| 1. |
- Holst, Jan, et al.
(författare)
-
The effect of protamine sulphate on plasma tissue factor pathway inhibitorreleased by intravenous and subcutaneous unfractionated and low molecularweight heparin in man
- 1997
-
Ingår i: Thrombosis Research. - 0049-3848 .- 1879-2472. ; 86:4, s. 343-348
-
Tidskriftsartikel (refereegranskat)abstract
- Heparin, a negatively charged sulphated glycosaminoglycan, is clinically the most important antithrombotic drug. Heparin augments the inhibitory activity of antithrombin (AT) towards thrombin, factor Xa (FXa) and other activated clotting enzymes. Tissue factor pathway inhibitor (TFPI) is an endogenous heparin releasable three domain Kunitz-type coagulation inhibitor which inhibits the crucial tissue factor-factor VIIa (TF-FVIIa) dependent coagulation pathway in the presence of FXa. The importance of the TF-FVIIa pathway and TFPI has recently been reviewed (1). TFPI is located to different vascular pools, the largest being the vascular endothelium from where TFPI can be released dose-dependently to the blood by heparins (2). TFPI is speculated to contribute to the anticoagulant properties of heparins, but to which degree is not yet fully understood. In recent years low molecular weight heparins (LMWH) have proven to be effective and safe both for prophylactic (3) and therapeutic treatment (4) of deep vein thrombosis (DVT). Protamine is the least toxic and clinically most commonly used antidote to heparin. However, in vitro and in vivo LMW heparinized blood is not fully neutralized by protamine, as substantial anti-Xa activity remains following neutralization (5). This post-protamine effect has been shown to be partly TFPI dependent when measured in a dilute TF-dependent assay (6,7). We undertook this in vivo study on healthy volunteers in order to investigate whether TFPI released by UH or LMWH (intravenous (iv) or subcutaneous (sc)) remains in the circulation following neutralization of the heparin activity with protamine sulphate (PS). We measured TFPI by three different methods-chromogenic activity, anticlotting activity and a new antigen assay specific for full-length and three-domain TFPI.
|
|
| 2. |
|
|
| 3. |
- Persson, E, et al.
(författare)
-
Plasma lipolytic activity after subcutaneous administration of heparin and a low molecular weight heparin fragment
- 1987
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 46:5, s. 697-704
-
Tidskriftsartikel (refereegranskat)abstract
- The effect of heparin and a low molecular weight heparin fragment (LMWH, mean molecular weight 4000-6000) on plasma anticoagulation and lipolysis was studied in eight healthy men. The activities of antifactor Xa (antiFXa), lipoprotein lipase (LPL), hepatic lipase (HL) and plasma levels of free fatty acids (FFA) were analysed after the injection of 5000 antiFXa units of heparin or LMWH subcutaneously. In comparison with heparin, the administration of LMWH resulted in a significantly higher antiFXa activity (p less than 0.001) but a lower release of LPL and HL (p less than 0.001), which did not increase plasma FFA. It is concluded that subcutaneous injection of LMWH in men elicits an adequate anticoagulant effect measured as antiFXa activity but has a negligible effect on plasma lipolytic activity.
|
|
| 4. |
|
|
| 5. |
- Deb, S., et al.
(författare)
-
Individual variation in hemostatic alterations caused by tyrosine kinase inhibitors : a way to improve personalized cancer therapy?
- 2016
-
Ingår i: Thrombosis Research. - : Elsevier. - 0049-3848 .- 1879-2472. ; 140:Suppl. 1, s. S196-S197
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: During the last two decades, Bcr-Abl tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myelogenous leukemia (CML), and are now considered standard treatment for this disease. However, TKIs can induce serious hemostatic side effects including cardiovascular disease and bleeding disorders. Blood platelet aggregation and formation of pro-coagulant platelets are important to allow a well-balanced hemostatic response. Therefore, a detailed understanding of what effect different TKIs exert on platelets and hemostasis could help to understand if there are differences of importance to minimize the risk of bleeding complications in treated patients.AIM: To investigate how TKIs used in CML (imatinib, dasatinib, nilotinib, bosutinib, and ponatinib) affect platelet activation and hemostasis.MATERIALS AND METHODS: We have developed a multi-parameter six color flow cytometry protocol to study different aspects of platelet function upon activation, e.g. formation of aggregatory (PAC-1-positive) and pro-coagulant (phosphatidylserine-exposing) platelets, exocytosis of alpha- and lysosomal granules and mitochondrial membrane potential.This protocol was performed in presence or absence of TKIs in blood from normal donors and in treated patients. Whole blood aggregometry (Multiplate®), thrombin generation in platelet-rich plasma and in vitro thrombus formation by free oscillation rheometry (ReoRox G2) was further evaluated in some situations.RESULTS: At clinically relevant concentrations, dasatinib significantly decreased the formation of procoagulant platelets. Ponatinib induced a slight decrease in formation of procoagulant platelets, whereas bosutinib and nilotinib showed opposite tendencies (n=7). Dasatinib also decreased platelet aggregation (n=4-6) and in vitro thrombus formation (n=3). Thrombin generation was not significantly affected by therapeutic levels of TKIs, whereas higher doses of dasatinib, bosutinib, ponatinib and imatinib significantly changed one or several of the thrombin generation parameters (n=7-8). Interestingly, large differences in response to the drugs were observed among the healthy donors, especially for dasatinib and bosutinib. Major inter-individual variations were also observed in dasatinib-treated patients, see Figure 1.CONCLUSIONS: Different TKIs show varying potency to affect platelet-based hemostasis. In addition, we found large inter-individual variations in how some drugs affected platelet function. Therefore, we suggest that development of a clinically useful protocol for platelet function testing could help to identify patients more susceptible to adverse drug reactions. Such a protocol could potentially help clinicians to gain insight into the risk of side effects, which could help to choose the most suitable drug for each individual patient.
|
|
| 6. |
- Eriksson, Stefan, et al.
(författare)
-
Endothelial cells release casein kinase II like activity capable of phosphorylating fibrinogen in response to thrombin
- 1993
-
Ingår i: Thrombosis Research. - 0049-3848 .- 1879-2472. ; 72:4, s. 315-320
-
Tidskriftsartikel (refereegranskat)abstract
- Rat liver endothelial cells cultivated in the absence of serum and activated with thrombin released up to 10% of the total protein kinase activity into the cell medium using casein or fibrinogen as the phosphate acceptor protein. The activity was partly inhibited by heparin, indicating that it was of the casein kinase II type. The release of kinase started directly after the addition of thrombin (2 NIH U/ml) to the media with two maxima; one after about 10 min and the second after around 30 min. The phosphorylating activity of media from cells incubated for longer times was less dependent on thrombin-induction which probably indicated the start of destruction of the cells. The results reported suggest that phosphorylation of fibrinogen could occur in the blood under acute phase conditions.
|
|
| 7. |
- Ernofsson, Mats, et al.
(författare)
-
Platelet-derived growth factor-BB and monocyte chemotactic protein-1 induce human peripheral blood monocytes to express tissue factor
- 1996
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 83:4, s. 307-320
-
Tidskriftsartikel (refereegranskat)abstract
- Monocytes induced to express tissue factor (TF), the initiator of the clotting cascade, might play an important role in the pathogenesis of atherosclerosis. We have investigated the TF-inducing capacity of two factors thought to be involved in atherogenesis, i.e. the platelet derived growth factor-BB (PDGF-BB) and monocyte chemotactic protein-1 (MCP-1), a member of the chemokine superfamily. PDGF-BB and MCP-1 are potent chemotactic and activating factors for human blood monocytes. alpha-thrombin which is known to induce TF in endothelial cells and that recently has been shown to induce secretion of MCP-1 from endothelial cells and monocytes was also studied. PDGF-BB induced a dose-dependent expression of TF-antigen in monocytes with maximal response at 20-50 ng/mL. At higher concentrations the expression was reduced. No synergistic effect between PDGF-BB and LPS was seen. MCP-1 also induced a dose-dependent TF-expression with maximal response at 50 ng/mL. In contrast to these results thrombin did not. MCP-1 had a slight, but not significant, priming effect on LPS-induced TF expression. These data show that PDGF-BB and MCP-1 are potent inducers of TF in human peripheral blood monocytes. We suggest that this TF-induction might be an important link between hemostasis and inflammation.
|
|
| 8. |
- Henriksson, Anders E., et al.
(författare)
-
Experimental haemorrhage and blood component transfusion in humans : no change in plasma concentration of thrombin-antithrombin complex and plasmin-antiplasmin complex.
- 1996
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 82:5, s. 409-15
-
Tidskriftsartikel (refereegranskat)abstract
- The influence of haemorrhage and blood transfusion on primary haemostasis, coagulation and fibrinolysis was investigated in ten healthy male volunteers. Acute loss of 10% of the blood volume did not give any significant alteration in thrombin- antithrombin III (TAT) complex and plasmin-alpha 2-antiplasmin (PAP) complex levels compared with a control series. The skin bleeding time with the Simplate II device was not altered after the 10% blood loss. Acute loss of 10% of blood volume followed by transfusion of packed red cells or stored plasma did not resulted in any significant change in bleeding time, TAT and PAP complex levels. It could be concluded that a controlled haemorrhage does not give any detectable changes of the platelet dependent primary haemostasis, blood coagulation and fibrinolysis. Transfusion of one unit of packed red cells or stored plasma does not seem to adversely affect the haemostasis.
|
|
| 9. |
- Järemo, Petter, et al.
(författare)
-
Elevated inflammatory parameters are associated with lower platelet density in acute myocardial infarctions with ST-elevation
- 2000
-
Ingår i: Thrombosis Research. - 0049-3848 .- 1879-2472. ; 100:6, s. 471-478
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Platelets and granulocytes play important roles in coronary disorders. We therefore, investigated platelet and granulocyte alterations in myocardial infarctions (MIs).Patients and study design: A total of 36 individuals having MI with raised ST-segments who were receiving thrombolytic therapy were studied. Sampling was carried out after thrombolysis within 24 h after hospital admission. After 3 to 6 months of recovery, 25 patients were reinvestigated. At the infarction, peak platelet density was determined using a special designed computerised apparatus. In addition, we did counts on platelets, neutrophils and monocytes. Moreover, plasma levels of soluble P-selectin, myeloperoxidase and interleukin 6 were determined to estimate the degree of platelet, neutrophil and monocyte activation, respectively. Peak platelet density was analysed at the MI. All other parameters were determined at the acute event and at recovery.Results: At the MI, compared to the recovery, platelet counts were lower (P<.001). In addition, increased neutrophil counts (P<.001), elevated monocyte counts (P<.001), enhanced myeloperoxidase (P<.001) and interleukin 6 (P<.001) levels were demonstrated. We failed to show elevated soluble P-selectin. Compared to individuals with ST-segment elevations and low platelet density (≤1.058 kg/l), patients having peak platelet densities >1.058 kg/l displayed lower neutrophil counts (P<.01) and decreased interleukin 6 levels (P<.01). Furthermore, we demonstrate that individuals with higher inflammatory response at the MI had higher neutrophil (r=.6; P<.01) and higher monocyte counts (r=.6; P<.001) at recovery.Conclusion: We conclude that MI is associated with an inflammatory response. However, a subgroup of patients having MI with ST-elevations and low peak platelet density was identified. Compared to subjects with higher platelet density, they had more severe inflammatory characteristics. The differences persisted during recovery.
|
|
| 10. |
- Martin, Steven, et al.
(författare)
-
Increased phosphate content of fibrinogen in vivo correlates with alteration in fibrinogen behaviour
- 1992
-
Ingår i: Thrombosis Research. - 0049-3848 .- 1879-2472. ; 68:6, s. 467-473
-
Tidskriftsartikel (refereegranskat)abstract
- Fibrinogen was purified from five patients admitted for hip-replacement surgery the day before (day 0), the day after (day 2) and and one week after the operation (day 8). The behaviour of each patient's three fibrinogens was compared in thrombin gelation assays and plasmin degradation experiments to investigate whether the reported increase in protein-bound phosphate at day 2 and day 8 had any effect on the functional behaviour of fibrinogen as has been demonstrated in vitro. It was found that the thickness of the fibrin fibres produced by thrombin increased markedly at day 2 and declined thereafter. Susceptibility to plasmin appeared to decrease post-operatively by 50% and remained at that level on day 8 despite the phosphate content returning to normal. This has also been shown for fibrinogen phosphorylated in vitro. We conclude, after testing the fibrinogens with and without alkaline phosphatase pretreatment, that our data most resemble the published findings for in vitro phosphorylation of fibrinogen by casein kinase II.
|
|
| 11. |
- Mutschler, Diana K., et al.
(författare)
-
Effects of mechanical ventilation on platelet microparticles in bronchoalveolar lavage fluid
- 2002
-
Ingår i: Thrombosis Research. - 0049-3848 .- 1879-2472. ; 108:4, s. 215-220
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Mechanical ventilation (MV) is considered to contribute to lung injury. Platelet membrane-derived microparticles (PMPs) are procoagulant and participate in the inflammatory process. The bronchoalveolar space could, besides plasma, be a site of origin of these microparticles. We evaluated the presence of these PMPs and two prostaglandin-derived metabolites in bronchoalveolar lavage fluid (BALF) regarding their possible relation to MV.MATERIALS AND METHODS: Before and after 1 h of MV, PMPs and prostaglandin metabolites were analyzed, in BALF from 14 anesthetized pigs, by flow cytometry and RIA, respectively. Tracheal mucus from five humans was analyzed for PMPs at extubation after surgery.RESULTS: Activated PMPs and prostaglandin metabolites were present in all BALF samples. The time needed to count 5000 cellular events was prolonged six-fold after 1 h of mechanical ventilation (p<0.001). The relative content of PMPs was constant in all samples. The PMPs were thrombogenic, i.e. they were fibrinogen, p-selectin and von Willebrand factor positive. Lavage did not per se affect the period necessary to count 5000 cellular events. PMPs in human tracheal mucus were in the same range as in the pig after 1 h of MV aiming at a PaCO(2) between 5.0 and 5.5 kPa.CONCLUSIONS: Activated PMPs are present in the pulmonary air-liquid interface. The prolongation of the time needed to count 5000 cellular events in BALF after MV indicates activation and adherence. Adherent microparticles bind neutrophils, which may aggravate pathological processes leading to pulmonary dysfunction. Evaluation of PMPs in BALF may be useful in evaluating strategies for lung-protective ventilator treatment.
|
|
| 12. |
- Ramström, Sofia, 1973-, et al.
(författare)
-
Effects of inhibition of P2Y1 and P2Y12 on whole blood clotting, coagulum elasticity and fibrinolysis resistance studied with free oscillation rheometry
- 2003
-
Ingår i: Thrombosis Research. - 0049-3848 .- 1879-2472. ; 109:5-6, s. 315-322
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: In vivo, initial platelet activation is likely caused by platelet contacts with collagen in the subendothelium or from the small amounts of thrombin formed by the tissue factor/factor VIIa complex. Our aim was to study the coagulative role of ADP released by the platelets after activation with strong stimuli such as collagen and/or thrombin, and the relative importance of the platelet ADP receptors P2Y1 and P2Y12.Materials and methods: We used 10 Hz free oscillation rheometry to measure clotting time, clot elasticity and fibrinolysis resistance of non-anticoagulated whole blood. The platelets were activated with a collagen-related peptide (CRP), with the PAR1 thrombin receptor activating peptide TRAP-6 or by thrombin, the latter generated by small amounts of thromboplastin. To inhibit the platelet ADP receptors, we used the P2Y1 antagonist MRS2179 and the P2Y12 antagonist AR-C69931MX.Results: Both antagonists significantly retarded the clotting induced by CRP. The effects were most pronounced with AR-C69931MX. For TRAP-6, the same trend was seen, but the retardation was only significant with AR-C69931MX. Clotting induced by small amounts of thromboplastin was not affected by any ADP-receptor antagonist. Addition of both antagonists did not change the results as compared to samples with AR-C69931MX alone. Nor did the antagonists, one at a time or in concert, effect fibrinolysis or the elastic properties of the clot.Conclusion: We conclude that ADP-receptor inhibition prolongs the clotting time for whole blood activated by CRP, but that it does not affect the properties of the subsequently formed coagulum.
|
|
| 13. |
- Ramström, Sofia, 1973-, et al.
(författare)
-
The role of platelets in blood coagulation : effects of platelet agonists and GPIIb/IIIa inhibitors studied by free oscillation rheometry
- 2002
-
Ingår i: Thrombosis Research. - 0049-3848 .- 1879-2472. ; 105:2, s. 165-172
-
Tidskriftsartikel (refereegranskat)abstract
- We have studied the contribution of platelets to the coagulation of plasma and the effects of activation or inhibition of platelets on the coagulation process in unanticoagulated fresh whole blood (subsequently termed native blood). For this purpose, we have used a free oscillation rheometer (FOR), the ReoRox4, a new instrument that enables noninvasive viscoelastic measurements of clot formation in plasma and whole blood. Platelets appear essential for the initiation of coagulation if no activating surface is present. We prepared platelet-free plasma by quick centrifugation and filtration of native blood, which did not coagulate if stored in plastic containers at 37 °C but clotted if transferred to glass containers. Addition of platelet agonists, such as collagen or the thrombin receptor agonist peptide, SFLLRN, significantly accelerated the clotting of native blood and also changed the rheometer curve appearance, accelerating both onset and completion of clot formation (i.e. fibrin gel formation). Inhibition of platelet glycoprotein (GP) IIb/IIIa with the peptide-derived compound MK-852 or the antibody-derived abciximab (Reopro) prevented clot retraction and prolonged the clotting time with SFLLRN. In collagen-stimulated samples, MK-852 accelerated clotting but delayed completion of clotting while abciximab prolonged both clotting time and completion of clotting. To our knowledge, this is the first report showing that activation of platelets in native whole blood shortens the coagulation time ex vivo. It also describes a new instrument that enables studies of the viscoelastic properties of a forming whole blood clot.
|
|
| 14. |
- Syvänen, Ann-Christine, et al.
(författare)
-
Kininogen in factor VIII-deficient plasma (haemophilia A)
- 1981
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 24:4, s. 275-284
-
Tidskriftsartikel (refereegranskat)abstract
- The HMr and LMr molecular forms of kininogen were found to occur in normal distribution in plasma from a patient with severe haemophilia A. Present findings indicate that lack of Factor VIII does not influence, the normal content and distribution of immunoreactive kininogens determined by single radial immunodiffusion and radioimmunoassay. The partially purified HMr and LMr kininogens were antigenically identical with the kininogens in normal human plasma determined using the monospecific antisera raised in rabbits against purified kininogen antigens. Low kallikrein activity on H-D-Pro-Phe-Arg-pNA in the haemophilic plasma was apparently due to preparative procedures. This concept is supported by the normal binding ratio of trypsin to pure α2-macroglobulin isolated from the haemophilic plasma.
|
|
| 15. |
|
|
| 16. |
- Agnelli, G, et al.
(författare)
-
Safety assessment of new antithrombotic agents : Lessons from the EXTEND study on ximelagatran.
- 2009
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 123:3, s. 488-497
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Ximelagatran, the first oral direct thrombin inhibitor, was shown to be an effective antithrombotic agent but was associated with potential liver toxicity after prolonged administration. OBJECTIVES AND METHODS: The aim of the EXTEND study was to assess safety and efficacy of extended administration (35 days) of ximelagatran or enoxaparin for the prevention of venous thromboembolism after elective hip replacement and hip fracture surgery. A follow-up period, including assessment of liver enzymes (in particular alanine aminotransferase; ALAT), until post-operative day 180 was planned, with visits at days 56 and 180. RESULTS: Randomization and administration of study drugs were stopped following a report of serious liver injury occurring 3 weeks after completion of ximelagatran treatment. At the time of study termination, 1158 patients had been randomized and 641 had completed the 35-day treatment; with 303 ximelagatran and 265 enoxaparin patients remaining in the study through to the day 56 follow-up visit. Overall, 58 patients showed an ALAT increase to >2x upper limit of normal: 31 treated with enoxaparin, 27 with ximelagatran. Three ximelagatran patients also showed symptoms potentially related to liver toxicity. Eleven ximelagatran patients showed an ALAT increase after study treatment ended. The clinical development of ximelagatran was terminated and the drug withdrawn from the market. Evaluation of the relative efficacy of the two treatments as specified in the protocol was impossible due to the premature termination of the study. CONCLUSIONS: Prolonged administration of ximelagatran was associated with an increased risk of liver toxicity. In a substantial proportion of patients, ALAT increase occurred after treatment withdrawal. The findings seen with ximelagatran should be considered when designing studies with new antithrombotic agents.
|
|
| 17. |
|
|
| 18. |
- Alfredsson, Joakim, et al.
(författare)
-
Large early variation of residual platelet reactivity in Acute Coronary Syndrome patients treated with clopidogrel : Results from Assessing Platelet Activity in Coronary Heart Disease (APACHE).
- 2015
-
Ingår i: Thrombosis Research. - : Pergamon Press. - 0049-3848 .- 1879-2472. ; 136:2, s. 335-340
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: There is a large inter-individual variation in response to clopidogrel treatment and previous studies have indicated higher risk of thrombotic events in patients with high residual platelet reactivity (HRPR), but the optimal time-point for testing is not established. The aim of this study was to investigate the optimal time-point for aggregometry testing and the risk of major adverse cardiac events associated with HRPR.METHOD AND RESULTS: We included 125 patients with ACS (73 with STEMI, and 71 received abciximab). The prevalence of HRPR varied substantially over time. The rate of HRPR in patients treated and not treated with abciximab were 43% vs 67% (p=0.01) before, 2% vs 23% (p=0.001) 6-8h after, 8% vs 9% (p=0.749) 3days after, and 23% vs 12% (p=0.138) 7-9 days after loading dose of clopidogrel. We found HRPR in 18% of the patients but only four ischemic events during 6months follow-up, with no significant difference between HRPR patients compared to the rest of the population. There were 3 TIMI major bleedings, all of which occurred in the low residual platelet reactivity (LRPR) group.CONCLUSION: There is a large variation in platelet reactivity over time, also depending on adjunctive therapy, which has a large impact on optimal time-point for assessment. We found HRPR in almost 1 in 5 patients, but very few MACE, and not significantly higher in HRPR patients. In a contemporary ACS population, with low risk for stent thrombosis, the predictive value of HRPR for ischemic events will probably be low.
|
|
| 19. |
- Alhadad, Alaa, et al.
(författare)
-
The value of tomographic ventilation/perfusion scintigraphy (V/PSPECT) for follow-up and prediction of recurrence in pulmonary embolism.
- 2012
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 1879-2472 .- 0049-3848.
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Pulmonary embolism (PE) is diagnosed with imaging techniques such as ventilation/perfusion (V/P) lung scintigraphy or multidetector computed tomography of the pulmonary arteries (MDCT). Lung scintigraphy can be performed with planar (V/P PLANAR) and tomographic (V/P SPECT) techniques. V/P SPECT has higher sensitivity and specificity than V/P PLANAR. As nephrotoxic contrast media are not used during V/P SPECT, examinations can be repeated for evaluation of resolution of perfusion defects after PE. However, the value of residual perfusion defects identified using V/P SPECT for the prediction of recurrent PE has not been thoroughly evaluated. MATERIAL AND METHODS: We evaluated resolution and recurrence of PE in 227patients (mean age 63±17years, 134[59%] women) with PE undergoing ≥2 SPECT examinations in 2005-2007. PE was defined as minor (<20% perfusion defect on SPECT, n=86), medium (20-50% perfusion defect on SPECT, n=99), or major (>50% perfusion defect on SPECT, n=42). RESULTS: At second V/P SPECT examination, complete resolution of perfusion defects had occurred in 45 (52%) patients with minor PE after 8.2±7.4months, in 29 (29%) of patients with medium PE after 6.2±5.9months, and in 2(5%) of patients with major PE after 6.5±0.7months. During 47±24months of follow up, 37(16 %) patients suffered recurrent PE. Of these 37, 34 (92%) showed residual perfusion defects at the second V/P SPECT examination. Recurrence of PE was also predicted by advanced age and female gender. However, in multivariate regression analysis, recurrence was only predicted by age (p=0.0013) and residual perfusion defect on V/P SPECT (p=0.0039). CONCLUSION: In conclusion, complete resolution of PE was common in patients with minor PE, whereas residual perfusion defects were widespread in patients with medium and major PE. PE patients identified with persistent perfusion defects at follow-up SPECT have a high risk of PE recurrence.
|
|
| 20. |
- Alström, Ulrica, et al.
(författare)
-
Platelet inhibition assessed with VerifyNow, flow cytometry and PlateletMapping in patients undergoing heart surgery
- 2009
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 124:5, s. 572-577
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: A substantial number of patients with coronary artery disease undergo cardiac surgery within five days of discontinuing anti-platelet treatment with aspirin and clopidogrel. The aims of this study were to describe the degree of platelet inhibition in patients with dual anti-platelet treatment scheduled for coronary artery bypass graft (CABG) surgery and to investigate whether the measured platelet inhibition correlated to intra- and postoperative risk for bleeding and transfusion requirements. MATERIAL AND METHODS: Sixty patients were included. Platelet inhibition was analysed with flow cytometry including phosphorylation status of the vasodilator-stimulated phosphoprotein (VASP-assay) and two bed-side analyzers, VerifyNow-System and PlateletMapping, a modified thrombelastograph. All 60 patients were analysed with VerifyNow and PlateletMapping, and 48 were analysed with flow cytometry and VASP-assay. RESULTS: There was a correlation between the ADP-receptor inhibition as measured by VASP-assay and VerifyNowP2Y(12) (r = -0.29, p<0.05), and between VASP-assay and the expression of P-selectin (r = 0.29, p<0.05) as measured by flow cytometry when platelets were stimulated with 5 microM ADP. VerifyNowP2Y(12) was the only measurement of platelet inhibition correlated to total blood loss (Spearman r = 0.29, p=0.03) and red blood cell transfusion (Spearman r = 0.43, p<0.01) requirements, although this might be confounded by aprotinin treatment. CONCLUSION: We found a modest agreement between the methods for preoperative platelet inhibition, though not for PlateletMapping-MA(ADP). There was a correlation between preoperative platelet inhibition measured by VerifyNowP2Y(12) and surgical blood loss or transfusion requirements. However, for the individual patient, preoperative use of VerifyNowP2Y(12) as an instrument to decide bleeding and transfusion risk does not seem helpful.
|
|
| 21. |
- Alström, Ulrica, et al.
(författare)
-
The platelet inhibiting effect of a clopidogrel bolus dose in patients on long-term acetylsalicylic acid treatment
- 2007
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 120:3, s. 353-359
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Addition of clopidogrel to patients treated with ASA has been shown to decrease the incidence of in-stent thrombosis after percutaneous coronary interventions. However, it has also been reported that up to 30% of patients do not achieve adequate platelet inhibition from standard dosages of ASA and clopidogrel. There is a demand for reliable methods to measure the individual platelet inhibiting effect of this combination therapy. MATERIALS AND METHODS: The primary aim of the present investigation was to compare three methods for evaluation of the platelet inhibiting effect of a clopidogrel bolus dose in patients on long-term acetylsalicylic acid treatment. Thirty patients presenting for coronary angiography/PCI were included. Two patients were excluded due to technical problems. All patients were on 75-100 mg ASA/day for at least 8 days. Blood samples were analysed before and 16 h after a 300 mg clopidogrel bolus dose. The platelet inhibiting effect was measured with (1) Whole blood flow cytometry (17 patients); (2) a bed-side test, Platelet Mapping assay for the thrombelastograph (28 patients); and (3) PFA (Platelet function analyser) -100 (26 patients). RESULTS: With flow cytometry, the percentage of platelets expressing P-selectin (p=0.03) on their surface decreased significantly after the bolus dose of clopidogrel. There was also a reduction of platelets binding fibrinogen when stimulated with ADP. A significantly (p=0.002) increased platelet inhibition could also be demonstrated with Platelet Mapping. PFA-100 could not measure any significant platelet inhibiting effect of clopidogrel. CONCLUSION: A significant platelet inhibition could be demonstrated with flow cytometry and the Platelet Mapping assay, but not with PFA-100. However, levels of response for the individual patient with these three methods were inconsistent. Further studies are needed to evaluate how the results correlate to the clinical risk of thrombosis and bleeding.
|
|
| 22. |
- Amisten, Stefan, et al.
(författare)
-
Gene expression profiling for the identification of G-protein coupled receptors in human platelets
- 2008
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 122:1, s. 47-57
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION AND MATERIALS AND METHODS: G-protein coupled receptors (GPCRs) play an important role in platelet aggregation. To identify new platelet GPCRs, a platelet gene expression profile was generated and validated using quantitative real-time PCR. RESULTS: In total, mRNA of 28 GPCR genes was detected in human platelets. The 12 most abundant platelet GPCR transcripts were: thrombin receptor PAR1 (1865+/-178%), ADP receptor P2Y(12) (459+/-88%), succinate receptor 1 (257+/-48%), ADP receptor P2Y(1) (100%), orphan P2RY(10) (68.2+/-3.3%), lysophosphatidic acid receptors GPR23 (48.2+/-11%) and GPR92 (26.1+/-3.3%), adrenergic receptor alpha(2A) (18.4+/-4.4%), orphan EBI2 (6.31+/-0.42), adenosine receptors A(2A) (2.94+/-0.24%) and A(2B) (2.88+/-0.16%) and lysophosphatidic acid receptor LPA(1) (2.59+/-0.39%) (% relative to the chosen calibrator P2Y(1)). A surprising G-protein coupled receptor redundancy was found: two ADP receptors (P2Y(1) and P2Y(12)), three adenosine receptors (A(2A), A(2B), and A(1)), four lysophosphatidic acid receptors (LPA(1), LPA(3), GPR23 and GPR92), two l-glutamate receptors (mGlu(3) and mGlu(4)) and two serotonin receptors (5-HT(1F) and 5-HT(4)). The adenosine receptor A(2B) gene expression was validated with protein expression and functional studies. Western blot confirmed A(2B) receptor protein expression and platelet flow cytometry demonstrated inhibition of the effect of NECA by the adenosine A(2B)-antagonist MRS1754. CONCLUSIONS: We have detected several GPCRs not previously known to be expressed in platelets, including a functional adenosine A(2B) receptor. The findings could improve our understanding of platelet aggregation and provide new targets for drug development.
|
|
| 23. |
- Andersson, Jonas, et al.
(författare)
-
Markers of fibrinolysis as predictors for maintenance of sinus rhythm after electrical cardioversion
- 2011
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 127:3, s. 189-192
-
Tidskriftsartikel (refereegranskat)abstract
- No fibrinolytic component alone was found to be a predictor of recurrence of atrial fibrillation. In multivariate models lower PAI-1 mass was associated with sinus rhythm even after adjusting for CRP, markers of the metabolic syndrome and treatment with atorvastatin. Our findings suggest a patophysiological link between AF and PAI-1 mass but the relation to inflammation remains unclear.
|
|
| 24. |
- Andersson, Jonas, et al.
(författare)
-
NT-proBNP predicts maintenance of sinus rhythm after electrical cardioversion.
- 2015
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 135:2, s. 289-291
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia. NT-proBNP is a fragment of the prohormone brain natriuretic peptide. Previous studies indicate that increased levels of NT-proBNP are associated with higher recurrence rates of AF after electrical cardioversion. Our null hypothesis was that NT-proBNP does not predict recurrence of AF after restoration of sinus rhythm.METHODS: We performed a hypothesis generating study within a double-blinded, placebo-controlled, randomized, prospective multicentre study of the effects of atorvastatin on recurrence of AF after electrical cardioversion. 199 patients with persistent AF and an indication for cardioversion were included in the present substudy. NT-proBNP was assessed prior to cardioversion. Cardioversion was performed according to local standard clinical practice on an elective outpatient basis. Patients were followed-up one month after cardioversion.RESULTS: 181 patients had a successful cardioversion and 91 of the study group remained in sinus rhythm at day 30. Recurrence of AF was observed in 108 patients at day 30. An optimal cutpoint for NT-proBNP at 500 ng/L predicted recurrence of AF after cardioversion (OR 2.94; 95% CI 1.30-6.63). In multivariate analysis adjusting for age, sex, hypertension, and treatment group strengthened the results (OR 3,56; 95% CI 1,44-8,81). When analysing the ROC curve of NT-proBNP in baseline and atrial fibrillation at day 30 the result was 0.57.CONCLUSION: NT-proBNP levels are a predictor of recurrence of AF 30 days after cardioversion. ROC curves indicates that the practical value of NT-proBNP for the individual patient is limited.
|
|
| 25. |
- Andersson Shams Hakimi, Caroline, et al.
(författare)
-
Effects of fibrinogen and platelet supplementation on clot formation and platelet aggregation in blood samples from cardiac surgery patients.
- 2014
-
Ingår i: Thrombosis research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 134:4, s. 895-900
-
Tidskriftsartikel (refereegranskat)abstract
- Bleeding after cardiac surgery may be caused by surgical factors, impaired haemostasis, or a combination of both. Transfusion of blood products is used to improve haemostasis, but little is known about what combination is optimal. We hypothesized that addition of both fibrinogen and platelets to blood samples from cardiac surgery patients would improve clot formation and platelet aggregation to a greater extent than if the components were added separately.
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
- Astermark, Jan
(författare)
-
Immune tolerance induction in patients with hemophilia A
- 2011
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 127, s. 6-9
-
Tidskriftsartikel (refereegranskat)abstract
- Replacement therapy with factor VIII (FVIII) concentrates has become the mainstay of treatment for hemophilia, but about 30% of patients with a severe disease develop neutralizing antibodies against FVIII, which can lead to treatment resistance and an increased risk of bleeding. Immune tolerance induction (ITI) overcomes the immune response to FVIII concentrates in the majority of patients. Several factors may influence the efficacy of ITI, including disease-related factors (e. g. peak inhibitor titer and pre-ITI titer), and genetic factors (e. g. type of mutation). Treatment-related factors, such as the type of FVIII concentrate used in ITI will also potentially influence the outcome. Specifically, higher success rates with von Willebrand factor (VWF)-containing factor VIII concentrates than with high-purity FVIII concentrates have been reported, but further studies are needed. Potential mechanisms involved include steric hindrance, inhibition of FVIII degradation, or immunomodulatory effects. However, the exact mechanism by which immune tolerance is induced remains unclear. High-dose FVIII ITI appears to induce immune tolerance more rapidly than low-dose protocols and with a reduced risk of bleeding episodes. The addition of immunosuppressive therapy, such as rituximab, to ITI may improve outcomes, although the optimal approach to combined ITI/immunosuppression has not been established. Ongoing studies are likely to provide further insight into the role of genetic features and the type of FVIII concentrate on the success rate of ITI. (C) 2010 Elsevier Ltd. All rights reserved.
|
|
| 29. |
|
|
| 30. |
|
|
| 31. |
- Bergen, Karin, et al.
(författare)
-
High levels of endothelial and platelet microvesicles in patients with type 1 diabetes irrespective of microvascular complications
- 2020
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 196, s. 78-86
-
Tidskriftsartikel (refereegranskat)abstract
- IntroductionPatients with type 1 diabetes have high risk of developing microvascular complications, and microangiopathy contributes to premature cardiovascular disease in this population. The role that microvesicles (MVs) may play in the development of microangiopathy in type 1 diabetes remains unclear.Materials and methodsPlasma levels of endothelial MVs (EMVs) and platelet MVs (PMVs) in 130 patients with type 1 diabetes without microangiopathy, 106 patients with microangiopathy and 100 matched healthy controls were analyzed using flow cytometry. MV expression of procoagulant phosphatidylserine (PS) and proinflammatory high mobility group box-1 protein (HMGB1) was also assessed.ResultsPatients with type 1 diabetes had markedly elevated levels of EMVs and PS+ EMVs as well as PMVs and PS+ PMVs compared to healthy controls (p < .001 for all). Furthermore, HMGB1+ EMVs and HMGB1+ PMVs were significantly increased in patients (p < .001 for all). After adjusting for potential confounders, there were no clear differences between patients with or without microvascular complications for any of the MV parameters.ConclusionType 1 diabetes is a prothrombotic and proinflammatory disease state that, regardless of the presence of clinical microangiopathy, is associated with elevated levels of plasma MVs, in particular those of an endothelial origin. We have for the first time demonstrated that patients with type 1 diabetes have higher levels of HMGB1+ MVs. HMGB1 is an alarmin with potent proinflammatory effects that drive endothelial dysfunction, and it would therefore be of interest to further study the role of HMGB1+ MVs in the development of macrovascular complications in type 1 diabetes.
|
|
| 32. |
|
|
| 33. |
- Bergendal, Annica, et al.
(författare)
-
Risk factors for venous thromboembolism in pre- and postmenopausal women
- 2012
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 130:4, s. 596-601
-
Tidskriftsartikel (refereegranskat)abstract
- IntroductionHemostasis in women is affected by changes of estrogen levels. The role of endogenous estrogens on risk of venous thromboembolism (VTE) remains unclear. The aim of this study was to investigate the importance of acquired and genetic risk factors for VTE in pre-and postmenopausal women.MethodIn a nationwide case–control study we included as cases 1470 women, 18 to 64 years of age with a first time VTE. The 1590 controls were randomly selected and matched by age to the cases. Information on risk factors was obtained by interviews and DNA-analyses. We used unconditional logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs).ResultsThe ORs were generally of similar magnitude in pre- and postmenopausal women. The highest risk was for the combination of surgery and cast (adjusted OR 54.12, 95% CI 16.62-176.19) in postmenopausal women. The adjusted OR for use of menopausal hormone therapy was 3.73 (95% CI 1.86-7.50) in premenopausal and 2.22 (95% CI 1.54-3.19) in postmenopausal women. Overweight was linked to an increased risk and exercise to a decreased risk, regardless of menopausal status.ConclusionMenopausal status had only minor influence on the risk levels. Acquired transient risk factors conveyed the highest risks for VTE.
|
|
| 34. |
|
|
| 35. |
|
|
| 36. |
- Berntorp, Erik
(författare)
-
Erik von Willebrand.
- 2007
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 120, s. 3-4
-
Tidskriftsartikel (refereegranskat)
|
|
| 37. |
- Berntorp, Erik, et al.
(författare)
-
The von Willebrand Disease Prophylaxis Network (vWD PN): Exploring a treatment concept.
- 2006
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 18, s. 19-22
-
Tidskriftsartikel (refereegranskat)abstract
- The von Willebrand Disease Prophylactic Network (vWD PN) has been initiated to study the natural history of vWD bleeding, and to prospectively study the role of von Willebrand Factor (vWF) concentrate prophylaxis in vWD. Patients with all types of vWD in need of treatment with vWF concentrate will be enrolled into the study. Quality of life will be measured and safety and efficacy will be monitored at pre-determined intervals. Between February 2005 and July 18, 2005, 62 investigators from Europe and North America were participating in the vWD PN, and 61 have submitted census data. A total 5343 patients have been identified for enrolment, and of these, 991 patients were treated with plasma-derived products in the preceding 12 months, and 99 patients have received prophylaxis, predominantly for joint-related bleeds. The vWD PN aims to further elucidate the role of vWF concentrate prophylaxis in vWD and to identify patients most Likely to benefit from prophylaxis.
|
|
| 38. |
|
|
| 39. |
- Bhiladvala, Pallonji, et al.
(författare)
-
Early identification of acute myocardial infarction by activated protein C-protein C inhibitor complex.
- 2006
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 118:Aug 10, s. 213-219
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Increased coagulation activity due to coronary thrombosis in a ruptured plaque should result in activation of the protein C anticoagulant system with formation of complexes between activated protein C (APC) and,the protein C inhibitor (PCI), which reflects coagulation activity. We hypothesized that elevated APC-PCI concentration might allow earlier detection of ongoing myocardial infarction than traditional biochemical markers. We have evaluated a newly devised immunofluorimetric assay for measuring plasma concentration of APC-PCI complexes among patients with suspected acute coronary syndrome. Materials and methods: Blood samples were taken from 340 patients (median 71 years, range 31-97) with suspected acute coronary syndrome at first presentation in the emergency department. Electrocardiogram was recorded and APC PCI, Troponin I and Creatine kinase-MB concentrations were repeatedly measured 3 times at 6 h interval. Results: The 74 patients who were eventually diagnosed with myocardial infarction had a higher median level of APC-PCI complex than those Without myocardial damage; 0.27 vs. 0.20 mu g/L (p = 0.001). In a multivariate regression model, APC-PCI level in the fourth quartile (> 0.32 mu g/L) independently predicted myocardial infarction with an odds ratio of 3.7 (95% CI 1.4-9.6, p < 0.01). Conclusion: Early APC-PCI elevation can be detected among patients with a normal first Troponin I and non-ST-elevation myocardial infarction and provides additional risk assessment in acute coronary syndrome. (c) 2005 Published by Elsevier Ltd.
|
|
| 40. |
|
|
| 41. |
- Björck, Fredrik, et al.
(författare)
-
Warfarin persistence among stroke patients with atrial fibrillation
- 2015
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 136:4, s. 744-748
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Warfarin treatment discontinuation is significant among patients with atrial fibrillation (AF). For AF patients with stroke a warfarin persistence rate of 0.45 after 2 years has previously been reported. No consistent predictors for discontinuation have been established. Aims: Evaluation of warfarin persistence and variables associated with discontinuation, in a large Swedish cohort with unselected stroke/TIA patients with AF treated with warfarin. Materials and methods: 4 583 patients with stroke/TIA and AF in the Swedish National Patient Register (NPR), from 1. Jan 2006 to 31. Dec 2011, were matched with the Swedish national quality register AuriculA. They were followed until treatment cessation, death or end of study. Baseline characteristics and CHA(2)DS(2)VASc score were retrieved from NPR. Treatment-time was retrieved from AuriculA. Results: Overall proportion of warfarin persistence was 0.78 (95% confidence interval (CI) 0.76 to 0.80) after one year, 0.69 (95% CI 0.67 to 0.71) after 2 years and 0.47 (95% CI 0.43 to 0.51) after 5 years. Variables clearly associated with higher discontinuation were dementia (hazard ratio (HR) 2.22, CI 1.51-3.27) and alcohol abuse (HR 1.66, CI 1.19-2.33). Chronic obstructive pulmonary disease (COPD), cancer and chronic heart failure (CHF) were each associated with over 20% increased risk of treatment discontinuation. Higher CHA(2)DS(2)VASc score and start-age lead to lower persistence (p < 0.001). Conclusions: Persistence to warfarin in unselected stroke/TIA patients with AF is in Sweden greater than previously reported. Lower persistence is found among patients with high treatment start-age, incidence of dementia, alcohol abuse, cancer, CHF, COPD and/or high CHA(2)DS(2)VASc score.
|
|
| 42. |
- Björck, Fredrik, et al.
(författare)
-
Warfarin treatment quality is consistently high in both anticoagulation clinics and primary care setting in Sweden
- 2015
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 136:2, s. 216-220
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Warfarin treatment in Sweden holds a high standard with time in therapeutic range (TTR) over 75%. Internationally, specialized anticoagulation clinics (ACC) have shown higher TTR compared to primary health care centres (PHCC). Objectives: To compare warfarin treatment quality in Sweden for ACC versus PHCC, thereby clarifying whether centralization is for the better. Patients/methods: In total 77.058 patients corresponding to 217.058 treatment years with warfarin in the Swedish national quality register AuriculA from 1. Jan 2006 to 31. Dec 2011. Information regarding TTR was calculated from AuriculA, while patient characteristics and complications were retrieved from the Swedish National Patient Register. Results: Of the 100.554 treatment periods examined, 78.7% were monitored at ACC. Mean TTR for INR 2-3 for all patients irrespective of intended target range was 76.5% with an annual risk of bleeding or thrombotic events of 2.24% and 2.66%, respectively. TTR was significantly higher in PHCC compared to ACC (79.6% vs. 75.7%, p < 0.001), with no significant difference in overall risk of complications. Treatment periods for atrial fibrillation, except intended direct current conversion, showed similar results between ACC and PHCC without significant difference in annual risk of bleeding (2.50% vs. 2.51%) or thrombosis (3.09% vs. 3.16%). After propensity score matching there was still no significant difference in complication risk found. Conclusions: Warfarin treatment quality is consistently high in both ACC and PHCC when monitored through AuriculA in Sweden, both measured as TTR and as risk of complications. In this setting, centralized warfarin monitoring is not likely to improve the results.
|
|
| 43. |
- Björkman, Jan-Arne, et al.
(författare)
-
Release of tissue-type plasminogen activator (t-PA) in the splanchnic circulation of the anaesthetised pig during high sympathetic tone.
- 2010
-
Ingår i: Thrombosis research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 125:3
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is a substantial local release of tissue-type plasminogen activator (t-PA) in the splanchnic vascular bed, and this release is increased at high sympathetic tone. Coronary t-PA release is also significant, and this release increases during cardiac nerve stimulation and during reperfusion after 10 min of local myocardial ischemia. However, by repeated cycles of myocardial ischemia/reperfusion coronary t-PA release progressively declines. OBJECTIVES: Accordingly, we hypothesised that splanchnic t-PA release might decrease after an initial peak during maintained and long-lasting sympathetic stimulation. METHODS: In 6 anaesthetised pigs sympathetic tone was augmented by bleeding (20-25 mL/kg over 30 minutes). During the subsequent 2 hours period portal vein (draining the splanchnic vascular bed) - and arterial blood samples were drawn every 20 min and portal vein blood flow was recorded continuously in order to estimate t-PA release in the splanchnic vascular bed. RESULTS: Relatively stable haemodynamic conditions were obtained after bleeding with mean arterial blood pressure at 50 to 65 mmHg and a portal vein flow at about the 50% of baseline value. Net splanchnic t-PA release rose to a peak 40 min after bleeding, but subsequently declined towards baseline values. Arterial t-PA activity rose after the bleeding period and to a peak value at end of the observation period. CONCLUSIONS: Net splanchnic t-PA release increased only transiently during the period with increased sympathetic stimulation, whereas the arterial t-PA level remained elevated. During a strong and longlasting sympathetic stimulation the lack of a continuously augmented splanchnic t-PA release might increase the risk for intravenous splanchnic thrombosis.
|
|
| 44. |
- Boknäs, Niklas, et al.
(författare)
-
Associations between hemostatic markers and mortality in COVID-19-Compounding effects of D-dimer, antithrombin and PAP complex
- 2022
-
Ingår i: Thrombosis Research. - : Pergamon-Elsevier Science Ltd. - 0049-3848 .- 1879-2472. ; 213, s. 97-104
-
Tidskriftsartikel (refereegranskat)abstract
- In this single-center cohort study, we applied a panel of laboratory markers to characterize hemostatic function in 217 consecutive patients that underwent testing for COVID-19 as they were admitted to Linkoping ¨ University Hospital between April and June 2020. In the 96 patients that tested positive for SARS-CoV-2 (COVID-19+), the cumulative incidences of death and venous thromboembolism were 24.0% and 19.8% as compared to 12.4% (p = 0.031) and 11.6% (p = 0.13) in the 121 patients that tested negative (COVID-19− ). In COVID-19+ patients, we found pronounced increases in plasma levels of von Willebrand factor (vWF) and fibrinogen. Excess mortality was observed in COVID-19+ patients with the following aberrations in hemostatic markers: high D-dimer, low antithrombin or low plasmin-antiplasmin complex (PAP) formation, with Odds Ratios (OR) for death of 4.7 (95% confidence interval (CI95) 1.7–12.9; p = 0.003) for D-dimer >0.5 mg/L, 5.9 (CI95 1.8–19.7; p = 0.004) for antithrombin (AT) ˂0.85 kIU/l and 4.9 (CI95 1.3–18.3; p = 0.019) for PAP < 1000 μg/L. Compounding increases in mortality was observed in COVID-19+ patients with combined defects in markers of fibrinolysis and coagulation, with ORs for death of 15.7 (CI95 4.3–57; p < 0.001) for patients with PAP <1000 μg/L and D-dimer >0.5 mg/L and 15.5 (CI95 2.8–87, p = 0.002) for patients with PAP <1000 μg/L and AT ˂0.85 kIU/L. We observed an elevated fraction of incompletely degraded D-dimer fragments in COVID-19+ patients with low PAP, indicating impaired fibrinolytic breakdown of cross-linked fibrin.
|
|
| 45. |
- Boman, Kurt, et al.
(författare)
-
Effects of carvedilol or metoprolol on PAI-1, tPA-mass concentration or Von Willebrand factor in chronic heart failure--a COMET substudy.
- 2010
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 125:2, s. e46-50
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: In COMET (Carvedilol or Metoprolol European Trial), carvedilol reduced mortality compared with metoprolol in patients with chronic heart failure. We hypothesized that carvedilol might have greater effects on endothelial derived haemostatic factors than metoprolol. We aimed to study the effects of carvedilol or metoprolol on tissue plasminogen activator (tPA), its inhibitor PAI-1 and Von Willebrand factor (VWF) in patients with heart failure. MATERIAL AND METHODS: We recruited 260 patients (134 on carvedilol, 126 on metoprolol), mean age 66 years and 84% of them men. Plasma mass concentrations of tPA and PAI-1and percent of VWF were measured at baseline and after one and two years of treatment. RESULTS: Plasma tPA, PAI-1 and VWF were similar between treatment groups at baseline and no significant differences between groups emerged after one or two years of treatment. In paired analyses in patients assigned to carvedilol, median PAI-1 level decreased from 37.2 to 32.1 microg/l at two years (p=0.034) and of VWF decreased from baseline to one year (240 vs. 218%, p=0.023) in patients assigned to carvedilol but were not reduced at any time in patients assigned to metoprolol. Plasma tPA increased over time in both treatment groups (p=0.013 and 0.027 respectively). CONCLUSION: We found no significant difference in the effects of carvedilol or metoprolol on tPA, PAI-1 and VWF. Comparison over time within treatment groups suggested that PAI-1 and VWF might have declined on carvedilol but not on metoprolol. Our hypothesis is not proved but this may reflect an inadequate sample size rather than lack of an effect.
|
|
| 46. |
- Braun, Oscar, et al.
(författare)
-
Concomitant use of warfarin and ticagrelor as an alternative to triple antithrombotic therapy after an acute coronary syndrome.
- 2015
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 135:1, s. 26-30
-
Tidskriftsartikel (refereegranskat)abstract
- Treatment with warfarin in combination with clopidogrel has been shown to reduce the incidence of major bleeding as compared to triple antithrombotic therapy (TT; warfarin, clopidogrel and aspirin). However, there are uncertainties regarding the risk for thrombosis since poor-responsiveness to clopidogrel is common. Ticagrelor is a more potent platelet inhibitor, but data supporting concurrent use of ticagrelor and warfarin (dual antithrombotic therapy, DT) is limited. This study therefore sought to evaluate the risk of bleeding and thrombosis associated with DT after an acute coronary syndrome (ACS).
|
|
| 47. |
|
|
| 48. |
|
|
| 49. |
- Bremme, K., et al.
(författare)
-
The APC-PCI concentration as an early marker of activation of blood coagulation A study of women on combined oral contraceptives
- 2012
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 130:4, s. 636-639
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The risk of venous tromboembolism (VTE) in women taking combined oral contraceptives (COCs) is attributed to changes in coagulation and fibrinolysis. The impact of the COCs may be greater in women with preexisting thrombophilic defects. Nevertheless most women who suffer from venous thrombosis do not have any of the well known hereditary or acquired risk factors. A simple and sensitive marker of "thrombogenicity" has not been identified. Objectives: To investigate the effects of two different monophasic combined oral contraceptives (COCs) on the plasma concentrations of activated protein C-inhibitor of protein C (APC-PCI) and on comparable hemostatic factors in fertile women. Method: Forty four healthy nulliparous women with regular menstrual periods were included and randomly assigned to start with a monophasic preparation containing 30 mu g ethinylestradiol and 150 mu g levonogestrel (LNG/EE) or a preparation containing 30 mu g ethinylestradiol and 150 mu g desogestrel (DG/EE). After a wash out period of two months, treatment with the alternate preparation was initiated and continued for two more cycles. Results: The plasma concentration of the APC-PCI complex and thrombin-antithrombin complex (TAT) increased during treatment with the two COCs. During DG/EE treatment the APC-PCI complex increased significantly more than during LNG/EE (p < 0,01). The plasma concentration of D-dimer did not increase during OC treatment. Conclusion: The APC-PCI complex concentration, which serves as a marker for thrombin generation and indicates hypercoagulability, was increased during COC treatment compared to baseline. The method is a sufficiently sensitive marker to detect even small differences in the activation of coagulation. c (c) 2011 Elsevier Ltd. All rights reserved.
|
|
| 50. |
- Bruzelius, Maria, et al.
(författare)
-
Influence of coronary artery disease-associated genetic variants on risk of venous thromboembolism
- 2014
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 134:2, s. 426-432
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: We investigated whether genetic variations robustly associated with coronary artery disease are also associated with risk of venous thromboembolism in a well-defined, female case-control study (n = 2753) from Sweden. Materials and Methods: 39 single nucleotide polymorphisms in 32 loci associated with coronary artery disease in genome-wide association studies were identified in a literature search and genotyped in the ThromboEmbolism Hormone Study (TEHS). Association with venous thromboembolism was assessed by logistic regression. Results: Only rs579459 in the ABO locus demonstrated a significant association with VTE. A tentative association between ANRIL and VTE in the discovery analysis failed to replicate in a meta-analysis of 4 independent cohorts (total n = 7181). Conclusions: It appears that only the ABO locus is a shared risk factor for coronary artery disease and VTE.
|
|
