1,720,993 research outputs found
Impact of pharmacokinetic (CYP2C9) and pharmacodynamic (VKORC1, GGCX, CALU, EPHX1, F7, PROC) gene variants on phenprocoumon therapy
No full textImpact of pharmacokinetic (CYP2C9) and pharmacodynamic (VKORC1, GGCX, CALU, EPHX1, F7, PROC) gene variants on phenprocoumon therapy
No full textMütterliche Thrombophilie und geburtshilfliche Komplikationen
No full textWomen with thrombophilic defects have been shown to be at increased risk, not only of pregnancy associated thromboembolism but also of other vascular complications of pregnancy, including preeclampsia and fetal loss. First trimester fetal loss is associated with factor V Leiden mutation, activated protein C resistance without factor V Leiden mutation and prothrombin G20210A mutation. Late nonrecurrent fetal loss is associated with factor V Leiden mutation, prothrombin mutation and protein S deficiency. Concerning acquired thrombophilia, recurrent fetal loss is a well-documented finding in patients with antiphospholipid antibodies. Associations between thrombophilia polymorphisms and an increased risk of intrauterine growth restriction have been discussed in small series of cases but could not be confirmed in large scale studies. Frequencies for anticardiolipin antibodies or lupus anticoagulants and antinuclear antibodies were significantly higher in women with infants small for gestational age compared to controls. Concerning preeclampsia, gestational hypertension and thrombophilia, a number of studies have examined these relationships with conflicting results. For factor V Leiden, MTHFR C677T and prothrombin mutation, no association with preeclampsia was observed, when severe cases were excluded. If studies were restricted to those of severe preeclampsia, an association with the factor V Leiden mutation was apparent and, to a lesser extent, with the MTHFR-mutation. For antithrombotic therapy, it was shown that in women with antiphospholipid syndrome and recurrent pregnancy loss, unfractionated heparin plus lowdose aspirin results in significantly better gestational outcome than lowdose aspirin alone. Concerning therapy of women with inherited thrombophilia and pregnancy loss, only small, uncontrolled studies are available, demonstrating improved pregnancy outcome when low molecular weight heparin (LMWH) is used for treatment. In conclusion, heritable thrombophilia and the antiphospholipid-syndrome are major causes of fetal loss after exclusion of other underlying pathologies like chromosomal abnormalities, and screening should be recommended. LMWH with or without aspirin may be used for treatment. There is little value in antenatal screening for prothrombotic polymorphisms to predict the development of small for gestational age infants, preeclampsia or gestational hypertension.Frauen mit einer Thrombophilie haben nicht nur ein erhöhtes Risiko für schwangerschaftsassoziierte Thrombosen, sondern können auch andere vaskulare Komplikationen wie eine Praeklampsie oder eine erhöhte Abortrate aufweisen. Frühaborte im ersten Trimester sind signifikant mit der Faktor V Leiden-Mutation, der aktivierten Protein C-Resistenz ohne Nachweis einer Faktor V Leiden-Mutation und mit einer Prothrombinmutation (G20210A) assoziiert. Bei Frauen mit Spataborten können eine Faktor V Leiden-Mutation, eine Prothrombinmutation oder ein Protein S-Mangel von klinischer Relevanz sein. Bezüglich der erworbenen thrombophilen Neigungen lassen sich wiederholte Aborte besonders häufig beim Antiphospholipid-Syndrom nachweisen. Assoziationen zwischen thrombophilen Polymorphismen und einem erhöhten Risiko für eine intrauterine Wachstumsretardierung sind wiederholt in Studien mit kleinen Fallzahlen beobachtet worden, konnten jedoch in Studien mit großen Fallzahlen nicht bestätigt werden. Anticardiolipin-Antikörper oder Lupusantikoagulantien und antinukleare Antikörper waren dagegen signifikant häufiger bei Frauen, die Kinder mit einem zu niedrigen Geburtsgewicht geboren hatten, nachweisbar. Bezüglich einer Praeklampsie sowie des schwangerschaftsinduzierten Hypertonus und einer Thrombophilie zeigten sich in den durchgeführten Studien widersprüchliche Ergebnisse. Eine Assoziation zwischen der Faktor V Leiden Mutation, der MTHFR-Mutante und der Prothrombin G20210AMutation und einer Praeklampsie konnte nach Ausschluss der schweren Falle nicht beobachtet werden. Bei Analyse der schweren Falle zeigte sich jedoch eine Assoziation mit der Faktor V Leiden Mutation, und zu einem geringeren Ausmass, mit der MTHFR-Mutation.
Bezüglich einer antithrombotischen Therapie konnte bei Frauen mit Antiphospholipidsyndrom und wiederholten Aborten gezeigt werden, dass die Gabe von unfraktioniertem Heparin in Kombination mit Aspirin im
Vergleich zu alleiniger Gabe von Aspirin signifikant die Anzahl erfolgreicher Schwangerschaften erhöhen konnte. Bezüglich der Behandlung von Frauen mit angeborener Thrombophilie und Aborten existieren derzeit nur unkontrollierte Studien mit kleinen Fallzahlen, die einen Benefit unter Therapie mit niedermolekularem Heparin nachweisen konnten.
Zusammenfassend können sowohl die hereditäre Thrombophilie, als auch das Antiphospholipidsyndrom wesentlich bei der Pathogenese von habituellen Aborten beteiligt sein. In diesen Fallen kann ein Thrombophiliescreening zur weiteren Abklärung empfohlen werden. Niedermolekulares Heparin alleine oder in Kombination mit Aspirin stellt eine mögliche Behandlungsoption bei diesen Frauen dar. Bisher gibt es jedoch keine Rationale für ein generelles Screening bei Patientinnen mit Praeklampsie, schwangerschaftsinduziertem Hypertonus oder intrauteriner Wachstumsretardierung
Globaltest versus Profil: Wird das endogene Thrombinpotential das etablierte Thrombophiliescreening ablösen? Contra
No full textGlobal coagulation assays versus differentiated testing: will endogenous thrombin potential replace established thrombophilia screening? Contra
No full textReply: Fondaparinux and Direct Oral Anticoagulants: Promising Anticoagulant for Management of Heparin-Induced Thrombocytopenia.
No full textThrombophilia and risk of VTE recurrence according to the age at the time of first VTE manifestation
No full textBACKGROUND
Whether screening for thrombophilia is useful for patients after a first episode of venous thromboembolism (VTE) is a controversial issue. However, the impact of thrombophilia on the risk of recurrence may vary depending on the patient's age at the time of the first VTE.
PATIENTS AND METHODS
Of 1221 VTE patients (42 % males) registered in the MAISTHRO (MAin-ISar-THROmbosis) registry, 261 experienced VTE recurrence during a 5-year follow-up after the discontinuation of anticoagulant therapy.
RESULTS
Thrombophilia was more common among patients with VTE recurrence than those without (58.6 % vs. 50.3 %; p = 0.017). Stratifying patients by the age at the time of their initial VTE, Cox proportional hazards analyses adjusted for age, sex and the presence or absence of established risk factors revealed a heterozygous prothrombin (PT) G20210A mutation (hazard ratio (HR) 2.65; 95 %-confidence interval (CI) 1.71 - 4.12; p < 0.001), homozygosity/double heterozygosity for the factor V Leiden and/or PT mutation (HR 2.35; 95 %-CI 1.09 - 5.07, p = 0.030), and an antithrombin deficiency (HR 2.12; 95 %-CI 1.12 - 4.10; p = 0.021) to predict recurrent VTE in patients aged 40 years or older, whereas lupus anticoagulants (HR 3.05; 95%-CI 1.40 - 6.66; p = 0.005) increased the risk of recurrence in younger patients. Subgroup analyses revealed an increased risk of recurrence for a heterozygous factor V Leiden mutation only in young females without hormonal treatment whereas the predictive value of a heterozygous PT mutation was restricted to males over the age of 40 years.
CONCLUSIONS
Our data do not support a preference of younger patients for thrombophilia testing after a first venous thromboembolic event
Antifactor Xa Activity for the Management of Anticoagulation during Cardiac Surgery
No full textBackground In patients with autoimmune diseases associated with antiphospholipid antibodies, precise management of anticoagulation during extracorporeal circulation (ECC) is complicated. It was the aim of the present study to determine whether antifactor Xa (aXa) activity is useful in guiding heparin therapy during ECC. Methods In 15 patients undergoing cardiac surgery, anticoagulation with unfractionated heparin (UFH) and its reversal with protamine were guided using activated clotting time (ACT) (>400 second during ECC; ≤100 second for UFH reversal). For each ACT, the corresponding aXa activity levels were measured. Results A total of 144 blood samples were obtained. ACT and aXa activity were significantly correlated (r = 0.771, p 400 seconds and 0.55 IU/mL (AUC: 0.85; inaccuracy rate: 13.3%) for ACT ≤ 100 seconds. Conclusion AXa activity is strongly correlated with ACT, and therefore may be feasible for managing anticoagulation with UFH during ECC
Nadroparin carries a potentially high risk of inducing cutaneous delayed-type hypersensitivity responses.
No full textBACKGROUND
Heparins are widely used for the prophylaxis/treatment of thromboembolic events. As adverse effects, heparin-induced skin lesions occur frequently (in 7.5-39% of patients). Skin lesions may be the only clinical manifestation of life-threatening immune-mediated heparin-induced thrombocytopenia, but are commonly caused by a delayed-type hypersensitivity response [heparin-induced delayed-type hypersensitivity (HIHS)]. Risk factors have not been prospectively identified.
OBJECTIVES
To identify possible risk factors for heparin-induced skin lesions from three independent clinical trials in a combined analysis.
METHODS
A pooled analysis from prospective studies was performed, and possible risk factors were included in a multiple logistic regression analysis.
RESULTS
Obesity (body mass index of > 25), prolonged anticoagulant therapy, prior heparin exposure and younger age (< 55 years) were confirmed as independent risk factors for HIHS. The choice of anticoagulant preparation had the greatest influence. On comparison of dalteparin, enoxaparin, fondaparinux, unfractionated heparin, and nadroparin, the latter was associated with the highest risk of eliciting HIHS (odds ratio of 30.2, 95%CI: 11.7-77.9).
CONCLUSIONS
The high risk associated with nadroparin has been validated in controlled trials, and this emphasizes the singularity of each heparin preparation in terms of allergenicity and that individualized anticoagulation is required
New oral anticoagulants in patients with nonvalvular atrial fibrillation: a review of pharmacokinetics, safety, efficacy, quality of life, and cost effectiveness
No full textHelen Mani, Edelgard Lindhoff-LastJohann Wolfgang Goethe-University Hospital Frankfurt/Main, Department of Internal Medicine, Division of Haemostasis, Frankfurt, GermanyAbstract: Atrial fibrillation (AF) continues to be a leading cause of cerebrovascular morbidity and mortality resulting from cardioembolic stroke. Oral anticoagulation therapy has been shown to decrease the incidence of cardioembolic stroke in patients with AF by more than 50%. Appropriate use of anticoagulation with vitamin K antagonists requires precise adherence and monitoring. A number of factors that potentially induce patients’ dissatisfaction reduce quality of patient life. New direct oral anticoagulants, such as the direct factor Xa inhibitors rivaroxaban, apixaban, edoxaban, and the thrombin inhibitor dabigatran, were developed to overcome the limitations of the conventional anticoagulant drugs. However, models to optimize the benefit of therapy and to ensure that therapy can be safely continued are missing for the new oral anticoagulants. This review will briefly describe the new oral anticoagulants dabigatran, rivaroxaban, apixaban, and edoxaban with focus on their use for prevention of embolic events in AF. Moreover, it will discuss the safety, efficacy, cost data, and benefit for patients' quality of life and adherence.Keywords: apixaban, edoxaban, rivaroxaban, dabigatran, oral anticoagulatio
- …
