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| 34. |
- Lauritzen, B, et al.
(författare)
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Recombinant human factor VIIa and a factor VIIa-analogue reduces heparin and low molecular weight heparin (LMWH)-induced bleeding in rats
- 2008
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 6:5, s. 804-811
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Tidskriftsartikel (refereegranskat)abstract
- Background: Heparin and low molecular weight heparin (LMWH) are widely used for prevention and treatment of thromboemobolic events, but may occasionally cause uncontrollable bleeding. Heparin can readily be antagonized with protamine, but this is less effective against LMWH. Objectives: To test the effects of rFVIIa or an analogue of rFVIIa, NN1731, on heparin- and LMWH-induced bleeding in rats. Methods: Initially the doses of heparin and tinzaparin (a LMWH) were determined by dose-titration. Following pretreatment with heparin or tinzaparin in rats, tail-transection was performed, and the effect of rFVIIa and NN1731 on the bleeding was observed. Results: rFVIIa (5, 10 and 20 mg kg(-1)) reduced bleeding time and blood loss caused by heparin- and tinzaparin-induced bleeding, using doses of 200 IU kg(-1) (n = 8) and 500 IU kg(-1) (n = 9), respectively. Similarly, 10 mg kg(-1) NN1731 significantly reduced both heparin- and tinzaparin-induced bleeding to the normal level. Following severe anticoagulation with 1800 IU kg(-1) tinzaparin, 10 mg kg(-1) NN1731 reduced and normalized the bleeding, while the effect of 20 mg kg(-1) rFVIIa failed to reach statistical significance. These data are consistent with the hypothesis that rFVIIa/NN1731 are capable of generating sufficient thrombin locally on the surface of activated platelets to induce hemostasis in the presence of heparin/LMWH. Conclusions: This study suggests that rFVIIa and NN1731 may have the potential to control bleedings caused by heparin or LMWH.
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| 35. |
- Lethagen, Stefan, et al.
(författare)
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Von Willebrand factor/factor VIII concentrate (Haemate(R) P) dosing based on pharmacokinetics: a prospective multicenter trial in elective surgery.
- 2007
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 5:Apr 16, s. 1420-1430
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Tidskriftsartikel (refereegranskat)abstract
- Background: While plasma-derived concentrates containing large amounts of von Willebrand factor (VWF) are effective in treating von Willebrand disease (VWD), optimal dosing remains to be fully characterized. Objectives: To determine the feasibility of dosing Haemate P-(R) VWF/factor VIII (FVIII) concentrate based on pharmacokinetics (PK) in the management of surgical subjects with VWD. Methods: VWD subjects scheduled for elective surgery were enrolled in a prospective multicenter open-label cohort study. A pre-operative loading dose of VWF/FVIII concentrate based upon prior individual subject PK analysis was administered followed by postoperative therapeutic/maintenance infusions. Results: Twenty-eight subjects with types 1, 2A or 3 VWD and one with type 2 M were enrolled. Median in vivo recovery of VWF ristocetin cofactor (VWF:RCo) was 1.9 IU dL(-1) (IU kg(-1))(-1) with an interquartile range (IQR) of 1.6-2.5 IU dL(-1) (IU kg(-1))(-1). Median response, half-life and clearance were 74.0% (IQR, 55.5-100%), 15.6 h (IQR, 9.0-28.4 h) and 3.26 mL kg(-1) h(-1) (IQR, 2.29-5.21 mL kg(-1) h(-1)), respectively. A PK-guided median VWF:RCo loading dose of 62.4 IU kg(-1) (IQR, 50.1-87.0 IU kg(-1)) was administered. Postoperative mean trough VWF:RCo levels of 62-73 IU dL(-1) were sufficient to prevent bleeding. Investigators rated hemostasis excellent or good in 96.3% of subjects on the day of surgery and 100% on the next day and on day 14. A subject with multiple risk factors developed pulmonary embolism, which resolved without sequelae. Conclusions: Haemate P-(R) provided effective and safe hemostasis in VWD subjects undergoing elective surgery. Selection of Haemate((R)) P loading dose on the basis of VWF PK proved feasible.
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| 36. |
- Lindqvist, P. G., et al.
(författare)
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Does an active sun exposure habit lower the risk of venous thrombotic events? A D-lightful hypothesis
- 2009
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 7:4, s. 605-610
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Tidskriftsartikel (refereegranskat)abstract
- Background: Venous and arterial thrombotic complications exhibit a seasonal variation, with risk peaking in winter and dropping to a nadir in summer. We sought a possible correlation between sun exposure habits and venous thromboembolism (VTE) events. Methods: This was a cohort study comprising 40 000 women (1000 per year of age from 25 to 64 years) who were drawn from the southern Swedish population registry for 1990 and followed for a mean of 11 years. Seventy-four per cent answered an inquiry at the inception of the study (n = 29 518), and provided detailed information on their sun exposure habits. Cox regression analysis was used with the presence of VTE as a dependent variable and selected demographics as independent variables. The main outcome was the relationship between VTE and sun exposure habits. Results: Swedish women who sunbathed during the summer, on winter vacations, or when abroad, or used a tanning bed, were at 30% lower risk of VTE than those who did not. Risk estimates did not change substantially after adjustment for demographic variables. The risk of VTE increased by 50% in winter as compared to the other seasons; the lowest risk was found in the summer. Conclusions: Women with more active sun exposure habits were at a significantly lower risk of VTE. We speculate that greater ultraviolet B light exposure improves a person's vitamin D status, which in turn enhances anticoagulant properties and enhances the cytokine profile.
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| 37. |
- Lindqvist, P G, et al.
(författare)
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Family secrets to be disclosed.
- 2006
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 4:10, s. 2180-2181
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Tidskriftsartikel (refereegranskat)
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