| 1. |
- Holm, Elena, et al.
(författare)
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Changes in bleeding patterns in von Willebrand disease after institution of long-term replacement therapy: results from the von Willebrand Disease Prophylaxis Network.
- 2015
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Ingår i: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 26:4, s. 383-388
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Tidskriftsartikel (refereegranskat)abstract
- Clinically, the leading symptom in von Willebrand disease (VWD) is bleeding, chiefly of mucosal type, for example, epistaxis, gingival, or gastrointestinal bleeding, and menorrhagia. In severe forms of VWD with secondary deficiency of factor VIII, spontaneous joint bleeding, resembling that observed in severe haemophilia A, may also be observed. The bleeding patterns of VWD can affect quality of life, and may be life-threatening. The von Willebrand Disease Prophylaxis Network is an international study group formed with the goal of investigating the role of prophylaxis in clinically severe VWD. The objective of the present study is to investigate the response to prophylaxis focusing primarily on epistaxis, joint bleeding, gastrointestinal bleeding, and heavy bleeding associated with menses. Data from 105 subjects, 10 enrolled in a prospective study and 95 in a retrospective study between 2008 and 2013, were available for analysis. The median annualized rate reductions in bleeding were significant for epistaxis (P < 0.0001), gastrointestinal bleeding (P = 0.0003), joint bleeding (P < 0.0001), and menorrhagia (P = 0.008). Doses on a group level were approximately the same prior to and during prophylaxis, but more patients with gastrointestinal bleeding had prophylaxis three or more times per week as well as higher dosages. Our study, which primarily used retrospective data, indicates that prospective studies are needed to better delineate the doses and dose intervals that should be used for prophylactic treatment of VWD.
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| 2. |
- Steen, Mårten, et al.
(författare)
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Functional characterization of Factor V-Ile359Thr, a novel mutation associated with thrombosis.
- 2004
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 103:9, s. 3381-3387
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Tidskriftsartikel (refereegranskat)abstract
- A missense mutation, FV-IIe359Thr (FV Liverpool), associated with thrombosis has recently been described. This mutation creates an additional potential N-linked glycosylation site (Asn-X-Ser/Thr) in factor V (FV) at Asn357 that could interfere with secretion and/or protein interactions. To investigate the molecular pathology of FV-IIe359Thr, the mutation was created by site-directed mutagenesis and expressed together with other mutations that could help explain the phenotype (FV-Arg306GIn/IIe359Thr/Arg679GIn, FV-IIe359Thr/Arg506GIn/Arg679GIn, and FV-Asn357GIn/IIe359Thr). The FV-IIe359Thr was secreted normally and had full procoagulant activity. Western blot analysis showed that FV-IIe359Thr migrated more slowly, while the FV-Asn357GIn/IIe359Thr was indistinguishable from FV-wild type (FV-WT), indicating that FV-IIe359Thr was expressed with an additional carbohydrate chain. Activated protein C (APC)-mediated inactivation in an FVa degradation assay showed that the IIe359Thr mutation significantly reduced the cleavage at Arg306 both in the presence and absence of protein S, whereas the cleavage at Arg506 was unaffected. When tested in an FVIIIa degradation assay, the FV-IIe359Thr variant exhibited equally low APC cofactor activity as FV Leiden (FVArg506GIn). In conclusion, the IIe359Thr mutation appears to affect anticoagulation by 2 mechanisms, impeding the APCmediated down-regulation of the FVa molecule and additionally being a poor APC cofactor for the down-regulation of FVIIIa. These findings explain the association of the FV-IIe359Thr mutation with thrombosis. (C) 2004 by The American Society of Hematology.
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| 3. |
- Toy, Pearl, et al.
(författare)
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Transfusion-related Acute Lung Injury: 36 Years of Progress (1985-2021)
- 2022
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Ingår i: Proceedings of the American Thoracic Society online. - : AMER THORACIC SOC. - 1546-3222 .- 1943-5665. ; 19:5, s. 705-712
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Forskningsöversikt (refereegranskat)abstract
- The term transfusion-related acute lung injury (TRALI) was coined in 1985 to describe acute respiratory distress syndrome (ARDS) after transfusion, when another ARDS risk factor was absent; TRALI cases were mostly associated with donor leukocyte antibody. In 2001, plasma from multiparous donors was implicated in TRALI in a randomized controlled trial in Sweden. In 2003 and in many years thereafter, the U.S. Food and Drug Administration reported that TRALI was the leading cause of death from transfusion in the United States. In 2003, the United Kingdom was the first among many countries to successfully reduce TRALI using male-predominant plasma. These successes are to be celebrated. Nevertheless, questions remain about the mechanisms of non-antibody TRALI, the role of blood products in the development of ARDS in patients receiving massive transfusion, the causes of unusual TRALI cases, and how to reduce inaccurate diagnoses of TRALI in clinical practice. Regarding the latter, a study in 2013-2015 at 169 U.S. hospitals found that many TRALI diagnoses did not meet clinical definitions. In 2019, a consensus panel established a more precise terminology for clinical diagnosis: TRALI type I and TRALI type II are cases where transfusion is the likely cause, and ARDS are cases where transfusion is not the likely cause. For accurate diagnosis using these clinical definitions, critical care or pulmonary expertise is needed to distinguish between permeability versus hydrostatic pulmonary edema, to determine whether an ARDS risk factor is present, and, if so, to determine whether respiratory function was stable within the 12 hours before transfusion.
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