| 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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