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The root cause of autoantibody formation against factor VIII (FVIII) in acquired hemophilia A (AHA) remains unclear. We aimed to assess whether AHA is exclusively associated with autoantibodies toward FVIII or whether patients also produce increased levels of autoantibodies against other targets. A case-control study was performed enrolling patients with AHA and age-matched controls. Human epithelial cell (HEp-2) immunofluorescence was applied to screen for antinuclear (ANA) and anticytoplasmic autoantibodies. Screening for autoantibodies against extractable nuclear antigens was performed by enzyme immunoassay detecting SS-A/Ro, SS-B/La, U1RNP, Scl-70, Jo-1, centromere B, Sm, double-stranded DNA, and α-fodrin (AF). Patients with AHA were more often positive for ANA than control patients (64% vs 30%; odds ratio [OR] 4.02, 1.98-8.18) and had higher ANA titers detected than controls. Cytoplasmic autoantibodies and anti-AF immunoglobulin A autoantibodies were also more frequent in patients with AHA compared with controls. Autoantibodies against any target other than FVIII were found in 78% of patients with AHA compared with 46% of controls (OR 4.16, 1.98-8.39). Results were similar preforming sensitivity analyses (excluding either subjects with autoimmune disorders, cancer, pregnancy, or immunosuppressive medication at baseline) and in multivariable binary logistic regression. To exclude that autoantibody staining was merely a result of cross-reactivity of anti-FVIII autoantibodies, we tested a mix of 7 well-characterized monoclonal anti-FVIII antibodies. These antibodies did not stain HEp-2 cells used for ANA detection. In conclusion, a diverse pattern of autoantibodies is associated with AHA, suggesting that a more general breakdown of immune tolerance might be involved in its pathology.

Acquired von Willebrand Syndrome (AVWS) is a rare coagulation disorder which can be associated with IgM paraproteinaemia. Recently, recombinant von Willebrand factor (rVWF) has become available for the treatment of bleedings in patients with inherited von Willebrand disease, but experience in patients with AVWS is limited. We report on 2 patients with AVWS with underlying IgM paraproteinaemia with distinct underlying pathomechanisms. In 1 patient, the paraprotein built unspecific complexes with von Willebrand factor (VWF). In the other patient, we were able to detect an IgM antibody against VWF. Bleeding in this patient was successfully treated with rVWF. To our knowledge, this is the first report about the successful use of rVWF in a patient with AVWS with the detection of a VWF-specific antibody.

In the last couple of years sex specific health issues have continually been gaining attraction by physicians of different medical specialities. Sex differences have been described e.g. in the pathogenesis and mortality in patients affected by COVID-19, in metabolic regulation and cancer mechanisms.1 2 3 In the field of haemostasis, many aspects concerning risk factors, clinical presentation and management of thromboembolic disease and bleeding disorders also display sex differences.

Antithrombin (AT) deficiency is a high-risk thrombophilia and a rare condition. The risk of venous thromboembolism (VTE) is increased in AT-deficient women during pregnancy and the postpartum period and is especially high in women with a prior history of VTE. A thorough assessment of VTE risk is recommended in pregnant AT-deficient women, comprising the degree and type of AT deficiency, genetic mutations, personal and family history, and additional preexisting or pregnancy-specific risk factors. Due to a lack of adequate study data, there is limited guidance on the management of AT deficiency in pregnancy, including the need for prophylactic anticoagulation, the appropriate dose of low-molecular-weight heparin (LMWH), and the role of AT substitution. LMWH is the medication of choice for the pharmacological prophylaxis and treatment of VTE in pregnancy. Patients with a history of VTE should receive full-dose LMWH during pregnancy and the postpartum period. AT concentrates are a treatment option when anticoagulation is withheld in potentially high-risk events such as childbirth, bleeding, or surgery and in cases of acute VTE despite the use of therapeutic dose anticoagulation. Women with AT deficiency should be counseled at specialized centers for coagulation disorders or vascular medicine, and close cooperation between obstetricians and anesthesiologists is warranted before delivery and during the peripartum period.

The lifetime risk of venous thromboembolism (VTE) is slightly higher in women than in men. There are several issues related to VTE that are unique to women. Combined hormonal contraceptives and pregnancy increase the risk of VTE in women of childbearing age, whereas hormone replacement therapy increases the VTE risk of postmenopausal women. Hereditary thrombophilia and risk factors such as older age, obesity, or smoking contribute to the risk increase. In women diagnosed with acute hormone-related VTE who are treated with oral anticoagulants, adequate contraception is mandatory to avoid unwanted pregnancies. According to current knowledge, hormonal contraception may be continued during anticoagulant therapy but must be switched to an estrogen-free contraception method at least 6 weeks before the termination of anticoagulation. VTE is also a major cause of maternal morbidity and mortality during pregnancy and the postpartum period. Currently, assisted reproduction technologies such as in vitro fertilization are widely used to treat couples affected by infertility. Complications of fertility treatment comprise VTE cases, especially in women with ovarian hyperstimulation syndrome. With this review, we intended to focus on VTE issues in women and summarize current evidence and guideline recommendations.

Zusammenfassung Hormonelle Kontrazeption und Thromboembolie-Risiko Kombinierte hormonelle Kontrazeptiva (KK) erhöhen das VTE-Risiko signifikant. Gestagen-Monopräparate sind mit Ausnahme der 3-Monatsspritze nicht mit einem erhöhten VTE-Risiko assoziiert und können bei Frauen mit vorausgegangener VTE oder thrombophilen Risikofaktoren mit Wunsch nach hormoneller Verhütung angewandt werden. Individuelle Risikofaktoren und hormonelle Kontrazeption Vor der Verschreibung einer hormonellen Kontrazeption soll eine sorgfältige Erhebung des VTE-Risikos erfolgen. Eine entsprechende Checkliste findet sich auf der Internetseite des BfArM. Eine routinemäßige Testung auf hereditäre Thrombophilie wird nicht empfohlen. Kontrazeption unter Antikoagulation Orale Antikoagulanzien sind plazentagängig und prinzipiell embryotoxisch und erfordern somit die Anwendung einer sicheren Empfängnisverhütung. Eine häufige Nebenwirkung unter oraler Antikoagulanzientherapie ist das Auftreten einer Hypermenorrhö. Die hormonelle Kontrazeption kann bei bestehender Antikoagulation auch mit einem Kombinationspräparat fortgeführt werden, sofern spätestens 6 Wochen vor Beendigung der Antikoagulation die Umstellung auf eine östrogenfreie Form der Kontrazeption erfolgt. Hormonassoziierte VTE und Rezidivrisiko VTE, die bei Frauen unter Verwendung von hormonellen Kontrazeptiva aufgetreten sind, gelten als provozierte Ereignisse. Das Rezidivrisiko einer hormonassoziierten VTE ist nach Absetzen der Antikoagulation und Umstellung auf eine östrogenfreie Form der Kontrazeption gering, sodass eine Antikoagulationsdauer von 3–6 Monaten in der Regel ausreichend ist. Nach hormonassoziierter VTE wird während einer künftigen Schwangerschaft und im Wochenbett eine medikamentöse VTE-Prophylaxe empfohlen.

Was ist neu? Scores zur Stratifizierung des VTE-Risikos bei ambulanten Tumorpatienten Neben dem seit vielen Jahren bekannten Khorana-Score wurde kürzlich der CAT-Score publiziert, mit dem sich das Risiko für eine VTE innerhalb von 6 Monaten nach Einleitung einer Systemtherapie berechnen lässt. Als Berechnungsgrundlage dienen 2 Variablen: Tumorentität sowie Höhe der D-Dimere. Prophylaxe mit niedermolekularem Heparin Für Tumorpatienten in der ambulanten Versorgung wird eine Thromboseprophylaxe derzeit routinemäßig nicht empfohlen. Eine Stratifizierung des VTE-Risikos vor Einleitung einer Systemtherapie sollte erfolgen. Weitere Risikofaktoren, die in die publizierten Scores nicht eingehen, z. B. VTE in der Anamnese oder Therapie mit antiangiogenen Substanzen, sollten berücksichtigt werden. Eine Prophylaxe mit NMH kann nach individueller Nutzen-Risiko-Abwägung bei Patienten mit erhöhtem VTE-Risiko und vertretbarer Erhöhung des Blutungsrisikos erwogen werden. Direkte orale Antikoagulanzien zur VTE-Prophylaxe In 2 Studien konnte kürzlich gezeigt werden, dass Rivaroxaban und Apixaban wirksam sind in der Verhinderung einer VTE beim ambulanten Tumorpatienten. Das Risiko für schwere Blutungen war hierbei erhöht. Rivaroxaban und Apixaban sind in dieser Indikation bislang nicht zugelassen. VTE-Prophylaxe bei Patienten mit multiplem Myelom Eine VTE-Prophylaxe ist bei Patienten mit multiplem Myelom, die unter Therapie mit Thalidomid oder Lenalidomid in Kombination mit hochdosiertem Dexamethason und/oder einem Anthrazyklin stehen, fest etabliert. Je nach zugrunde liegender Risikostratifizierung wird eine Prophylaxe mit Aspirin bei niedrigem Risiko oder NMH bei hohem Risiko empfohlen.

Venous thromboembolism (VTE) is a major cause of maternal morbidity and mortality during pregnancy and the postpartum period. Due to a lack of adequate study data, therapeutic strategies for pregnancy-related VTE are deduced from observational studies and extrapolated from recommendations for nonpregnant patients. Because heparins do not cross the placenta, weight-adjusted therapeutic-dose low-molecular-weight heparins (LMWHs) are the anticoagulant treatment of choice in cases of VTE during pregnancy. Once- and twice-daily dosing regimens are suitable. There is no evidence that measurement of factor Xa activities and consecutive LMWH dose adjustments improve clinical outcomes. There is no support for the routine use of vitamin K antagonists, direct oral thrombin or factor Xa inhibitors, fondaparinux, or danaparoid in uncomplicated pregnancy-related VTE. Management of delivery deserves special attention, and treatment strategies depend on the time interval between the diagnosis of acute VTE and the expected delivery date. In lactating women, an overlapping switch from LMWH to warfarin is possible. Anticoagulation should be continued for at least 6 weeks postpartum or for a minimum period of 3 months.Venöse Thromboembolien (VTE) sind eine der Hauptursachen für mütterliche Morbidität und Mortalität während der Schwangerschaft und postpartal. Aufgrund fehlender randomisierter kontrollierter Studien sind therpeutische Strategien vorzugsweise aus Beobachtungsstudien und aus Therapieempfehlungen für Nicht-Schwangere abgeleitet. Heparine sind nicht plazentagängig und gelten in der Schwangerschaft als sicher. Niedermolekulare Heparine (NMH) in gewichts-adaptierter volltherapeutischer Dosierung sind daher Mittel der Wahl für die VTE-Therapie in der Schwangerschaft. Dosisregime mit Einmal- oder Zweimalgabe sind möglich. In Abhängigkeit des Präparates wird das NMH ein- oder zweimal täglich subkutan appliziert. Da es keine Evidenz für einen Nutzen einer Dosisanpassung an anti-Faktor-Xa-Spiegel gibt, werden routinemäßige Spiegelkontrollen nicht empfohlen. Andere Antikoagulanzien wie Vitamin-K-Antagonisten, die direkten oralen Thrombin- und Faktor-Xa-Inhibitoren (DOAKs), Fondaparinux und Danaparoid haben in der VTE-Behandlung bei unkompliziertem Schwangerschaftsverlauf keinen Stellenwert. Das peripartale Vorgehen hängt wesentlich vom Zeitabstand zwischen VTE-Manifestation und dem Geburtszeitpunkt ab. In der Stillzeit kann die NMH-Therapie fortgeführt oder überlappend auf Warfarin umgestellt werden. Bei schwangerschafts-assoziierter VTE sollte eine Antikoagulation für die Mindestdauer von 3 Monaten und bis mindestens 6 Wochen postpartum fortgeführt werden.

Objectives: Multipotent mesenchymal stromal cells (MSC) play a pivotal role in the bone marrow (BM) niche. Stanniocalcin 1 (STC1) secreted by MSC has been demonstrated to promote the survival of neoplastic cells and was suggested a marker for minimal residual disease of acute myeloid leukemia (AML). Therefore, we evaluated the expression of STC1 in MSC from AML patients (MSCAML) compared to MSC from healthy donors (MSCHD). Methods: Liquid culture assays of MSCAML and MSCHD were performed to compare expansion capacity. Gene expression profiles of MSCAML vs. MSCHD were established. Secretion of STC1 was tested by ELISA in MSCAML vs. MSCHD and expression of STC1 in AML- vs. HD-BM by immunohistochemistry. In addition, co-cultures of AML cells on MSC were initiated and ultrastructural intercellular communication patterns were investigated. Finally, the effect of blocking STC1 on AML cells was evaluated. Results: MSCAML showed significant decreased expansion capacity compared to MSCHD. Gene analysis revealed marked overexpression of STC1 in MSCAML. ELISA and immunohistochemical findings confirmed this observation. Electron microscopy analysis showed reciprocal stimulation between AML cells and MSC. Blockade of STC1 did not significantly affect AML cell proliferation and apoptosis. Discussion: Characteristics of MSC differ depending on whether they originate from AML patients or from HD. STC1 was mostly overexpressed in MSCAML compared to MSCHD. In vitro blockade of STC1, however, was not associated with AML cell proliferation and apoptosis. Conclusion: Differences in expression levels of glycoproteins from MSCAML compared to MSCHD not necessarily assume that these molecules are niche-relevant in leukemic disease.

The use of combined hormonal contraceptives (CHC) is a well-established risk factor for venous thromboembolism (VTE). The VTE risk depends on the specific combination of oestrogen and gestagen components. Progestin-only contraceptives with the exception of depot medroxyprogesterone acetate are not associated with a significant VTE risk and can therefore be offered to women with known thrombophilia or a prior VTE. The recent German S3 guideline "Contraception" advises to carefully assess individual VTE risk factors before prescribing CHC. According to recent data there is no evidence suggesting that VTE risk is increased during oral anticoagulation. To reduce the risk of vaginal bleeding complication and the risk of unplanned pregnancy, the use of CHC can be continued under anticoagulation treatment provided that the patient is switched to an oestrogen-free contraception no later than six weeks before the end of anticoagulation. The risk of recurrence is low in women with hormone-associated VTE. Anticoagulation is therefore in general discontinued after 3-6 months. Thromboprophylaxis with low molecular heparin is recommended for women with prior hormone-associated VTE during pregnancy and the postpartum period.Kombinierte hormonelle Kontrazeptiva (KK) erhöhen das VTE-Risiko signifikant. Gestagen-Monopräparate sind mit Ausnahme der 3-Monatsspritze nicht mit einem erhöhten VTE-Risiko assoziiert und können bei Frauen mit vorausgegangener VTE oder thrombophilen Risikofaktoren mit Wunsch nach hormoneller Verhütung angewandt werden.Vor der Verschreibung einer hormonellen Kontrazeption soll eine sorgfältige Erhebung des VTE-Risikos erfolgen. Eine entsprechende Checkliste findet sich auf der Internetseite des BfArM. Eine routinemäßige Testung auf hereditäre Thrombophilie wird nicht empfohlen.Orale Antikoagulanzien sind plazentagängig und prinzipiell embryotoxisch und erfordern somit die Anwendung einer sicheren Empfängnisverhütung. Eine häufige Nebenwirkung unter oraler Antikoagulanzientherapie ist das Auftreten einer Hypermenorrhö. Die hormonelle Kontrazeption kann bei bestehender Antikoagulation auch mit einem Kombinationspräparat fortgeführt werden, sofern spätestens 6 Wochen vor Beendigung der Antikoagulation die Umstellung auf eine östrogenfreie Form der Kontrazeption erfolgt.VTE, die bei Frauen unter Verwendung von hormonellen Kontrazeptiva aufgetreten sind, gelten als provozierte Ereignisse. Das Rezidivrisiko einer hormonassoziierten VTE ist nach Absetzen der Antikoagulation und Umstellung auf eine östrogenfreie Form der Kontrazeption gering, sodass eine Antikoagulationsdauer von 3–6 Monaten in der Regel ausreichend ist. Nach hormonassoziierter VTE wird während einer künftigen Schwangerschaft und im Wochenbett eine medikamentöse VTE-Prophylaxe empfohlen.

Cancers 13(12), 2905 (2021). doi:10.3390/cancers13122905, Published by MDPI, Basel

Venous thromboembolism (VTE) is a major cause of maternal morbidity during pregnancy and the postpartum period. Because there is a lack of adequate study data, management strategies for the prevention of VTE during pregnancy have mainly been deduced from case–control and observational studies and extrapolated from recommendations for non-pregnant patients. The decision for or against pharmacologic thromboprophylaxis must be made on an individual basis weighing the risk of VTE against the risk of adverse side effects such as severe bleeding complications. A comprehensive, multidisciplinary approach is often essential as the clinical scenario is made more complex by the specific obstetric context, especially in the peripartum period. As members of the Working Group in Women's Health of the Society of Thrombosis and Haemostasis (GTH), we summarize the evidence from the available literature and aim to establish a more uniform strategy for VTE risk assessment and thromboprophylaxis in pregnancy and the puerperium. In this document, we focus on women with hereditary thrombophilia, prior VTE and the use of anticoagulants that can safely be applied during pregnancy and the lactation period.

A thrombophilic disorder is a hereditary or acquired condition that increases the risk of thrombosis. The most common hereditary thrombophilias that predispose to venous thrombosis in the Caucasian population are the heterozygous forms of the factor V Leiden and prothrombin G20210A mutation that are generally detected by direct DNA genotyping. Immunologic antigen assays and chromogenic or clot-based activity assays are used to identify deficiencies in the natural coagulation inhibitors antithrombin, protein C and protein S. Because pre-analytical errors and acquired causes of low antithrombin, protein C or protein S levels are considerably more common than hereditary deficiencies, all potential conditions that may lower activity levels of the natural coagulation inhibitors (e.g. concomitant liver disease, pregnancy, anticoagulant therapy) must be considered and excluded before the diagnosis of an inhibitor deficiency can be made. To avoid misclassification, the diagnosis should not be made based on a single abnormal test result. Thus, repetitive testing when the patient is not on anticoagulant therapy is mandatory to confirm the diagnosis. Screening for antiphospholipid syndrome (APS) comprises testing for lupus anticoagulants (LAs) and the presence of IgG or IgM antibodies directed against phospholipids and phospholipid-binding proteins such as β-2-glycoprotein-I. A combination of clot-based assays has been recommended to demonstrate LA activity, whereas solid-phase immunoassays allow the detection of anti-cardiolipin and anti-β-2-glycoprotein-I antibodies. The diagnosis of APS requires the persistence of antiphospholipid antibodies for at least 12 weeks together with thrombotic and/or obstetric features of APS.Thrombophilie bezeichnet eine genetisch bedingte oder erworbene Thromboseneigung. Bei Europäern sind Faktor V Leiden und die Prothrombin-G20210A-Mutation in jeweils heterozygoter Form die häufigsten Genvarianten, die zu venösen Thrombosen prädisponieren. Beide Mutationen werden durch direkte DNA-Genotypisierung nachgewiesen. Für den Nachweis von Mangelzuständen der physiologischen Gerinnungsinhibitoren Antithrombin, Protein C und Protein S finden immunologische Antigen-Assays und chromogene bzw. gerinnungs-basierte Aktivitäts-Assays Anwendung. Bevor die Diagnose eines Inhibitormangels gestellt wird, sind die häufiger vorkommenden sekundären Ursachen (z.B. Lebererkrankung, Schwangerschaft, Antikoagulanzientherapie) auszuschließen. Da auch präanalytische Fehler vorkommen können, ist eine Diagnose nie auf Basis einer einzigen Bestimmung zu stellen, sondern erfordert die Bestätigung durch wiederholte Testung. Die Suche nach Antiphospholipid-Antikörpern erfolgt über den Nachweis von Lupusantikoagulans und die Testung auf Cardiolipin- und β-2-Glykoprotein-I-Antikörper vom IgG- und IgM-Typ. Für den Nachweis von Lupusantikoagulans-Aktivität werden mindestens zwei unterschiedliche gerinnungs-basierte Testverfahren eingesetzt, während spezifische Immunoassays anti-Cardiolipin- und anti-β-2-Glykoprotein-I-Antikörper nachweisen. Die Diagnose eines Antiphospholipid-Syndroms erfordert die Persistenz von Antiphospholipid-Antikörpern über mindestens 12 Wochen in zeitlichem Zusammenhang mit dem Auftreten von vaskulären Thrombosen und/oder Schwangerschaftskomplikationen.

Students learn more than science knowledge in a science classroom; they also acquire important messages about the purposes and contexts of science. Roberts (2011) calls these messages a companion story. In this article, we present a case study of high-profile Australian contemporary scientists to argue that there is a need to broaden the range of companion stories presented to students. A key companion story presently conveyed in schools is that the products of science are more important than the involvement of scientists in the construction of scientific knowledge. By contrast, the experiences and insights of the scientists in this case study shifts our understanding away from the idea that science is something that humans do—although that is true—to a deeper understanding that science is a discipline in which being human is important. We identify fresh companion stories that arise from these data and argue that the inclusion of such companion stories in the science curriculum is likely to better meet the needs of all citizens, scientists and non-scientists alike.

Eine hamorrhagische Diathese kann sich anamnestisch, klinisch und laborchemisch auf unterschiedliche Art und Weise zeigen. Das Erkennen und die weitere Abklarung ist fur Betroffene nicht nur vor operativen Eingriffen essenziell. In diesem Beitrag geben wir einen Uberblick uber die wichtigsten Gerinnungsstorungen und stellen dar, wie der Verdacht auf eine hamorrhagische Diathese erhartet und erste diagnostische Schritte eingeleitet werden konnen.

Background: Heparin-induced thrombocytopenia (HIT) is a rare cause of thrombocytopenia and a potentially life-threatening adverse drug reaction. Clinical overdiagnosis of HIT results in costly laboratory tests and anticoagulation. Criteria and algorithms for diagnosis are established, but their translation into clinical practice is still challenging. Study design and methods: In a retrospective approach we studied all HIT related laboratory test requests within four years and evaluated data before (1st period, 24 month) and after (2nd period, 24 month) replacing particle gel immunoassay (PaGIA) and enzyme-linked immunosorbent assay (ELISA) by a chemiluminescent immunoassay (CLIA). HIT was confirmed by heparin-induced platelet activation (HIPA) test. Clinical pretest probability for HIT using an implemented simplified 4Ts score and platelet count were evaluated. Costs for laboratory tests and alternative anticoagulation were calculated. Results: In 1850 patients with suspected HIT, 2327 laboratory orders were performed. In 87.2% of these orders an intermediate/high simplified 4Ts score was found. Thrombocytopenia was present in 87.1%. After replacing PaGIA and ELISA by CLIA the number of immunological and functional laboratory tests was reduced by 38.2%. The number of positive HIT immunoassays declined from 22.6% to 6.0%, while the number of positive HIPA tests among positive immunological tests increased by 19%. Altogether, acute HIT was confirmed in 59 patients. A decline in the use of alternative anticoagulants was observed in the 2nd period. Conclusion: Our study shows that in a university hospital setting HIT is well-known, but diagnosis requires a precise laboratory confirmation. Replacing PaGIA and ELISA by CLIA did not influence laboratory order behavior but results in reduced overall costs for laboratory diagnostics and alternative anticoagulation.

Ambulatory cancer patients receiving systemic cancer therapy are at varying risk for venous thromboembolism (VTE). The VTE risk depends on different cancer types, cancer stage, anti-cancer treatment and individual patient risk factors. Whereas pharmacologic thromboprophylaxis is recommended in most hospitalized cancer patients with an acute medical condition and in patients undergoing major cancer surgery, the role of primary thromboprophylaxis in the ambulatory setting is not clear. A VTE risk stratification using specific scoring systems, e. g. the Khorana score or the recently published CAT-score should be performed. Recently, two large randomized controlled studies using rivaroxaban (CASSINI trial) and apixaban (AVERT trial) versus placebo as primary VTE prevention in high-risk ambulatory cancer patients were published. When considered together, the two trials showed a significant benefit for the prevention of VTE with a low incidence of major bleeding. The DOAC had no effect on mortality. Primary thromboprophylaxis may be offered to high-risk outpatients with cancer, e. g. patients with advanced pancreatic carcinoma, provided there are no risk factors for bleeding and no drug-interactions. The patient's preference should also be respected. Current guidelines differ in their recommendations concerning the choice of anticoagulation. Whereas LMWH is still preferred to DOAC in the current German guideline, the ISTH guidance suggest to use DOAC in high-risk ambulatory cancer patients with no drug-drug interactions and not at high risk for bleeding. Of note, DOAC are currently not approved in this indication.SCORES ZUR STRATIFIZIERUNG DES VTE-RISIKOS BEI AMBULANTEN TUMORPATIENTEN: Neben dem seit vielen Jahren bekannten Khorana-Score wurde kürzlich der CAT-Score publiziert, mit dem sich das Risiko für eine VTE innerhalb von 6 Monaten nach Einleitung einer Systemtherapie berechnen lässt. Als Berechnungsgrundlage dienen 2 Variablen: Tumorentität sowie Höhe der D-Dimere.Für Tumorpatienten in der ambulanten Versorgung wird eine Thromboseprophylaxe derzeit routinemäßig nicht empfohlen. Eine Stratifizierung des VTE-Risikos vor Einleitung einer Systemtherapie sollte erfolgen. Weitere Risikofaktoren, die in die publizierten Scores nicht eingehen, z. B. VTE in der Anamnese oder Therapie mit antiangiogenen Substanzen, sollten berücksichtigt werden. Eine Prophylaxe mit NMH kann nach individueller Nutzen-Risiko-Abwägung bei Patienten mit erhöhtem VTE-Risiko und vertretbarer Erhöhung des Blutungsrisikos erwogen werden.In 2 Studien konnte kürzlich gezeigt werden, dass Rivaroxaban und Apixaban wirksam sind in der Verhinderung einer VTE beim ambulanten Tumorpatienten. Das Risiko für schwere Blutungen war hierbei erhöht. Rivaroxaban und Apixaban sind in dieser Indikation bislang nicht zugelassen.Eine VTE-Prophylaxe ist bei Patienten mit multiplem Myelom, die unter Therapie mit Thalidomid oder Lenalidomid in Kombination mit hochdosiertem Dexamethason und/oder einem Anthrazyklin stehen, fest etabliert. Je nach zugrunde liegender Risikostratifizierung wird eine Prophylaxe mit Aspirin bei niedrigem Risiko oder NMH bei hohem Risiko empfohlen.

We report on findings from a qualitative study of Australian scientists whose work brings them into contact with the public. This research sought to understand how a school science curriculum could better represent the work of scientists today. We discuss the views expressed by our participant scientists about the importance of openness and open-mindedness in their work, including their engagement with the public. They described openness as an important characteristic of science. Our participants also see open-mindedness on the part of both scientists and members of the public as important for productive relationships. They see the development of such relationships as an essential facet of their work. The views expressed by these scientists provide a provocative insight into the ways in which contemporary scientists see their work and relationships with their communities. Their perspectives have important implications for approaches to teaching science in schools.

This article presents a case study of 10 high-profile Australian research scientists. These scientists are highly committed to engaging with the public. They interact with a wide range of groups in the community, including the traditional media. They are aware that they are seen as representatives of science at a time when the authority of science and scientists is threatened in Australia by controversy around issues such as climate change and vaccination. Through their experiences of interacting with non-scientists, they have developed views about qualities, characteristics and knowledge that contribute to, or inhibit, positive interactions between scientists and non-scientists. Their experiences and insights highlight aspects of contemporary science that are not generally acknowledged in science curricula.

The phase III non-vitamin K dependent oral anticoagulants (NOAC) studies and recently published real world data on the use of dabigatran and rivaroxaban have shown that the bleeding profile in particular of intracranial and other life-threatening bleeding of NOAC is more favourable than that of warfarin. In case of a bleeding complication in a patient treated with a NOAC the recently updated EHRA practical guide offers management strategies. Idarucizumab, the specific antidot for dabigatran is approved to reverse the anticoagulant effect of dabigatran-treated patients who have serious bleeding and require an urgent procedure. Andexanet alfa, a specific antidot for direct and indirect factor Xa-inhibitors will be available in the future. The frequency of thrombocytopenia in ICU patients is high whereas the heparin induced thrombocytopenia (HIT) only counts for a small minority of patients with thrombocytopenia. To avoid an overdiagnosis of HIT a reliable and complete clinical and laboratory workup has to be performed. New immunoassays have been developed to provide results within a short period of time. These tests appear to have improved diagnostic accuracy compared with ELISAs in patients with suspected HIT and may reduce misdiagnosis and overtreatment. Acquired haemophilia (AH) is a rare and often life threatening bleeding disorder caused by autoantibodies against factor VIII. Susoctocog alfa is a B-domain deleted recombinant factor VIII porcine sequence that has recently been approved to treat severe bleeding in patients with AH. Susoctocog alfa offers the ability to effectively titrate and monitor dosing based on factor VIII activity levels.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of complex and still poorly understood etiology. Loss of upper and lower motoneurons results in death within few years after diagnosis. Recent studies have proposed neuroprotective and disease-slowing effects of granulocyte-colony stimulating factor (G-CSF) treatment in ALS mouse models as well as humans. In this study, six ALS patients were monitored up to 3.5 years during continuous high-dose G-CSF administration. Repetitive analyses were performed including blood count parameters, CD34+ hematopoietic stem and progenitor cell (HSPC) and colony forming cell (CFC) counts, serum cytokine levels and leukocyte telomere length. We demonstrate that continuous G-CSF therapy was well tolerated and safe resulting in only mild adverse events during the observation period. However, no mobilization of CD34+ HSPC was detected as compared to baseline values. CFC mobilization was equally low and even a decrease of myeloid precursors was observed in some patients. Assessment of telomere length within ALS patients’ leukocytes revealed that G-CSF did not significantly shorten telomeres, while those of ALS patients were shorter compared to age-matched healthy controls, irrespective of G-CSF treatment. During G-CSF stimulation, TNF-alpha, CRP, IL-16, sVCAM-1, sICAM-1, Tie-2 and VEGF were significantly increased in serum whereas MCP-1 levels decreased. In conclusion, our data show that continuous G-CSF treatment fails to increase circulating CD34+ HSPC in ALS patients. Cytokine profiles revealed G-CSF-mediated immunomodulatory and proteolytic effects. Interestingly, despite intense G-CSF stimulation, telomere length was not significantly shortened.

Die Einfuhrung der neuen, nicht Vitamin K abhangigen oralen Anitkoagulanzien (NOAK) Dabigatran, Rivaroxaban, Apixaban und Edoxaban hat die klinische Praxis verandert, da diese Medikamente im Gegensatz zu den Vitamin-K-Antagonisten kein Labormonitoring benotigen. Es gibt jedoch spezielle klinische Situationen wie invasive Notfalleingriffe, schwere Blutungen oder eine sich verschlechternde Nierenfunktion, die eine Spiegelbestimmung bzw. eine Abschatzung der antikoagulatorischen Restwirkung erforderlich machen konnen. Die Auswirkung einer Einnahme eines direkten oralen Inhibitors auf die gangigen Gerinnungsteste wie die Prothrombinzeit (PTZ), die aktivierte partielle Thromboplastinzeit (aPTT) und die Thrombinzeit (TZ) hangt vom individuellen direkten Inhibitor, der Dosierung und dem Zeitpunkt der letzten Einnahme sowie der Sensitivitat des Testreagenzes ab. Eine quantitative Bestimmung der Xa-Inhibitoren Rivaroxaban, Apixaban und Edoxaban ist mittels spezifisch kalibrierter Anti-Faktor Xa-Assays im Gerinnungslabor moglich. Die verdunnte Thrombinzeit (Hemoclot) ist geeignet um die Plasmakonzentration des Thrombininhibitors Dabigatran zu ermitteln. Bei der Interpretation von Gerinnungstesten von Patienten unter Antikoagulation mit NOAK ist zu beachten, dass diese neuen Medikamente sowohl Screening Teste wie auch spezielle Gerinnungsteste beeinflussen konnen. Eine gute Kommunikation zwischen behandelndem Arzt und Labor ist unabdingbar, um mit den verschiedenen Effekten der NOAK auf die Gerinnungsteste sicher umgehen zu konnen.

The amount of substance and its unit the mole is a basic concept in chemistry. However, previous research has shown that teaching and learning the concept are challenging tasks for both teachers and students. The purpose of this study was to pinpoint the problems which emerge in the teaching and learning process, and provide integrated suggestions for classroom instruction. By means of videotaping and interviews, the case studies explored how the mole is presented and conceptualized in two secondary classrooms in two different countries, Australia and Taiwan. Data analysis was based on a concept map and focused on how two key ideas were presented in the lessons and perceived by the students: (1) the definition of the mole, and (2) the concept of molar mass. The findings show that during the lessons on the mole, most of the time was spent on solving stoichiometric problems. Conceptually, the number aspect of the mole, that is, Avogadro's number, was emphasized; the concept of molar mass was introduced without meaningfully connecting it to the concept of relative atomic/molecular mass. Although the students were able to solve relevant problems, they could not coherently explain the relations among the concepts. Two critical components for a conceptual understanding of the mole emerged: (1) the number aspect of the mole needs to be justified by its mass aspect, and (2) the connection between molar mass and relative atomic/molecular mass needs to be explicitly explained. The two components provide one explanation for students' algorithmic learning and their confusion in learning about the mole, and serve as concrete suggestions for improving classroom instruction. The study once again manifested the significance of teaching for conceptual understanding in science education. It also exemplifies how a concept map of a specific scientific concept can also be a useful analytical tool in educational research. © 2015 Wiley Periodicals, Inc. J Res Sci Teach 53: 181–214, 2016.

This study examines how a class of Grade 7 students employed linguistic resources to explain density differences. Drawing from the same data-set as a previous study by, we take a language perspective to investigate the challenges students face in learning the concept of density. Our study thus complements previous research on learning about density which has mostly focussed on the conceptual challenges. The data consist of transcripts of lessons on density and students’ written assignments. Using selected analytical categories from the Systemic Functional Linguistics framework, we first examined students’ use of linguistic resources in their written reports of a practical activity. We then compared the language employed by the students with the instructional language, identifying possible links. Our analysis identified specific aspects of language that the students need to appropriate in order to express an understanding of density that aligns with a scientific perspective. The findings from this study il...

Disruptive technologies, such as communicative reprogramming (anakoinosis) with cellular therapies in situ for treating refractory metastatic cancer allow patient care to accelerate along a totally new trajectory and highlight what may well become the next sea change in the care of patients with many types of advanced neoplasia. Cellular therapy in situ consisted of repurposed drugs, pioglitazone plus all-trans retinoic acid or dexamethasone or interferon-alpha (dual transcriptional modulation) combined with metronomic low-dose chemotherapy or low-dose 5-azacytidine, plus/minus classic targeted therapy. The novel therapeutic tools for specifically designing communication processes within tumor diseases focus on redirecting (1) rationalizations of cancer hallmarks (constitution of single cancer hallmarks), (2) modular events, (3) the 'metabolism' of evolutionary processes (the sum of therapeutically and intrinsically inducible evolutionary processes) and (4) the holistic communicative context, which determines validity and denotation of tumor promoting communication lines. Published data on cellular therapies in situ (6 histologic tumor types, 144 patients, age 0.9-83 years) in castration-resistant prostate cancer, pretreated renal clear cell carcinoma, chemorefractory acute myelocytic leukemia, multiple myeloma > second-line, chemorefractory Hodgkin lymphoma or multivisceral Langerhans cell histiocytosis, outline the possibility for treating refractory metastatic cancer with the hope that this type of reprogrammed communication will be scalable with minimal toxicity. Accessibility to anakoinosis is a tumor inherent feature, and cellular therapy in situ addresses extrinsic and intrinsic drug resistance, by redirecting convergent organized communication tools, while been supported by quite different pattern of (molecular-) genetic aberrations.