| 1. |
- Casslén, B, et al.
(författare)
-
Plasminogen activators in the human endometrium, cellular origin and hormonal regulation.
- 1992
-
Ingår i: Blood Coagulation and Fibrinolysis. - 0957-5235 .- 1473-5733. ; 3:2, s. 133-8
-
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.
|
|
| 2. |
- Ekstrand, Charlotta, et al.
(författare)
-
Patient characteristics when starting treatment and patterns of treatment in adults with chronic immune thrombocytopenia
- 2019
-
Ingår i: Blood Coagulation and Fibrinolysis. - : LIPPINCOTT WILLIAMS & WILKINS. - 0957-5235 .- 1473-5733. ; 30:7, s. 350-356
-
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.
|
|
| 3. |
- Eriksson, Andreas C, et al.
(författare)
-
Adhesion of human platelets to albumin is synergistically increased by lysophosphatidic acid and adrenaline in a donor-dependent fashion
- 2006
-
Ingår i: Blood Coagulation and Fibrinolysis. - : Ovid Technologies (Wolters Kluwer Health). - 0957-5235 .- 1473-5733. ; 17:5, s. 359-368
-
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.
|
|
| 4. |
- Eriksson, Maria A, 1965-, et al.
(författare)
-
Sex-related differences in the associations between hyperleptinemia, insulin resistance and dysfibrinolysis
- 2008
-
Ingår i: Blood Coagulation and Fibrinolysis. - : Lippincott Williams & Wilkins. - 1473-5733 .- 0957-5235. ; 19:7, s. 625-632
-
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.
|
|
| 5. |
- Henriksson, Anders E., et al.
(författare)
-
Time course of clotting and fibrinolytic markers in acute upper gastrointestinal bleeding : relation to diagnosis and blood transfusion treatment.
- 1993
-
Ingår i: Blood Coagulation and Fibrinolysis. - 0957-5235 .- 1473-5733. ; 4:6, s. 877-80
-
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.
|
|
| 6. |
- Jennersjö, Cecilia, 1963-, et al.
(författare)
-
Normal D-dimer concentration is a common finding in symptomatic outpatients with distal deep vein thrombosis
- 2005
-
Ingår i: Blood Coagulation and Fibrinolysis. - 0957-5235 .- 1473-5733. ; 16:7, s. 517-523
-
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.
|
|
| 7. |
- Lawrie, Andrew S., et al.
(författare)
-
Procoagulant activity in patients with sickle cell trait
- 2012
-
Ingår i: Blood Coagulation and Fibrinolysis. - 0957-5235 .- 1473-5733. ; 23:4, s. 268-270
-
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.
|
|
| 8. |
- Lövdahl, Susanna, et al.
(författare)
-
Malignancies in Swedish persons with haemophilia : a longitudinal registry study
- 2016
-
Ingår i: Blood Coagulation and Fibrinolysis. - 0957-5235 .- 1473-5733. ; 27:6, s. 631-636
-
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.
|
|
| 9. |
- Nylander, Sven, et al.
(författare)
-
Thrombin-induced platelet activation and its inhibition by anticoagulants with different modes of action
- 2003
-
Ingår i: Blood Coagulation and Fibrinolysis. - : Ovid Technologies (Wolters Kluwer Health). - 0957-5235 .- 1473-5733. ; 14:2, s. 159-167
-
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.
|
|
| 10. |
- Osman, Abdimajid, et al.
(författare)
-
Plasma S/R ratio of warfarin co-varies with VKORC1 haplotype
- 2007
-
Ingår i: Blood Coagulation and Fibrinolysis. - 0957-5235 .- 1473-5733. ; 18:3, s. 293-296
-
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.
|
|
