| 1. |
- Alehagen, Urban, et al.
(författare)
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Low plasma concentrations of coagulation factors II, VII and XI indicate increased risk among elderly with symptoms of heart failure.
- 2010
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Ingår i: Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis. - 1473-5733. ; 21:1, s. 62-9
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Tidskriftsartikel (refereegranskat)abstract
- Heart failure is a serious condition, and it is, therefore, important to identify patients at high risk as early as possible in order to initiate appropriate treatment. The condition results in complicated disease mechanisms including disturbances in blood coagulation. The aim of the present study was to evaluate whether low plasma concentrations of coagulation factors (F) II, VII and XI influence cardiovascular mortality in an elderly population with possible heart failure. A cardiologist evaluated 450 elderly patients who attended primary healthcare because of symptoms associated with heart failure. He recorded new patient history, conducted a clinical examination, took blood samples, determined concentrations of B-type natriuretic peptide and FII, FVII, FXI and performed Doppler echocardiography. The patients were followed over almost a 10-year period during which all mortality was registered. In patients with suspected heart failure, those with low plasma concentrations of FII, FVII, FXI or all had a significantly higher mortality rate during the follow-up period of 10 years as compared with those with higher plasma concentrations, in contrast with findings in previous reports on patients with acute coronary syndromes. In the group with a plasma concentration of the first versus the ninth decile of FII, FVII, FXI or all, the risk of cardiovascular mortality increased two to three times.
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| 2. |
- Alikhan, R, et al.
(författare)
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Prevention of venous thromboembolism in medical patients with enoxaparin: a subgroup analysis of the MEDENOX study
- 2003
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Ingår i: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 14:4, s. 341-346
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Tidskriftsartikel (refereegranskat)abstract
- The Medical Patients with Enoxaparin (MEDENOX) trial was a randomized, placebo-controlled study that defined the risk of venous thromboembolism (VTE) in acutely ill, immobilized, general medical patients and the efficacy of the low-molecular-weight heparin, enoxaparin, in preventing thrombosis. We performed a post-hoc analysis to evaluate the effect of 40 mg enoxaparin once daily on MEDENOX patient outcome in different types of acute medical illness (heart failure, respiratory failure, infection, rheumatic disorder and inflammatory bowel disease) and pre-defined risk factors (chronic heart and chronic respiratory failure, age, immobility, previous VTE and cancer). The primary outcome was the occurrence of documented VTE between days 1 and 14. The relative risk reduction [95% confidence intervals (CI)] for VTE comparing 40 mg enoxaparin with placebo in the subgroups were: acute heart failure, 0.29 (95% CI, 0.10-0.84); acute respiratory failure, 0.25 (95% CI, 0.10-0.65); acute infectious disease, 0.28 (95% CI, 0.09-0.81); and acute rheumatic disorder, 0.48 (95% CI, 0.11-2.16). The relative risk reduction for VTE in the pre-defined risk factor subgroups were: chronic heart failure, 0.26 (95% Cl, 0.08-0.92); chronic respiratory failure, 0.26 (95% CI, 0.10-0.68); age, 0.22 (95% CI, 0.09-0.51); immobility, 0.53 (95% CI, 0.14-1.72); previous VTE, 0.49 (95% CI, 0.15-1.68); and cancer, 0.50 (95% CI, 0.14-1.72). The beneficial effects of enoxaparin extend to a wide range of acutely ill medical patients. (C) 2003 Lippincott Williams Wilkins.
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| 3. |
- Berntorp, Erik, et al.
(författare)
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A retrospective study of Octaplex in the treatment of bleeding in patients with haemophilia A complicated by inhibitors.
- 2010
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Ingår i: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 21, s. 577-583
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Tidskriftsartikel (refereegranskat)abstract
- The nonactivated prothrombin complex concentrate (PCC) Octaplex (Octapharma PPGmbH, Vienna, Austria) has been used successfully for the treatment of congenital and acquired coagulation factor deficiencies and associated bleeding. The aims of this study were to assess retrospectively whether Octaplex is an effective treatment option for haemophilia A patients with high-titre inhibitors of factor VIII (FVIII) and to investigate the impact of Octaplex on thrombin generation in vitro and ex vivo. Retrospective data were collected from 15 haemophilia A patients with FVIII inhibitors who had been treated with Octaplex. Mild bleeds were treated for a median of 1 day with a median dose of 77 IU/kg and moderate bleeds for 3 days with 57 IU/kg. The physician's overall satisfaction with Octaplex, taking into account efficacy, safety and cost in comparison with other treatment options, was assessed for each bleed. The overall rating was good, very good or excellent for 29 of 41 (71%) bleeds. No adverse drug reactions were reported. In in-vitro studies of thrombin generation with normal plasma samples, experimental inhibition of FVIII activity prolonged the lag phase, diminished the peak thrombin concentration and decreased the area under the concentration-time curve, as expected. Marked improvement in thrombin generation parameters was achieved by adding 0.5-3 IU factor IX/ml PCC into the samples. The same held true when using plasma samples from haemophilia A patients with FVIII inhibitors. These results demonstrate that Octaplex overcomes inhibition of FVIII in in-vitro and ex-vivo assays of thrombin generation, and that Octaplex is an effective treatment option for haemophilia A patients with FVIII inhibitors.
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| 4. |
- Berntorp, Erik, et al.
(författare)
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Long-term prophylaxis in von Willebrand disease
- 2005
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Ingår i: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 16:Suppl 1, s. 23-26
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Tidskriftsartikel (refereegranskat)abstract
- The majority of patients with von Willebrand disease (VWD) have a mild bleeding tendency that primarily involves mucosal bleeding. Some patients with the disorder, however, have severe episodes of mucosal or joint bleeding that can hamper daily activities and lead to significant joint impairment. Experience in the setting of severe hemophilia has shown the feasibility and benefits of prophylactic treatment to prevent bleeding and development of arthropathy. This approach also needs to be evaluated in patients with VWD who require repetitive treatment for bleeding episodes. Data from a series of 35 patients (with VWD types 3, 2A, 2B, and 1) who have received long-term prophylaxis at Malmo University Hospital and Karolinska University Hospital in Stockholm, Sweden, have demonstrated a substantial reduction of bleeding episodes since initiation of treatment. Patients who began prophylaxis at a young age (younger than 5 years) to prevent nose and mouth bleeds have had no joint bleeds and have no clinical signs of arthropathy. Treatment has been safe, with no cases of thrombosis, and no viral transmission among patients who received virus-aftenuated von Willebrand factor-containing factor VIII concentrate. These data thus suggest that long-term prophylaxis is warranted in the majority of patients with type 3 VWD and in other subtypes with severe bleeding tendencies, and that such an approach may help in the avoidance of joint disease if started early. More clinical data and controlled trials are needed in order to formulate recommendations for prophylaxis in patients with VWD.
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| 5. |
- Berntorp, Erik, et al.
(författare)
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NovoSeven in warfarin-treated patients
- 2000
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Ingår i: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 11:Suppl 1, s. 113-115
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Tidskriftsartikel (refereegranskat)abstract
- Haemorrhages represent a major complication of treatment with vitamin K antagonists. In cases of severe bleeding, a prompt effect on the increased International Normalized Ratio value is vital to achieve haemostasis. As conventional treatment, that is plasma or plasma-derived concentrates, carries the risk of blood-borne virus transmission, new treatments are needed. An open, multicentre pilot trial is currently under way to determine the effect of recombinant activated factor VII (rFVIIa; NovoSeven) administered to patients experiencing a bleeding episode after receiving vitamin K antagonists. When rFVIIa was given to a patient with a warfarin-induced nosebleed, it had an immediate haemostatic effect and the International Normalized Ratio value virtually normalized.
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| 6. |
- Brophy, Donald F, et al.
(författare)
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Overcoming delayed in-vitro response to rFVIIa: effects of rFVIIa and rFVIIa analogue (vatreptacog alfa) concentration escalation in whole blood assays.
- 2011
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Ingår i: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 22, s. 541-546
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Tidskriftsartikel (refereegranskat)abstract
- In a previous pharmacokinetic/pharmacodynamic study in nonbleeding hemophilia patients, variability in laboratory response to recombinant factor VIIa (rFVIIa) 90 μg/kg was noted, and the patients were described as delayed or rapid laboratory responders based on time to clot formation. The current study determined whether in-vitro experiments could reproduce previous in-vivo findings; whether the delayed laboratory response to rFVIIa 90 μg/kg is improved by spiking with high-dose rFVIIa or rFVIIa analogue (vatreptacog alfa); whether a dose-response is observed with our method. In-vitro experiments were conducted in our previous patient cohort using rFVIIa 1.28 and 3.84 μg/ml and vatreptacog alfa 0.28 and 0.56 μg/ml. Whole blood studies were conducted using the Hemodyne Hemostasis Analysis System (platelet contractile force, clot elastic modulus, force onset time) and rotational thromboelastometry (clotting time, maximum clot firmness). Spiking with rFVIIa 1.28 μg/ml showed the same distribution of delayed and rapid laboratory response as observed previously. Increasing in-vitro rFVIIa concentrations improved the coagulation parameters; however, there remained delayed and rapid responders. Vatreptacog alfa improved the coagulation parameters at all concentrations tested, and the 0.56 μg/ml concentration normalized the force onset time, platelet contractile force, clot elastic modulus and clotting time parameters. A dose-response was observed with both assays. There was good agreement between the laboratory responses obtained after intravenous administration of rFVIIa 90 μg/kg and in-vitro spiking studies. Escalating rFVIIa and vatreptacog alfa concentrations improved coagulation parameters in all patients compared to rFVIIa 1.28 μg/ml. Vatreptacog alfa produced more pronounced coagulation effects at lower concentrations than rFVIIa; and the 0.56 μg/ml concentration completely normalized responses in all patients.
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| 7. |
- Brunkwall, J, et al.
(författare)
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The effect of unfractionated and low-molecular-weight heparin on the release of prostacyclin from the arterial wall
- 1990
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Ingår i: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 1:6, s. 641-645
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Tidskriftsartikel (refereegranskat)abstract
- Heparin is widely used as an antithrombotic agent, but one reported complication is thrombocytopenia associated with platelet aggregation. The mechanism is not fully clear but heparin interference in the prostaglandin production has been proposed. To investigate if heparin interacts with the production of prostacyclin from the vessel wall, and if low-molecular-weight heparin differs from unfractionated heparin in this respect, excised rabbit aortas were studied in a perfusion model. The vessels were perfused ex vivo for 5 x 15 min and in the last period arachidonic acid was added. Unfragmented heparin (500 IU/kg body weight) or low-molecular-weight heparin (LMWH) (500 antifactor Xa units/kg body weight) were given either 15 min before harvesting the vessels or added directly to the perfusate. The stable degradation product for prostacyclin, 6-keto-PGF1 alpha was not altered by addition of these agents. It is concluded that heparin and LMWH per se do not interact with the prostacyclin system in normal rabbit aortas in the doses studied.
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| 8. |
- Casslén, B, et al.
(författare)
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Plasminogen activators in the human endometrium, cellular origin and hormonal regulation.
- 1992
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Ingår i: Blood Coagulation and Fibrinolysis. - 0957-5235 .- 1473-5733. ; 3:2, s. 133-8
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Tidskriftsartikel (refereegranskat)abstract
- Endometrial tissue explants in culture were found to release urokinase-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA). In order to identify their cellular origin and possible hormonal regulation, enriched cultures of glandular epithelial cells and stromal cells were prepared from fresh endometrium, and the cultures treated with hormones. Both epithelial and stromal cell cultures were found to secrete u-PA and t-PA. Treatment of epithelial cell cultures with oestradiol, progesterone and DH-testosterone had no effect on the secretion of t-PA or u-PA. In stromal cell cultures, on the other hand, the secretion of u-PA was significantly reduced after treatment with progesterone, whereas oestradiol and DH-testosterone had no effect. This reduction of u-PA antigen in the tissue culture medium did not result from a reduction of the relative level of u-PA mRNA in the cells, suggesting that the synthesis of u-PA was not reduced. Alternatively, an increased clearance of u-PA by the cells from the medium may explain the reduction. This in vitro observation probably reflects the in vivo reduction of u-PA in endometrial secretion during the secretory phase.
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| 9. |
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| 10. |
- Ekstrand, Charlotta, et al.
(författare)
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Patient characteristics when starting treatment and patterns of treatment in adults with chronic immune thrombocytopenia
- 2019
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Ingår i: Blood Coagulation and Fibrinolysis. - : LIPPINCOTT WILLIAMS & WILKINS. - 0957-5235 .- 1473-5733. ; 30:7, s. 350-356
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Tidskriftsartikel (refereegranskat)abstract
- Asymptomatic patients with primary chronic immune thrombocytopenia (ITP) are not recommended treatment if their platelet counts are above 30 x 10(9)/l. Factors such as age and comorbidities may influence clinical manifestations and should be considered for treatment decisions. The aim of this study was to determine the impact of clinical characteristics for initiation of ITP treatment, and the patterns of ITP treatment given. We performed an observational cohort study in Sweden with information from medical records and National Health Registers. Adults diagnosed with incident primary ITP between years 2009 and 2016 were included. Multinomial logistic regression was used to assess the impact of factors predicting treatment start. Out of 858 patients with chronic ITP from 71 hospitals we identified 585 (68%) with a first ITP treatment. For 537 (92%) corticosteroids were the first choice. The median platelet counts at start of treatment was 12 x 10(9)/l (interquartile range 5-27 x 10(9)/l). The variables predicting treatment start were platelet counts below 20 x 10(9)/l and treatment with antihypertensive drugs. Patients with diabetes were less likely to receive corticosteroids. Severe bleeding occurred in 75 (13%) of the patients. Platelet counts below 20 x 10(9)/l, antihypertensive treatment and bleedings were the strongest predictors of treatment start, diabetes yielded lower odds to start corticosteroid treatment. The majority of the patients had corticosteroids as first treatment while second treatment was diverse. Asymptomatic thrombocytopenia is not considered a reason as such for initiating treatment. In the latter years, splenectomy seemed to occur later in the course of treatment.
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| 11. |
- Engström, Martin, et al.
(författare)
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Ethanol impairs coagulation and fibrinolysis in whole blood: a study performed with rotational thromboelastometry.
- 2006
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Ingår i: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 17:8, s. 661-665
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Tidskriftsartikel (refereegranskat)abstract
- The objective was to study the effects of ethanol on coagulation and fibrinolysis in whole blood. Blood samples from healthy volunteers were analyzed before and after in-vitro addition of ethanol in order to achieve ethanol concentrations of 0, 1, 2 and 4[per mille sign], respectively (0, 22, 44 and 88 mmol/l). Coagulation and fibrinolysis were then assessed using rotational thromboelastometry. We found that increasing ethanol levels increasingly impaired coagulation as evaluated with rotational thromboelastometry, with a maximum prolongation of the clot formation time of 118% at an ethanol level of 4[per mille sign] (P < 0.000001). We also found a very strong impairment of fibrinolysis already at an ethanol level of 1[per mille sign]. This is the first study assessing the effects of ethanol on coagulation and fibrinolysis in a whole blood model. The impairment of coagulation is similar in nature to the impairment found in patients suffering from hypothermia. The impairment is at a level that may be of clinical importance (e.g. in patients suffering from trauma). The inhibition of fibrinolysis is obvious already at an ethanol level of 1[per mille sign] and it may be a contributing factor to the increased amount of coronary and cerebrovascular ischemic events after binge drinking.
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| 12. |
- Eriksson, Andreas C, et al.
(författare)
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Adhesion of human platelets to albumin is synergistically increased by lysophosphatidic acid and adrenaline in a donor-dependent fashion
- 2006
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Ingår i: Blood Coagulation and Fibrinolysis. - : Ovid Technologies (Wolters Kluwer Health). - 0957-5235 .- 1473-5733. ; 17:5, s. 359-368
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Tidskriftsartikel (refereegranskat)abstract
- Lysophosphatidic acid (LPA) and adrenaline are weak platelet activators considered important for thrombus formation, and were previously shown to synergistically increase platelet aggregation. Here we investigate synergistic activation by LPA and adrenaline when measuring platelet adhesion. Platelet-rich plasma from healthy blood donors together with adrenaline and/or LPA were added to protein-coated microplates. Platelets were allowed to adhere and the amount of adhesion detected enzymatically. The LPA and adrenaline combination induced a synergistic increase of platelet adhesion to a normally non-adhesive albumin surface. The degree of synergy varied markedly between individuals; these variations could not be explained by age, gender, blood type or different amounts of platelets, oxidized low-density lipoprotein, insulin or glucose in plasma. There was a trend indicating increased synergistic effect for platelets sensitive to adrenaline stimulation. The synergistic effect was blocked by the α2-adrenoceptor antagonist yohimbine and inhibited by the ADP scavenger system creatine phosphate/creatine phosphokinase and antibodies against αIIbβ3. Furthermore, platelets adhering to albumin after adrenaline and LPA treatment expressed P-selectin. In conclusion, LPA and adrenaline act synergistically to increase αIIbβ3-mediated platelet adhesion to albumin, dependent on α2-adrenoceptor signalling and platelet secretion. We also confirm that synergistic platelet activation achieved with LPA and adrenaline is highly donor dependent.
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| 13. |
- Eriksson, Maria A, 1965-, et al.
(författare)
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Sex-related differences in the associations between hyperleptinemia, insulin resistance and dysfibrinolysis
- 2008
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Ingår i: Blood Coagulation and Fibrinolysis. - : Lippincott Williams & Wilkins. - 1473-5733 .- 0957-5235. ; 19:7, s. 625-632
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Tidskriftsartikel (refereegranskat)abstract
- The adipocyte-derived hormone leptin is associated with insulin resistance and reduced fibrinolytic status - or dysfibrinolysis - in humans. As leptin associates differentially to the development of cardiovascular disease and diabetes in men and women, we hypothesized that leptin and insulin sensitivity are related to dysfibrinolysis in a sex-dependent manner. Thirty-two men and 40 women were recruited from the Monitoring of trends and determinants in Cardiovascular disease (MONICA) population sample, representing the highest and lowest quartiles of fasting insulin levels. Lipids, fibrinolytic status [plasminogen activator inhibitor 1 (PAI-1) activity, tissue plasminogen activator (tPA) mass and activity, and tPA-PAI complex], leptin, testosterone and sex-hormone-binding globulin were measured. Insulin sensitivity was estimated using the euglycaemic clamp technique. Body composition was determined by bioimpedance. Determinants for circulating levels of fibrinolytic factors were explored in a multivariate linear regression analysis. Levels of fibrinolytic variables and estimated insulin sensitivity did not differ between men and women. Leptin was independently associated with reduced fibrinolytic status high PAI-1 activity, low tPA activity, high tPA mass, and high tPA-PAI complex) in men (P<0.001-0.002). In women, fat mass and/or insulin sensitivity were related to these factors (P<0.001-0.03), and leptin only to reduced tPA activity (P = 0.002). Hyperleptinemia, dysfibrinolysis, insulin sensitivity and androgenicity associate differentially in men and women. Blood Coagul Fibrinolysis 19:625-632 (C) 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins.
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| 14. |
- Fager Ferrari, Marcus, et al.
(författare)
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A rare heterozygous variant in FGB (Fibrinogen Merivale) causing hypofibrinogenemia in a Swedish family
- 2020
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Ingår i: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 31:7, s. 481-484
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Tidskriftsartikel (refereegranskat)abstract
- Fibrinogen is essential for normal hemostasis. Congenital fibrinogen disorders (afibrinogenemia, hypofibrinogenemia, dysfibrinogenemia and hypodysfibrinogenemia), caused by pathogenic variants in the genes FGA, FGB and FGG, have the potential of causing bleeding diathesis and/or thrombotic events of variable severity. We describe a case of familial hypofibrinogenemia in a Swedish family. The proband is a 27-year-old woman, with a history of significant bleeding diathesis. She was diagnosed with moderate hypofibrinogenemia (0.8 g/l), and genetic screening identified a rare heterozygous missense variant in FGB (c.854G>A, p.Arg285His) (Fibrinogen Merivale) previously described in a New Zealand European family with symptomatic hypofibrinogenemia. The father, sister and brother of the proband also harbored the FGB variant, segregating with hypofibrinogenemia (0.9-1.2 g/l). The proband showed a more severe bleeding phenotype compared with her other hypofibrinogenemic family members; this was attributed to a concomitant platelet dysfunction, also present in her normofibrinogenemic mother.
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| 15. |
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| 16. |
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| 17. |
- Guné, Henrik, et al.
(författare)
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Impact of ABO blood group on bleeding complications after surgery for acute type A aortic dissection
- 2021
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Ingår i: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 32:4, s. 253-258
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Tidskriftsartikel (refereegranskat)abstract
- Excessive bleeding is a serious complication associated with impaired survival after surgery for acute type A aortic dissection (ATAAD). Different ABO blood groups are associated with variable levels of circulating von Willebrand factor and therefore potentially altered risks of surgical haemorrhage. The current study aimed to assess the impact of blood group on bleeding complications after ATAAD surgery. This was a retrospective cohort study including 336 patients surgically treated for ATAAD between January 2004 and January 2019. Patients with blood group O were compared with non-O patients. In total, 152 blood group O patients were compared with 184 non-O patients. There were no differences in rates of massive bleeding (27.0 vs. 25.5%, P = 0.767) or re-exploration for bleeding (16.4 vs. 13.0%, P = 0.379) in blood group O and non-O patients, respectively. Median chest tube output 12 h after surgery was 520 ml (350-815 ml) in blood group O and 490 ml (278-703 ml) in non-O patients (P = 0.229). Blood group O patients received more fibrinogen concentrate (6.1 ± 4.0 vs. 4.9 ± 3.3 g, P = 0.023) but administered units of packed red blood cells [5 (2-8) vs. 4 (2-9) U, P = 0.736], platelets [4 (2-4) vs. 3 (2-5) U, P = 0.521] or plasma [4 (1-7) vs. 4 (0-7) U, P = 0.562] were similar. This study could not demonstrate any association between blood group and bleeding after surgery for ATAAD. It cannot be ruled out that potential differences were levelled out by blood group O patients receiving significantly more fibrinogen concentrate.
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| 18. |
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| 19. |
- Henriksson, Anders E., et al.
(författare)
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Time course of clotting and fibrinolytic markers in acute upper gastrointestinal bleeding : relation to diagnosis and blood transfusion treatment.
- 1993
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Ingår i: Blood Coagulation and Fibrinolysis. - 0957-5235 .- 1473-5733. ; 4:6, s. 877-80
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Tidskriftsartikel (refereegranskat)abstract
- One hundred consecutive patients with acute upper gastrointestinal bleeding were investigated. Blood coagulation and fibrinolytic activity were monitored by levels of plasma thrombin-antithrombin III (TAT) complex and plasmin-alpha 2-antiplasmin (PAP) complex in samples obtained from patients at admission with haematemesis and/or melana and in samples obtained from patients the first day after admission. Blood was transfused according to a restrictive policy. Median plasma TAT complex was significantly elevated both at admission and on the first day after admission compared with a reference group. Plasma PAP complex levels were normal at admission but decreased on the first day after admission. This decrease was independent of blood transfusion. The results indicate hypercoagulability at admission among patients with upper gastrointestinal haemorrhage reinforced by the development of a hypofibrinolytic state during the first day after admission. Restricted blood transfusion was not associated with any detectable change in blood coagulation or fibrinolysis in these patients.
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| 20. |
- Holm, Elena, et al.
(författare)
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Changes in bleeding patterns in von Willebrand disease after institution of long-term replacement therapy: results from the von Willebrand Disease Prophylaxis Network.
- 2015
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Ingår i: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 26:4, s. 383-388
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Tidskriftsartikel (refereegranskat)abstract
- Clinically, the leading symptom in von Willebrand disease (VWD) is bleeding, chiefly of mucosal type, for example, epistaxis, gingival, or gastrointestinal bleeding, and menorrhagia. In severe forms of VWD with secondary deficiency of factor VIII, spontaneous joint bleeding, resembling that observed in severe haemophilia A, may also be observed. The bleeding patterns of VWD can affect quality of life, and may be life-threatening. The von Willebrand Disease Prophylaxis Network is an international study group formed with the goal of investigating the role of prophylaxis in clinically severe VWD. The objective of the present study is to investigate the response to prophylaxis focusing primarily on epistaxis, joint bleeding, gastrointestinal bleeding, and heavy bleeding associated with menses. Data from 105 subjects, 10 enrolled in a prospective study and 95 in a retrospective study between 2008 and 2013, were available for analysis. The median annualized rate reductions in bleeding were significant for epistaxis (P < 0.0001), gastrointestinal bleeding (P = 0.0003), joint bleeding (P < 0.0001), and menorrhagia (P = 0.008). Doses on a group level were approximately the same prior to and during prophylaxis, but more patients with gastrointestinal bleeding had prophylaxis three or more times per week as well as higher dosages. Our study, which primarily used retrospective data, indicates that prospective studies are needed to better delineate the doses and dose intervals that should be used for prophylactic treatment of VWD.
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| 21. |
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| 22. |
- Jennersjö, Cecilia, 1963-, et al.
(författare)
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Normal D-dimer concentration is a common finding in symptomatic outpatients with distal deep vein thrombosis
- 2005
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Ingår i: Blood Coagulation and Fibrinolysis. - 0957-5235 .- 1473-5733. ; 16:7, s. 517-523
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Tidskriftsartikel (refereegranskat)abstract
- The D-dimer analysis has been shown to have a high sensitivity and a high negative predictive value for the exclusion of deep vein thrombosis (DVT). However, most D-dimer studies, including recent clinical management studies, are performed without examination of the calf veins and/or performed on patient populations with a predominance of proximal DVT. The purpose of this study was to evaluate the diagnostic performance of the D-dimer test in a population with a suspected high incidence of distal DVT. In the present study, 393 outpatients with clinically suspected symptomatic DVT of the lower extremities were examined with whole-leg duplex ultrasonography. The D-dimer analysis was performed using an automated micro-latex assay (Tina-quant). A total of 137 of 393 patients had a proven DVT, with the majority presenting with distal DVT (59%). Twenty-eight out of 81 patients with distal DVT had a normal D-dimer, compared with two of 56 patients with proximal DVT. The sensitivity for distal DVT was only 65% compared with 96% for proximal DVT, the negative predictive values were 84 and 99%, respectively. In conclusion, the prevalence of distal DVT in a study population seems to have a great impact on the diagnostic performance of the D-dimer analysis. The study results also show that normal D-dimer levels do not exclude distal DVT in outpatients, instead, it can be hypothesized that normal D-dimer levels exclude DVT that require treatment, as indicated by the good outcome in recent management studies. © 2005 Lippincott Williams & Wilkins.
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| 23. |
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| 24. |
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| 25. |
- Khawaji, Mohamed, et al.
(författare)
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Physical activity and joint function in adults with severe haemophilia on long-term prophylaxis.
- 2011
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Ingår i: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 22:1, s. 50-55
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Tidskriftsartikel (refereegranskat)abstract
- It has been shown that patients with severe haemophilia treated on demand are not as physically active as their healthy peers and often have a sedentary lifestyle that contributes to chronic joint disease. The use of prophylaxis provides opportunities for participation in physical activities with fewer bleeding episodes. The objective of the study was to describe the type, intensity and duration of physical activity among adult patients with severe haemophilia and to find out whether a joint function dependency exists. Patients with severe haemophilia, divided into two groups (group A: patients who started prophylaxis at the age of ≤3 years and group B: patients who started prophylaxis at the age of >3 years), and 190 controls were included. Physical activity was assessed using the self-report Modifiable Activity Questionnaire. Time involved and intensity of all aspects of physical activity for group A were almost similar to their healthy peers. Group B had significantly lower vigorous, leisure and total physical activities than group A and their healthy peers. Positive significant correlations were found between leisure and total physical activities and joint score in group A, whereas in group B, there was negative significant correlation between only nonweight-bearing activity and joint score. The early start of long-term, primary prophylaxis has been successful in reducing frequency of bleeds and thereby preventing or delaying subsequent chronic joint disease, and enables the patients to lead a physically normal life also during adulthood when patients with haemophilia treated on demand are expected to have substantial joint disease impacting their physical activity.
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| 26. |
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| 27. |
- Lawrie, Andrew S., et al.
(författare)
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Procoagulant activity in patients with sickle cell trait
- 2012
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Ingår i: Blood Coagulation and Fibrinolysis. - 0957-5235 .- 1473-5733. ; 23:4, s. 268-270
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Tidskriftsartikel (refereegranskat)abstract
- Patients with sickle cell trait (STr) are usually considered to be asymptomatic. However, complications, including hypercoagulability, increased risk of venous thromboembolism and the exertional exercise syndrome with rhabdomyolysis and sudden death, have been described. The exact cause of these adverse events is unclear. We have investigated two patients, a set of monozygotic twins with STr, to establish their procoagulant activity status as a potential indicator of thrombotic risk. In-vivo thrombin generation was assessed by the measurement of prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin complexes (TAT). D-dimer was used as a marker of fibrinolytic activity. The potential to generate thrombin was determined using an ex-vivo thrombin generation test (TGT). The impact of red blood cell (RBC)-derived microparticle shedding and RBC rheology were examined. TAT (>60 mu g/l) and F1+2 (948 pmol/l) were markedly elevated in patient 2 but within the normal reference range in patient 1 (TAT=2.5 mu g/l; F1+2=138 pmol/l). D-dimer levels (0.9 mg/l FEU) were similarly elevated in both patients. TGT peak thrombin and endogenous thrombin potential (ETP) were elevated to similar degrees in both patients. Flow cytometric analysis for RBC-derived microparticles showed that both patients had elevated levels on two occasions. RBC deformability, blood viscosity and RBC aggregation were normal and similar in both patients. The results demonstrated different coagulation activity in the patients with one patient in a prothrombotic state, suggesting that there may be two levels of hypercoagulability in STr. Measurement of such differences would allow for separation of high and low-risk patients from serious complications.
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| 28. |
- Lippert, Barbara, et al.
(författare)
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Cost effectiveness of haemophilia treatment: a cross-national assessment.
- 2005
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Ingår i: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 16:7, s. 477-485
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to assess the incremental cost effectiveness of on-demand versus prophylactic haemophilia therapy in Germany, Sweden, the United Kingdom and The Netherlands from the third-party payers' perspective. Using a decision tree model, the cost effectiveness of on-demand versus prophylactic therapy was analysed by extrapolating data from the European Haemophilia Economic Study to a 1-year analytic time horizon. Five hundred and six patients with severe haemophilia A and B, without inhibitors and at least 14 years of age, were enrolled in this study. Patients treated prophylactically had fewer bleeds than patients treated on-demand. With prophylactic treatment, the incremental cost per avoided bleeding ranged from [Euro sign]6650 for patients 30 years of age or younger in Germany to [Euro sign]14 140 for patients over 30 years old in Sweden. If quality of life was taken into account, patients receiving prophylactic treatment had higher mean utilities than patients on on-demand therapy. The incremental effectiveness ratios in Germany were [Euro sign]1.2 million per quality-adjusted life year gained for patients 30 years or younger and HIV-positive and [Euro sign]2.2 million for patients 30 years or younger and HIV-negative. In the group aged over 30 years and HIV-positive the on-demand treatment strategy was dominant, whereas in the over 30 years/HIV-negative group the incremental cost-utility ratio was [Euro sign]4.7 million per quality-adjusted life year. Based on our decision analysis, the use of prophylactic treatment was overall more effective than on-demand therapy in young haemophiliacs, but at extremely high cost.
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| 29. |
- Lövdahl, Susanna, et al.
(författare)
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Malignancies in Swedish persons with haemophilia : a longitudinal registry study
- 2016
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Ingår i: Blood Coagulation and Fibrinolysis. - 0957-5235 .- 1473-5733. ; 27:6, s. 631-636
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to investigate, over time, the incidence of and mortality due to malignant diseases among persons with haemophilia, compared to matched controls. Persons with haemophilia A or B were enrolled via registries at each haemophilia centre, as well as from the National Patient Registry, and were compared to five sex and age-matched controls per patient. Data from the national Cancer Registry were linked to the study participants. A total of 1431 persons with haemophilia and 7150 matched controls were enrolled. Between the years 1972 and 2008, 164 malignancies were reported. The most common type of cancer among patients was prostate cancer, followed by haematologic malignancies, including lymphoma and leukaemia, which were significantly more frequent in patients [ n=35 (2.4%) vs. n=60 (0.8%); P < 0.001]. Malignancies in bladder and other urinary organs were also significantly different [ n=21 (1.5%) vs. n=46 (0.6%); P < 0.01]. The overall incidence rate ratio of malignancies per 1000 person-years compared to the controls was 1.3 [95% confidence interval (CI) 1.1, 1.6]. In subgroup analysis, the corresponding incidence rate ratios per 1000 person-years for persons with severe haemophilia was 1.7 (95% CI 0.9, 3.1) and that for mild/moderate haemophilia 1.1 (95% CI 0.8, 1.5). Swedish persons with haemophilia had a significantly higher incidence of malignant diseases than controls. These were primarily haematologic malignancies and cancer in urinary organs, and the difference independent of any co-infections with HIV and/or viral hepatitis. The findings indicate the importance of further studies and close follow-up of malignancies in persons with haemophilia.
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| 30. |
- Madsen-Härdig, Bjarne, et al.
(författare)
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Direct action on the molecule is one of several mechanisms by which ultrasound enhances the fibrinolytic effects of reteplase.
- 2006
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Ingår i: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 17:2, s. 105-112
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Tidskriftsartikel (refereegranskat)abstract
- Enhanced fibrinolytic reperfusion therapy may improve the outcome in embolic stroke, where ultrasound exposure has been shown to be one option. We recently verified that the fibrinolytic properties of streptokinase were modulated following ultrasound exposure of the molecule. We have now explored this possibility following ultrasound exposure of the reteplase molecule. The effects on clot lysis of reteplase and ultrasound both separately and in combination were studied by evaluating cumulated release of haemoglobin from whole blood clots following 1 h of exposure. Specifically, we investigated how clot lysis was modulated following pulsed 1 MHz ultrasound pre-exposure of the reteplase solution at intensities ranging between 0.125 and 4 W/cm2 spatial-average temporal-average intensity (SATA) and the effects of reteplase following 1 h of pre-exposure of clots to ultrasound at high intensity (4 W/cm2SATA). Significant enhancement of clot lysis during concomitant reteplase and pulsed ultrasound exposure were observed in two intensity ranges: 0.125-0.25 and 2-4 W/cm2SATA. Pre-exposing reteplase solution to ultrasound significantly increased clot lysis only in the lower intensity range. At high ranges, pre-exposure of clots to ultrasound was followed by an increased fibrinolytic action of reteplase. Pre-exposing reteplase solution to low-intensity ultrasound induced changes in the reteplase molecule that enhanced its fibrinolytic effects. Although this effect disappeared at moderately higher ultrasound intensity, the pre-exposure of clots to ultrasound of higher intensity induced increased fibrinolytic effects of reteplase solution.
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| 31. |
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| 32. |
- Mätzsch, Thomas, et al.
(författare)
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No transplacental passage of standard heparin or an enzymatically depolymerized low molecular weight heparin
- 1991
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Ingår i: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 2:2, s. 273-278
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Tidskriftsartikel (refereegranskat)abstract
- In 21 women who had an abortion by hysterotomy between the 15th and 23rd week of pregnancy, the possibility that unfragmented heparin or low molecular weight heparin (LMWH) passed the placental barrier to the foetus was studied. Laboratory analyses included amidolytic assays of factor Xa inhibitory activity (XaI), antithrombin III (ATIII) and a direct measurement of heparin-like substances in plasma with a competitive binding assay. The ATIII concentration in foetal plasma was about 20% of that in normal human plasma and varied considerably between individuals (2-27%). The XaI activity did not differ between the two treated groups, but the mean XaI activity of the combined groups differed from zero (P less than 0.05). If the XaI activity was corrected for the ATIII concentration, the heparin activities no longer differed significantly from zero. As the concentration of heparin-like substances were above the detection limit (0.35 microgram/ml) in 6/16 analysable samples of foetal plasma, a further 15 women who had not received any heparin were included as controls. In 12/14 analysable foetal plasmas heparin-like substances in concentrations above 0.35 micrograms/ml could be detected. Determination of heparin activity in foetal plasma is thus difficult due to the influence of endogenous ATIII on heparin assays. In conclusion, this study did not demonstrate any evidence for the passage of heparin or LMWH across the placental barrier. No differences were detected whether unfragmented heparin or LMWH had been given to the mothers. Our results also indicate the presence of an endogenous glycosaminoglycan in foetal plasma.
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| 33. |
- Mätzsch, Thomas, et al.
(författare)
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The influence of surgical trauma on factor XaI and IIaI activity and heparin concentration after a single dose of low-molecular-weight heparin
- 1991
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Ingår i: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 2:5, s. 651-657
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Tidskriftsartikel (refereegranskat)abstract
- To study the influence of surgical trauma on the XaI and IIaI activity after injection of a low-molecular-weight heparin (LMWH) 24 patients undergoing elective cholecystectomy received one subcutaneous injection of the LMWH Fragmin. Each group of eight patients received either 2,500 or 5,000 XaI U 2 h before operation or 5,000 XaI U 10 h before surgery. For comparison an additional eight patients received 5,000 IU unfragmented heparin (UH) before operation. Laboratory analyses included amidolytically measured XaI- and IIaI-activities and direct measurements of heparin. Dose-dependent increase in the XaI- and IIaI-activity with maximal levels about 3-4 h after injection was seen. Patients given the LMWH 2 h before operation had lower levels of XaI-activity 2 h after injection than those receiving it 10 h before surgery, despite the same dose given. This correlated with the heparin concentrations, where the highest concentration was measured in patients given the LMWH 10 h before surgery. In conclusion, the surgical trauma of a cholecystectomy does not seem to have any major influence on the XaI- or IIaI-activity after administration of the studied LMWH. Alterations of the absorption and/or elimination rates cannot, however, be ruled out, but are related to factors other than the operative trauma per se, such as effects of premedication or circadian rhythmic variations.
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| 34. |
- Nilsson, Caroline, et al.
(författare)
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Monitoring fondaparinux with the Sonoclot
- 2007
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Ingår i: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 18:7, s. 619-622
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Tidskriftsartikel (refereegranskat)abstract
- Fondaparinux is a new anticoagulant that interacts with antithrombin III and activated coagulation factor X resulting in an inhibition of the coagulation system. It has been successful in doses of 2.5 mg for thromboprophylaxis as well as in higher therapeutic doses of 5-7.5 mg. No optimal method for monitoring the effects of fondaparinux has been proposed. The aim of the present study was to investigate whether a viscoelastic coagulation analyzer, the Sonoclot (Sienco, Denver, Colorado, USA), could be used for in-vitro monitoring of fondaparinux. Different concentrations of fondaparinux were added in vitro to whole blood taken from eight volunteers. The blood samples mixed with the various amounts of fondaparinux were analyzed using the Sonoclot. The whole-blood activated partial thromboplastin time with the Hemochron Jr (ITC, Edison, New Jersey, USA) was used as the reference coagulation analysis. All analyses were started expeditiously, within 30s from sampling, and were performed at 37 degrees C. The values of the Sonoclot parameter clot rate, which measures the rate of fibrin formation, fibrin polymerization and platelet-fibrin interactions, were significantly correlated to increasing concentrations of fondaparinux (R= -0.90). The Sonoclot parameters of activated coagulation time, time to peak and clot retraction had weaker, butstill significant, correlations to fondaparinux concentrations. At prophylactic doses (0.38 mu g/ml blood) the clot rate decreased 15% compared with the initial unanticoagulated value, whereas at therapeutic doses (1.53 mu blood) there was a 27% decrease. In conclusion, the Sonoclot parameter clot rate could be of clinical value to individualize the fonclaparinux dosage, especially the higher, therapeutic, dosages. Blood Coagul Fibrinolysis 18:619-622 (c) 2007 Lippincott Williams & Wilkins.
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| 35. |
- Nylander, Sven, et al.
(författare)
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Thrombin-induced platelet activation and its inhibition by anticoagulants with different modes of action
- 2003
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Ingår i: Blood Coagulation and Fibrinolysis. - : Ovid Technologies (Wolters Kluwer Health). - 0957-5235 .- 1473-5733. ; 14:2, s. 159-167
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Tidskriftsartikel (refereegranskat)abstract
- Thrombin-induced platelet activation involves cleavage of protease-activated receptors (PARs) 1 and 4, and interaction, via glycoprotein (Gp)Ibα, with the platelet GpIb/IX/V complex. This study investigated inhibition of platelet activation by thrombin inhibitors with different modes of action: two reversible direct thrombin inhibitors, melagatran and inogatran; hirudin, a tightly binding direct thrombin inhibitor; and two indirect thrombin inhibitors, heparin and dalteparin. Up-regulation of P-selectin (CD62P) and PAR-1 cleavage was measured in human whole blood, by flow cytometry. The thrombin concentration that induced 50% of maximum (EC50) PAR-1 cleavage was 0.028 nmol/l, while that of platelet activation (CD62P) was over two-fold higher (0.64 nmol/l). The EC50 of a PAR-1-independent component, defined as a further activating effect of thrombin on top of the maximum PAR-1-activating peptide (AP) effect, was 3.2 nmol/l. All anticoagulants were concentration-dependent inhibitors of thrombin-induced platelet activation and PAR-1 cleavage, but none inhibited PAR-1-AP or PAR-4-AP induced activation. Melagatran and inogatran were more potent inhibitors of CD62P up-regulation than of PAR-1 cleavage; conversely, hirudin, heparin and dalteparin were more potent inhibitors of PAR-1 cleavage.Thus, reversible direct thrombin inhibitors, such as melagatran, are potent inhibitors of thrombin-induced platelet activation, acting mainly by inhibition of a PAR-1-independent component.
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| 36. |
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| 37. |
- Olsson, Anna, et al.
(författare)
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Clotting factor level is not a good predictor of bleeding in carriers of haemophilia A and B.
- 2014
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Ingår i: Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis. - 1473-5733. ; 25:5, s. 471-475
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Tidskriftsartikel (refereegranskat)abstract
- Carriers of haemophilia are known to have a wide range of clotting factor levels and bleeding symptoms. This study aimed at investigating whether carriers of severe and moderate haemophilia had an increased bleeding tendency, compared with a control group, using a condensed version of a bleeding assessment tool developed by the Molecular and Clinical Markers for the Diagnosis and Management of Type 1 VWD study group (MCMDM-1VWD). One hundred and twenty-six genetically verified carriers of severe and moderate haemophilia and 90 controls were interviewed regarding bleeding symptoms. A bleeding score of at least 4 was considered positive, indicating a significant bleeding tendency. Clotting factor levels were tested in the carriers.Nineteen of the women were carriers of haemophilia B, with a mean factor (F)IX:C level of 0.54 (± 0.27) kIU/l, and 107 were carriers of haemophilia A, with a mean FVIII:C level of 0.74 (± 0.32) kIU/l. The median bleeding score was 2 (-3-12) among carriers and -1 (-3-8) among controls (P<0.001). The bleeding score was weakly correlated to clotting factor levels in carriers of haemophilia A (rs=-0.36, P<0.001). We conclude that the bleeding tendency in our cohort of carriers differed significantly from that in the controls and that clotting factor levels might not be sufficient to predict the bleeding tendency.
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| 38. |
- Osman, Abdimajid, et al.
(författare)
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Plasma S/R ratio of warfarin co-varies with VKORC1 haplotype
- 2007
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Ingår i: Blood Coagulation and Fibrinolysis. - 0957-5235 .- 1473-5733. ; 18:3, s. 293-296
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Tidskriftsartikel (refereegranskat)abstract
- We recently reported that the low-dose VKORC1*2 haplotype is an important genetic determinant for warfarin dose requirement and is associated with difficulties to attain stable therapeutic prothrombin time-International Normalized Ratio in patients undergoing anticoagulation therapy. The aim of this study was to investigate whether patients with VKORC1*2 compared with patients carrying high-dose haplotypes VKORC1*3 or VKORC1*4 had different warfarin S/R ratios in their plasma, and whether that was related to CYP2C9 variants CYP2C9*2 and CYP2C9*3 or other factors. Samples from patients previously haplotyped for VKORC1 and measured for plasma warfarin concentration were genotyped for the CYP2C9 variants CYP2C9*2 and CYP2C9*3. Nonparametric statistical analysis was performed to elucidate whether there was any significant difference in the warfarin S/R ratio between the two patient groups. Our result shows that there is a significant difference (P < 0.01) in warfarin S/R ratios between VKORC1*2 and VKORC1*3 or VKORC1*4 patients. This difference did not originate from CYP2C9 variants CYP2C9*2 and CYP2C9*3. We speculate that VKORC1 haplotypes possibly are linked to some unidentified factors involved in the metabolic clearance of warfarin enantiomers. Dose-dependent variations in (S)-warfarin and (R)-warfarin clearance in these patients can also be a probable explanation for the difference in warfarin S/R ratios.
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| 39. |
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| 40. |
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| 41. |
- Ramström, Sofia, 1973-
(författare)
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Clotting time analysis of citrated blood samples is strongly affected by the tube used for blood sampling
- 2005
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Ingår i: Blood Coagulation and Fibrinolysis. - 0957-5235 .- 1473-5733. ; 16:6, s. 447-452
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Tidskriftsartikel (refereegranskat)abstract
- Our aim was to establish whether differences in clotting times for recalcified blood and plasma samples might be explained by the use of different blood collection tubes. Samples obtained from different plastic vacuum tubes were recalcified and clotting times determined by free oscillation rheometry. The clotting times for blood collected in Vacutainer (Becton Dickinson, Rutherford, New Jersey, USA) or Vacuette (Greiner Bio-One, Kremsmünster, Austria) tubes decreased with time, with maximal effect after 30 min. Blood from Monovette (Sarstedt, Nümbrecht, Germany) tubes displayed longer clotting times, which did not decrease with time. Clotting times for plasma prepared after 1 h storage in Vacutainer or Vacuette tubes were unaffected by subsequent addition of corn trypsin inhibitor to inhibit factor XIIa, although an antibody against factor XI prolonged the clotting time markedly. In Monovette plasma, both corn trypsin inhibitor and anti-factor XI effectively prolonged the clotting time. When corn trypsin inhibitor or anti-factor XI was added to the tubes before blood collection, but both additions clearly prolonged the clotting times in all types of tubes, even though corn trypsin inhibitor was less effective in whole blood. Antibodies against human tissue factor did not affect the clotting times. The amounts of platelet or leukocyte microparticles in plasma were low and similar in all tubes. This indicates that blood collection in Vacutainer or Vacuette tubes induces a rapid activation of factor XII and factor XI.
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| 42. |
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| 43. |
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| 44. |
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| 45. |
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| 46. |
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| 47. |
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| 48. |
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| 49. |
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| 50. |
- Srinivasa, Chandramma, et al.
(författare)
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Caesalpinia cristacoat extract protects red blood cell from sodium nitrite-induced oxidative stress and exhibits antiplatelet activity
- 2020
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Ingår i: Blood Coagulation and Fibrinolysis. - : LIPPINCOTT WILLIAMS & WILKINS. - 0957-5235 .- 1473-5733. ; 31:5, s. 293-302
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Tidskriftsartikel (refereegranskat)abstract
- To understand the RBC protecting efficiency and antiplatelet activity of methanolic extract ofCaesalpinia cristacoat (MECCC). RBC-protecting activity of MECCC was evaluated using assays, such as DPPH, level of lipid peroxidation, protein carbonyl content, superoxide dismutase and catalase as a marker of oxidative stress whereas, platelet aggregation inhibition was performed using human platelet-rich plasma (PRP). MECCC showed about 76% of DPPH-scavenging activity, with an IC(50)value of 71.89 mu g/ml. The MECCC reduced the level of lipid peroxidation and protein carboxylation in RBC caused by NaNO(2)in a dose-dependent manner. In addition, MECCC normalized the levels of superoxide dismutase (SOD) and catalase (CAT) in oxidative stress-induced RBC in a dose-dependent manner. This suggested the protective effect of MECCC on RBC against oxidative stress. Furthermore, MECCC also exhibited mild antiplatelet activity by inhibiting both ADP and epinephrine agonists that induced platelet aggregation. The noticed inhibition percentage was found to be 28 and 23%, respectively at the concentration of 150 mu g. Interestingly, MECCC did not hydrolyse the RBC suggesting its nontoxic properties. MECCC possesses protective effect of RBC against NaNO2(10 mmol/l) induce oxidative stress and inhibits platelet aggregation.
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