Volume Plaquetário Médio está Associado com Reperfusão Inadequada Detectada por Angiografia em Pacientes com Terapia Fibrinolítica Bem Sucedida / Mean Platelet Volume is Associated with Inadequate Reperfusion Detected by Angiography in Patients with Successful Fibrinolytic Therapy

Fundamento: Volume plaquetário médio (VPM) elevado está associado com falha na fibrinólise e eventos adversos em pacientes com infarto agudo do miocárdio com supradesnivelamento do segmento ST (IAMCSST). No entanto, não há dados sobre os efeitos do VPM sobre o fluxo sanguíneo coronariano anterógrado e o grau de reperfusão em pacientes com fibrinólise bem sucedida. Objetivo: O objetivo deste estudo foi investigar o papel do VMP sobre a circulação coronariana via contagem de quadros angiográficos (TFC) na trombólise no infarto do miocárdio (TIMI) após terapia fibrinolítica bem sucedida. Métodos: Entre 145 pacientes tratados com agentes fibrinolíticos, 123 (84,8%) pacientes consecutivos com fibrinólise bem sucedida, determinados por eletrocardiografia, foram incluídos. Os pacientes foram divididos em dois grupos de acordo com TFC. Um TCF > 40 foi considerado como um marcador de reperfusão inadequada, e um TCF ≤ 40 aceito como um indicador de reperfusão completa. Resultados: Após a angiografia coronária, 57 pacientes apresentaram TFC ≤ 40 e 66 pacientes apresentaram TFC > 40. O VPM foi significativamente mais alto no grupo com reperfusão inadequada (8,93 ± 0,87 fl vs. 7,92 ± 0,80 fl, p < 0,001). Um VPM elevado foi identificado como um indicador de reperfusão inadequada, e coordenadas da curva ROC indicaram um ponto de corte de 8,3 fl para VPM. Conclusão: VPM elevado na admissão em pacientes com IAMCSST tratados com terapia fibrinolítica bem sucedida associou-se com reperfusão inadequada detectada por TFC

Background: Higher Mean platelet volume (MPV) is associated with fibrinolysis failure and adverse outcomes in patients with ST elevation myocardial infarction (STEMI). However, there are no data about the effects of MPV on antegrade coronary blood flow and the degree of reperfusion in patients with successful fibrinolysis. Objective: The aim of our study was to investigate the role of MPV on coronary circulation via thrombolysis in myocardial infarction (TIMI) frame count (TFC) after successful fibrinolytic therapy. Methods: Among 145 patients treated with fibrinolytics, 123 (84.8%) consecutive patients with successful fibrinolysis determined by electrocardiography criteria were included. The patients were divided into two groups according to TFC. TFC > 40 was accepted as a marker for inadequate reperfusion and TFC ≤ 40 was accepted as an indicator of complete reperfusion. Results: After coronary angiography, 57 patients had TFC ≤ 40 and 66 patients had TFC > 40. MPV was significantly higher in the inadequate reperfusion group (8.93 ± 0.87 fl vs 7.92 ± 0.80 fl, p < 0.001). Higher MPV was found to be an indicator of inadequate reperfusion and coordinates of the ROC curve indicated a cutoff value of 8.3 fl for MPV. Conclusion: Higher MPV on admission in STEMI patients treated with successful fibrinolytic therapy was found to be associated with inadequate reperfusion detected by TFC

Predictive factors for anterior chamber fibrin formation after vitreoretinal surgery / Fatores preditivos para formação de fibrina na câmara anterior após cirurgia vitreorretiniana

Purpose: The aim of this study was to investigate possible predictive factors related to anterior chamber fibrin formation after vitreoretinal surgery in a large series of patients. Methods: The data of 185 eyes of 185 patients submitted to vitreoretinal surgery was reviewed. The following variables were evaluated: the postoperatively presence of fibrin, age, diabetes mellitus, the vitrectomy system gauge (20, 23 or 25 gauge), the type of vitreous substitute, the influence of prior surgical procedures and the combination with cataract extraction. To evaluate predictive factors for anterior chamber fibrin formation, univariate analysis was performed. A multivariate stepwise logistic regression model was adjusted to investigate factors associated with fibrin formation (p<0.05). Results: Fibrinoid anterior chamber reaction was found in 12 (6.4%) patients. For multivariate logistic regression analysis, balanced salt solution (BSS), the chance of fibrin occurrence was 5 times greater (odds ratio 4.83, CI 95% 1.302 - 17.892; p=0.019), while combination with phacoemulsification increased the chance of fibrin formation by 20 times (odds ratio 20, CI 95% 2.480 - 161.347; p=0.005). No significant difference was found regarding other variables. Conclusion: Anterior chamber fibrin formation is an unwanted complication after vitreoretinal surgery. Factors such as combined performance of phacoemulsification and the use of balanced salt solution as a vitreous substitute may predispose the occurrence of this complication. .

Objetivo: Avaliar os possíveis fatores relacionados à formação de fibrina na câmara anterior após cirurgia vitreorretiniana em uma grande série de casos. Métodos: Foi realizado um estudo retrospectivo, observacional, caso-controle, onde os dados de 185 olhos de 185 pacientes submetidos à cirurgia vitreorretiniana foram avaliados. Os seguintes dados foram analisados: presença ou não de fibrina na câmara anterior na primeira semana de pós-operatório, idade, presença ou não de diabetes mellitus, calibre do sistema de vitrectomia utilizado (20,23 ou 25 gauge), substituto vítreo, a influência de cirurgias oftalmológicas prévias e a realização de cirurgia de catarata combinada. Para avaliação dos fatores preditivos para formação de fibrina, a análise univariada foi realizada. O modelo de regressão logística multivariada foi utilizado para investigar os fatores associados com a formação de fibrina (p<0,05). Resultados: A presença de fibrina na câmara anterior foi encontrada em 12 (6,4%) pacientes. Pela análise de regressão logística multivariada, o uso de solução salina balanceada (BSS) como substituto vítreo, a chance da presença de fibrina foi 5 vezes maior (odds ratio 4,83, IC 95% 1,302 - 17,892; p=0,019), enquanto que a realização de cirurgia facoemulsificação combinada aumentou a chance de formação de fibrina 20 vezes (odds ratio 20, IC 95% 2,480 - 161,347; p=0,005). Nenhuma diferença estatisticamente significativa foi encontrada para as outras variáveis. Conclusão: A formação de fibrina na câmara é uma complicação indesejada após cirurgia vitreorretiniana. Fatores como realização de cirurgia de facoemulsificação combinada e ...

In vivo analgesic, antipyretic, and anti-inflammatory potential in Swiss albino mice and in vitro thrombolytic activity of hydroalcoholic extract from Litsea glutinosaleaves

BACKGROUND: The study was conducted to evaluate the in vitro thrombolytic activity, and in vivo analgesic, anti-inflammatory and antipyretic potentials of different hydrocarbon soluble extracts of Litsea glutinosaleaves for the first time widely used in the folkloric treatments in Bangladesh. This work aimed to create new insights on the fundamental mechanisms of the plant extracts involved in these activities. RESULTS: In thrombolytic activity assay, a significant clot disruption was observed at dose of 1 mg/mL for each of the extracts (volume 100 µL) when compared to the standard drug streptokinase. The n-hexane, ethyl acetate, chloroform, and crude methanolic extracts showed 32.23 ± 0.26, 37.67 ± 1.31, 43.13 ± 0.85, and 46.78 ± 0.9% clot lysis, respectively, whereas the positive control streptokinase showed 93.35 ± 0.35% disruption at the dose of 30,000 I.U. In hot plate method, the highest pain inhibitory activity was found at a dose of 500 mg/kg of crude extract (15.54 ± 0.37 sec) which differed significantly (P <0.01 and P <0.001) with that of the standard drug ketorolac (16.38 ± 0.27 sec). In acetic acid induced writhing test, the crude methanolic extract showed significant (P <0.01 and P <0.001) analgesic potential at doses 250 and 500 mg/kg body weight (45.98 and 56.32% inhibition, respectively), where ketorolac showed 64.36% inhibition. In anti-inflammatory activity test, the crude methanolic extract showed significant (P <0.001) potential at doses 250 and 500 mg/kg body weight (1.51 ± 0.04 and 1.47 ± 0.03 mm paw edema, respectively), where ketorolac showed 1.64 ± 0.05 mm edema after 3 h of carrageenan injection. In antipyretic activity assay, the crude extract showed notable reduction in body temperature (32.78 ± 0.46°C) at dose of 500 mg/kg-body weight, when the standard (at dose 150 mg/kg-body weight) exerted 33.32 ± 0.67°C temperature after 3 h of administration. CONCLUSIONS: Our results yield that the crude hydroalcoholic extract has better effects than the other in all trials. In the context, it can be said that the leaves of L. glutinosa possess remarkable pharmacological effects, and justify its traditional use as analgesic, antipyretic, anti-inflammatory, and thrombolytic agent.

In silico design of novel anticoagulant peptides targeting blood coagulation factor VIIa

The coagulation cascade initiated during vascular injury prevents bleeding. Unwanted clot formation is however detrimental and requires the use of anticoagulants for prophylaxis and treatment. Anticoagulants targeting a specific step or an enzyme in the clotting process are most preferred as they minimise disadvantageous side-effects. A principal step in the discovery of novel anticoagulants encompasses the in silico design of potential leads. This study depicts the in silico design of peptide anticoagulants targeting coagulation factor VIIa. Applying the proline bracket rule and using various bioinformatics tools: the basic alignment search tool [BLAST] of National Center for Biotechnology Information; the T-coffee module provided by European Molecular Biology Laboratory-European Bioinformatics Institute, and several modules available on the ExPASy server, we designed five bivalent chimeric anticoagulants targeting factor VIIa, using factor VIIa inhibitors - hemextin A from Hemachatus haemachatus [African Ringhals cobra] venom and factor VIIa exosite-inhibitor peptide as templates. Six peptides were derived from hemextin A, which were concomitantly fused with factor VIIa exosite-inhibitor peptide intermediated by a polyalanine spacer, and analysed for structural stability using the SWISS-MODEL software developed at the Swiss Institute of Bioinformatics and WebLab ViewerPro [Version 4.2]. Twelve chimeric peptides were obtained; only five exhibited stable structures in silico. The five peptides obtained are probable anticoagulant leads that should be further evaluated using suitable in vitro and in vivo assays. Further, this study shows how simple web-based modules can be used for the rational design of probable leads targeting specific physiological molecular targets

Blood pressure lowering, fibrinolysis enhancing and antioxidant activities of Cardamom (Elettaria cardamomum).

Elettaria cardamomum (L.) Maton. (Small cardamom) fruit powder was evaluated for its antihypertensive potential and its effect on some of the cardiovascular risk factors in individuals with stage 1 hypertension. Twenty, newly diagnosed individuals with primary hypertension of stage 1 were administered 3 g of cardamom powder in two divided doses for 12 weeks. Blood pressure was recorded initially and at 4 weeks interval for 3 months. Blood samples were also collected initially and at 4 weeks interval for estimation of lipid profile, fibrinogen and fibrinolysis. Total antioxidant status, however, was assessed initially and at the end of the study. Administration of 3 g cardamom powder significantly (p<0.001) decreased systolic, diastolic and mean blood pressure and significantly (p<0.05) increased fibrinolytic activity at the end of 12th week. Total antioxidant status was also significantly (p<0.05) increased by 90% at the end of 3 months. However, fibrinogen and lipid levels were not significantly altered. All study subjects experienced a feeling of well being without any side-effects. Thus, the present study demonstrates that small cardamom effectively reduces blood pressure, enhances fibrinolysis and improves antioxidant status, without significantly altering blood lipids and fibrinogen levels in stage 1 hypertensive individuals.

Effect of estrogen-progestin hormonal replacement therapy on blood coagulation and fibrinolysis in postmenopausal women

OBJECTIVE: To evaluate antithrombin III (AT), thrombin (Fragment 1+2 [F1+2] and thrombin-antithrombin [TAT]) generation markers, as well as other coagulation parameters, such as prothrombin time, partial activated thromboplastin time, thrombin time, fibrinogen, euglobulin lysis time, and platelet count, in postmenopausal women after hormonal therapy. STUDY DESIGN: Forty-five patients who received either 0.625 mg/day unopposed oral conjugated equine estrogen (CEE), 0.625 mg/day oral CEE plus medroxyprogesterone acetate (MP), or 50 µg/day transdermal 17beta-estradiol plus MP, were included. Tests were performed before (T0) and after 3 (T3), 6 (T6) and 12 (T12) months of treatment. AT was determined by an amidolytic method, whereas F1+2 and TAT complex were measured by ELISA. RESULTS: There was a significant reduction in the AT level of patients who received oral CEE plus MP at T3. There was no AT reduction in patients taking either oral CEE alone or transdermal 17beta-estradiol plus MP. F1+2 increased in all patients, but it reached statistical significance only in patients receiving transdermal 17beta-estradiol MP at T3. CONCLUSIONS: The CEE associated with MP treatment may reduce AT levels, whereas unopposed CEE or transdermal 17beta-estradiol plus MP does not change AT. These changes might not be clinically relevant in the general population; however, hormonal replacement therapy may increase the risk of thrombosis in women with congenital or acquired thrombophilia.

OBJETIVO: Avaliar os marcadores antitrombina III (AT), fragmento 1 + 2 da trombina (F1+2) e complexo trombina-antitrombina (TAT), bem como outros parâmetros da coagulação, como tempo de pró-trombina, tempo parcial de tromboplastina ativado, tempo de trombina, fibrinogênio e tempo de lise da euglobulina em mulheres na pós-menopausa após terapia hormonal. DESENHO DO ESTUDO: Foram incluídas 45 voluntárias que receberam estrogênios conjugados eqüinos (ECE) 0,625 mg/dia, isoladamente ou associado ao acetato de medroxiprogesterona (AMP) ou usaram o 17beta-estradiol (50 µg/dia) transdérmico com AMP. Os exames foram realizados antes do tratamento (T0) e após três (T3), seis (T6) e doze (T12) meses após o início do tratamento. AT foi avaliada pelo método amidolítico, enquanto que o F1+2 e o complexo TAT por ELISA. RESULTADOS: Houve redução significante nos níveis de AT em pacientes que receberam ECE associado ao AMP no T3. Não houve redução na AT em mulheres que usaram ECE isoladamente ou aquelas com 17beta-estradiol transdérmico e AMP. O F1+2 aumentou em todos os grupos, mas apenas o grupo com 17beta-estradiol transdérmico e AMP apresentou diferença significante durante o T3. CONCLUSÕES: A associação de ECE e AMP pode reduzir os níveis de AT, enquanto ECE isoladamente ou 17beta-estradiol transdérmico com AMP não modificam-o acentuadamente. Essas alterações poderiam ser mais relevantes clinicamente na análise populacional. Todavia, a terapia de reposição hormonal aumentaria o risco de trombose em mulheres com trombofilia prévia congênita ou adquirida.

Vino, fibrinolisis y salud / Wine, fibrinolysis and health

Cardiovascular diseases are the leading cause of death in both men and women in the world. Epidemiological and experimental studies have associated moderate wine consumption (1 to 2 glasses/day) with a decrease in cardiovascular diseases. This decrease is probably due to the effect of ethanol and polyphenols present in the wine. The cardioprotective benefit of wine may be due, in part, to a modulation of the expression of proteins involved in fibrinolysis. Endothelial cells (ECs) play a major role in maintaining normal hemostasis, regulating the balance between the synthesis and interaction of proteins that promote clot formation (thrombosis) and fibrinolytic proteins that facilitate clot lysis. These cells are a major site of synthesis of fibrinolytic proteins, such as tissue type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA) and the major inhibitor/regulator of fibrinolysis, PAI-1. EC-mediated fibrinolysis is regulated and localized to the EC surface through specific receptors for u-PA, t-PA and plasminogen. Evidence indicates that ethanol and polyphenols present in wine increase EC localized fibrinolisis. Upregulation of t-PA and u-PA activity and downregulation of PAI-1 may account, at least in part, for this net increase in fibrinolytic activity. The purpose of this review is to cover the main molecular and physiological aspects of moderate wine consumption mediated increase in fibrinolysis and reduction in cardiovascular risk.

A randomized, double-blind, and placebo-controlled study with tranexamic acid of bleeding and fibrinolytic activity after primary coronary artery bypass grafting

Cardiopulmonary bypass is frequently associated with excessive blood loss. Platelet dysfunction is the main cause of non-surgical bleeding after open-heart surgery. We randomized 65 patients in a double-blind fashion to receive tranexamic acid or placebo in order to determine whether antifibrinolytic therapy reduces chest tube drainage. The tranexamic acid group received an intravenous loading dose of 10 mg/kg, before the skin incision, followed by a continuous infusion of 1 mg kg-1 h-1 for 5 h. The placebo group received a bolus of normal saline solution and continuous infusion of normal saline for 5 h. Postoperative bleeding and fibrinolytic activity were assessed. Hematologic data, convulsive seizures, allogeneic transfusion, occurrence of myocardial infarction, mortality, allergic reactions, postoperative renal insufficiency, and reopening rate were also evaluated. The placebo group had a greater postoperative blood loss (median (25th to 75th percentile) 12 h after surgery (540 (350-750) vs 300 (250-455) mL, P = 0.001). The placebo group also had greater blood loss 24 h after surgery (800 (520-1050) vs 500 (415-725) mL, P = 0.008). There was a significant increase in plasma D-dimer levels after coronary artery bypass grafting only in patients of the placebo group, whereas no significant changes were observed in the group treated with tranexamic acid. The D-dimer levels were 1057 (1025-1100) æg/L in the placebo group and 520 (435-837) æg/L in the tranexamic acid group (P = 0.01). We conclude that tranexamic acid effectively reduces postoperative bleeding and fibrinolysis in patients undergoing first-time coronary artery bypass grafting compared to placebo.

Long-term Effect of Plasmin on the Vitreolysis in Rabbit Eyes

The aim was to investigate the proteolytic activity of plasmin and its long-term complications. Plasmin was injected into the vitreous cavity of rabbits' eyes. Slit lamp biomicroscopy and electroretinography were performed. Rabbits were serially sacrificed at four months, and globes fixated and prepared for light and transmission electron microscopy. In both the plasmin-injected and control eyes, electroretinography showed a transient decrease in the amplitude, but this recovered to the baseline level in a week. Under the light microscope, the plasmin-treated eyes had a smooth retinal surface, implying separation of the vitreous cortex from the retina. In the control eyes, the collagen fibers remained on the retinal surface. By transmission electron microscopy, the plasmin-treated eyes showed a vitreous-free retinal surface, but no vitreoretinal separation was observed in the control eyes. Plasmin induces a cleavage between the vitreous and the internal limiting membrane, with no long-term complications, so may be a useful pharmacologic adjunct to vitrectomy.

Fibrinolytic action on fresh human clots of whole body extracts and two semipurified fractions from Lonomia achelous caterpillar

The severe bleeding diathesis produced by intoxication with the venom of Lonomia achelous caterpillars is characterized by prolonged bleeding from superficial skin wounds as well as massive hemorrhage into body cavities. The aim of the present study was to evaluate the effect of the crude venom and its fibrinolytic fractions on in vitro lysis of whole blood clots. Venom fractions with fibrinolytic activity were obtained by gel filtration chromatography on Sephadex G75 using imidazole buffer, pH 7.4, at a flow rate of 24 ml/h. Four peaks with fibrinolytic activity were obtained by this method. The highest activity was found in the first two peaks (both peaks were used for the experiments). The results show that the caterpillar venom degraded the preformed clots at a slower rate than plasmin. In addition, plasma protease inhibitors of the fibrinolytic system (a2-antiplasmin, a2-macroglobulin, PAI, etc.) only weakly inhibited the lytic effect of the caterpillar venom. These characteristics, as well as the pattern of fibrinogen degradation products, the delay period on fibrin plate lysis and amidolytic activity on chromogenic substrate, reported previously, indicate that the caterpillar enzymes are different from plasmin and trypsin

Effect of growth hormone on fibrinolytic system in rat.

Growth hormone deficiency (GHD) is associated as a risk factor in increased mortality from cardiovascular diseases. Abnormal lipid profile and increased levels of plasminogen activator inhibitor (PAI) and fibrinogen have been noted in GHD patients. Present study was carried out to investigate the effect of growth hormone (GH) on plasminogen activator (PA) activity in heart, levels of PA, PAI, glucose and fibrinogen in plasma and serum lipid profile. Rats were injected 125 mU GH kg-1 body weight subcutaneously daily for one week. PA activity was significantly higher in the heart of GH treated rats as compared to controls. GH treatment decreased plasma glucose and fibrinogen levels significantly. No significant differences were seen in PA, PAI in plasma, triglycerides and total cholesterol in serum of the two groups of rats. A significant increase in high density lipoprotein cholesterol (HDL) occurred in GH treated group resulting into a decrease in LDL/HDL ratio. The results indicate that GH may be beneficial in cardiovascular diseases as it decreases the levels of plasma fibrinogen and increases the level of HDL in blood and also increases the level of PA in heart.

Effects of garlic [allium sativum] administration on: 2- some blood and hemostatic parameters in healthy male subjects

Garlic is a potent spice and medicine with broad therapeutic properties ranging from antibacterial to anticancer. Twenty two healthy male volunteers aged [35-50 years] comprising garlic administered group consumed 4-5 garlic cloves daily for 30 days [N = 14] and control group [N -8] participated in the study, to evaluate the effects of garlic administration on certain blood and hemostatic factors. Garlic ingestion resulted in significant reduction in platelets count, plasma fihrinogen level and longer prothrombin time. No changes in total and ionized calcium, hematocrit value, red blood cells count, serum total protein, albumin andferritin levels were noticed as effect of garlic ingestion. The findings suggest that garlic consumption may be benificial in diseases associated with platelets function, plasma fibrinoly tic activity and thrombosis

Novel thrombolytic therapy discovered from traditional oriental medicine using the earthworm.

Since a few thousand years ago, the earthworm has been used as a drug for various diseases in China and the Far East. However, modern scientific pharmacological studies have not so far been performed. We extracted a very strong fibrinolytic enzyme from the earthworm, Lumbricus rubellus. This enzyme was heat-stable and displayed a very broad optimal pH range. Purification of the enzyme was performed and three partially purified fractions were obtained. These three fractions were further subdivided, and six purified fractions (F-I-0, 1, 2, F-II, and F-III-1,2) were finally obtained. Based on results of their enzymatic activities against various substrates, the fraction I enzymes are thought to represent chymotrypsin-like enzymes and the fraction III enzymes to represent trypsin-like enzymes. The fraction II enzyme appears to be neither a trypsin-nor chymotrypsin-like enzyme nor an elastase. We therefore designed trials for in vivo experiments on human volunteers. 120 mg of lyophilized earthworm powder was administered orally to 7 healthy volunteers (aged 28-52 years old) three times after meals every day for 17 days. Blood was withdrawn once a day before and at 1, 2, 3, 8, 11 and 17 days after commencing the administration. The fibrin degradation products (FDP) value, tissue plasminogen activator (t-PA) antigen level and t-PA activities were measured in the blood. Before the administration, the t-PA antigen level was 5.6 +/- 0.38 ng/ml, and it gradually increased until the 17th day. The FDP level was increased on the 1st and 2nd day after the administration, but had decreased and normalized by the 17th day. The fibrinolytic activities also tended to show an increase during the experiment. These results suggest that earthworm powder represents a possible oral thrombolytic agent. The earthworm enzyme may thus be applicable for treating patients with thalassemia.

Effect of ingestion of raw garlic on serum cholesterol level, clotting time and fibrinolytic activity in normal subjects.

The effect of raw garlic on serum cholesterol, fibrinolytic activity and clotting time was studied in 50 medical students of the age group of 17 to 22 years before and after feeding raw garlic. All pre-experimental values ranged within normal limits. The volunteers were then divided into experimental and control groups. The subjects of the experimental group were given 10 gm of raw garlic daily after breakfast for two months. Fasting blood samples of all the subjects were investigated after two months. In the control group, there was no significant change in any of the above parameters. In the experimental group, there was a significant decrease in serum cholesterol and an increase in clotting time and fibrinolytic activity. Hence, garlic may be an useful agent in prevention of thromboembolic phenomenon.

Clinical study on antithrombotic effects of ticlopidine in ischemic stroke.

The investigators conducted a clinical study on antithrombotic effectiveness in ischemic stroke at Siriraj Hospital Medical School, Mahidol University from May 1987 to May 1989. Twenty-nine patients, 16 males and 13 females were enrolled in the study. The ages of the patients ranged from 30-87 years with a mean age of 63 +/- 11 years. Ticlopidine (250 mg) could significantly inhibit platelet aggregation induced by ADP and collagen within 24 hours of drug administration. After 1 week to 6 months, only aggregation by ADP was still inhibited significantly without significant effects on fibrinolytic activity and prostacyclin. Hematocrit was significantly decreased at the 1st and 2nd month of treatment. Serious side effects were skin rash and severe headache while the other common ones were dizziness, and diarrhea but these effects disappeared without discontinuing the drug. Most patients who suffered from nausea, diarrhea and headache, had temporary elevated SGPT. It may be concluded that only half of the recommended dose of ticlopidine has inhibitory effects on both phases of ADP-induced aggregation without interfering with fibrinolytic activity and can maintain prostacyclin. However, it also possesses either serious or common side-effects. This drug, therefore, should be used with the awareness of the clinician.

Efecto del APP sobre la trombosis experimental en ratas / APP effect on experimental thrombosis in rats

En 1978 Díaz et al. descubrieron la presencia de un activador del plasminógeno en el plasma humano (APP) el cual fue aislado, purificado y caracterizado desde el punto de vista físico-químico, así como fue objeto de una patente. En 1982 Cuevas et al. describieron las propiedades biológicas de este producto in vitro, y en este trabajo se comprobó la eficiencia del mismo como agente trombolítico, pues éste es capaz de lograr un tanto por ciento de reducción del trombo de 50,5%, en relación con el grupo control y además se logra una activación rápida en el sistema fibrinolítico del animal, a diferencia del resultado obtenido en el grupo en que se empleó SK, donde el tanto por ciento de reducción del trombo fue del 42,9% y no hubo activación significativa del sistema fibrinolítico. Se considera necesario realizar otras investigaciones en este sentido que nos aclaren cómo varían algunos parámetros hemostáticos por la administración de este agente trombolítico en estudio

Resolution of experimental intravitreal fibrin by tissue plasminogen activator

Intravitreal fibrin clots were produced by intravitreal injection of 0.2 ml of autologous plasma in 62 rabbit eyes. The intravitreal injection of 0.25 micrograms or more of tissue plasminogen activator(tPA) resulted in a total clearing of intravitreal fibrin within one day in all treated eyes. This was significantly faster than in the control eyes, in which complete clearing was not seen until 8 days later. This represents the plateau on the dose-response curve in doses ranging from 0.25 to 200 micrograms. With light microscopy and transmission electron microscopy, retinal toxicity was demonstrated in eyes enucleated seven days after injection of 25 micrograms or more of tPA. This study demonstrates that tPA was effective and safe at 12.5 micrograms or less in clearing intravitreal fibrin in an experimental model. These results suggest that low dosages of tPA, probably of 3 micrograms or less, may be useful in the treatment of severe postvitrectomy fibrin formation seen clinically.

Prostaglandin E1 (PGE1): effect on the human fibrinolytic system.

The in vitro effect of prostaglandin E1 on the fibrinolytic process was assessed in 30 patients with acute myocardial infarction (MI) using Thrombin Time (TT) and Euglobulin Clot Lysis time (ECLT) as parameters. Thrombin time was shortened and ECLT was prolonged (p less than 0.001) in acute MI as compared to thirty age and sex matched controls. In both groups, preincubation of sera with PGE1 (3.3 micrograms/ml) produced prolongation of TT and shortening of ECLT (p less than 0.001). Thus PGE1, which is a naturally occurring vasodilator and antiplatelet agent, also appears to have fibrinolytic activity.