Increase In Partial Thromboplastin Time Research Articles

Anti-thrombotic Mechanisms of Echinochrome A on Arterial Thrombosis in Rats: In-Silico, In-Vitro and In-Vivo Studies.

Arterial thrombosis is one of the most significant healthcare concerns in the world. Echinochrome A (Ech-A) is a natural quinone pigment isolated from sea urchins. It has a variety of medicinal values associated with its antioxidant, anticancer, antiviral, anti-diabetic, and cardio-protective activities. The current study aims to investigate the effect and mechanism of Ech-A to inhibit thrombus formation induced by ferric chloride in rats. Twenty-four rats were assigned into four groups (n= 6); sham and thrombotic model groups were orally administered 2% DMSO, while the other groups were treated with two dosages of Ech-A (1 and 10 mg/kg, body weight). After seven days of administration, all groups were exposed to 50% ferric chloride for 10 min, except the sham group exposure to normal saline. The molecular docking showed the free binding energies of Ech-A and vitamin K (Vit. K) with Vit. K epoxide reductase were -8.5 and -9.8 kcal/mol, which confirm the antithrombotic activity of Ech-A. The oral administration of Ech-A caused a significant increase in partial thromboplastin time, prothrombin time, clotting time, platelet count, fibrinogen levels, factor VIII, glutathione reduced, catalase, nitric oxide, and glutathione S-transferase. While white blood cells count, calcium level, and malondialdehyde concentration significantly decreased. The histological examination revealed a definite improvement in the carotid and cardiac tissues in the Ech-A groups. The study results showed that Ech-A prevented thrombosis by several mechanisms, including chelating calcium ions, increasing the NO concentration, suppressing oxidative stress, and antagonizing Vit. K.

The Results of Proximal Femoral Nail for Intertrochanteric Fracture in Hemodialysis Patient.

PurposeHip fractures in hemodialysis patients are accompanied by high rates of complications and morbidities. Previous studies have mainly reported on nonunion and avascular necrosis of femoral neck fractures in this patient group. In this study the complication and clinical results of hemodialysis patients with intertrochanteric fractures treated with proximal femoral intramedullary nailing have been investigated through comparison with patients with normal kidney function.Materials and MethodsForty-seven patients were included; the hemodialysis group (n=17) and the control group with normal kidney function (n=30). The medical history and clinical findings including preoperative and postoperative blood examinations, radiological examinations and ambulatory status (measured using the Koval score). The rate of complications and morbidities were also investigated and compared.ResultsPreoperative hemoglobin/hematocrit was lower but a significant increase in partial thromboplastin time was observed in the hemodialysis group. The amount of bleeding/transfusions were higher and operative time was longer in the hemodialysis group. Upon radiologic examination, there was no significant difference in rate of unstable fracture and nonunion between the two groups. However the postoperative Koval score was significantly worse and the odds ratio of inability to walk after surgery was 13.5 times higher in the hemodialysis group.ConclusionThere was no significant difference in radiological results, but the risk of inability to walk after surgery was 13.5 times higher in the hemodialysis group. Hemodialysis patients have more morbidities and are hemodynamically unstable therefore require special attention. Accurate reduction and firm fixation is required and attentive postoperative rehabilitation is needed.

Fish Oil Supplementation May Improve Partial Thromboplastin Time in Individuals with Blood Type A

Individuals with non‐O blood types are at an increased risk for developing and dying from heart disease. Non‐O blood type also increases risk for pulmonary embolism. Thrombotic occlusion is often the cause of both myocardial infarction and embolism. Increased levels of the von Willebrand factor (VWF) have been associated with an increased risk of arterial thrombosis, and VWF concentrations are higher in the plasma of individuals with non‐O blood types compared to those with the O blood type. Some research suggests that fish oil supplementation will reduce the hypercoaguable state in individuals with shortened partial thromboplastin time (PTT). Forty‐eight healthy individuals (24 blood type A [BTA] and 24 blood type O [BTO]; M/F, 12/36; 26.5±8.5 y, BMI, 24.5±3.6 kg/m2)were recruited for an 8‐wk trial to evaluate the impact of fish oil supplementation on PTT. Participants were stratified by blood type, gender, age, and BMI and randomly assigned to one of two supplement groups: fish oil (2000 mg/d) or coconut oil (2000 mg/d). At baseline, there was a significant mean difference in PTT between the BTA and BTO groups (27.9±1.9 and 29.2±1.7 sec, respectively) (p=0.013). Moreover, a higher percentage of BTA individuals fell into the hypercoaguable category (PTT < 30 sec) compared to the BTO individuals, 87% versus 54% respectively (p=0.033). Preliminary data (18 of 48 participants have completed the intervention) reveal an increase in PTT in the BTA group ingesting fish oil supplements daily (+0.6 seconds) versus the BTA group consuming coconut oil daily (‐0.7 seconds) (p=0.057). There were no differences in PTT between the two BTO groups. This trial will offer insights regarding the relationship of fish oil supplementation and the hypercoaguable state in BTA.

Aspectos clínico-patológicos e laboratoriais do envenenamento crotálico experimental em bovinos

Reproduziu-se experimentalmente o envenenamento crotálico, através da inoculação, por via subcutânea, do veneno de Crotalus durissus terrificus (cascavel sul-americana) em dez bovinos mestiços. Dois animais foram utilizados como controle. O bovino que recebeu dose de 0,03mg/kg de peso corporal, morreu 7h40min após a inoculação. A dose de 0,015mg/kg causou a morte em quatro de sete bovinos inoculados, enquanto os dois animais que receberam 0,0075mg/kg adoeceram discretamente e se recuperaram. Os sintomas tiveram início entre 1h30min e 13h45min após a inoculação. A evolução oscilou entre 5h25min e 45h para os animais que morreram e entre 33h15min e 17 dias entre os animais que se recuperaram. Os principais sinais nervosos observados foram diminuição da resposta aos estímulos externos, reflexos hipotônicos, arrastar dos cascos no solo, aparente apatia, paralisia do globo ocular e da língua, decúbito esternal e lateral. Verificaram-se também adipsia e, por vezes, petéquias nas mucosas vaginal e conjuntival. Houve discreto a moderado aumento do tempo de sangramento e moderado aumento do tempo de tromboplastina parcial ativada. Houve moderada leucocitose com neutrofilia, linfopenia relativa, eosinopenia, monocitose e discreto aumento do número de bastões. Foi evidenciado significativo aumento dos níveis séricos de creatinaquinase, contudo, não foram observadas alterações significativas através da urinálise. À necropsia constataram-se edema quase imperceptível no local da inoculação, discretas petéquias e sufusões no epicárdio, omento, vesícula biliar e mucosa da bexiga em alguns dos animais envenenados experimentalmente. Os exames histopatológicos revelaram necrose (hialinização) de grupos de miócitos ou em miócitos isolados em dez diferentes músculos esqueléticos examinados, próximos ou distantes do local de inoculação em todos os animais necropsiados. Concluí-se que o envenenamento por Crotalus Sul-americanas em bovinos não cursa com mioglobinúria e que o quadro marcado de paralisia flácida mimetiza o observado no botulismo. Adicionalmente foram feitas observações sobre o diagnóstico do envenenamento crotálico e sua diferenciação com enfermidades que cursam com paralisia e necrose muscular em bovinos do Brasil.

The effect of three different doses of sodium pentosan polysulphate on haematological and haemostatic variables in adult horses.

To evaluate the effects of three different doses of sodium pentosan polysulphate (PPS) on haematological and haemostatic variables in adult horses. Eight adult standardbred horses were used. All horses received a single injection of 0, 3, 6, and 10 mg/kg of PPS at the beginning of each treatment week for 4 weeks so that by the end of the study all horses had received all four doses of PPS. Blood samples were collected at 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 168 h after each weekly injection of PPS. Variables measured were packed cell volume, haemoglobin, red blood cell count, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, platelet count, white cell count, neutrophil count, lymphocyte count, eosinophil count, monocyte count, serum protein, fibrinogen, prothrombin time, and activated partial thromboplastin time (PTT). Data were analysed using an ANOVA. Significance was set at P < 0.05. There was a dose-dependent increase in PTT. A significant increase in PTT occurrred in all treatment groups when compared to horses receiving 0 mg/kg in which there was no change over time. The PTT values all returned to baseline by 48 h after treatment. The mean neutrophil count was higher 3 h after treatment when compared to time 0. Horses receiving 3 mg/kg of PPS had a higher lymphocyte count 4 h after injection, and those receiving 6 and 10 mg/kg had higher counts at 3,4,6 and 8 h after injection when compared to time 0. At 8 h after injection horses receiving 6 and 10 mg PPS had higher lymphocyte counts than horses not receiving PPS. PPS causes a dose-dependent prolongation of PTT in horses. At the dose rates currently recommended for treatment of joint problems in horses this increase was small and remained elevated from baseline for up to 24 h. Based on these findings doses of PPS up to 3 mg/kg should not be administered to horses within 24 h of high stress activities or where physical injury may occur.

Heparin, Derived from the Mast Cells of Human Lungs Is Responsible for the Generation of Kinins in Allergic Reactions due to the Activation of the Contact System

Background: In a recent study mast cell heparin proteoglycan (HepPG) of a cell line derived from a mouse mastocytoma was isolated. Glycosaminoglycans proved to be an initiating surface for starting contact activation and could explain kinin generation present in allergic reactions. It is the aim of the present study to prove that HepPG or glycosaminoglycan derived from human mast cells is also capable of acting as a physiologic macromolecule and to induce contact activation. Methods: HepPG molecules were isolated by anionic column chromotography. Their ability to accelerate reciprocal activation of factor XII was investigated by spectrophotometry. The anticoagulant effect was demonstrated by an increase in partial thromboplastin time. HPLC was performed to correlate these effects with molecular weight (MW). Results: The isolated heparin showed high contact–activating and anticoagulant potency. Both actions were suppressed by incubation with heparinase I. The maximum contact activation peak appeared at a lower MW than the anticoagulant effect. Conclusion: These in vitro results explain the results of in vivo allergen challenge studies where a high degree of kinin generation occurs. Heparin derived from human mast cells therefore seems to represent the physiological macromolecule capable of activating the contact system and could be a missing link between cellular and humoral responses in allergic reactions.

HES 200/0.5 Is not HES 200/0.5

The plasma clearance of hydroxyethyl starch (HES) depends on the initial molecular weight and the degree of substitution. So far, little attention has been paid to the clinical relevance of the C2/C6 substitution ratio of hydroxyethyl starch. 10 patients with cerebrovascular circulatory disturbance received hemodilution therapy for 10 days, consisting of 10% HES 200/0.5 (mean molecular weight 200 kD, degree of substitution 0.5) with a C2/C6 ratio of 13.4. A second group of 10 patients received a starch solution with identical initial molecular weight and degree of substitution but with a C2/C6 ratio of 5.7. After the administration of a single dose, no significant differences between the two groups were observed. After repeated administration, significant differences could be detected in hemorheology, coagulation and elimination (p < 0.01). The larger C2/C6 ratio led to a higher intravascular mean molecular weight (95 vs. 84 kD), which in turn led to a higher increase in serum concentration during the therapy (14.7 vs. 8.6 mg/ml). Hematocrit was lowered more (-30.5 vs. -23.5%) and plasma viscosity was increased more. There was also a more pronounced increase in partial thromboplastin time (+30% vs. +13%) and a factor of 2 larger decrease of factor VIII/von Willebrand factor-complex (p < 0.01), which exceeded the dilution effect. The higher C2/C6 ratio of HES 200/0.5/13.4 slows down enzymatic degradation. After repeated administration of this starch, large molecules accumulate which are inefficiently degraded. The same effect has been observed after therapy with highly-substituted HES. This accumulation of large molecules leads to a beneficial longer lasting volume effect. The disadvantages include an increase in plasma viscosity and coagulation disturbances, which cannot be explained with the respective dilution effect alone. For these reasons, the C2/C6 ratio is of clinical relevance and should be included in the product labeling in the future.

In vitro study of the hemocompatibility of superparamagnetic contrast agent for magnetic resonance imaging

Five different nanoparticles, potentially useful in magnetic resonance imaging (MRI) after venous administration, were studied for their hemo-compatibility. The in vitro methodology evaluated these materials by several parameters: cytotoxicity towards cells cultured in vitro, aggregation ability of platelets, hemolysis inducibility, intrinsic and extrinsic coagulation pathway activation, and complement activation. With the proposed clinical dose, regardless of the cell type used (murine cell line or human endothelial cells) no toxicity was observed. The presence of the particles in blood did not produce any considerable damage: either hemolysis or platelet aggregation or blood coagulation were recorded. However, a slight decrease in aggregation ability of platelets was noticed as well as an increase in partial thromboplastin time. Because of the quick removal of the particles from the bloodstream, these phenomena must be short-lived, thus avoiding significant adverse clinical effects.

In Vivo Effects of Stroma-Free Hemoglobin and Polyhemoglobin on Coagulation Factors in Rats

We studied the effects of rat stroma-free hemoglobin (rSFH), human stroma-free hemoglobin (hSFH), rat polyhemoglobin (rPoly), and human polyhemoglobin (hPoly) on coagulation factors in rats. Albumin and saline infused rats were controls. The infusion volume was 10% of the rat's blood volume. The concentrations of hemoglobin in this study were 7 g/dl. Measurements for prothrombin time (PT) and activated partial thromboplastin time (PTT) were at 5 minutes, 2, 6, 24 and 72 hours after infusion. Factor X, fibrinogen, plasminogen, antithrombin III, and antiplasmin were followed at 24 and 72 hours after infusion. Compared with saline infused rats PT and PTT did not change significantly in those rats infused with Hb preparations. There was a transient increase of PTT from 2 to 24 hours after infusion in albumin infused rats. Factor X, fibrinogen, antithrombin III and antiplasmin showed no significant differences between Hb infused groups and saline infused group. Twenty-four hours and 72 hours after infusion plasminogen decreased in all groups except the albumin infused rats at 24 hours after infusion when compared with normal rat plasma pool. However, there were no significant differences in plasminogen levels between the hemoglobin infused groups and the control saline group. Stroma-free and polyHb solutions (rSFH, hSFH, rPoly and hPoly) did not cause significant changes in prothrombin time and activated partial thromboplastin time in rats. The rats infused with hemoglobin solutions (rSFH, hSFH, rPoly, and hPoly) did not show significant differences in Factor X, fibrinogen, antithrombin III and antiplasmin levels compared with the control group.

Experimental model of venous thrombosis in rats and effect of some agents

An experimental model of venous thrombosis was produced in rats by insertion of a stainless steel wire coil into the inferior vena cava. The thrombus was developed onto the wire and the endothelium of the vein wall with the maximum size at 2–3 days after the wire insertion and persisted for more than 10 days with gradual thrombolysis and organization. At the early stage, the thrombus was composed of platelets, red blood cells and some fibrin. It grew up to the fibrinous structure with enmeshed blood cells and then underwent organization. Development of thrombosis was accompanied by reduction of the fibrinolytic activity at the initial phase and by decrease in platelet counts and increase in partial thromboplastin time at the early and progression phases. Thrombus formation was effectively inhibited by heparin, ticlopidine and bisobrin, but it was not affected by aspirin and tranexamic acid. The present procedures, together with simple quantification of thrombus size, gave a reproducible result and provided a tool for screening or evaluating of anti-thrombotic and thrombolytic agents in a routine study.