| 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. |
- 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 KG. - 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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| 4. |
- 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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| 5. |
- 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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| 6. |
- 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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| 7. |
- Lubenow, Norbert, et al.
(författare)
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Hirudin in heparin-induced thrombocytopenia.
- 2002
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Ingår i: Seminars in Thrombosis and Hemostasis. - : Georg Thieme Verlag KG. - 0094-6176 .- 1098-9064. ; 28:5, s. 431-8
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Tidskriftsartikel (refereegranskat)abstract
- Heparin-induced thrombocytopenia (HIT), a serious side effect of heparin treatment, requires alternative anticoagulation in most affected patients. The recombinant hirudin (r-hirudin) lepirudin has been approved for this purpose after two prospective trials in laboratory-confirmed HIT patients. Other drugs available for this purpose are danaparoid sodium (a heparinoid) and argatroban, a synthetic direct thrombin inhibitor. In this article, recommendations for optimal use of r-hirudin in HIT are given, covering therapy in uncomplicated patients as well as in special situations such as heparin reexposure of HIT patients. Because lepirudin's half-life depends on renal function, it may vary between 1 and 200 hours, which requires individual dose adjustments. Lepirudin compares favorably with danaparoid, based on retrospective data. No direct comparisons of lepirudin with argatroban are available, but argatroban might offer advantages in patients with renal failure, because it is mainly eliminated hepatically. Major hemorrhage, the main risk of lepirudin treatment, occurring in about 15% of patients, makes close monitoring important. New monitoring tools, such as the ecarin clotting time (ECT), might further reduce bleeding risks. Antihirudin antibodies, which can alter the pharmacokinetics as well as the pharmacodynamics of hirudin, can also be countered by close monitoring and appropriate dose adjustments. Whereas hirudins have not yet managed to gain importance in non-HIT indications such as unstable coronary syndromes, they have a major role to play in the treatment of HIT. The choice between the available drugs for HIT, namely lepirudin, danaparoid, and argatroban, has to be made according to the clinical presentation of the patient.
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