scholarly journals The main pathogenetic mechanisms of hypercoagulation in diabetes and the possibility of its drug correction

2021 ◽  
Vol 23 (2) ◽  
pp. 165-174
Author(s):  
Evgeny V. Kryukov ◽  
Alexey N. Kuchmin ◽  
Elena P. Umanskaya ◽  
Mikhail B. Nagorny ◽  
Andrey A. Shevelev
Keyword(s):  
Coagulation System ◽  
Diabetic Patients ◽  
Hypolipidemic Effect ◽  
Clotting Factors ◽  
Clotting System ◽  
Kinin System ◽  
Functional Changes ◽  
Increased Sensitivity ◽  
Lowering Drug ◽  
High Level

Disorders in the blood coagulation system play an important role in the development of cardiovascular pathology in diabetes. Factors that cause them are hyperglycemia, insulin deficiency, insulin resistance, dyslipidemia, oxidative stress. The most significant changes are observed in the vascular-platelet link of hemostasis. Diabetes is characterized by morphological and functional changes in the endothelium of blood vessels. The activity of platelets increases, which is manifested by their high level of spontaneous aggregation and increased sensitivity to the action of activating factors. The role in the disturbance of hemostasis is played by increasing the activity of the von Willebrand factor, reflecting damage to endothelial cells. Diabetes is characterized by an increase in the activity of plasma clotting factors (I, II, III, VII, VIII, IX, XI, XII and XIII), activation of the callicrein-kinin system. In some cases, this correlates with the development of complications of diabetes. Characteristic disorders in the coagulation inhibition system are a decrease in the activity of antithrombin III, reduced formation of thrombin-antithrombin complexes, reduction of thrombomodulin and protein C. In diabetes, there is a decrease in fibrinolysis, due to a decrease in the expression of tissue activator plasminogen and an increase in the level of the inhibitor of the activator plasminogen. The possibilities of drug correction of hypercoagulation factors in diabetes are to achieve glycemic control with sugar-reducing drugs and elimination of dyslipidemia through hypolipidemic therapy. The most well-studied sugar-lowering drug that improves the state of the blood clotting system is metformin. The system of hemostasis in diabetic patients is positively affected by statins both due to the direct hypolipidemic effect, and by improving endothelial function and increasing fibrinolysis.

Experimental Thrombocytopenia Induced by Busulphan (Myleran) in Rabbits: Extremely Low Platelet Levels and Intact Plasma Clotting System

1968 ◽  
Vol 19 (03/04) ◽  
pp. 570-577 ◽  
Author(s):  
S. A Evensen ◽  
M Jeremic ◽  
P. F Hjort
Keyword(s):  
Alkylating Agent ◽  
Normal Values ◽  
Coagulation System ◽  
Lag Phase ◽  
Injection Level ◽  
Minimum Level ◽  
Clotting Factors ◽  
Clotting System ◽  
Plasma Coagulation

SummaryThe effects of 2 intraperitoneal injections of the alkylating agent Busulphan (each of 25 mg/kg body weight, 3 days between injections) on the circulating elements of the blood and on the plasma coagulation system in rabbits have been investigated.Platelets fell progressively after a lag-phase of 7 days, reached a mean minimum level of about 3 % of the pre-injection level in 14 days, and then returned slowly towards normal values. Bleeding was an occasional complication and a rare cause of death. Granulocytopenia developed synchronously with the fall in platelets. The plasma clotting factors remained intact.We conclude that this is a useful experimental model for studies on the role of platelets in hemostasis and thrombosis.

Haemostatic Changes; Plasma Levels of Alpha2-Antiplasmin-Plasmin Complex and Thrombin-Antithrombin III Complex in Female Breast Cancer

1998 ◽  
Vol 84 (3) ◽  
pp. 364-367 ◽  
Author(s):  
Özgür Özyılkan ◽  
Eşmen Baltalı ◽  
Oktay Özdemir ◽  
Gülten Tekuzman ◽  
Şerafettin Kirazlı ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Plasma Levels ◽  
Antithrombin Iii ◽  
Female Breast Cancer ◽  
Fibrinolytic System ◽  
Coagulation System ◽  
Clotting Factors ◽  
Clotting System ◽  
Thrombin Antithrombin Iii Complex ◽  
Blood Clotting Factors

Aims and background Disorders of hemostasis in patients with malignancies are based on several mechanisms, such as ability of the tumor to alter the coagulation system by producing blood clotting factors or decreasing their inhibitors by increasing fibrinolysis, and by inducing an alteration of blood vessels in relation to the state of local invasion. We investigated the fibrinolytic system marker alpha2-antiplasmin-plasmin complex (APP) and clotting system marker thrombin-antithrombin III complex (TAT) in patients with breast cancer and compare them with CA 15-3, the most well-known breast cancer antigen. Methods Plasma levels of APP and TAT and serum level of CA 15-3 were determined in 57 patients with breast cancer (28 in remission and 29 with active breast cancer) and 13 healthy women. Results In patients with active breast cancer, plasma APP levels were significantly elevated compared to those of other groups (P<0.05). In addition, we observed a poor but positive correlation between plasma levels of APP and those of CA 15-3 (r=0.24; P=0.038). Plasma TAT levels, which reflect the activation of thrombin, were also significantly elevated in patients with active breast cancer (P<0.01), and there was a significant correlation between CA 15-3 and TAT (r=0.24; P=0.041). Conclusions We demonstrated that increased APP and TAT levels might reflect enhanced activation of coagulation and the fibrinolytic system in patients with active breast cancer.

Heparin Response and Clearance in Acute and Chronic Liver Disease

1985 ◽  
Vol 54 (03) ◽  
pp. 591-594 ◽  
Author(s):  
H Sette ◽  
R D Hughes ◽  
P G Langley ◽  
A E S Gimson ◽  
R Williams
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Peak Level ◽  
Chronic Liver ◽  
Clotting System ◽  
Activated Clotting Time ◽  
At Iii ◽  
Increased Sensitivity ◽  
Low Levels ◽  
Normal Controls

SummaryPatients with liver disease are at risk of bleeding due to abnormalities of the clotting system although they must be anticoagulated if they require haemodialysis or haemoperfusion. The anticoagulant of choice is heparin.In this study we have investigated heparin kinetics in patients with fulminant hepatic failure (FHF) after a single intravenous dose of heparin (2,500 units) and found there was an increased clearance of heparin whether measured by its anti-Xa effect (t1/2 = 27.8 ± 2.9 min compared to t1/2 = 50.2 ± 2.7 min in normal controls p <0.001) or by the whole blood activated clotting time (t1/2 = 23.7 ± 2.2 min compared to t1/2 = 37.0 ± 2.0 min p <0.001). There was a decreased peak level of heparin measured by anti-Xa effect (peak level in FHF = 0.48 ± 0.05 u/ml and in controls = 0.69 ± 0.04 u/ml, p <0.02), but an increased sensitivity to heparin (sensitivity in FHF = 0.072 ± 0.011 sec/unit, in controls 0.033 ± 0.003 sec/unit, p <0.001). Patients with FHF had very low levels of antithrombin III (AT III), but there was no correlation between this and any parameters of heparin effect or clearance. In a group of patients with chronic liver disease heparin kinetics did not differ from controls despite low levels of AT III.The changes in heparin kinetics in FHF are likely to be complex with the balance between the proteins that act as cofactors, (e.g. AT III) and the proteins that have heparin neutralising activity, controlling the response of added heparin.

Coagulation Disorders in Thrombocythaemia, a Study of Seven Cases

1962 ◽  
Vol 07 (01) ◽  
pp. 114-128 ◽  
Author(s):  
Stefan Niewiarowski ◽  
Halina Zywicka ◽  
Zbigniew Latałło
Keyword(s):  
Liver Parenchyma ◽  
Platelet Factor 4 ◽  
Coagulation System ◽  
Severe Bleeding ◽  
Clotting Factors ◽  
Platelet Factor ◽  
Antiheparin Activity ◽  
Thromboplastic Activity ◽  
Bleeding Episodes ◽  
Routine Coagulation

SummaryThe blood coagulation system has been studied in 7 patients with thrombocythaemia. 4 of these patients had thrombocythaemia after splenectomy, 2 of them had thrombocythaemia associated with myeloid leukemia, and 1 thrombocythaemia associated with polycythaemia. Severe bleeding episodes were noted in 5 cases, 2 patients had only mild bleeding symptoms.Each patient was examined several times. The period of observations varied from 2 months to 3 years. Platelet count varied from 350 000 to 3 800 000 per mm3.Bleeding time and tourniquet test were normal in all cases. Routine coagulation and fibrinolysis studies did not reveale characteristic abnormalities in plasma clotting factors. A decrease of prothrombin complex components was observed in 4 cases. This disturbance was due to the coexisting injury of liver parenchyma or myeloid changes but not to an increase of platelets or to the abnormalities in the platelet system.An increase of antiheparin activity was found in the plasma of 4 patients. This activity is probably due to the escape of platelet factor 4 from destroyed or qualitatively changed platelets into plasma.Platelet clotting factors were investigated in isolated platelet suspensions, A significant decrease of platelet factor 1 was observed in all patients and a decrease of platelet factor 4 in 5 patients. In 2 cases platelet factor 4 increased. Platelet thromboplastic activity showed a great variety of disturbances in conformity with other workers observations.Recent views on the pathogenesis of bleedings in thrombocythaemia are discussed. On the basis of their own investigations the authors suggest that the significant disturbances of platelet function may contribute to the development of bleeding, and that the increase of antiheparin activity in plasma may produce hypercoagulability and favorize the formation of thrombi.

scholarly journals Management of the Bleeding Patient Receiving New Oral Anticoagulants: A Role for Prothrombin Complex Concentrates

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Lisa M. Baumann Kreuziger ◽  
Joseph C. Keenan ◽  
Colleen T. Morton ◽  
David J. Dries
Keyword(s):  
Recombinant Factor Viia ◽  
Factor Viia ◽  
Oral Anticoagulants ◽  
New Oral Anticoagulants ◽  
Coagulation Cascade ◽  
Clotting Factors ◽  
Prothrombin Complex Concentrates ◽  
Clotting System ◽  
Clinical Trial Evidence

Ease of dosing and simplicity of monitoring make new oral anticoagulants an attractive therapy in a growing range of clinical conditions. However, newer oral anticoagulants interact with the coagulation cascade in different ways than traditional warfarin therapy. Replacement of clotting factors will not reverse the effects of dabigatran, rivaroxaban, or apixaban. Currently, antidotes for these drugs are not widely available. Fortunately, withholding the anticoagulant and dialysis are freqnently effective treatments, particularly with rivaroxaban and dabigatran. Emergent bleeding, however, requires utilization of Prothrombin Complex Concentrates (PCCs). PCCs, in addition to recombinant factor VIIa, are used to activate the clotting system to reverse the effects of the new oral anticoagulants. In cases of refractory or emergent bleeding, the recommended factor concentrate in our protocols differs between the new oral anticoagulants. In patients taking dabigatran, we administer an activated PCC (aPCC) [FELBA] due to reported benefit in human in vitro studies. Based on human clinical trial evidence, the 4-factor PCC (Kcentra) is suggested for patients with refractory rivaroxaban- or apixaban-associated hemorrhage. If bleeding continues, recombinant factor VIIa may be employed. With all of these new procoagulant agents, the risk of thrombosis associated with administration of factor concentrates must be weighed against the relative risk of hemorrhage.

scholarly journals ampG Gene of Pseudomonas aeruginosa and Its Role in β-Lactamase Expression

2010 ◽  
Vol 54 (11) ◽  
pp. 4772-4779 ◽  
Author(s):  
Ying Zhang ◽  
Qiyu Bao ◽  
Luc A. Gagnon ◽  
Ann Huletsky ◽  
Antonio Oliver ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Amino Acid ◽  
Transmembrane Protein ◽  
Amino Acid Identity ◽  
Clinical Isolates ◽  
Signal Molecules ◽  
Carbonyl Cyanide ◽  
Increased Sensitivity ◽  
Potential Strategy ◽  
High Level

ABSTRACT In enterobacteria, the ampG gene encodes a transmembrane protein (permease) that transports 1,6-GlcNAc-anhydro-MurNAc and the 1,6-GlcNAc-anhydro-MurNAc peptide from the periplasm to the cytoplasm, which serve as signal molecules for the induction of ampC β-lactamase. The role of AmpG as a transporter is also essential for cell wall recycling. Pseudomonas aeruginosa carries two AmpG homologues, AmpG (PA4393) and AmpGh1 (PA4218), with 45 and 41% amino acid sequence identity, respectively, to Escherichia coli AmpG, while the two homologues share only 19% amino acid identity. In P. aeruginosa strains PAO1 and PAK, inactivation of ampG drastically repressed the intrinsic β-lactam resistance while ampGh1 deletion had little effect on the resistance. Further, deletion of ampG in an ampD-null mutant abolished the high-level β-lactam resistance that is associated with the loss of AmpD activity. The cloned ampG gene is able to complement both the P. aeruginosa and the E. coli ampG mutants, while that of ampGh1 failed to do so, suggesting that PA4393 encodes the only functional AmpG protein in P. aeruginosa. We also demonstrate that the function of AmpG in laboratory strains of P. aeruginosa can effectively be inhibited by carbonyl cyanide m-chlorophenylhydrazone (CCCP), causing an increased sensitivity to β-lactams among laboratory as well as clinical isolates of P. aeruginosa. Our results suggest that inhibition of the AmpG activity is a potential strategy for enhancing the efficacy of β-lactams against P. aeruginosa, which carries inducible chromosomal ampC, especially in AmpC-hyperproducing clinical isolates.

scholarly journals The Threshold of Admission Glycemia as a Predictor of Adverse Events in Diabetic and Non-Diabetic Patients with Acute Coronary Syndrome

2009 ◽  
Vol 3 ◽  
pp. CMC.S2289 ◽  
Author(s):  
Taysir S. Garadah ◽  
Salah Kassab ◽  
Qasim M. Al-Shboul ◽  
Abdulhai Alawadi
Keyword(s):  
Acute Coronary Syndrome ◽  
Adverse Events ◽  
Diabetic Patients ◽  
Stress Hyperglycemia ◽  
Coronary Syndrome ◽  
History Of ◽  
Group 3 ◽  
Group 2 ◽  
High Level ◽  
Group 1

Recent studies indicated a high prevalence of hyperglycemia in non-diabetic patients presenting with acute coronary syndrome (ACS). However, the threshold of admission glucose (AG) as a predictor of adverse events in ACS is unclear. Objective The aim of this study was to assess the threshold of admission glucose (AG) as a predictor of adverse events including Major Acute Cardiac Events (MACE) and mortality, during the first week of admitting patients presenting with ACS. Material and Methods The data of 551 patients with ACS were extracted and evaluated. Patients were stratified according to their blood glucose on admission into three groups: group 1: <7 mmol/L (n = 200, 36.3%) and group 2: >7 mmol/L and <15 mmol/L (n = 178, 32.3%) and group 3: ≥15 mmol/L (n = 173, 31.4%). Stress hyperglycemia was arbitrarily defined as AG levels > 7 mmol/L (group 2 and 3). Patients with ACS were sub-divided into two groups: patients with unstable angina (UA, n = 285) and those with ST segment elevation myocardial Infarction (STEMI, n = 266) and data were analyzed separately using multiple regression analysis. Results The mean age of patients was 59.7 ± 14.8 years and 63% were males. The overall mortality in the population was 8.5% (5.4% in STEMI and 3.1% in UA) patients. In STEMI patients, the odds ratio of stress hyperglycemia as predictor of mortality in group 3 compared with group 1 was 3.3 (CI 0.99-10.98, P < 0.05), while in group 2 compared with group 1 was 2.4 (CI: 0.75-8.07, P = 0.065) after adjustment for age and sex. Similarly, in UA patients, the odds ratio of stress hyperglycemia in group 3 compared with group 1 was 2.7 (CI 0.37-18.98, P < 0.05), while in group 2 compared with group 1 was 2.4 (CI: 0.4-15.2, P = 0.344) after adjustment for age and sex. The incidence of more than 2 MACE in both STEMI and UA patients was higher in group 3 compared with the other two groups. Regression analysis showed that history of DM, high level of LDL cholesterol, high level of HbA1c, and anterior infarction were significant predictors of adverse events while other risk factors such as BMI, history of hypertension and smoking were of no significance. Conclusion This study indicates that the stress hyperglycemia on admission is a powerful predictor of increased major adverse events and hospital mortality in patients with acute coronary syndrome.

scholarly journals Clinico-expert diagnostics of gastrointestinal form of diabetic neuropathy

2011 ◽  
Vol 14 (2) ◽  
pp. 94-97
Author(s):  
Irina Alekseevna Kurnikova ◽  
Tatiana Evgen'evna Chernyshova ◽  
Irina Vladimirovna Gur'eva ◽  
Guzyal' Ilgisovna Kliment'eva
Keyword(s):  
Gastrointestinal Tract ◽  
Diabetic Neuropathy ◽  
Diabetic Patients ◽  
Parasympathetic Innervation ◽  
Gastric Tone ◽  
Functional Changes ◽  
Gastrointestinal Pathology ◽  
Upper Gastrointestinal

Aim. To estimate dynamics of secretory and motor-evacuational functions of the stomach in patients with type 1 diabetes mellitus and gastrointestinalform of diabetic neuropathy. Materials and methods. 32 patients with DM1 without gastrointestinal pathology allocated to different groups depending on DM duration (gr. 1 lessthan 10 yr, gr. 2 over 10 yr). Vegetative equilibrium was estimated from the Kerdo index, rehabilitative potential from its basic constituent (morphophysiologicalindex). The motor-evacuational function of the stomach was studied with the use of a scintillation gamma-chamber, the gastric secretoryfunction by pH measurements. Results. Half of the patients in gr 2 presented with hypersympathicotony. The frequency of hypertonic form of gastric tone increased with durationof DM while the acid-producing and evacuational functions of the stomach decreased (as estimated by pH-measurement and gastroscintiographyrespectively). The propulsive function most significantly decreased in the pyloric part. The efficacy of rehabilitation of diabetic patients with gastrointestinalform of diabetic neuropathy was much lower than in those with preserved vegetative function of the stomach. Conclusion. Impairment of evacuational function of the stomach and duodenum with DM1 duration may be a cause of unstable blood glucose level.Hypomotor dyskinesia of the upper gastrointestinal tract due to DM1 and deficit of parasympathetic innervation occurs more frequently in patientswith low rehabilitative potential. Functional changes in the gastrointestinal tract of DM1 patients do not depend on the quality of compensation ofmetabolic disorders but correlate (r=-0.39) with DM duration. It is concluded that the gastrointestinal form of diabetic neuropathy impairs rehabilitativepotential of fhe patients.

Chronic exposure to ozone causes tolerance to airway hyperresponsiveness in guinea pigs: lack of SOD role

1998 ◽  
Vol 84 (5) ◽  
pp. 1749-1755 ◽  
Author(s):  
Mario H. Vargas ◽  
Laura Romero ◽  
Bettina Sommer ◽  
Pedro Zamudio ◽  
Pascal Gustin ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Airway Hyperresponsiveness ◽  
Chronic Exposure ◽  
Neutral Endopeptidase ◽  
Respiratory Effects ◽  
Functional Changes ◽  
Independent Mechanism ◽  
Increased Sensitivity ◽  
Pressure Changes

Tolerance to respiratory effects of O3 has been demonstrated for anatomic and functional changes, but information about tolerance to O3-induced airway hyperresponsiveness (AHR) is scarce. In guinea pigs exposed to air or O3 (0.3 parts/million, 4 h/day, for 1, 3, 6, 12, 24, or 48 days, studied 16–18 h later), pulmonary insufflation pressure changes induced by intravenous substance P (SP, 0.032–3.2 μg/kg) were measured, then the animals were subjected to bronchoalveolar lavage (BAL). Bronchial rings with or without phosphoramidon were also evaluated 3 h after air or a single O3 exposure. O3 caused in vivo AHR (increased sensitivity) to SP after 1, 3, 6, 12, and 24 days of exposure compared with control. However, after 48 days of exposure, O3 no longer caused AHR. Total cell, macrophage, neutrophil, and eosinophil counts in BAL were increased in most O3-exposed groups. When data from all animals were pooled, we found a highly significant correlation between degree of airway responsiveness and total cells ( r = 0.55), macrophages ( r = 0.54), neutrophils ( r = 0.47), and eosinophils ( r = 0.53), suggesting that airway inflammation is involved in development of AHR to SP. Superoxide dismutase (SOD) levels in BAL fluids were increased ( P < 0.05) after 1, 3, 6, and 12 days of O3 exposure and returned to basal levels after 24 and 48 days of exposure. O3 failed to induce hyperresponsiveness to SP in bronchial rings, and phosphoramidon increased responses to SP in air- and O3-exposed groups, suggesting that neutral endopeptidase inactivation was not involved in O3-induced AHR to SP in vivo. We conclude that chronic exposure to 0.3 ppm O3, a concentration found in highly polluted cities, resulted in tolerance to AHR to SP in guinea pigs by an SOD-independent mechanism.

Innocent blood

2021 ◽  
pp. 291-296
Author(s):  
Michael Obladen
Keyword(s):  
Vitamin K ◽  
Symptomatic Treatment ◽  
Water Soluble ◽  
Coagulation System ◽  
Clotting System ◽  
Water Soluble Vitamin ◽  
High Doses ◽  
Haemorrhagic Disease ◽  
The 19Th Century

Haemorrhages occurring in the newborn without trauma have been observed by obstetricians since the 17th century, but were considered different diseases depending on their location. Umbilical haemorrhage associated with obstructed bile canals was described by Cheyne in 1802. Grandidier in 1871 and Townsend in 1894 grouped together various forms of neonatal bleeds and associated them with disturbed coagulation. When the clotting system became better understood in the last decade of the 19th century, effective symptomatic treatment was developed: gelatine, serum injection, and the transfusion of fresh blood. In 1935, Dam detected the function of vitamin K in the coagulation system and 4 years later, Waddell introduced vitamin K administration into therapy and prevention of neonatal haemorrhagic disease. When high doses of synthetic water-soluble vitamin K analogues were given to preterm infants, kernicterus occurred, reminding physicians that progress in neonatal therapy rests on the cornerstones of controlled trials and follow-up.

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