| 11. |
- Berntorp, Erik
(författare)
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Prophylaxis and treatment of bleeding complications in von Willebrand disease type 3.
- 2006
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Ingår i: Seminars in Thrombosis and Hemostasis. - : Georg Thieme Verlag. - 1098-9064 .- 0094-6176. ; 32:6, s. 621-625
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Tidskriftsartikel (refereegranskat)abstract
- Treatment of type 3 von Willebrand disease (vWD) relies on infusion with plasma-derived factor concentrates containing von Willebrand factor (vWF). Patients with types 1 and 2 vWD who do not respond satisfactorily after receiving desmopressin need treatment with concentrates. The rationale for long-term prophylaxis in vWD is obvious: prophylaxis has been successfully used in hemophilia, and joint hemorrhages with development of hemophilic arthropathy can occur, especially in type 3 vWD. In Sweden, prophylaxis for vWD began during the 1960s, and we now have experience from a cohort of 37 patients treated for a median of 11 years (range, 2 to 45 years). The majority of subjects (n = 28) have type 3 vWD. The mean dose used for treatment is 24 units factor VIII/kg body weight given one to three times weekly. Indications for prophylaxis have included joint bleeds, bleeds from nose and mouth, menorrhagia and gastrointestinal bleeds. The annual number of bleeds has decreased dramatically following onset of prophylaxis. We conclude that long-term prophylactic treatment of vWD is warranted in the majority of cases with type 3 and in some cases, depending on the clinical phenotype, for patients with other subtypes. Additional studies are ongoing in an international effort, the von Willebrand Disease Prophylaxis Network.
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| 12. |
- Berntorp, Erik, et al.
(författare)
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Prophylaxis for Hemophilia in the Era of Extended Half-Life Factor VIII/Factor IX Products
- 2016
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Ingår i: Seminars in Thrombosis and Hemostasis. - : Georg Thieme Verlag. - 0094-6176 .- 1098-9064. ; 42:5, s. 518-525
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Tidskriftsartikel (refereegranskat)abstract
- There are two main bioengineering approaches to extending the half-life of factor (F)VIII or FIX products used for hemophilia replacement therapy. These are fusion to Fc-immunoglobulin G (FVIII and FIX) or to albumin (FIX) or pegylation/glycopegylation (FVIII and FIX). Four FVIII and three FIX products are in clinical development or have recently been licensed in regions of the world. The reported half-life extension is approximately 1.5-fold for FVIII and 2.5-fold, or even longer, for FIX. Clinical trials have shown promising results with respect to extension of dose intervals and efficacy in the treatment and prevention of bleeding events. The role of these products in clinical practice has been discussed in terms of either improving convenience and adherence through prolongation of the interval between infusions or maintaining current intervals thereby increasing trough levels and the safety margin against bleeds. This review of extended half-life products addresses the possibilities and problems of their introduction in hemophilia treatment.
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| 13. |
- Berntorp, Erik
(författare)
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Recombinant FVIIa in the treatment of warfarin bleeding
- 2000
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Ingår i: Seminars in Thrombosis and Hemostasis. - : Georg Thieme Verlag. - 1098-9064 .- 0094-6176. ; 26:4, s. 433-433
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Tidskriftsartikel (refereegranskat)abstract
- Patients receiving oral anticoagulant treatment have abnormally low levels of functional vitamin K-dependent coagulation proteins and consequently a clear risk of hemorrhagic complications. The incidence of hemorrhages has been reported to be around 0.6-0.7% per month at a therapeutic International Normalized Ratio (INR) and the incidence of major hemorrhagic events is substantial. Therefore, the ability to reverse the anti-vitamin K effect is of utmost importance, and if an immediate reversal is necessary, plasma or prothrombin complex concentrates are used. As plasma-derived products carry the risk of transmission of blood-borne viruses and also of thromboembolic complications, it is desirable to test new potential tools for oral anticoagulant reversal. Recombinant factor VIIa (FVIIa) has been tested in rats and humans treated with antivitamin K drugs with seemingly good effect on hemostasis and laboratory parameters. Even if more data are needed before any definite conclusions can be drawn, the outlook so far seems promising.
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| 14. |
- Berntorp, Erik, et al.
(författare)
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Standardization and clinical utility of thrombin-generation assays.
- 2008
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Ingår i: Seminars in Thrombosis and Hemostasis. - : Georg Thieme Verlag. - 1098-9064 .- 0094-6176. ; 34:7, s. 670-682
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Tidskriftsartikel (refereegranskat)abstract
- Thrombin generation is a key process that determines the extent of a hemostatic plug or a thrombotic process. The ensuing thrombin burst is crucial for the formation of a stable fibrin clot. During its active life, thrombin exerts a multitude of highly regulated actions on the blood and the vessel wall, including the clotting of fibrinogen. The inappropriate generation of thrombin may lead to pathologic processes, foremost of which are hemorrhagic or thrombotic diseases. The coagulation system is usually investigated by means of two in vitro classic clotting tests, the activated partial thromboplastin time (APTT) and prothrombin time (PT), which assess only time to initiation of clot formation and do not entirely reflect global hemostatic balance. The APTT and PT permit identification of connectivity between the component activities identified as required for plasma coagulation and define the concept of intrinsic and extrinsic coagulation pathways, which converge at the point of formation of the prothrombinase complex. However, the mechanisms established by in vitro tests are not always mirrored in the human pathologies associated with bleeding or thrombosis. The recent development of newer tests based on the continuous registration of thrombin generation under in vitro conditions that mimic more closely what occurs in vivo prompt a reinvestigation of the balance between procoagulants and anticoagulants in patients with various hemostatic disorders. Thrombin-generation assays not only provide an overall assessment of hemostasis but also target potential extrahemostatic effects of the generated thrombin, a potent agonist of a multitude of cellular activation pathways. Moreover, estimation of an individual's thrombin-generation potential may correlate more closely with a hypercoagulable or hypocoagulable phenotype when compared with traditional coagulation tests. In this review, we discuss to what extent thrombin generation can be expected to reflect the clotting function of blood, the development and use of different thrombin-generation assay systems suitable for detecting changes in the kinetics of thrombin generation, and the clinical utility of thrombin generation.
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| 15. |
- Berntorp, Erik, et al.
(författare)
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The next generation of hemophilia treatment specialists
- 2006
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Ingår i: Seminars in Thrombosis and Hemostasis. - : Georg Thieme Verlag. - 1098-9064 .- 0094-6176. ; 32, s. 39-42
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Tidskriftsartikel (refereegranskat)abstract
- We currently are witnessing a serious attrition of physicians specializing in hemophilia treatment in Europe and the United States while most physicians who complete training in hematology-oncology choose oncology practice as their career. Nevertheless, recent therapeutic developments, including advances in prophylaxis and inhibitor management, have renewed the demand for experts in hemophilia and related disorders. To meet this demand, several specialty training programs have been developed in the United States and Europe, specifically the International Course in Hemophilia in Malmo, Sweden, the Children's Hospital of Los Angeles International Pediatric Hemostasis and Thrombosis Program, and the Baxter/National Hemophilia Foundation Fellowship Programs. The purpose of these programs is to enhance the clinical expertise and further the professional development of individuals dedicated to treating patients with coagulation disorders.
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| 16. |
- Birgegard, Gunnar
(författare)
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Anagrelide treatment in myeloproliferative disorders
- 2006
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Ingår i: Seminars in Thrombosis and Hemostasis. - : Georg Thieme Verlag KG. - 0094-6176 .- 1098-9064. ; 32:3, s. 260-266
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Tidskriftsartikel (refereegranskat)abstract
- Platelet-lowering therapy in myeloproliferative disorders includes cytostatic drugs, mainly hydroxyurea, interferon alpha, and anagrelide. Anagrelide is the latest addition to the therapeutic arsenal, and the basis for its use is reviewed. The platelet-lowering efficacy is 70 to 80% in essential thrombocythemia, and the response is rapid; most of the patients reach the treatment goal within a few weeks. Side effects are common, mainly caused by the vascular effects, and include palpitation, headache, loose stools/diarrhea, and edema. Some side effects are time-limited, but late dropout from therapy is not uncommon. The total dropout rate in prospective studies is 30 to 50%. Pharmacologic treatment of side effects is often helpful. Cardiac insufficiency may be worsened in patients with previous heart failure, and special caution is warranted in such patients. Anagrelide has recently been registered in Europe as a second-line therapy in ET but is often used as first-line therapy in the United States, especially in younger patients, due to the concern about increased leukemia risk with cytostatic treatment. The first randomized anagrelide study, with its limitations, gives support for the second-line registration. Given that dose escalation is a problem in some patients with all therapeutic agents used, combination of two drugs in lower doses is a practical option already used by many clinicians without basis in any published study.
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| 17. |
- Cao, YH, et al.
(författare)
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Angiostatin
- 2004
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Ingår i: Seminars in thrombosis and hemostasis. - : Georg Thieme Verlag KG. - 0094-6176 .- 1098-9064. ; 30:1, s. 83-93
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Tidskriftsartikel (refereegranskat)
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| 18. |
- Dahlbäck, Björn
(författare)
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C4b-Binding Protein: A Forgotten Factor in Thrombosis and Hemostasis
- 2011
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Ingår i: Seminars in Thrombosis and Hemostasis. - : Georg Thieme Verlag. - 1098-9064 .- 0094-6176. ; 37:4, s. 355-361
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Tidskriftsartikel (refereegranskat)abstract
- Blood coagulation and complement pathways are two important natural defense systems. The high affinity interaction between the anticoagulant vitamin K-dependent protein S and the complement regulator C4b-binding protein (C4BP) is a direct physical link between the two systems. In human plasma, similar to 70% of total protein S circulates in complex with C4BP; the remaining is free. The anticoagulant activity of protein S is mainly expressed by the free form, although the protein S-C4BP complex has recently been shown to have some anticoagulant activity. The high affinity, binding of protein S to C4BP provides C4BP with the ability to bind to negatively charged phospholipid membranes, which serves the purpose of localizing complement regulatory activity close to the membrane. Even though C4BP does not directly affect the coagulation system, it still influences the regulation of blood coagulation through its interaction with protein S. This is particularly important in states of inherited deficiency of protein S where the tight binding of protein S to C4BP results in a pronounced and selective drop in concentration of free protein S, whereas the concentration of protein S in complex with C4BP remains relatively unchanged. This review summarizes the current knowledge on C4BP with respect to its association with thrombosis and hemostasis.
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| 19. |
- Dahlbäck, Björn
(författare)
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Vitamin K–Dependent Protein S : Beyond the Protein C Pathway
- 2018
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Ingår i: Seminars in Thrombosis and Hemostasis. - : Georg Thieme Verlag. - 0094-6176 .- 1098-9064. ; 44:2, s. 176-184
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Tidskriftsartikel (refereegranskat)abstract
- Protein S is a vitamin K–dependent plasma glycoprotein circulating in plasma at a concentration of around 350 nM. Approximately 60% of protein S in human plasma is bound to the complement regulatory protein C4b-binding protein (C4BP) in a high-affinity, high-molecular-weight complex. Protein S in plasma has multiple anticoagulant properties and heterozygous protein S deficiency is associated with increased risk of venous thrombosis. Homozygous deficiency in man and mice is associated with severe thrombosis in fetal life, defects in the vascular system development, and not compatible with life. Protein S has additional functions beyond being an anticoagulant. It affects the complement regulatory properties of C4BP, and moreover, protein S interacts with tyrosine kinase receptors of the TAM family, which comprises Tyro3, Axl, and Mer. The TAM receptor interaction is important for the ability of protein S to stimulate phagocytosis of apoptotic cells. This review will discuss the multiple functions of protein S, describing its role as cofactor to activated protein C with a subsequent focus on the other functions of protein S.
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| 20. |
- Fischer, Kathelijn, et al.
(författare)
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Targeting Factor Replacement Therapy in Severe Hemophilia: Which Level Is Important?
- 2015
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Ingår i: Seminars in Thrombosis and Hemostasis. - : Georg Thieme Verlag. - 1098-9064 .- 0094-6176. ; 41:8, s. 860-863
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Tidskriftsartikel (refereegranskat)abstract
- The original aim of prophylactic replacement therapy was to convert the bleeding pattern of severe hemophilia to that of moderate hemophilia through regular infusions of clotting factor concentrates. However, targeting prophylaxis on minimum trough levels does not prevent all bleeding. At the group level, there is a clear association of factor levels with bleeding and outcome. But bleeding phenotype in individual patients shows large variation, independent of trough levels maintained. The association of peak levels with bleeding on prophylaxis is not established. Experience with surgery suggests that certain peak levels need to be achieved during other hemostatic challenges, such as playing sports. Individualization of prophylaxis should include timing of infusion according to special activities. The clinical relevance of factor levels is even more urgent since the recent introduction of long-acting clotting factor concentrates with their different pharmacokinetic profiles and the prospect of gene therapy resulting in constant factor levels. It should be considered that the success of any prophylactic regimen is also dependent on other factors, such as the age at initiation of prophylaxis, adherence, lifestyle, cartilage susceptibility, and the other components of the clotting system. Factor levels are thus an important but quite small piece in the total picture of treating hemophilia and we currently cannot identify a specific trough or peak level to use for monitoring. At the same time, knowledge of a patients' level during the infusion intervals may help to individualize and adjust treatment according to the clinical symptoms.
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