| 1. |
- Astermark, Jan
(författare)
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Treatment of the bleeding inhibitor patient
- 2003
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Ingår i: Seminars in Thrombosis and Hemostasis. - : Georg Thieme Verlag KG. - 1098-9064 .- 0094-6176. ; 29:1, s. 77-85
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Tidskriftsartikel (refereegranskat)abstract
- The development of inhibitory antibodies to factor (F) VIII and FIX continues to be a major challenge in the treatment of patients with hemophilia. In patients with low-responding inhibitors, it is usually possible to saturate the inhibitor with the deficient factor and to achieve hemostasis, but in patients with high-responding inhibitors, two major tasks have to be considered. One is how to treat the acute bleedings and the other is how to permanently eliminate the immune response, in other words, to induce tolerance. There are several hemostatic agents available for bleeding patients with high-responding inhibitors. Nonactivated and activated prothrombin complex concentrates (PCCs) have been used for almost 30 years, and since the beginning of the 1980s, porcine FVIII has also been used. In more recent years, recombinant FVIIa has been added to the therapeutic armamentarium and has been shown to control hemostasis in most patients. Immunoadsorption may temporarily reduce the inhibitor, enabling replacement therapy for several days. Available data on these alternative regimens will be discussed with a focus on the mechanisms of action, pharmacokinetics, safety, monitoring, and clinical experience.
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| 2. |
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| 3. |
- Lethagen, Stefan
(författare)
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Desmopressin in mild hemophilia A: indications, limitations, efficacy, and safety.
- 2003
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Ingår i: Seminars in Thrombosis and Hemostasis. - : Georg Thieme Verlag KG. - 1098-9064 .- 0094-6176. ; 29:1, s. 101-105
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Tidskriftsartikel (refereegranskat)abstract
- Replacement therapy with blood products has long been the only available therapeutic option for patients with bleeding disorders. Plasma-derived cryoprecipitate and factor (F) VIII concentrates, which have been used for hemophilia A patients, involve the risk of transmitting blood-borne diseases. Both plasma-derived and recombinant FVIII concentrates are expensive, and there is a global shortage. The synthetic vasopressin analogue desmopressin acetate (1-deamino-[8-D-arginine]-vasopressin, DDAVP) increases plasma concentrations of coagulation FVIII and von Willebrand factor (vWF) two fold to six fold through endogenous release. The drug is an attractive therapeutic alternative because it carries no risk of transmission of infectious diseases. Desmopressin is today a widely used hemostatic agent not only in patients with mild hemophilia A or von Willebrand disease (vWD) but also in those with congenital or acquired platelet dysfunction. There is a long clinical experience with the drug because it has been used for prevention of bleedings in connection with invasive procedures and for treatment of bleedings since the mid-1970s. Not all hemophilia A patients can be treated. The clinical usefulness depends on the postdesmopressin plasma concentration of FVIII, which in turn depends on the patient's basal FVIII level. Therefore, a test dose is recommended in candidate patients. In general, only the mildest hemophilia A patients respond sufficiently. Optimal hemostatic effect is achieved with a dosage of 0.3 μg/kg given intravenously. An intranasal desmopressin spray is suitable for the home treatment.
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| 4. |
- Ljung, Rolf, et al.
(författare)
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Genetic counselling of haemophilia carriers
- 2003
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Ingår i: Seminars in Thrombosis and Hemostasis. - : Georg Thieme Verlag KG. - 1098-9064 .- 0094-6176. ; 29:1, s. 31-36
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Tidskriftsartikel (refereegranskat)abstract
- Basic analysis of a potential carrier includes calculation of the probability, or odds, for carriership based on pedigree and clotting factor analysis. Genotype assessment constitutes a more accurate method of carrier detection. Where circumstances permit, the genetic diagnosis of hemophilia should be based on the direct identification of the pathogenic mutation in the factor (F) VIII gene. Neutral mutations in the FVIII gene and the risk of mosaicism (a mixture of normal and mutation carrying cells) in sporadic families may cause misclassification. If it is not possible to use the mutation for diagnostic purposes, it may be possible to use linked polymorphic markers (restriction fragment length polymorphisms [RFLP]) to trace the inheritance of the hemophilia gene within a pedigree. Linkage analysis is limited because of uninformative patterns of polymorphic markers, ethnic variation, linkage disequilibrium, and the need for participation of family members, and it is not useful in sporadic families, which constitute more than half of the hemophilia families. Potential carriers of hemophilia should be offered qualified assistance in genetic information, testing, and counseling to help them to cope with the psychological and ethical problems related to carriership of a genetic disorder.
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