Rivaroxaban and Hemostasis in Emergency Care

Rivaroxaban is an oral, direct Factor Xa inhibitor, approved for the prevention and treatment of several thromboembolic disorders. Rivaroxaban does not require routine coagulation monitoring and has a short half-life. However, confirmation of rivaroxaban levels may be required in circumstances such as life-threatening bleeding or perioperative management. Here, we explore the management strategies in patients receiving rivaroxaban who have a bleeding emergency or require emergency surgery. Rivaroxaban plasma concentrations can be assessed quantitatively using anti-Factor Xa chromogenic assays, or qualitatively using prothrombin time assays (using rivaroxaban-sensitive reagents). In patients receiving long-term rivaroxaban therapy who require elective surgery, discontinuation of rivaroxaban 20-30 hours beforehand is normally sufficient to minimize bleeding risk. For emergency surgery, we advise against prophylactic use of hemostatic blood products, even with high rivaroxaban concentrations. Temporary rivaroxaban discontinuation is recommended if minor bleeding occurs; for severe bleeding, rivaroxaban withdrawal may be necessary, along with compression or appropriate surgical treatment. Supportive measures such as blood product administration might be beneficial. Life-threatening bleeding demands comprehensive hemostasis management, including potential use of agents such as prothrombin complex concentrate. Patients taking rivaroxaban who require emergency care for bleeding or surgery can be managed using established protocols and individualized assessment

Angiotensin converting enzyme intron 16 insertion/deletion genotype is associated with plasma C-reactive protein concentration in uteroplacental dysfunction

Introduction: Disturbance of the uteroplacental circulation (UPC) and the renin-angiotensin system are involved in the pathogenesis of preeclampsia. In women with history of preeclampsia persistently elevated C-reactive protein (CRP) levels have been described. The angiotensin-converting enzyme (ACE) intron 16 insertion/deletion (I/D) genotype is associated with ACE activity and assumed to be a risk factor for preeclampsia. As ACE generates proinflammatory angiotensin II, we analysed, whether ACE intron 16 I/D genotype is associated with CRP and whether this association exhibited a relation to uteroplacental dysfunction. Materials and methods: A total of 639 women have been followed during pregnancy with repeated measurements of CRP levels (observations: n=2333). ACE intron 16 I/D genotype was determined, and its association with CRP was assessed with adjustment for non-independent observations. Results: CRP levels of ACE D allele carriers were significantly higher than those of the ACE II (wild-type) genotype (p=0.0003, p adj=0.04). This relation was allele-dose dependent (p<10−4, p adj<0.02). Association between ACE I/D and CRP was significantly restricted to patients presenting with impaired UPC in univariate (p<0.04) and multivariate analyses (p=0.01). Conclusions: The ACE I/D genotype is significantly associated with CRP elevations during pregnancies complicated by disturbed UPC. Whether this effect on CRP is involved in pathogenesis of preeclampsia has to be elucidated

Diagnosis and treatment of peripartum bleeding

Severe peripartum hemorrhage (PPH) contributes to maternal morbidity and mortality and is one of the most frequent emergencies in obstetrics, occurring at a prevalence of 0.5-5.0%. Detection of antepartum risk factors is essential in order to implement preventive measures. Proper training of obstetric staff and publication of recommendations and guidelines can effectively reduce the frequency of PPH and its resulting morbidity and mortality. Therefore, an interdisciplinary expert committee was formed, with members from Germany, Austria, and Switzerland, to summarize recent scientific findings. An up-to-date presentation of the importance of embolization and of the diagnosis of coagulopathy in PPH is provided. Furthermore, the committee recommends changes in the management of PPH including new surgical options and the off-label use of recombinant factor VII

Gentherapie der Hämophilie: Empfehlung der Gesellschaft für Thrombose- und Hämostaseforschung (GTH).

Gene therapy has recently become a realistic treatment perspective for patients with haemophilia. Reviewing the literature and our personal experience from clinical trials, we discuss key aspects of haemophilia A and B gene therapy with vectors derived from adeno-associated virus (AAV), including predictable results, risks, adverse events, and patient-reported outcomes. Patient selection, informed consent, administration, and monitoring of gene therapy as well as data collection are explained. We also discuss the need for interdisciplinary cooperation with hepatology and other specialties. We emphasize structural and organizational requirements for treatment centres according to the hub-and-spoke model and recommend the use of electronic diaries to ensure safe and timely collection and exchange of data. Electronic diaries will play a key role as primary source of data for pharmacovigilance, post-marketing clinical studies, national and international registries, as well as health technology and benefit assessment. Reimbursement aspects and the future of gene therapy in adolescents and children are also considered. In a rapidly evolving scientific environment, these recommendations aim to support treatment providers and payers to prepare for the implementation of gene therapy following marketing authorization

Molecular characterization of Miraflores peach variety and relatives using SSRs

The definitive version is published in: http://www.sciencedirect.com/science/journal/03044238Some traditional peach varieties, originated from the region of Aragón (Spain), were analysed by SSRs (Simple Sequence Repeats). The aim of this research was to characterize 19 clones related to ‘Miraflores’ variety, with unknown pedigrees, to assess their genetic diversity and to elucidate their possible relationships with 10 traditional peach varieties. Twenty SSR primer pairs with high levels of polymorphism, which have been previously developed for peach, were used in this study. A total of 46 alleles were obtained for all the microsatellites studied, ranging from one to six alleles per locus, with a mean value of 2.3 alleles per locus. Fourteen SSRs were polymorphic in the set of varieties studied and permitted to distinguish 16 different genotypes out of the 30 initially studied, although fourteen ‘Miraflores’ clones showed identical gel profiles. The genetic distance matrix was used to construct Neighbor joining cluster and to perform principal coordinate analysis which allowed the arrangement of all the genotypes according to their genetic relationships. The genetic relationships among these traditional peach varieties, and in particular among ‘Miraflores’ clones are discussed. The obtained results confirm that microsatellite markers are very useful for these purposes.We are thankful to T.N. Zhebentyayeva and G.L. Reighard for helpful comments on the manuscript. This research was funded by CICYT (Comisión Interministerial de Ciencia y Tecnología, AGL2002-04219 and AGL 2005-05533), INIA (Instituto Nacional de Investigación y Tecnología Agraria y Alimentación, RF03-014-C2), Bilateral Spain-France (HF03-273) and DGA (A28, A44) projects and co-funded by the European Regional Development Fund. M. Bouhadida was supported by a fellowship from the AECI (Agencia Española de Cooperación Internacional) of the Spanish Ministry of Foreign Affairs.Peer reviewe

Modernes präoperatives Screening und Management primärer Hämostasestörungen

In einem präoperativen Screening mit Hilfe eines standardisierten Blutungsanamnesebogens und dem PFA-100 sind primäre Hämostasestörungen häufig, sekundäre (plasmatische) selten. Nach einer positiven Blutungsanamnese können mit dem PFA-100 über 90% der Hämostasestörungen erfaßt werden. In unserer Untersuchung wären ohne den PFA-100 27% der Patienten mit Hämostasestörungen nicht erkannt worden. Wenn die standardisierte Blutungsanamnese eindeutig negativ ist, kann auf ein präoperatives Screening mit den sogenannten Routinetests (aPTT u. Quick-Wert) verzichtet werden. Wenn der Quick-Wert, die aPTT, die Thrombozytenzahl und der PFA-100: Kollagen-Epinephrin nur in den indizierten Fällen mit positiver Blutungsanamnese (11.2%) durchgeführt würden, bedeutet das in Deutschland pro Jahr eine Einsparung von 14.2 Millionen Euro. In einer eigenen ersten Untersuchung wurde die Mikroangiopathie im Bereich der nutritiven Hautkapillaren (Fingernagelfalz) erstmal beim von Willebrand-Jürgens-Syndrom systematisch mit der intravitalen Videokapillarmikroskopie diagnostiziert. Die Nachfolgeuntersuchung an über 500 Patienten mit Hämostasestörungen im Vergleich zu einer Kontrollgruppe an Gesunden (n=100) bestätigte die Meßergebnisse für das von Willebrand-Jürgens-Syndrom (Typ 1 und 2a) und zeigte eine hohen positiven predictive value von 98%. Insbesondere die einfach und schnell durchgeführte Begutachtung der Kapillarmorphologie mit Veränderungen in Form von Kapillardilatationen, Extravasaten (frische oder alte Kapillarblutungen oder Blutungssäume) und gleichzeitig vorliegender Torquierung (Schlängelung) der Kapillaren ist bereits hoch prädiktiv (98%) für das Vorliegen eines von-Willebrand-Jürgens-Syndroms (Typ 1 und Typ 2a). In dem präoperativen therapeutischen Stufenkonzept zum Management primärer Hämostasestörungen zeigt sich die gute Wirksamkeit von DDAVP. Transfusionspflichtige Blutungen können bei Patienten mit primären Hämostasestörungen durch dieses präoperative Therapieregime verhindert werden. In der Patientengruppe mit primären Hämostasestörungen ohne präoperatives blutstillendes Management steigen die durchschnittlichen Kosten für die Transfusion von Blutkomponenten um das 5-fache auf ungefähr 1700 Euro. Hierbei sind Patientengruppen aller operativen Disziplinen berücksichtigt.In a preoperative screening using a standardized questionaire of bleeding history and the PFA-100 platelet analyzer, primary hemostatic disorders are frequently found, whereas secondary disorders are rare. In cases with a positive bleeding history more than 90% of hemostatic disorders can be identified by PFA-100 platelet analyzer. In our investigation 27% of patients with impaired hemostasis would have been missed without using the PFA-100 platelet analyzer. In cases where the standardized bleeding history is clearly negative, the "so-called" routine preoperative coagulation tests (aPTT and prothrombin time) can be left out. Assuming that PT, aPTT, platelet count and PFA-100:collagen-epinephrine would only be performed in indicated cases with positive bleeding history (11.2%), this would lead to reduction of costs of 14.2 million Euro. Our investigations started with a systematic examination of the micrangiopathy in the nutritive nailfold capillaries of patient with von Willebrand Disease (vWD) using the intravital video capillary microscopy. In a follow-up investigation microangiopathy in the nutritive nailfold capillaries was examined in more than 500 patients with hemostatic disorders and 100 healthy volunteers. The results confirmed the findings for the vWD (type 1 and type 2a) and showed a high positive predictive value of 98%. In the preoperative phased therapy plan approach in the management of primary hemostatic disorders, DDAVP shows a good drug action. In these patients, the PFA-100 platelet analyzer is able to determinate the hemostatic effect of drugs, such as DDAVP, tranexamic acid, aprotinin, conjugated estrogens and platelet transfusion. In the patient group with primary hemostatic disorders without preoperative management, the average costs for blood transfusions increases 5-fold to roughly 1700 Euro. In this consideration patients of all operative disciplines are included

Rivaroxaban and Hemostasis in Emergency Care

Rivaroxaban is an oral, direct Factor Xa inhibitor, approved for the prevention and treatment of several thromboembolic disorders. Rivaroxaban does not require routine coagulation monitoring and has a short half-life. However, confirmation of rivaroxaban levels may be required in circumstances such as life-threatening bleeding or perioperative management. Here, we explore the management strategies in patients receiving rivaroxaban who have a bleeding emergency or require emergency surgery. Rivaroxaban plasma concentrations can be assessed quantitatively using anti-Factor Xa chromogenic assays, or qualitatively using prothrombin time assays (using rivaroxaban-sensitive reagents). In patients receiving long-term rivaroxaban therapy who require elective surgery, discontinuation of rivaroxaban 20–30 hours beforehand is normally sufficient to minimize bleeding risk. For emergency surgery, we advise against prophylactic use of hemostatic blood products, even with high rivaroxaban concentrations. Temporary rivaroxaban discontinuation is recommended if minor bleeding occurs; for severe bleeding, rivaroxaban withdrawal may be necessary, along with compression or appropriate surgical treatment. Supportive measures such as blood product administration might be beneficial. Life-threatening bleeding demands comprehensive hemostasis management, including potential use of agents such as prothrombin complex concentrate. Patients taking rivaroxaban who require emergency care for bleeding or surgery can be managed using established protocols and individualized assessment