| 1. |
- Lawrie, Andrew S., et al.
(författare)
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Procoagulant activity in patients with sickle cell trait
- 2012
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Ingår i: Blood Coagulation and Fibrinolysis. - 0957-5235 .- 1473-5733. ; 23:4, s. 268-270
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Tidskriftsartikel (refereegranskat)abstract
- Patients with sickle cell trait (STr) are usually considered to be asymptomatic. However, complications, including hypercoagulability, increased risk of venous thromboembolism and the exertional exercise syndrome with rhabdomyolysis and sudden death, have been described. The exact cause of these adverse events is unclear. We have investigated two patients, a set of monozygotic twins with STr, to establish their procoagulant activity status as a potential indicator of thrombotic risk. In-vivo thrombin generation was assessed by the measurement of prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin complexes (TAT). D-dimer was used as a marker of fibrinolytic activity. The potential to generate thrombin was determined using an ex-vivo thrombin generation test (TGT). The impact of red blood cell (RBC)-derived microparticle shedding and RBC rheology were examined. TAT (>60 mu g/l) and F1+2 (948 pmol/l) were markedly elevated in patient 2 but within the normal reference range in patient 1 (TAT=2.5 mu g/l; F1+2=138 pmol/l). D-dimer levels (0.9 mg/l FEU) were similarly elevated in both patients. TGT peak thrombin and endogenous thrombin potential (ETP) were elevated to similar degrees in both patients. Flow cytometric analysis for RBC-derived microparticles showed that both patients had elevated levels on two occasions. RBC deformability, blood viscosity and RBC aggregation were normal and similar in both patients. The results demonstrated different coagulation activity in the patients with one patient in a prothrombotic state, suggesting that there may be two levels of hypercoagulability in STr. Measurement of such differences would allow for separation of high and low-risk patients from serious complications.
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| 2. |
- Alehagen, Urban, et al.
(författare)
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Low plasma concentrations of coagulation factors II, VII and XI indicate increased risk among elderly with symptoms of heart failure.
- 2010
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Ingår i: Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis. - 1473-5733. ; 21:1, s. 62-9
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Tidskriftsartikel (refereegranskat)abstract
- Heart failure is a serious condition, and it is, therefore, important to identify patients at high risk as early as possible in order to initiate appropriate treatment. The condition results in complicated disease mechanisms including disturbances in blood coagulation. The aim of the present study was to evaluate whether low plasma concentrations of coagulation factors (F) II, VII and XI influence cardiovascular mortality in an elderly population with possible heart failure. A cardiologist evaluated 450 elderly patients who attended primary healthcare because of symptoms associated with heart failure. He recorded new patient history, conducted a clinical examination, took blood samples, determined concentrations of B-type natriuretic peptide and FII, FVII, FXI and performed Doppler echocardiography. The patients were followed over almost a 10-year period during which all mortality was registered. In patients with suspected heart failure, those with low plasma concentrations of FII, FVII, FXI or all had a significantly higher mortality rate during the follow-up period of 10 years as compared with those with higher plasma concentrations, in contrast with findings in previous reports on patients with acute coronary syndromes. In the group with a plasma concentration of the first versus the ninth decile of FII, FVII, FXI or all, the risk of cardiovascular mortality increased two to three times.
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| 3. |
- Berntorp, Erik, et al.
(författare)
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A retrospective study of Octaplex in the treatment of bleeding in patients with haemophilia A complicated by inhibitors.
- 2010
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Ingår i: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 21, s. 577-583
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Tidskriftsartikel (refereegranskat)abstract
- The nonactivated prothrombin complex concentrate (PCC) Octaplex (Octapharma PPGmbH, Vienna, Austria) has been used successfully for the treatment of congenital and acquired coagulation factor deficiencies and associated bleeding. The aims of this study were to assess retrospectively whether Octaplex is an effective treatment option for haemophilia A patients with high-titre inhibitors of factor VIII (FVIII) and to investigate the impact of Octaplex on thrombin generation in vitro and ex vivo. Retrospective data were collected from 15 haemophilia A patients with FVIII inhibitors who had been treated with Octaplex. Mild bleeds were treated for a median of 1 day with a median dose of 77 IU/kg and moderate bleeds for 3 days with 57 IU/kg. The physician's overall satisfaction with Octaplex, taking into account efficacy, safety and cost in comparison with other treatment options, was assessed for each bleed. The overall rating was good, very good or excellent for 29 of 41 (71%) bleeds. No adverse drug reactions were reported. In in-vitro studies of thrombin generation with normal plasma samples, experimental inhibition of FVIII activity prolonged the lag phase, diminished the peak thrombin concentration and decreased the area under the concentration-time curve, as expected. Marked improvement in thrombin generation parameters was achieved by adding 0.5-3 IU factor IX/ml PCC into the samples. The same held true when using plasma samples from haemophilia A patients with FVIII inhibitors. These results demonstrate that Octaplex overcomes inhibition of FVIII in in-vitro and ex-vivo assays of thrombin generation, and that Octaplex is an effective treatment option for haemophilia A patients with FVIII inhibitors.
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| 4. |
- Brophy, Donald F, et al.
(författare)
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Overcoming delayed in-vitro response to rFVIIa: effects of rFVIIa and rFVIIa analogue (vatreptacog alfa) concentration escalation in whole blood assays.
- 2011
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Ingår i: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 22, s. 541-546
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Tidskriftsartikel (refereegranskat)abstract
- In a previous pharmacokinetic/pharmacodynamic study in nonbleeding hemophilia patients, variability in laboratory response to recombinant factor VIIa (rFVIIa) 90 μg/kg was noted, and the patients were described as delayed or rapid laboratory responders based on time to clot formation. The current study determined whether in-vitro experiments could reproduce previous in-vivo findings; whether the delayed laboratory response to rFVIIa 90 μg/kg is improved by spiking with high-dose rFVIIa or rFVIIa analogue (vatreptacog alfa); whether a dose-response is observed with our method. In-vitro experiments were conducted in our previous patient cohort using rFVIIa 1.28 and 3.84 μg/ml and vatreptacog alfa 0.28 and 0.56 μg/ml. Whole blood studies were conducted using the Hemodyne Hemostasis Analysis System (platelet contractile force, clot elastic modulus, force onset time) and rotational thromboelastometry (clotting time, maximum clot firmness). Spiking with rFVIIa 1.28 μg/ml showed the same distribution of delayed and rapid laboratory response as observed previously. Increasing in-vitro rFVIIa concentrations improved the coagulation parameters; however, there remained delayed and rapid responders. Vatreptacog alfa improved the coagulation parameters at all concentrations tested, and the 0.56 μg/ml concentration normalized the force onset time, platelet contractile force, clot elastic modulus and clotting time parameters. A dose-response was observed with both assays. There was good agreement between the laboratory responses obtained after intravenous administration of rFVIIa 90 μg/kg and in-vitro spiking studies. Escalating rFVIIa and vatreptacog alfa concentrations improved coagulation parameters in all patients compared to rFVIIa 1.28 μg/ml. Vatreptacog alfa produced more pronounced coagulation effects at lower concentrations than rFVIIa; and the 0.56 μg/ml concentration completely normalized responses in all patients.
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| 8. |
- Khawaji, Mohamed, et al.
(författare)
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Physical activity and joint function in adults with severe haemophilia on long-term prophylaxis.
- 2011
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Ingår i: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 22:1, s. 50-55
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Tidskriftsartikel (refereegranskat)abstract
- It has been shown that patients with severe haemophilia treated on demand are not as physically active as their healthy peers and often have a sedentary lifestyle that contributes to chronic joint disease. The use of prophylaxis provides opportunities for participation in physical activities with fewer bleeding episodes. The objective of the study was to describe the type, intensity and duration of physical activity among adult patients with severe haemophilia and to find out whether a joint function dependency exists. Patients with severe haemophilia, divided into two groups (group A: patients who started prophylaxis at the age of ≤3 years and group B: patients who started prophylaxis at the age of >3 years), and 190 controls were included. Physical activity was assessed using the self-report Modifiable Activity Questionnaire. Time involved and intensity of all aspects of physical activity for group A were almost similar to their healthy peers. Group B had significantly lower vigorous, leisure and total physical activities than group A and their healthy peers. Positive significant correlations were found between leisure and total physical activities and joint score in group A, whereas in group B, there was negative significant correlation between only nonweight-bearing activity and joint score. The early start of long-term, primary prophylaxis has been successful in reducing frequency of bleeds and thereby preventing or delaying subsequent chronic joint disease, and enables the patients to lead a physically normal life also during adulthood when patients with haemophilia treated on demand are expected to have substantial joint disease impacting their physical activity.
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| 9. |
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| 10. |
- Olsson, Anna, et al.
(författare)
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Clotting factor level is not a good predictor of bleeding in carriers of haemophilia A and B.
- 2014
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Ingår i: Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis. - 1473-5733. ; 25:5, s. 471-475
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Tidskriftsartikel (refereegranskat)abstract
- Carriers of haemophilia are known to have a wide range of clotting factor levels and bleeding symptoms. This study aimed at investigating whether carriers of severe and moderate haemophilia had an increased bleeding tendency, compared with a control group, using a condensed version of a bleeding assessment tool developed by the Molecular and Clinical Markers for the Diagnosis and Management of Type 1 VWD study group (MCMDM-1VWD). One hundred and twenty-six genetically verified carriers of severe and moderate haemophilia and 90 controls were interviewed regarding bleeding symptoms. A bleeding score of at least 4 was considered positive, indicating a significant bleeding tendency. Clotting factor levels were tested in the carriers.Nineteen of the women were carriers of haemophilia B, with a mean factor (F)IX:C level of 0.54 (± 0.27) kIU/l, and 107 were carriers of haemophilia A, with a mean FVIII:C level of 0.74 (± 0.32) kIU/l. The median bleeding score was 2 (-3-12) among carriers and -1 (-3-8) among controls (P<0.001). The bleeding score was weakly correlated to clotting factor levels in carriers of haemophilia A (rs=-0.36, P<0.001). We conclude that the bleeding tendency in our cohort of carriers differed significantly from that in the controls and that clotting factor levels might not be sufficient to predict the bleeding tendency.
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