| 1. |
- Persson, Kristina, et al.
(författare)
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Använd hela "analyspaketet" vid utredning av trombospatienten! Och glöm inte släktingarna ...
- 2000
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Ingår i: Läkartidningen. - 0023-7205. ; 97:47, s. 5452-5456
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Tidskriftsartikel (refereegranskat)abstract
- During the last few years several genetic markers have been discovered that contribute to an increased risk of venous thrombosis. Patients who have several genetic markers are at a considerably higher risk of being affected than patients with only one marker. Recommendations are made as to which patients should be investigated, with appropriate laboratory analyses, when an increased risk of venous thrombosis is suspected. Most of the analyses can be done even if the patient is undergoing warfarin treatment.
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| 2. |
- Giri, Tusar K, et al.
(författare)
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A new direct, fast and quantitative enzyme-linked ligandsorbent assay for measurement of free protein S antigen
- 1998
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 79:4, s. 767-772
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Tidskriftsartikel (refereegranskat)abstract
- A new method to determine the concentration of the free protein S in plasma is described. It is an enzyme-linked ligandsorbent assay (ELSA) which utilises the protein S binding capacity of the natural ligand C4b-binding protein (C4BP) to capture the free protein S from plasma samples. The use of C4BP as ligand in the assay is possible due to the high affinity (Kd = 0.1 nM) of the interaction between protein S and C4BP and to a slow rate of complex dissociation. A monoclonal antibody (HPS 54) was conjugated with horseradish peroxidase and used as target antibody. This antibody recognises a Ca2+ dependent epitope in the first EGF-like domain of protein S and does not interfere with C4BP binding sites of protein S. Addition of calcium in the assay helped prevent dissociation of the C4BP-protein S-HPS 54 complex. Three different experiments demonstrated the assay to be specific for free protein S. First, near-identical dose response curves were obtained with protein S in plasma and with purified protein S. Second, addition of purified C4BP to normal plasma resulted in loss of free protein S. Third, protein S depleted plasma gave zero values and around 80% of purified protein S added to protein S depleted plasma, and approximately 70% of protein S added to protein S deficient plasma samples, was recovered with the assay. The assay is fast (involves only a single incubation step of 30 min), sensitive and the range of measurement is 3% to 200% of free protein S when plasma dilution 1:20 represents 100%. Intra- and inter-assay coefficients of variation at two levels were 2.3-4.3% and 5.1-7.4%, respectively. In a large protein S deficient family, the assay showed 100% sensitivity and specifity for the causative mutation. Moreover, free protein S levels in anticoagulated protein S deficient patients were completely separated from those obtained in non-anticoagulated controls. The new assay for free protein S is suitable for automation and it provides a useful means for routine clinical purposes to detect protein S deficiencies.
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| 3. |
- Hillarp, Andreas, et al.
(författare)
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The 20210 A allele of the prothrombin gene is a common risk factor among Swedish outpatients with verified deep venous thrombosis
- 1997
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 78:3, s. 2-990
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Tidskriftsartikel (refereegranskat)abstract
- A dimorphism in the 3'-untranslated region of the prothrombin gene (G to A transition at position 20210) has recently been reported to be associated with increases in plasma prothrombin levels and in the risk of venous thrombosis. We have examined the prothrombin dimorphism among 99 unselected outpatients with phlebography verified deep venous thrombosis, and in 282 healthy controls. The prevalence of the 20210 A allele was 7.1% (7/99) in the patient group, and 1.8% (5/282) in the healthy control group (p = 0.0095). The relative risk of venous thrombosis was calculated to be 4.2 (95% CI, 1.3 to 13.6), and was still significant when adjustment was made for age, sex and the factor V:R506Q mutation causing APC resistance [odds ratio 3.8 (95% CI, 1.1 to 13.2)]. As previously reported, 28% of the patients were carriers of the factor V:R506Q mutation. Thus, 34% (one patient carried both traits) of unselected patients with deep venous thrombosis were carriers of an inherited prothrombotic disorder. To sum up, our results confirm the 20210 A allele of the prothrombin gene to be an important risk factor for venous thrombosis.
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| 4. |
- Dahlbäck, Björn, et al.
(författare)
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Inherited resistance to activated protein C caused by presence of the FV:Q506 allele as a basis of venous thrombosis
- 1996
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Ingår i: Haemostasis. - 0301-0147. ; 26:SUPPL. 4, s. 301-314
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Tidskriftsartikel (refereegranskat)abstract
- Inherited resistance to activated protein C (APC) was recently discovered as a cause of familial thrombophilia and is now known to be the most common genetic risk factor for venous thrombosis. In a majority of cases, APC resistance is associated with a single point mutation in the factor V gene, which results in substitution of arginine (R) at position 506 by glutamine (Q) (FV:Q506). The mutation renders factor Va partially resistant to degradation by activated protein C (APC), which leads to a hypercoagulable state and a life-long 5-10-fold increased risk of venous thrombosis. The previously known inherited deficiencies of antithrombin, protein S or protein C, are in western societies together found in less than 10-15% of thrombosis patients, whereas APC resistance is present in 20 to 60% of the patients. A functional APC resistance test, which includes predilution of the patient plasma with factor V deficient plasma, is 100% sensitive and specific for the presence of FV:Q506. The FV:Q506 allele is common in populations of Caucasian origin (prevalence ranging between 1 and 15%), whereas it is not found in certain other ethnic groups such as in Japanese and Chinese. The thrombotic risk in individuals with APC resistant may be further increased by other genetic defects such as protein C or protein S deficiency and by exposure to circumstantial risk factors such as oral contraceptives, pregnancy, immobilisation and surgery.
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| 5. |
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| 6. |
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| 7. |
- Hillarp, Andreas, et al.
(författare)
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Activated protein C resistance : from phenotype to genotype and clinical practice
- 1995
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Ingår i: Blood Reviews. - 0268-960X. ; 9:4, s. 201-212
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Tidskriftsartikel (refereegranskat)abstract
- The anticoagulant protein C system is an important regulator of the blood coagulation process. Its targets are the procoagulant cofactors factor Va and factor VIIIa, which are cleaved and inactivated by activated protein C, protein S and intact factor V working as cofactors. Genetic defects of protein C or protein S were, together with antithrombin III deficiency, the previously established major causes of familial venous thromboembolism. However, these abnormalities are found in less than 5-10% of patients with thrombosis. Inherited resistance to activated protein C was recently identified as a major risk factor for venous thromboembolism. The activated protein C-resistance phenotype is found in 20-60% of the patients with venous thrombosis, depending on selection criteria and on the prevalence of activated protein C-resistance in the population. The frequency of activated protein C-resistance is 2-10% in the normal populations studied so far. In more than 90% of cases, the molecular background for the activated protein C-resistance is a single point mutation in the factor V gene, which predicts substitution of an arginine at position 506 by a glutamine. Mutated factor V is activated by thrombin or factor Xa in the normal way, but impaired inactivation of mutated factor Va by activated protein C results in a life-long hypercoagulability. Owing to the high prevalence of activated protein C-resistance in the population, it occasionally occurs in patients with deficiency of protein S, protein C or antithrombin III. Individuals with combined defects suffer more severely from thrombosis, and often at a younger age, than those with single defects, suggesting thrombophilia to be a multigenetic disease.
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