Thesis (M. Phil.)--University of Hong Kong, 2005. / Title proper from title frame. Also available in printed format.

La maladie thromboembolique veineuse (MTEV) résulte de l’interaction entre des facteurs environnementaux et génétiques. Cinq anomalies constitutionnelles constituent le bilan de thrombophilie (BT) : les déficits en AT, PC et PS, le facteur V Leiden et la mutation de la prothrombine. Seule la moitié des déficits « présumés » en PS trouvent une explication moléculaire. Dans le premier article, seuls les patients présentant une mutation délétère du gène de la PS (PROS1) étaient à risque de MTEV. Seuls des taux <30%, permettaient de dépister les mutations délétères. La mutation Heerlen située sur PROS1 est réputée neutre. Dans le second article, la mutation Heerlen était associée à un risque de MTEV de 6,57. De récentes études ont identifié une trentaine de polymorphismes associés à la MTEV. Cependant, leur impact dans les familles présentant un facteur biologique de risque est méconnu. De même, l’impact de facteurs environnementaux tels que l’obésité et le tabagisme est mal évalué dans ces familles. Dans le troisième article, la prise en compte de 5 facteurs de risque fréquents à effet faible (obésité, tabac, groupe sanguin et deux polymorphismes situés sur F11 et FGG) en complément du dépistage de l’anomalie familiale permettait de mieux caractériser le risque individuel. Nous avons testé la même stratégie dans une population spécifique de femmes sous contraceptifs oraux combinés (4ème article). Trois facteurs de risque fréquents (groupe sanguin, obésité et un polymorphisme de F11) étaient associés à un OR de 13 lorsqu’ils étaient combinés. Au total, la prise en compte de facteurs de risque fréquents à effet faible, permettait une meilleure évaluation du risque individuel. / Venous thromboembolism (VT) results from the interaction between environmental and genetic factors. Five inherited hemostatic defects are part of the thrombophilia screening (TS): AT, PC and PS deficiencies, factor V Leiden and prothrombin mutation. A molecular defect is identified in only half of assumed PS deficiencies. In the first article, only detrimental mutations (DM) located on PROS1 (PS gene) increased VT risk. Only free PS levels below 30% enabled the identification of DM. PS Heerlen mutation located within PROS1 has been considered neutral for a long time. In the second article, the association between PS Heerlen and VT has been tested in a sample of 4173 patients with VT history and 5970 healthy individuals. PS Heerlen was associated with a 6.57 increased risk of VT. Recent genome wide association studies identified nearly 30 polymorphisms associated with VT. However, the impact of such polymorphisms in families with known defects is uncertain. We therefore tested in a third article the association between 11 selected polymorphisms, obesity, smoking and VT in 651 families with known thrombophilia. Considering 5 common risk factors (obesity, smoking, ABO blood group, two polymorphisms located on FGG and F11) together with the TS resulted in a better assessment of VT risk in individuals from families with thrombophilia. We then applied the same strategy in a sample of women using combined oral contraceptives. Three common risk factors (non-O blood groups, obesity and a polymorphism located on F11), when combined, were associated with a 13 OR. In conclusion, considering common risk factors improved the individual assessment of VT risk.

Made available in DSpace on 2014-06-11T19:23:47Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-06-29Bitstream added on 2014-06-13T20:51:06Z : No. of bitstreams: 1 romao_fg_me_botfmvz.pdf: 283357 bytes, checksum: 4cd1941c7a961da873a50abf01bf8fba (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Os distúrbios trombóticos e tromboembólicos aparentemente são menos comuns em felinos e caninos do que em humanos. A trombose foi reconhecida clinicamente associada a algumas doenças, como o hiperadrenocorticismo (HAC). Vários fármacos podem alterar o equilíbrio hemostático; dentre elas a prednisona, corticosteroide amplamente utilizado na medicina veterinária principalmente por seus efeitos imunossupressivos e anti-inflamatórios. Além disso, sabe-se que o hipercortisolismo pode estimular a formação de trombos pelo aumento de fatores de coagulação e diminuição da fibrinólise. O objetivo do presente estudo, portanto, foi demonstrar o efeito da prednisona sobre o perfil hemostático. Para tanto, foram constituídos dois grupos experimentais, sendo o grupo I, composto de 10 cães hígidos que receberam a dose de 1,0 mg/kg/BID por 15 dias, e ogrupo II, composto de 10 cães hígidos que receberam a dose de 2,0 mg/kg/BID por 15 dias. Houve diminuição significativa dos níveis de antitrombina em ambos os grupos, aumento da agregação plaquetária e diminuição do fator de von Willebrand no grupo II. Não foram observadas alterações estatisticamente significativas em relação ao tempo de sangramento da mucosa oral (TSMO), tempo de protrombina (TP), tempo de tromboplastina parcial ativada (TTPA), tempo de trombina (TT), contagem plaquetária, e dos valores de fibrinogênio, fator VIII e produtos de degradação da fibrina (PDFs) em nenhum dos grupos. Pode-se concluir que a prednisona pode aumentar o risco tromboembólico especialmente por diminuição de fatores anticoagulantes, não importando a dose utilizada / Thrombotic and thromboembolic disorders apparently are less common in cats and dogs than in humans.Thrombosis was clinically recognized associated with some diseases, such as hyperadrenocorticism (HAC). Several drugs can change the hemostatic balance, such as the corticosteroid prednisone, widely used in veterinary medicine mainly by its immunosuppresive and anti-inflammatory effects. In addition, it is known that hypercortisolism can stimulate the thrombi formation by the increase of coagulation factors and reduced fibrinolysis.The aim of this study, therefore, was to demonstrate the effect of prednisone on haemostatic profile. For this purpose, two experimental groups were set up, the group I composed by 10 higid dogs, which received a dose of 1,0 mg/kg/BID for 15 days, and group II, composed by 10 higid dogs that received the dose of 2,0 mg/kg/BID for 15 days.There was a significant decrease on antithrombin levels in both groups, increase on platelet aggregation and decrease of von Willebrand factor activity on group II. No statistically significant changes were observed in relation to oral mucosal bleeding time (OMBT), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), platelet count, plasmatic fibrinogen values,factor VIII activityand fibrin degradation products (FDPs) in both groups. It can be concluded that the prednisone can increase the thromboembolic risk, especially by the decrease of anticoagulant factors, regardless of the dosage

Orientador: regina Kiomi Takahira / Banca: Luiz Henrique de Araújo Machado / Banca: Ricardo Duarte Silva / Resumo: Os distúrbios trombóticos e tromboembólicos aparentemente são menos comuns em felinos e caninos do que em humanos. A trombose foi reconhecida clinicamente associada a algumas doenças, como o hiperadrenocorticismo (HAC). Vários fármacos podem alterar o equilíbrio hemostático; dentre elas a prednisona, corticosteroide amplamente utilizado na medicina veterinária principalmente por seus efeitos imunossupressivos e anti-inflamatórios. Além disso, sabe-se que o hipercortisolismo pode estimular a formação de trombos pelo aumento de fatores de coagulação e diminuição da fibrinólise. O objetivo do presente estudo, portanto, foi demonstrar o efeito da prednisona sobre o perfil hemostático. Para tanto, foram constituídos dois grupos experimentais, sendo o grupo I, composto de 10 cães hígidos que receberam a dose de 1,0 mg/kg/BID por 15 dias, e ogrupo II, composto de 10 cães hígidos que receberam a dose de 2,0 mg/kg/BID por 15 dias. Houve diminuição significativa dos níveis de antitrombina em ambos os grupos, aumento da agregação plaquetária e diminuição do fator de von Willebrand no grupo II. Não foram observadas alterações estatisticamente significativas em relação ao tempo de sangramento da mucosa oral (TSMO), tempo de protrombina (TP), tempo de tromboplastina parcial ativada (TTPA), tempo de trombina (TT), contagem plaquetária, e dos valores de fibrinogênio, fator VIII e produtos de degradação da fibrina (PDFs) em nenhum dos grupos. Pode-se concluir que a prednisona pode aumentar o risco tromboembólico especialmente por diminuição de fatores anticoagulantes, não importando a dose utilizada / Abstract: Thrombotic and thromboembolic disorders apparently are less common in cats and dogs than in humans.Thrombosis was clinically recognized associated with some diseases, such as hyperadrenocorticism (HAC). Several drugs can change the hemostatic balance, such as the corticosteroid prednisone, widely used in veterinary medicine mainly by its immunosuppresive and anti-inflammatory effects. In addition, it is known that hypercortisolism can stimulate the thrombi formation by the increase of coagulation factors and reduced fibrinolysis.The aim of this study, therefore, was to demonstrate the effect of prednisone on haemostatic profile. For this purpose, two experimental groups were set up, the group I composed by 10 higid dogs, which received a dose of 1,0 mg/kg/BID for 15 days, and group II, composed by 10 higid dogs that received the dose of 2,0 mg/kg/BID for 15 days.There was a significant decrease on antithrombin levels in both groups, increase on platelet aggregation and decrease of von Willebrand factor activity on group II. No statistically significant changes were observed in relation to oral mucosal bleeding time (OMBT), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), platelet count, plasmatic fibrinogen values,factor VIII activityand fibrin degradation products (FDPs) in both groups. It can be concluded that the prednisone can increase the thromboembolic risk, especially by the decrease of anticoagulant factors, regardless of the dosage / Mestre

17β-Estradiol (E2) and progesterone (P4) have various important functions but the effect of these endogenous hormone concentrations on fibrin network formation has not been established. It is essential to understand natural hormone mechanisms since these hormones are still present in circulation while hormonal contraceptives, which are associated with increased risk of venous thromboembolism, are used. In this study the formation of a fibrin network is analysed when different physiological concentrations of E2 and P4 is added to platelet poor plasma. Blood coagulation is critical for haemostasis but when the formation of a stable clot is influenced in such a way that hypercoagulation takes its course, it can have detrimental effects as it increases the risk of venous thrombosis. During blood coagulation fibrinogen is converted into fibrin in the presence of thrombin. The formation of a dense fibrin clot structure is quite an intense process and packaged in very specific ways. Both E2 and P4 has the ability to shift the haemostatic balance to a hypercoagulable state and therefore viscoelastic studies, morphological analysis as well as turbidimetry were used in this study to observe the possible changes in the fibrin network formation. Viscoelastic studies included thromboelastography (TEG) which gave insight to the properties of clot formation. Morphological studies included scanning electron microscopy (SEM) and atomic force microscopy (AFM) which delivered an investigation in fibrin network morphology, fibrin fiber diameter and surface roughness. Turbidimetry included further analysis of plasma fibrin clot formation and clot lysis time (CLT). Results showed that E2 and P4 showed hypercoagulable viscoelastic properties with decreased fibrin diameter and surface roughness while increased occurrence of dense matted deposits (DMDs) were evident. Turbidimetry showed decreased CLT for E2, but not P4. These results suggest in the presence of endogenous estrogen and progesterone, which is associated with hypercoagulability, the additional burden of synthetic hormones may result in a prothrombotic and hypercoagulable state in females with an inflammatory predisposition. It appears that both E2 and P4, which are known for their anti- and pro-inflammatory action, may influence fibrin network formation on a molecular level. These results are of clinical importance when considering hormones as either a pathological agent or therapeutic intervention. / Dissertation (MSc)--University of Pretoria, 2016. / Physiology / MSc / Unrestricted

Objective: To determine whether dosage adjustment of enoxaparin during pregnancy, in order to maintain a peak anti-Xa of 1.0-1.2 U/ml, is safe for women with mechanical prosthetic heart valves (MPHV). Methods: This was a prospective observational study performed at Charlotte Maxeke Johannesburg Academic Hospital from 2007 to 2009. 15 women with MPHVs were treated with enoxaparin with dosage adjustment throughout pregnancy to achieve a peak anti-Xa of 1.0-1.2 U/ml. Main outcomes measured were prosthetic valve thrombosis, bleeding and maternal mortality. Results: There was no maternal mortality. None of the women developed valvular thrombosis during pregnancy. Two women developed epistaxis and another developed spotting per vagina. There was no foetal mortality. Conclusion: Our data show that enoxaparin may be administered safely during pregnancy to pregnant women with mechanical prosthetic heart valves when there is dosage adjustment throughout pregnancy in order to maintain an anti-Xa of 1.0-1.2 U/ml.

Aims: The Pulmonary Embolism in Syncope Italian Trial reported 17.3% prevalence of pulmonary embolism (PE) in patients admitted with syncope. We investigated the prevalence of venous thromboembolism [VTE, including PE and deep vein thrombosis (DVT)] in syncope vs. non-syncope admissions and readmissions, and if syncope is an independent predictor of VTE. Methods and results: We conducted an observational study of index admissions of the 2013-14 Nationwide Readmission Database. / National Institutes of Health / Revisión por pares

Eight dogs were enrolled in a randomized, cross-over study that used optical aggregometry and a platelet function analyzer to evaluate platelet function before and after the administration of 5 aspirin dosages: 0.5 mg/kg q24h, 1 mg/kg q24h, 2 mg/kg q24h, 4 mg/kg q24h and 10 mg/kg q12h. Urine 11-dehydro-thromboxane-B2 (11-dTXB2) and 6-keto-prostaglandin-F1alpha (6-keto-PGF1alpha), were measured. Compared to pre-treatment, there were significant decreases in maximum aggregometry amplitude and increases in PFA-100 closure times for all doses except 0.5 mg/kg q24h. There was no difference in amplitude or closure time between the 2 mg/kg, 4 mg/kg, and 10 mg/kg q12h dosages. At 2 mg/kg q24h, 100 percent (aggregometry) of dogs were aspirin responders. There was a significant decrease in urinary 11-dTXB2- and 6-keto-PGF1alpha-to-creatinine ratios with aspirin administration. An aspirin dosage of 2 mg/kg q24h consistently inhibits platelet function in healthy dogs without decreasing prostacyclin synthesis significantly more than lower aspirin dosages.

Background: A D-dimer threshold <500ug/L has high negative predictive value (NPV) for venous thromboembolism (VTE), but is non-specific. Two strategies increase the specificity and utility (defined as the proportion of patients with a negative test) of D-dimer testing: 1) using a higher D-dimer threshold with increasing age (IAIT Strategy); and 2) using a high threshold in low clinical pretest probability (CPTP) patients and the standard threshold in moderate CPTP patients (CPTP Strategy). It is unknown whether the gain in specificity of the IAIT Strategy is simply due to using a higher threshold in some patients and whether the CPTP Strategy has better diagnostic accuracy than the IAIT Strategy. Methods: In a retrospective analysis of 1649 outpatients with suspected VTE, I compared the diagnostic accuracy of the IAIT Strategy to 1) its opposite: using a higher D-dimer threshold with decreasing age (DAIT strategy); 2) using a higher D-dimer threshold in all patients (Median Age Strategy); and 3) the CPTP Strategy. Results: The NPV of both the IAIT and DAIT Strategies was 99.6% and the NPV of the Median Age Strategy was 99.7%. The utility was almost identical in the IAIT and DAIT Strategies (50.9% vs. 50.6%) and greater in the Median Age Strategy (53.9%, p<0.001). The NPV of the CPTP and IAIT Strategies were 99.6% and 99.7%, respectively. The utility was higher in the CPTP Strategy than the IAIT Strategy (56.1% vs. 50.9%, p<0.001). Conclusions: The NPV and utility of using a higher D-dimer threshold in older patients (IAIT Strategy) is the same as using a higher D-dimer threshold in younger patients. The CPTP Strategy had the greatest utility while maintaining a high NPV and therefore appeared to be the optimal strategy of D-dimer interpretation. / Thesis / Master of Health Sciences (MSc)

A research report submitted to the University of Witwatersrand, Johannesburg in fulfilment for the requirements of the degree of Master of Medicine 4 June 2019 Descriptive study of Venous Thromboembolic Disease in the adult population admitted to Tshepong Hospital comparing the proportion of HIV and non-HIV infected patients / Background HIV and TB independently incur increased risk for venous thromboembolic disease (VTE): deep vein thrombosis (DVT) and/or pulmonary embolism (PE). Data from high HIV and TB burden settings describing VTE is scarce. The Wells’ DVT and PE scores are widely used but their utility in these settings has not been reported on extensively. We therefore report clinical and treatment aspects of in-patients with newly diagnosed VTE to assess HIV and TB prevalence, and their Wells’ score. Setting Tshepong Hospital in the North West Province of South Africa. Methods A prospective cohort of adult in-patients with radiologically confirmed VTE were recruited. Demographics, presence of TB, HIV status, duration of treatment, CD4 count, viral load, VTE risk factors, and parameters to calculate the Wells’ score were collected. Results One hundred patients were recruited, of whom 59 were HIV-infected; 39 had TB disease and 32 were HIV/TB co-infected. Eighty -three patients had a DVT only; 11 patients had a PE, and six had both a DVT and PE. Eighteen of 42 patients on antiretroviral treatment (ART) were on treatment for less than six months. Twenty patients of 39 were on TB treatment for less than one month. The median DVT and PE Wells’ score in all sub-groups was 3.0 (IQR: 1.0-4.0) and 3.0 (IQR: 2.5-4.5), respectively. There were nine deaths. Conclusion HIV /TB co-infection appear to confer a risk for VTE, especially early after ART and/or TB treatment, and therefore require careful monitoring for VTE and early initiation of thrombo-prophylaxis. / E.K. 2019