| 41. |
- Negrier, Claude, et al.
(författare)
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Surgical evaluation of a recombinant factorVIII prepared using a plasma/albumin-free method: Efficacy and safety of Advate in previously treated patients
- 2008
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 100:2, s. 217-223
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Tidskriftsartikel (refereegranskat)abstract
- Evaluation of factor F(V)III replacement in patients with haemophilia A undergoing surgery is critical for FVIII concentrates, yet large scale, multi-center prospective studies, particularly using continuous infusion, are generally lacking for new products. This study evaluated efficacy and safety of a newly developed recombinant FVIII (rAHF-PFM) administered by bolus or continuous infusion in haemophilia A patients undergoing surgery. Subjects >= 5 years of age with baseline FVIII:C <= 2%, and >= 150 prior FVIII exposure days were included in this prospective, international, open-label, uncontrolled clinical trial. rAHF-PFM was administered perioperatively by bolus infusion (BI) or continuous infusion (CI) according to the standard use at the center to prevent bleeding complication. Both the surgeon and haematologist rated efficacy during hospitalization. Fifty-eight subjects underwent 65 surgical procedures (22 major haemorrhagic risk; 35 minor, 8 dental procedures). Bolus infusion was used exclusively in 47 procedures and continuous infusion, with or without supplemental bolus infusions, in 18. Haemostatic efficacy was assessed as excellent or good for 100% of intraoperative ratings (17 CI, 44 BI, 61 total procedures), and 100% of postoperative ratings performed at time of discharge (18 CI, 44 BI, 62 total procedures). Median total consumption of rAHF-PFM during hospitalization was 822 IU/kg/surgery with CI and 910 IU/kg/surgery with BI. Overall rAHF-PFM was well tolerated, and FVIII inhibitors were not detected. In conclusion, rAHF-PFM administered via continuous infusion or bolus injections is safe, non-immunogenic, and effective for perioperative hemostatic management in previously treated haemophilia A patients.
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| 42. |
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| 43. |
- Nilsson, Gunnar, et al.
(författare)
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The APC-PCI complex concentration predicts outcome of aortic surgery.
- 2007
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Ingår i: Thrombosis Research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 120, s. 237-244
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Coagulation activation may be related to complications during surgery for abdominal aortic aneurysm. The complex formed between activated protein C (APC) and the serpin, protein C inhibitor (PCI), is a sensitive indicator of the activation of blood coagulation. The purpose of the study was to establish whether the APC-PCI complex can provide information useful for the assessment of outcome after aortic surgery. Materials and methods: In 38 patients, the APC-PCI complex was initially determined every 6 h and daily from day three. Protein C, antithrombin, global haemostatic tests, and clinical scores were investigated. Length of stay at the intensive care unit (ICU) and hospital, and vital status up to two years were recorded. Results: The median APC-PCI complex concentration in samples drawn 0-6 h after surgery was more than 20-fold higher than the upper Limit of the reference interval. The level then declined rapidly, but remained elevated during the first two days. In patients with higher initial APC-PCI complex concentrations, Sequential Organ Failure Assessment (SOFA) scores were higher, the ICU stay was longer, and survival up to two years was lower. Patients who did not survive the ICU care had higher APC-PCI complex levels at 6-12 h and 12-18 h. Conclusions: High concentrations of the APC-PCI complex within 6-18 h after the aortic surgery predict a sinister outcome. The results suggest that the APC-PCI complex is indicative of the severity of the disease.
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| 44. |
- Rask, Olof, et al.
(författare)
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Lower incidence of procoagulant abnormalities during follow-up after creation of the Fontan circulation in children.
- 2009
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Ingår i: Cardiology in the Young. - 1467-1107. ; 19, s. 152-158
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Children who undergo surgery for complex congenital cardiac disease are reported to be at increased thrombotic risk. Our aim was to evaluate long-term changes in the haemostatic system after surgery, to compare markers of activated coagulation in children having surgery with those in a healthy control population, and to relate them to adverse clinical outcome.Patients and methodsWe studied, prior to surgery, the coagulation profiles of a cohort of 28 children admitted for a modified Fontan operation, studying them again after a period of mean follow-up of 9.6 years. Median age at the time of final surgery was 18.5 months, with a range from 12 to 76 months. We compared generation of thrombin, and levels of the activated protein C-protein C inhibitor complex to controls at follow-up. Thrombophilia and clinical outcome were evaluated. RESULTS: At long-term follow-up, a lower incidence of procoagulant abnormalities was observed compared to that before surgery. Of 27 patients, 3 (11%), but none of 45 controls, had levels of activated protein C-protein C inhibitor complex above the reference range. There were no significant differences in generation of thrombin between patients and controls. No thrombotic events were recorded, and the patients were generally in good clinical condition. CONCLUSIONS: Overall, haemostasis appeared to be in balance, and less prothrombotic, after surgery. A subset of the cohort did show indications of activated coagulation. The current therapeutic approach seems to be sufficient to protect the majority of patient. New tests of global coagulation, nonetheless, may be helpful in improving identification of individuals at increased thrombotic risk.
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| 45. |
- Rask, Olof, et al.
(författare)
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Oestrogen treatment of constitutional tall stature in girls: is there a risk of thrombosis or bleeding?
- 2008
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Ingår i: Acta Pædiatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 97:3, s. 342-347
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To evaluate haemostatic effects and clinical outcome of oestrogen treatment of constitutionally tall stature in girls. Methods: We conducted a single-centre cohort study, 63 girls referred over a period of 15 years were investigated. The girls were given oestrogen treatment for constitutional tall stature at a median initial dose of 300 ug ethinyl estradiol/day and were consecutively examined for changes in coagulation. Medical records were retrospectively reviewed, additional data were collected at follow-up by blood sampling and interviews. Results: After 1 year of treatment, levels of antithrombin and von Willebrand factor (VWF) were significantly decreased (p < 0.001 and p = 0.015, respectively), whereas there was no significant change in levels of plasminogen inhibitor type 1. No venous thromboembolism (VTE) or major side effects were observed. Genetic risk factors for thrombosis were present, as was expected. The mean height reduction was 5.5 cm. The height-reducing effect was inversely correlated with chronological age (r =-0.44, p < 0.01) and bone age (r =-0.61, p < 0.01). Conclusions: Changes in coagulation parameters occurred both towards pro- and anticoagulation. Treatment with high-dose ethinyl estradiol can successfully limit final height, and it is most effective when started at a younger bone age.
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| 46. |
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| 47. |
- Salvagno, G. L., et al.
(författare)
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Impact of different inhibitor reactivities with commercial factor VIII concentrates on thrombin generation
- 2007
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 13:1, s. 51-56
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Tidskriftsartikel (refereegranskat)abstract
- In order to describe the haemostatic role of a variation in inhibitor reactivity with different factor VIII (FVIII) concentrates, we have compared inhibitor titres against a panel of FVIII concentrates and correlated titre with the capacity to inhibit thrombin generation. Three plasma-derived concentrates were tested in vitro in mixing experiments with inhibitor plasmas from 11 patients with severe haemophilia A: Fanhdi, which contains von Willebrand factor (VWF) with a final ratio of approximately 1:1 (VWF IU per IU FVIII:Q; Haemate-P with a ratio of 2.5:1 and Hemofil-M containing only trace amounts of VWF. In addition, the recombinant FVIII concentrate Kogenate Bayer containing no VWF was included. Inhibitor titres and the capacity to generate thrombin were measured. A statistically significant difference in measured titres was found with the highest titres recorded against Hemofil-M. The inhibitor titres needed to inhibit 50% maximum thrombin generation were the lowest for Kogenate Bayer and the highest and similar for Fanhdi and Haemate-P with intermediate titres needed for inhibition of Hemofil-M. In this study, the thrombin generation assay provides additional indications for the role of VWF in the treatment of patients with inhibitors. The VWF-containing concentrates Fanhdi and Haemate-P, added to FVIII-deficient plasma with the presence of inhibitor, generate more thrombin than do the purified concentrates Hemofil-M and Kogenate Bayer.
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| 48. |
- Salvagno, G. L., et al.
(författare)
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Thrombin generation assay: a useful routine check-up tool in the management of patients with haemophilia?
- 2009
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 15:1, s. 290-296
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Tidskriftsartikel (refereegranskat)abstract
- Severity assessment of patients with haemophilia A (HA) is traditionally based on FVIII activity (FVIII:C). Clinical phenotype of HA patients often differs between individuals with the same FVIII:C determined with clotting and chromogenic assays. The aim of this study was to assess the influence of the FVIII:C on thrombin generation (TG) assay parameters both in vitro and ex-vivo postinfusion plasma. For in-vitro approach, influence of FVIII:C was evaluated on TG parameters in several dilutions of a normal plasma pool with commercial FVIII-depleted-plasma (FVIIIDP) and in others experiments, adding increasing amounts of different commercial FVIII concentrates (Fanhdi, Haemate-P, Hemofil-M and Kogenate Bayer) to FVIIIDP. In a series of 50 postinfusion samples, from HA patients of different severity, we assayed TG and FVIII:C (chromogenic and clotting). In vitro experiments, the 50% of maximum TG peak (TGMP) was achieved using only 5% FVIII:C and the TGMP was obtained with 40% of normal VIII:C. Impaired response compared with normal plasma was found in FVIIIDP using addition of increasing amounts of different commercial FVIII concentrates. An overall good correlation between the two FVIII assays was observed (y = 0.9115x - 0.273, r = 0.975, P < 0.001); TGMP and the Lag-Phase-Time (LPT) provided some discrepant results when compared with the total range of FVIII:C measurements. In contrast, correlations for TGMP, LPT and endogenous thrombin potential were improved in samples restricted to FVIII:C < 5%. We conclude that TG parameters tentatively could be a tool to tailor the global haemostatic capacity in haemophilic patients.
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| 49. |
- Steen Carlsson, Katarina, et al.
(författare)
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Cost and outcome: comparisons of two alternative bypassing agents for persons with haemophilia A complicated by an inhibitor.
- 2008
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 99:6, s. 1060-1067
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Tidskriftsartikel (refereegranskat)abstract
- The development of inhibitory antibodies to factor VIII is a serious complication of haemophilia. Two haemostatic agents with different bypassing mechanisms have been used in the treatment of patients with inhibitors: activated prothrombin complex concentrate (aPCC) and recombinant factor VIIa (rFVIIa). The objective was to compare cost and outcome of aPCC and rFVIIa in the treatment of joint bleeds. The analyses were based on the FENOC (FEIBA NovoSeven Comparative Study) crossover study where 48 patients used aPCC and rFVIIa to treat two joint bleeds. Incremental cost-effectiveness ratios were calculated for three outcome measures and the variation in cost was analyzed using two alternative regression methods. Results were subjected to sensitivity analyses. Key determinants of cost were prescribed dose, bodyweight and treatment in addition to protocol. The cost of aPCC was on average lower than rFVIIa. At all but one time point, patients rated slightly higher (but not statistically significantly) percentages of treatment efficacy and stopping of the bleed by aPCC. The reported reduction in pain from start of treatment up to 48 hours varied considerably among individuals. The different relative prices in the US, Turkey and Sweden mattered, but did not reverse the main results. In conclusion, the cost per episode was significantly lower for aPCC. The large individual-level variation in reduction of pain supports decisions that consider the individual patient's experience and that accept trade-offs between cost and reduction in pain rather than focusing on cost only.
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| 50. |
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