads to the selection of virus variants that bind heparan sulfate (HS) with high affinity. In this study we investigated the susceptibility of strains of dengue virus (DENV) to oversulfated heparin an analogue of HS after passages in BHK-21 cells. Field isolates of the four serotypes of DENV with a limited number of passes in mosquito cells C6/36HT were serially passaged eight times in BHK-21 cells. The adaptation of the DENV to the cell culture selected viral variants with an increased replicative capacity in BHK-21 cells and an increased susceptibility to heparin compared with the original not adapted strains, with a more significant inhibition of the infectivity in DENV-2 and DENV-4.The E protein of the adapted strains showed changes in the amino acid sequence, particularly at the position K204R to DENV-1, N67K to DENV-2, K308R and V452A for DENV-3 and E327G to DENV-4. These substitutions implicated a gain of basic residues that increased the net positive charge of the protein. These results suggest that adaptation of DENV strains to BHK-21 cells implies changes in the envelope protein, changes associated to the protein reactivity with heparin, the inhibitory effectiveness of this compound varying depending on the viral strain. In addition, these results suggest that the HS can play an important role in the infectivity of the DENV strains adapted to vertebrate cell culture, but not in the infectivity of non-adapted DENV isolates.

Coronary artery bypass grafting in a patient with protein S deficiency: Perioperative implications.

Protein S (PS) along with activated protein C plays an important role in the down-regulation of in vivo thrombin generation. Its defi ciency can cause abnormal and inappropriate clot formation within the circulation necessitating chronic anticoagulation therapy. The risk of developing thrombotic complications is heightened in the perioperative period in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Heparin resistance is very rare in these patients, especially when antithrombin levels are near normal. Management of CPB in this scenario is quite challenging. We report the perioperative management, particularly the CPB management, of a patient with type I PS defi ciency and incidentally detected heparin resistance, who underwent coronary artery bypass grafting with CPB.

Comparison of effects of unfractionated heparin and low molecular weight heparin on skin wound healing of rats / Comparação dos efeitos da heparina não fracionada e heparina de baixo peso molecular na cicatrização de feridas na pele de ratos

PURPOSE: To compare the effects of unfractionated heparin (UH) and a low molecular weight heparin (LMWH) on skin wound healing of rats. METHODS: Forty eight male Sprague-Dawley rats underwent 8mm full thickness dorsal skin wounds and were randomly assigned to three equal groups. In experimental group A, heparin sodium was injected at a concentration of 1000U/kg. In experimental group B, enoxaparin was injected at a concentration of 1mg/kg. Physiologic saline (0.5ml) was administered to the control group. Injections were made subcutaneously, once daily, for seven days. At 7th and 10th days tissue samples were taken from all rats. Histologic examination of these tissues was made under light microscope and scored. RESULTS: Histological examination showed a significant difference between the 7th and 10th day groups in wound healing. It was observed that wound healing of LMWH injected group is better. This difference is statistically significant at 10th day. CONCLUSIONS: Daily administration of single doses of unfractionated heparin and a low molecular weight heparin improves wound healing positively. Low molecular weight heparin induces wound healing more than unfractionated heparin.

OBJETIVO: Comparar os efeitos da heparina não fracionada (HNF) e da heparina de baixo peso molecular (HBPM) na cicatrização de feridas cutâneas de ratos. MÉTODOS: Quarenta e oito ratos machos Sprague-Dawley foram submetidos à ferida na pele dorsal com espessura total de 8mm e foram distribuídos aleatoriamente em três grupos iguais. No grupo experimental A, a heparina sódica foi injetada a uma concentração de 1000U/kg. No grupo experimental B, a enoxaparina foi injetada a uma concentração de 1mg/kg. Solução salina fisiológica (0,5ml) foi administrada para o grupo controle. As injeções foram feitas por via subcutânea, uma vez por dia, durante sete dias. Nos dias 7º e 10º amostras de tecido foram obtidas de todos os ratos. O exame histológico destes tecidos foi realizado em microscópio de luz. RESULTADOS: O exame histológico mostrou uma diferença significativa entre os grupos no 7º e 10º dias na cicatrização das feridas. Observou-se que a cicatrização de feridas do grupo com heparina de baixo peso molecular foi melhor. Esta diferença foi estatisticamente significante no 10º dia. CONCLUSÕES: A administração diária de doses únicas de heparina não fracionada e de heparina de baixo peso molecular melhora a cicatrização de feridas. A heparina de baixo peso molecular induz melhor a cicatrização de feridas do que a heparina não fracionada.

Heparan sulphate, its derivatives and analogues share structural characteristics that can be exploited, particularly in inhibiting microbial attachment

Heparan sulphate (HS) and the related polysaccharide, heparin, exhibit conformational and charge arrangement properties, which provide a degree of redundancy allowing several seemingly distinct sequences to exhibit the same activity. This can also be mimicked by other sulphated polysaccharides, both in overall effect and in the details of interactions and structural consequences of interactions with proteins. Together, these provide a source of active compounds suitable for further development as potential drugs. These polysaccharides also possess considerable size, which bestows upon them an additional useful property: the capability of disrupting processes comprising many individual interactions, such as those characterising the attachment of microbial pathogens to host cells. The range of involvement of HS in microbial attachment is reviewed and examples, which include viral, bacterial and parasitic infections and which, in many cases, are now being investigated as potential targets for intervention, are identified.

Regional Anticoagulation with Citrate is Superior to Systemic Anticoagulation with Heparin in Critically Ill Patients Undergoing Continuous Venovenous Hemodiafiltration

BACKGROUND/AIMS: Short hemofilter survival and anticoagulation-related life-threatening complications are major problems in systemic anticoagulation with heparin (SAH) for continuous renal replacement therapy (CRRT). The present study examined if regional anticoagulation with citrate (RAC) using commercially available solutions can overcome the associated problems of SAH to produce economical benefits. METHODS: Forty-six patients were assigned to receive SAH or RAC. We assessed the coagulation state, clinical outcomes, and adverse events. A Kaplan-Meier analysis was used to estimate hemofilter life span. The economical benefit related to the prolonged hemofilter survival was examined on the basis of the average daily cost. RESULTS: The mean age of patients was 66.5 +/- 13.8 years and the majority were male (60.9%). While elective discontinuation was most common cause of early CRRT interruption in the RAC group (34.3%, p < 0.01), hemofilter clotting was most prevalent in the SAH group (82.2%, p < 0.01). The patient metabolic and electrolyte control and survival rate were not different between the two groups. When compared with the RAC group, the anticoagulation-associated bleeding was a major complication in the SAH group (15.0% vs. 61.5%, p < 0.01). Regional anticoagulated hemofilters displayed a significantly longer survival time than systemic anticoagulated hemofilters (59.5 +/- 3.8 hr vs. 15.6 +/- 1.3 hr, p < 0.01). Accordingly, the mean daily continuous venovenous hemodiafiltration costs in the RAC and SAH groups were $575 +/- 268 and $1,209 +/- 517, respectively (p < 0.01). CONCLUSIONS: RAC prolonged hemofilter survival, displaying an economical benefit without severe adverse effects. The present study therefore demonstrates that RAC, using commercially available solutions, may be advantageous over SAH as a cost-effective treatment in CRRT.

A repetição da valvuloplastia aórtica por balão é uma boa estratégia para alívio dos sintomas e seleção de pacientes para substituição percutânea da valva aórtica / Repeat balloon aortic valvuloplasty is a good strategy for symptom relief and patient selection for percutaneous aortic valve replacement

A valvuloplastia aórtica por balão voltou a ganhar interesse desde o início da era da substituição percutânea da valva aórtica, por ser um procedimento que pode ser repetido como ponte e também por ser boa estratégia para a seleção de pacientes para o novo procedimento. Método: De janeiro de 2001 a janeiro de 2009, 174 pacientes consecutivos com estenose aórtica sintomática grave e alto risco cirúrgico calculado pelo EuroSCORE/STS foram submetidos a valvuloplastia aórtica por balão na França e na Argentina, utilizando-se a mesma técnica. Desse total, 21 (12,1 por cento) precisaram repetir a valvuloplastia aórtica por balão em decorrência de reestenose e os resultados foram comparados aos dos 153 pacientes que realizaram somente o primeiro procedimento. A técnica mais utilizada foi o acesso retrógrado com abordagem femoral utilizando introdutores de 10 F, 12 F ou 14 F, com tamanhos de balão...

Effects of heparin and dalteparin on oxidative stress during hemodialysls in patients with end-stage renal disease

Dialysis-induced oxidative stress is one of the mechanisms of atherosclerotic changes. Heparin, used in hemodialysis, is an anticoagulant drug with anti-inflammatory and antioxidant effects. This study was planned in order to evaluate the antioxidant effects of heparin and dalteparin [low-molecular weight heparin]. Twenty-two patients underwent 3 hemodialysis sessions with 48-hour intervals. They underwent hemodialysis with heparin, with a bolus dose of 1000 U followed by 1000 U/h during the procedure. The second hemodialysis was done using hypertonic saline solution instead of heparin, and the third, using dalteparin, 4000 U, infused during hemodialysis. Before and after each dialysis session, we measured serum levels of total blood cholesterol, triglyceride, high- and low-density lipoprotein cholesterols and oxidized low-density lipoprotein cholesterol, in addition to total antioxidant capacity and paraoxonase 1 activity. Serum concentrations of triglyceride, cholesterol, and oxidized low-density lipoprotein cholesterol, as well as paraoxonase activity and total antioxidant capacity equally increased after the three hemodialysis sessions. Heparin and daltepain increased total antioxidant capacity, but they did not change the ratio of paraoxonase 1 to high-density lipoprotein cholesterol after hemodialysis. No significant differences were found through the study between the two heparin products in their antioxidant activities. Regarding these findings and considering higher price and less availability of dalteparin in comparison to conventional heparin, we recommend using conventional heparin during hemodialysis as the anticoagulant-antioxidant agent

El Laboratorio de Urgencia en la detección de errores preanalíticos. Exceso de Heparina en una muestra de sangre arterial para evaluación de gases, electrolitos y equilibrio ácido-base / The urgency laboratory in the preanalytical mistakes detection

Introducción: La utilización de solución de heparina sódica como anticoagulante en muestras de sangre para determinación de gases y electrolitos, si bien es una práctica muy empleada en nuestro medio, no es aconsejable ya que es la causa más importante de múltiples errores pre-analíticos de distinta magnitud. Objetivo: describir la detección de errores pre-analíticos en el laboratorio de urgencia en un caso clínico. Material y métodos: Dos muestras de sangre de un paciente para determinación de gases en sangre y electrolitos. La muestra N° 1 de sangre arterial fue tomada en una jeringa descartable Prexajet con solución de heparina sódica 25.000 UI/5ml siguiendo el método usual de obtener dicha solución directamente de la ampolla y descartando el exceso de líquido de la jeringa antes de realizar la punción a la paciente. La Muestra N° 2 se obtuvo con jeringa heparinizada para extracción de sangre arterial tamponada con calcio y liofilizada (BD A-Line, Becton-Dickinson). Las determinaciones fueron efectuadas con el equipo automático multiparamétrico de gases en sangre RAPIDLAB 865 (Bayer). Resultados: (Ver Tabla 1). Estos datos no se validaron por falta de lectura del Ca iónico, evidencia de error preanalítico por exceso de solución de heparina. (Ver Tabla 2) Estos datos se validaron y enviaron inmediatamente al profesional tratante. Conclusiones: El procedimiento adecuado propuesto es: a) Toma de muestra en jeringas con heparinato de litio liofilizado tamponado con calcio, anulando por completo los errores causados por la dilución. b) Saturación de la molécula de heparina con iones calcio para minimizar el error en la determinación de calcio iónico.

Trombofilias congénitas impacto reproductivo y perspectivas de tratamiento / Congenital thrombophilias reproductive impact and treatment

La intención de esta publicación ha sido revisar la relación existente entre las condiciones pro-trombóticas hereditarias conocidas como trombofilias congénitas y algunas de las patologías más severas que pueden ocurrir durante la gestación. Las trombofilias pueden afectar desde la implantación, formación y funcionamiento de la placenta, manifestándose como abortos a repetición, cuadros hipertensivos severos, restricción de crecimiento y hasta la muerte fetal. Estas enfermedades, al estar relacionadas a trombofilias, abren una ventana a la posibilidad de establecer nuevas estrategias de prevención, diagnóstico y tratamiento.