| 1. |
- Agewall, S, et al.
(author)
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Association between AMPD1 gene polymorphism and coagulation factors in patients with coronary heart disease
- 2006
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In: Pathophysiology of haemostasis and thrombosis. - : S. Karger AG. - 1424-8832 .- 1424-8840. ; 35:6, s. 440-444
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Journal article (peer-reviewed)abstract
- The aim of this study was to investigate whether the C34T and G468T variations in the adenosine monophosphate deaminase-1 (AMPD1) gene were associated with intima-media thickness of the carotid and brachial artery, endothelial function of the brachial artery, glucose metabolism, haemostatic variables and cardiac hypertrophy in patients (n = 109) with coronary heart disease. The plasminogen activator inhibitor-1 activity and the von Willebrand factor were higher in the CC homozygote group compared to the CT/TT group (p < 0.05). There were no differences between the groups regarding intima-media complex of the carotid and brachial artery, presence of plaque in the carotid region, flow-mediated dilatation, ejection fraction or dimensions of the heart. In conclusion, there were no differences between the mutant AMPD1 allele carriers and CC homozygotes regarding surrogate values for atherosclerosis, endothelial function, dimensions and ejection fraction of the heart, glucose tolerance and other well-known cardiovascular risk factors, whereas plasminogen activator inhibitor-1 activity and von Willebrand levels were lower in the mutant AMPD1 allele carriers.
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| 2. |
- Bergqvist, David, et al.
(author)
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Cost-Effectiveness of Prolonged Out-of-Hospital Prophylaxis with Low-Molecular-Weight Heparin following Total Hip Replacement
- 2000
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In: Pathophysiology of haemostasis and thrombosis. - : S. Karger AG. - 1424-8840 .- 1424-8832. - 9783805571777 - 3805571771 ; 30:2, s. 130-135
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Journal article (peer-reviewed)abstract
- Several studies have demonstrated that prolongation of thromboprophylaxis after elective hip replacement significantly reduces the frequency of venographically demonstrated deep vein thrombosis. This paper reports an economic evaluation of prolonged prophylaxis with low-molecular-weight heparin (LMWH), based on outcome data from one of these trials. Analysis showed a net saving per patient of 3,400 Swedish kronor. Consequently, if the costs of administering the LMWH – which includes the cost of teaching the patient to self-administer whilst in hospital and the cost of a follow-up visit by a district nurse to ensure compliance – are below this amount, the intervention will prove to be cost saving.
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| 3. |
- Buller, H, et al.
(author)
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General discussion
- 2005
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In: Pathophysiology of haemostasis and thrombosis. - : S. Karger AG. - 1424-8832 .- 1424-8840. ; 3434 Suppl 1, s. 31-34
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Journal article (peer-reviewed)
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| 4. |
- Dahl, O. E., et al.
(author)
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Assessment of bleeding after concomitant administration of antiplatelet and anticoagulant agents in lower limb arthroplasty
- 2006
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In: Pathophysiol Haemost Thromb. - : S. Karger AG. - 1424-8832. ; 35:6, s. 428-34
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Journal article (peer-reviewed)abstract
- In an analysis of the Melagatran Thrombosis Prophylaxis in Orthopedic Surgery (METHRO) III study, we evaluated whether concomitant administration of aspirin (ASA) and non-steroidal anti-inflammatory drugs (NSAIDs) with the direct thrombin inhibitor melagatran/ximelagatran or the low-molecular-weight heparin enoxaparin increased bleeding in patients undergoing major joint surgery. Further objectives were to compare the influence of the timing of initial postoperative administration of melagatran/ximelagatran on bleeding in orthopedic patients receiving ASA/NSAIDs and in comparison with the preoperative administration of enoxaparin. ASA or NSAIDs in conjunction with melagatran/ximelagatran or enoxaparin did not increase bleeding. Bleeding rates were not significantly different, irrespective of the timing of the initial postoperative dose of melagatran/ximelagatran (4-8 vs. 4-12 h) when compared with preoperative (12 h) administration of enoxaparin. Transfusion rates were significantly lower with administration of melagatran/ximelagatran compared with enoxaparin.
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| 5. |
- Holst, Jan, et al.
(author)
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Does glycosylation influence the experimental antithrombotic effect of a two-domain tissue factor pathway inhibitor?
- 1996
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In: Pathophysiology of Haemostasis and Thrombosis. - : S. Karger AG. - 1424-8832 .- 1424-8840. ; 26:1, s. 23-30
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Journal article (peer-reviewed)abstract
- We have earlier shown that both full-length and truncated glycosylated tissue factor pathway inhibitor (TFPI) lacking the third Kunitz domain and the c-terminal region has an antithrombotic effect comparable to low-molecular-weight heparin (LMWH) in an experimental venous thrombosis model. The aim of this study was to investigate whether a recombinant truncated non-glycosylated TFPI (117QTFPI1-161) had an antithrombotic effect similar to the glycosylated TFPI1-161 and LMWH. We also followed the coagulation parameters. The thrombi were induced in rabbit jugular veins with a combination of endothelium destruction and restricted blood flow. Group 1: placebo; group 2: LMWH 60 anti-Xa IU/kg, i.v.; groups 3 and 4: TFPI1-161 0.8 and 0.2 mg/kg, i.v. respectively; groups 5 and 6: 0.8 and 0.2 mg/kg 117QTFPI1-161, i.v. respectively, in a randomized double-dummy fashion. Twelve animals were included in the placebo group and 6 in each of the other groups. The frequency of thrombosis and also of occlusive thrombosis was reduced in all groups compared to placebo. The thrombus weight was reduced (0-9.9 mg) in all groups, significantly in groups 2, 4 and 5 (p = 0.004-0.02) compared to placebo (21.1 mg). In group 3, a borderline p value was achieved (0.06 likely a β-error). The two forms of TFPI1-161 given in the higher doses showed a significantly greater increase of anti-Xa activity, but with a shorter duration compared to LMWH (1.7-1.9 vs. 0.9 anti-Xa IU/ml). Activated partial thromboplastin time (aPTT)-analysis revealed that only LMWH (52 s) caused a significant transient elevation 2 min after injection. In the other groups, a temporary but insignificant elevation of aPTT (27-37 s) was seen. No detectable effect on anti-Xa activity and prothrombin time (PT) was seen in any TFPI group. The glycosylation of the second domain on TFPI does not substantially contribute to the antithrombotic effect of TFPI. Regardless of the glycosylation of TFPl1-161, it has a dose-dependent effect on anti-Xa, a small effect on the aPTT, but no effect on anti-Xa and PT. LMWH has a more pronounced and sustained impact on these parameters.
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| 6. |
- Jackson, Craig M, et al.
(author)
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A critical evaluation of the prothrombin time for monitoring oral anticoagulant therapy
- 2003
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In: Pathophysiology of Haemostasis and Thrombosis. - : S. Karger AG. - 1424-8832 .- 1424-8840. ; 33:1, s. 43-51
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Journal article (peer-reviewed)abstract
- The Quick prothrombin time is the most common clotting test performed, principally for monitoring oral anticoagulant therapy. The International Normalized Ratio (INR) for comparing patient results from prothrombin time measurements and the International Standardized Index (ISI) for achieving greater consistency of results using different thromboplastins have made it possible to compare the results of vitamin K antagonist drug therapy that was impossible before the introduction of the INR and ISI. However, INR values obtained from the same patient plasma sample using different thromboplastins are significantly different. This is so even when the thromboplastins have nearly the same ISI values. We suggest that investigation of patient-specific differences can provide a means by which the INR discrepancies can be identified and understood and thus lead to better methods for monitoring oral anticoagulant therapy.
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| 7. |
- Järemo, Petter, et al.
(author)
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Inverse relationship between platelet density and reactivity alterations at coronary angiography
- 2001
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In: Haemostasis. - Basel : S. Karger. - 0301-0147 .- 1423-0038. ; 31:1, s. 55-60
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Journal article (peer-reviewed)abstract
- This work investigates relationships between platelet density and reactivity. 21 individuals subject to coronary angiography were studied. Peak platelet density was analyzed using a newly developed electronic device. The apparatus measures light transmission through test tubes containing density-separated platelets, thus allowing an estimation of the platelet distribution in the gradient. A flow cytometry technique was used for determining platelet reactivity after stimulating with ADP. Platelet counts, mean platelet volumes, peak platelet density and platelet reactivity were determined immediately before (day 1) and 24 h after cardiac catheterization (day 2). For all parameters changes during the day of angiography were compared with platelet density alterations. The subjects were divided into two groups according to density changes at angiography. Group 1 individuals showed density alterations (i.e. day 2 – day 1 value) ≥–8 × 10–5 kg/l. In contrast, group 2 subjects either displayed density changes <–8 × 10–5 kg/l or grossly disturbed platelet density patterns on day 2. Before angiography both groups had similar platelet counts and volumes. Then platelet reactivity when stimulating with ADP did not differ significantly between the two groups. After angiography, the number of fibrinogen-positive cells when stimulating with ADP rose by 6 ± 8% for group 2 patients. The corresponding figure for group 1 was –1 ± 6%. The difference was significant (p = 0.01). No such relationships were found when comparing density alterations and changes of platelet counts and volumes. We conclude that in this study platelet density alterations at coronary angiography are inversely related to variations of platelet reactivity.
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| 8. |
- Knobe, Karin, et al.
(author)
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Factor VIII inhibitors in two families with mild haemophilia A: structural analysis of the mutations
- 2000
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In: Haemostasis. - : S. Karger AG. - 0301-0147. ; 30:5, s. 268-279
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Journal article (peer-reviewed)abstract
- The development of inhibitory antibodies against coagulation factor VIII (FVIII) in patients with mild haemophilia A is uncommon. We describe here two families in which three or two members have developed inhibitors, suggesting a familial predisposition. The mutations found, in the A2 (Arg593Cys) and C1 domains (Tyr2105Cys), have been reported to give rise to inhibitor development in single individuals in addition to the family cluster we describe, strongly suggesting that these amino acid substitutions give rise to a more immunogenic protein. The analysis of structural models of activated factor VIII revealed that Arg593 is solvent-exposed and involved in a network of electrostatic interactions while Tyr2105 is partially buried and has hydrophobic interactions essentially with Ile2144. All these residues are strictly conserved in the FVIII amino acid sequence from man, pig and mouse, suggesting, at least, that they have structural roles. We propose that the two mutations in these families could cause mild haemophilia A because they induce local conformational changes (and possible secretion or intermolecular interaction problems, e.g., with von Willebrand factor) compatible with immunogenicity and production of inhibitors against the infused wild-type FVIII.
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| 9. |
- Knobe, Karin, et al.
(author)
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Functional Analysis of the Factor IX Epidermal Growth Factor-Like Domain Mutation Ile66Thr Associated with Mild Hemophilia B.
- 2006
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In: Pathophysiology of Haemostasis and Thrombosis. - : S. Karger AG. - 1424-8832 .- 1424-8840. ; 35:5, s. 370-375
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Journal article (peer-reviewed)abstract
- he present study focused on the functional role of the mutation Ile66Thr located in the N-terminal epidermal growth factor-like domain of coagulation factor IX (FIX). This mutation causes mild hemophilia B with approximately 25% FIX coagulant activity and FIX antigen levels of around 90% of normal. In the 3-dimensional structure of porcine FIXa and in the subsequent 3-dimensional model of human FIXa that we have previously developed, residue 66 is exposed to the solvent and can be replaced by many amino acids, including Thr, without affecting the major folding/stability of the molecule. This is consistent with the basically normal antigen levels observed. We found that the FIX Ile66Thr mutant was activated to a normal extent by FVIIa/TF and FXIa. However, the ability of FIX Ile66Thr to activate FX was impaired in both the presence and absence of FVIIIa, indicating that Ile66 is not directly involved in the binding of FIX to FVIIIa.
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| 10. |
- Lubenow, Norbert
(author)
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New developments in diagnosis and treatment of heparin-induced thrombocytopenia.
- 2003
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In: Pathophysiology of Haemostasis and Thrombosis. - : S. Karger AG. - 1424-8832 .- 1424-8840. ; 33:5-6, s. 407-12
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Journal article (peer-reviewed)abstract
- Heparin-induced thrombocytopenia (HIT) is a drug induced immune mediated thrombocytopenia that affects up to 3% of patients treated with unfractionated heparin (UFH). It is less frequent when low molecular weight heparins (LMWH) are used. Fondaparinux does not seem to induce HIT. A functional and an antigen assay should be performed to confirm the clinical diagnosis of HIT. Immediate cessation of heparin and start of compatible anticoagulant is mandatory when HIT is suspected clinically. Danaparoid (a heparinoid)and the direct thrombin inhibitors lepirudin and argatroban are available for this purpose. Short-term reexposure with heparin, for example during cardiopulmonary bypass, is possible in patients with history of HIT, provided HIT antiodies are no longer detectable. In children systematic data on treatment of HIT are lacking.
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| 11. |
- Milovanovic, Micha, 1966-, et al.
(author)
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Platelet Density Distribution in Essential Thrombocythemia
- 2010
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In: Pathophysiology of Haemostasis and Thrombosis. - Basel, Switzerland : S. Karger. - 1424-8832 .- 1424-8840. ; 37:1, s. 35-42
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Journal article (peer-reviewed)abstract
- Essential thrombocythemia (ET) is characterized by high platelet counts and a slightly increased bleeding risk. Why severe hemorrhage does not occur more frequently is not known. Variations of platelet density (kg/l) depend mainly on cell organelle content in that high-density platelets contain more alpha and dense granules. This study compares ET patients (n = 2) and healthy volunteers (n = 2) with respect to platelet density subpopulations. A linear Percoll gradient containing prostaglandin E(1) was employed to separate platelets according to density. The platelet population was subsequently divided by density into 16 or 17 subpopulations. Determination of platelet counts was carried out. In each density fraction, platelet in vivo activity, i.e. platelet-bound fibrinogen, was measured using a flow cytometer. To further characterize platelet subpopulations, we determined intracellular concentrations of CD40 ligand (CD40L) and P-selectin in all fractions. Patients and controls demonstrated similar density distributions, i.e. 1 density peak. High-density platelets had more surface-bound fibrinogen in conjunction with signs of platelet release reactions, i.e. with few exceptions they contained less CD40L and P-selectin. Peak density platelets showed less surface-bound fibrinogen. These platelets contained less CD40L and P-selectin than nearby denser populations. The light platelets had more surface-bound fibrinogen than peak platelets together with elevated concentrations of CD40L. In ET, the malignant platelet production could exist together with platelets originating from normal megakaryocytes. It is also possible that clonal megakaryocytes produce platelets covering the entire density span. The 'normal' density distribution offers a tenable explanation as to why serious bleedings do not occur more frequently.
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| 12. |
- Mätzsch, Thomas
(author)
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Thromboprophylaxis with low-molecular-weight heparin: economic considerations
- 2000
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In: Haemostasis. - : S. Karger AG. - 0301-0147. ; 30:Suppl. 2, s. 141-145
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Journal article (peer-reviewed)abstract
- Postoperative thromboembolic events are a major cost factor for every healthcare system. Although thromboprophylaxis carries its own costs, the application of a thromboprophylactic regimen is cost-effective in most instances, at least in high-risk patients. A regimen of general postoperative prevention of deep vein thrombosis is always more cost-effective than surveillance programmes with treatment after diagnosis, and is almost always more cost-effective than no prophylaxis. For patients with a high risk of postoperative thromboembolism, such as after orthopaedic surgery, low-molecular-weight heparins have a rather clear advantage over prophylaxis with unfractionated heparin and warfarin, also in terms of cost- effectiveness. With regard to moderate-risk patients, such as after general surgery, the economic benefits are less clear. However, since the results of economic analyses are heavily dependent on the healthcare system, and since there are methodological difficulties and uncertainties connected with the analyses, the implications are difficult -- if not impossible -- to generalize. There is an urgent need for further prospective studies, which should be performed with defined economic variables a priori and in close cooperation with health economists.
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| 13. |
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| 14. |
- Schulman, S
(author)
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Long-term prophylaxis in venous thromboembolism: LMWH or oral anticoagulation?
- 1998
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In: Haemostasis. - : S. Karger AG. - 0301-0147. ; 2828 Suppl 3, s. 17-21
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Journal article (peer-reviewed)abstract
- Warfarin remains the standard drug for secondary prophylaxis following venous thromboembolism, however this treatment is not ideal. In patients for whom monitoring is problematic or who have a high risk of bleeding complications, other possible solutions have been explored. Unfractionated heparin has been used to a limited extent in these situations and requires dose adjustment in order to achieve an acceptable efficacy. Low-molecular-weight heparin (LMWH) is a valuable alternative to warfarin for these patients and for thromboprophylaxis during pregnancy. In several subgroups of patients with venous thromboembolism the use of a LMWH instead of warfarin could offer specific advantages. The combination of warfarin and LMWH is warranted in patients for whom it is predicted that warfarin treatment alone may fail. The optimal dose of LMWH in long-term prophylaxis has not been evaluated in a properly designed study and the optimal duration of prophylaxis with LMWH is thought to be similar to that for warfarin.
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| 15. |
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| 16. |
- Schulman, S
(author)
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The role of ximelagatran in the treatment of venous thromboembolism
- 2005
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In: Pathophysiology of haemostasis and thrombosis. - : S. Karger AG. - 1424-8832 .- 1424-8840. ; 3434 Suppl 1, s. 18-24
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Journal article (peer-reviewed)abstract
- Clinical-based evidence demonstrates that long-term oral anticoagulant therapy with the vitamin K antagonists is highly effective for the secondary prevention of venous thromboembolism (VTE). However, owing to fear of bleeding complications and the inconvenience of coagulation monitoring, many patients do not receive the required duration of treatment. This can lead to a high incidence of recurrent VTE events and has prompted the evaluation of alternative treatment strategies and the development of new anticoagulants for VTE management. For patient groups in which it is particularly difficult to maintain the target intensity of anticoagulation, low-molecular-weight heparin (LMWH) has been found to significantly reduce the risk of recurrent VTE without increasing bleeding risk. The parenteral administration of LMWH, however, is a drawback for long-term use in the outpatient setting. Long-term warfarin use at a lower intensity (international normalized ratio [INR] 1.5–2.0) has also been assessed as a possible strategy to reduce bleeding complications and the need for monitoring, but results were disappointing when compared with conventional-intensity warfarin (INR 2.0–3.0). New therapies in development that may potentially offer a more favourable benefit-risk profile and greater consistency and predictability of response include the synthetic pentasaccharides, fondaparinux and idraparinux. These par enterally administered indirect factor Xa inhibitors have a predictable pharmacokinetic profile, allowing use without coagulation monitoring. Fondaparinux to date has only been evaluated in the initial treatment (5–7 days) of symptomatic deep vein thrombosis. In contrast, idraparinux, with its longer half-life (80 h) allowing once-weekly parenteral dosing, has the potential for long-term treatment and is currently being assessed in phase III trials for the secondary prevention of VTE. Currently, the most promising new therapeutic option is the first of the oral direct thrombin inhibitors, ximelagatran. The THRombin Inhibitor in VEnous thromboembolism (THRIVE) clinical trial programme has demonstrated that this agent is as effective as standard therapy for the acute treatment (THRIVE Treatment) and secondary prevention (THRIVE lll) of VTE events and is well tolerated when used for 6 months or over extended periods up to 1.5 years. Furthermore, with oral administration, fixed dosing and no requirement for anticoagulation monitoring, ximelagatran has the potential to facilitate optimal use and duration of VTE treatment by overcoming the limitations of current agents.
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| 17. |
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| 18. |
- Strandberg, LE, et al.
(author)
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Anticoagulant effects of low-molecular-weight heparin following thrombolytic therapy in acute myocardial infarction: a dose-finding study
- 1996
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In: Haemostasis. - : S. Karger AG. - 0301-0147. ; 26:5, s. 247-257
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Journal article (peer-reviewed)abstract
- The aim of the present study was to gain clinical experience with different dose levels of dalteparin, a low-molecular-weight heparin, following thrombolytic therapy in acute myocardial infarction. Compared to heparin, dalteparin has a longer half-life and a greater and highly predictable bioavailability, which would suggest dalteparin to be a convenient alternative. Twenty patients with ECG signs of acute transmural myocardial ischemia received streptokinase (1.5 million IU for 60 min) and were allocated to a control group or to open treatment with 50, 75 or 100 IU of dalteparin/kg b.w. s.c. b.i.d., starting 4 h later, for 6 days. Each group consisted of 5 patients. Except for the control group, aspirin was withheld during dalteparin treatment. Anti-factor-Xa (anti-FXa) values increased dose-dependently during the first 24 h and were maintained throughout the study period. On day 6, anti-FXa levels after 100 IU/kg b.w. were 0.79 (0.59-1.00) IU/ml (median, min.-max.) 4 h after administration of dalteparin, and 0.51 (0.34-0.82) IU/ml before the subsequent dose of dalteparin. In conclusion, our results indicate that a dalteparin dose slightly higher than 100 IU/kg b.w. is required in order to obtain the presumed therapeutic range of anti-FXa (0.6-1.0 IU/ml).
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| 19. |
- Turecek, PL, et al.
(author)
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Factor VIII inhibitor-bypassing agents act by inducing thrombin generation and can be monitored by a thrombin generation assay
- 2003
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In: Pathophysiology of Haemostasis and Thrombosis. - : S. Karger AG. - 1424-8832 .- 1424-8840. ; 33:1, s. 16-22
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Journal article (peer-reviewed)abstract
- Factor VIII (FVIII)-bypassing agents have complex modes of action but all control bleeding in inhibitor patients by triggering the generation of thrombin. No routine test is available for monitoring this therapy in patients with inhibitors against FVIII. We present an assay that records FEIBA- or FVIIa- mediated changes in thrombin generation (TG) in FVIII inhibitor plasma samples. In plasma samples spiked with FEIBA TG was normalized above 0.4 U/ml, while for recombinant FVIIa ( rFVIIa) more than 12.5 mug/ml were required to induce TG in the absence of tissue factor (TF). Addition of TF increased the TG potential of rFVIIa in vitro. This assay seems suitable for monitoring the pharmacokinetics of inhibitor bypassing agents during treatment and possibly for predicting responses to treatment. Copyright (C) 2003 S. Karger AG, Basel.
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| 20. |
- Zoucas, E., et al.
(author)
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Effect of latex-stimulated granulocytes on platelet aggregation in man
- 1985
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In: Haemostasis. - : S. Karger AG. - 0301-0147. ; 15:3, s. 176-181
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Journal article (peer-reviewed)abstract
- The effect of granulocytes on human platelet aggregation was investigated in vitro. Platelet function was assayed by photometric technique. Incubation of platelets with latex-stimulated granulocytes for 1 h at room temperature resulted in total inhibition of arachidonic acid-induced platelet aggregation. ADP-induced platelet aggregation was suppressed, lacked secondary wave and was pursued by swift disaggregation. Platelet aggregates induced by collagen dispersed faster under the influence of stimulated granulocytes. The present results indicate that granulocytes may play a role in the hemostatic mechanism in man.
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| 21. |
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| 22. |
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