| 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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