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Biomedical subjects

A Hillarp

Publications and source records attributed to A Hillarp.

At least 19 recordsLinked to original sources
PubMed2004

A comparative in vitro evaluation of six von Willebrand factor concentrates.

UNLABELLED: The efficacy of von Willebrand factor (VWF) concentrates for treatment of von Willebrand disease (VWD) is dependent on their content of VWF and factor VIII (FVIII). STUDY OBJECTIVES: To measure the content and quality of VWF and FVIII in six VWF concentrates: Haemate-P (Aventis Behring), Immunate (Baxter Bioscience), Koate (Bayer Corp.), 8Y (BPL), Innobrand (LFB) and Facteur Willebrand (LFB). METHODS: The VWF antigen content (VWF:Ag), ristocetin cofactor activity (VWF:RCo), collagen-binding activity (VWF:CB), VWF multimers with electrophoresis and densitometry, FVIII activity and total protein content. RESULTS: Specific activity (VWF:RCo/total protein) varied considerably (4.7-129.5 IU mg(-1)). Activity measures, VWF:RCo and VWF:CB, correlated well, but we found no correlation between any of these and VWF:Ag. The content of high-molecular weight multimer (HMWM) was normal or close to normal in Haemate-P, Innobrand and Facteur Willebrand, moderately reduced in Koate and 8Y, and significantly reduced in Immunate. The HMWM content correlated significantly with the VWF:RCo/VWF:Ag ratio. Only Haemate-P, Innobrand and Facteur Willebrand had VWF:RCo/VWF:Ag ratios >0.7. We found large differences in the content of FVIII and in the FVIII/VWF:RCo ratio. Facteur Willebrand had the lowest (0.02) and Immunate the highest (6.00) ratio. CONCLUSION: Treating physicians must be aware of the large differences between different VWF concentrates and the potential clinical implications. Concentrates lacking HMWM are probably less efficient for mucosal bleedings. FVIII is most important for surgical bleedings, but concentrates with high FVIII/VWF-ratio may induce very high FVIII levels with increased risk of thrombosis. A low FVIII content may be preferable except in case of acute surgery.

Enzyme-Linked Immunosorbent Assay↗
PubMed2004

Co-segregation of the PROS1 locus and protein S deficiency in families having no detectable mutations in PROS1.

Inherited deficiency of protein S constitutes an important risk factor of venous thrombosis. Many reports have demonstrated that causative mutations in the protein S gene are found only in approximately 50% of the cases with protein S deficiency. It is uncertain whether the protein S gene is causative in all cases of protein S deficiency or if other genes are involved in cases where no mutation is identified. The aim of the current study was to determine whether haplotypes of the protein S gene cosegregate with the disease phenotype in cases where no mutations have been found. Eight protein S-deficient families comprising 115 individuals where previous DNA sequencing had failed to detect any causative mutations were analyzed using four microsatellite markers in the protein S gene region. Co-segregation between microsatellite haplotypes and protein S deficiency was found in seven of the investigated families, one family being uninformative. This suggests that the causative genetic defects are located in or close to the protein S gene in a majority of such cases where no mutations have been found.

DNA Mutational Analysis↗
PubMed2003

Influence of factor V Leiden on the development of neovascularisation secondary to central retinal vein occlusion.

AIMS: To investigate if the presence of factor V Leiden has an influence on the prognosis in central retinal vein occlusion (CRVO). METHODS: 166 patients with CRVO were studied retrospectively. They were tested for factor V Leiden using DNA analysis. The presence of the mutation was studied in correlation with the development of neovascular complications 1 year after the thrombotic event. RESULTS: 56 of 166 patients (34%) developed neovascular complications after 1 year. In the patients who had the studied mutation 11 of 20 (55%) had developed neovascular complications after 1 year, compared to 45 of 146 patients (31%) in the group without factor V Leiden (p=0.04). CONCLUSION: The presence of factor V Leiden seems to enhance the risk of developing neovascular complications in CRVO.

Activated Protein C Resistance↗
PubMed2003

Increased sensitivity to ADP-aggregation in aspirin treated patients with recurrent ischemic stroke?

AIM: Antiplatelet therapy in order to reduce the platelet aggregability is widely used to prevent recurrent stroke events. Data from several studies indicates that the inter-individual variation concerning the ability of standard doses of aspirin to inhibit platelet aggregation is substantial. The rationale of the present study was to test whether platelet aggregation in whole blood was enhanced in subjects that had suffered an ischemic stroke event under aspirin treatment. METHODS: Two groups of patients were included: 1) patients that have suffered 1 stroke event and were thereafter under continuous treatment with aspirin 75-160 mg once daily (n=17); 2) patients that have suffered at least 2 stroke events, and aspirin 75-160 mg was prescribed after the 1(st) event (n=17). Platelet aggregation was tested in whole blood with collagen (5 microg/mL and 1 microg/mL), ADP (5 microMol/L) and arachidonic acid (0.5 microg/mL). Aggregation was recorded as change in impedance and release of ATP after the addition of a luciferin-luciferase reagent. RESULTS: The inhibitory effect of aspirin tested with arachidonic acid as an agonist was complete in all the tested subjects. Aggregation induced by ADP 5 microMol/L was significantly higher in the subjects with recurrent stroke compared to those with a single stroke, when tested as impedance change. ATP release with ADP as an agonist was the same in both groups. CONCLUSION: The present study gives some indication that differences in ADP-induced aggregation, with a higher remaining aggregating ability after ASA treatment, might be of importance for the risk of stroke recurrence.

Adenosine Diphosphate↗
PubMed2001

[New in vitro analysis tested: bleeding time is still the best method for evaluation of primary hemostasis].

The need is great for a simple, cheap and readily accessible method for the evaluation of primary hemostasis in work-ups at both out-patient clinics and units caring for surgical or intensive care patients. PFA-100 is a recently introduced instrument for in vitro testing of platelet function. We report experiences from Stockholm, Gothenburg and Malmo of PFA-100 measurements performed on samples from healthy controls and from patients with von Willebrand disease or platelet disorders. It is shown that the PFA-100 system has a high sensitivity for von Willebrands disease, while the sensitivity for hereditary platelet dysfunction is low. In its present design this new device could not replace the template bleeding time as a screening test for primary hemostasis.

Bleeding Time↗
PubMed2001

Combined effect of factor V Leiden and prothrombin 20210A on the risk of venous thromboembolism--pooled analysis of 8 case-control studies including 2310 cases and 3204 controls. Study Group for Pooled-Analysis in Venous Thromboembolism.

Factor V Leiden and factor II G20210A mutations are two frequent genetic risk factors involved in venous thromboembolism (VTE). The goal of this pooled analysis of 8 case-control studies, comprising a total of 2310 cases and 3204 controls, was to precisely estimate the risk of VTE in patients bearing both mutations (double heterozygotes). Odds ratios for VTE were 4.9 (95% CI; 4.1-5.9) for the factor V Leiden and 3.8 (3.0-4.9) for the factor II G20210A mutation. Fifty-one cases (2.2%) and none of the controls were double heterozygotes. The odds ratio for venous thrombosis in double heterozygotes was 20.0 (11.1-36.1). Twelve percent of patients heterozygous for factor V Leiden were also heterozygous for factor II G20210A and conversely 23% of patients heterozygous for factor II G20210A were also heterozygous for factor V Leiden. Furthermore, in this large population we analyzed the effect of oral contraceptive (OC) in women carrying one of these mutations. Odds ratio for VTE associated with OC was 2.29 (1.72-3.04). In factor V Leiden carriers using OC, the odds ratio for VTE was 10.25 (5.69-1 8.45). The odds ratio of the association of factor II mutation and OC use was 7.14 (3.39-15.04). Finally, we also confirmed that the frequency of factor V Leiden was lower in patients with pulmonary embolism than in patients with deep vein thrombosis without PE (odds ratio 0.69). Conversely, factor II G20210A mutation was equally balanced in both patient groups.

3' Untranslated Regions↗
PubMed2001

Analytical considerations for free protein S assays in protein S deficiency.

Protein S is an anticoagulant protein that circulates in plasma in complex with C4b-binding protein (C4BP) or in free form. Deficiency of protein S increases the risk of venous thrombosis. Measurement of free protein S, as compared to total levels, has been shown to be superior for prediction of protein S deficiency. We studied the effects of different handling protocols for an immuno- and a ligand (C4BP)-based assay for free protein S. When the assay was performed at 37 degrees C, the levels of free protein S in plasma from protein S deficient patients were approximately twice those obtained at room temperature. The reason for this phenomenon was that plasmas from protein S deficient patients exhibited a time-, temperature-, and dilution-dependent increase in free protein S, which was more pronounced than corresponding dilution of the normal plasma that was used to create the standard curve. These findings demonstrate the importance of assay procedure and sample handling in assays for free protein S.

Aged↗
PubMed2000

[Use the entire "analysis package" when investigating patients with venous thrombosis! Don't forget the relatives...].

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.

Activated Protein C Resistance↗
PubMed2000

Hyperhomocysteinemia and the MTHFR C677T mutation in central retinal vein occlusion.

BACKGROUND: Hyperhomocysteinemia is a factor that predisposes to thrombosis, and the C677T mutation in methylene-tetrahydrofolate reductase (MTHFR) is known to give increased plasma homocysteine. We wanted to investigate if these factors were overrepresented in a group of patients with central retinal vein occlusion. METHODS: 116 patients with a history of central retinal vein occlusion were examined for the presence of hyperhomocysteinemia and the MTHFR C677T mutation. RESULTS: Compared to the control groups, there was no significant increase, neither in plasma homocysteine nor in the frequency of the MTHFR C677T mutation in the patients. Even when we looked selectively at the young patients, age less than 50 years, no difference could be detected. CONCLUSION: It seems that neither hyperhomocysteinemia nor the MTHFR C677T mutation is an important risk factor for the aetiology of central retinal vein occlusion.

Adult↗
PubMed1999

The prothrombin gene G20210A mutation and the platelet glycoprotein IIIa polymorphism PlA2 in patients with central retinal vein occlusion.

The prothrombin gene G20210A mutation and the platelet glycoprotein IIIa polymorphism PlA2 have been shown to be associated with thromboembolic disease. We wondered if mutations were overrepresented in patients with central retinal vein occlusion. We studied 129 consecutive patients with a history of central retinal vein occlusion. We analysed for the prothrombin gene G20210A mutation and the platelet glycoprotein IIIa polymorphism PlA2 and compared the results to controls with no history of thrombosis. For the platelet glycoprotein IIIa polymorphism PlA2, 69% were normal, 26% were heterozygous, and 5% were homozygous. For the G20210A prothrombin mutation, 97% were normal and 3% were heterozygous. Neither the prothrombin gene G20210A mutation nor the platelet glycoprotein IIIa polymorphism PlA2 seem to be associated with central retinal vein occlusion.

Adult↗
PubMed1999

Changes in levels of factor VII and protein S after acute myocardial infarction: effects of low-dose warfarin.

Persistent coagulation activity after an acute myocardial infarction may increase the risk of reinfarction. We prospectively investigated the effects on plasma coagulation of a low, fixed dose of warfarin in combination with aspirin after myocardial infarction. We also evaluated the influence of coagulation activity on clinical outcome. Plasma samples from 97 patients, randomised to 1.25 mg of warfarin daily in combination with 75 mg of aspirin or aspirin alone were drawn 4 days, 1 month, and 6 months after myocardial infarction. Patients receiving warfarin had a greater reduction in factor VII coagulation activity (FVII:C) after 6 months: 0.18 vs. 0.06 U/mL,(95% CI, 0.02-0.22), whereas no differences were seen in levels of protein C, protein S, or prothrombin fragment 1+2. In the acute phase, the level of free protein S was lower than after 6 months in both groups: 25.6 vs. 28.8% (95% CI, 4.19--2.35). Cardiovascular mortality, reinfarction, and stroke were evaluated after 4 years (median). In a survival analysis, every 0.1 U/mL increase in the level of FVII:C1 month after myocardial infarction was associated with an 15% increase in risk of cardiovascular events (95% C1, 1.01-1.30). Warfarin at 1.25 mg daily reduces FVII:C but not systemic thrombin generation measured as prothrombin fragment 1 +2. Low levels of the anticoagulant protein S may contribute to a procoagulant state.

Adult↗
PubMed1999

Activated protein C resistance and anticoagulant proteins in young adults with central retinal vein occlusion.

BACKGROUND: Central retinal vein occlusion is a disease that is most common in old people, and often associated with atherosclerosis, hypertension, diabetes or glaucoma. Since these diseases are much less evident in young people, we wanted to investigate the prevalence of disorders in the most common anticoagulant proteins in a group of young patients with central retinal vein occlusion. METHODS: 37 consecutive patients younger than 50 years and with a history of central retinal vein occlusion, were analysed for deficiencies of natural inhibitors of coagulation (protein C, S, and antithrombin III), plasminogen, resistance to activated protein C, and the presence of anticardiolipin or lupus anticoagulants. RESULTS: Anticoagulant protein deficiencies were found in 4 patients (11%) and activated protein C resistance in 7 patients (19%). Anticardiolipin or lupus anticoagulants were not found in the patients. CONCLUSION: Activated protein C resistance and anticoagulant protein deficiencies seem to be important factors to the etiology to central retinal vein occlusion in young patients.

Activated Protein C Resistance↗
PubMed1999

Thrombophilia as a multigenic disease.

BACKGROUND AND OBJECTIVE: Venous thrombosis is a common disease annually affecting 1 in 1000 individuals. The multifactorial nature of the disease is illustrated by the frequent identification of one or more predisposing genetic and/or environmental risk factors in thrombosis patients. Most of the genetic defects known today affect the function of the natural anticoagulant pathways and in particular the protein C system. This presentation focuses on the importance of the genetic factors in the pathogenesis of inherited thrombophilia with particular emphasis on those defects which affect the protein C system. INFORMATION SOURCES: Published results in articles covered by the Medline database have been integrated with our original studies in the field of thrombophilia. STATE OF THE ART AND PERSPECTIVES: The risk of venous thrombosis is increased when the hemostatic balance between pro- and anti-coagulant forces is shifted in favor of coagulation. When this is caused by an inherited defect, the resulting hypercoagulable state is a lifelong risk factor for thrombosis. Resistance to activated protein C (APC resistance) is the most common inherited hypercoagulable state found to be associated with venous thrombosis. It is caused by a single point mutation in the factor V (FV) gene, which predicts the substitution of Arg506 with a Gln. Arg506 is one of three APC-cleavage sites and the mutation results in the loss of this APC-cleavage site. The mutation is only found in Caucasians but the prevalence of the mutant FV allele (FV:Q506) varies between countries. It is found to be highly prevalent (up to 15%) in Scandinavian populations, in areas with high incidence of thrombosis. FV:Q506 is associated with a 5-10-fold increased risk of thrombosis and is found in 20-60% of Caucasian patients with thrombosis. The second most common inherited risk factor for thrombosis is a point mutation (G20210A) in the 3' untranslated region of the prothrombin gene. This mutation is present in approximately 2% of healthy individuals and in 6-7% of thrombosis patients, suggesting it to be a mild risk factor of thrombosis. Other less common genetic risk factors for thrombosis are the deficiencies of natural anticoagulant proteins such as antithrombin, protein C or protein S. Such defects are present in less than 1% of healthy individuals and together they account for 5-10% of genetic defects found in patients with venous thrombosis. Owing to the high prevalence of inherited APC resistance (FV:Q506) and of the G20210A mutation in the prothrombin gene, combinations of genetic defects are relatively common in the general population. As each genetic defect is an independent risk factor for thrombosis, individuals with multiple defects have a highly increased risk of thrombosis. As a consequence, multiple defects are often found in patients with thrombosis.

3' Untranslated Regions↗