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Seminars in Thrombosis and Hemostasis

Job Harenberg, Rupert Schreiner, Svetlana Hetjens, Christel Weiss
The assessment of the anticoagulant effect of direct oral anticoagulants (DOACs) can be important for rapid medical decision-making, especially in patients needing immediate management. An assay that screens for the absence or presence of a DOAC would help accelerate treatment in these situations. Chromogenic and coagulation methods have several limitations, including limited accuracy, long turnaround time, and their need of specialized laboratories. Oral factor Xa and thrombin inhibitors are also eliminated by the kidneys and can be detected in patient urine samples using a single, rapid, sensitive, and patient-specific qualitative assay...
August 22, 2018: Seminars in Thrombosis and Hemostasis
Emmanuel J Favaloro
Although the landscape of anticoagulation therapy is evolving, vitamin K antagonists (VKAs) such as warfarin remain an anticoagulant of choice for many clinicians and their patients. Nevertheless, management of VKA therapy remains challenging, largely because of patient variability and drug and food interactions; thus, VKA dosing has to be personalized. This is achieved by regular monitoring using a test called the prothrombin time (PT) , mathematically converted to an international normalized ratio (INR). The INR system is meant to harmonize laboratory test results by taking into account reagent and instrumentation variability that is otherwise expected to give rise to variable PT values, but which should accordingly lead to less variable INR values...
August 22, 2018: Seminars in Thrombosis and Hemostasis
Vincenzo Russo, Roberta Bottino, Anna Rago, Pierpaolo Di Micco, Antonio D' Onofrio, Biagio Liccardo, Paolo Golino, Gerardo Nigro
Atrial fibrillation (AF) is commonly diagnosed in the setting of active cancer. Because of an increased risk of either thromboembolic events or bleeding, the decision to initiate therapeutic anticoagulation in patients with active cancer can be challenging. Moreover, little is still known about the optimal anticoagulation therapy in the setting of AF and cancer, and no guidelines are as yet available. Considering that nonvitamin K antagonist oral anticoagulants (NOACs) are recommended as alternatives to vitamin K antagonists for stroke prevention in AF patients with CHA2 DS2- VASc score ≥2, the authors performed a systematic review of the current literature to describe the efficacy and safety of NOACs in AF patients with malignancy...
August 17, 2018: Seminars in Thrombosis and Hemostasis
Giuseppe Lippi, Gian Luca Salvagno, Cantor Tarperi, Matteo Gelati, Martina Montagnana, Elisa Danese, Luca Festa, Fabian Sanchis-Gomar, Emmanuel J Favaloro, Federico Schena
Since the impact of possible prothrombotic factors on blood coagulation resulting from exercise remains elusive, this study investigated the acute effects of middle-distance endurance running on blood coagulation parameters in middle-aged athletes. The study population consisted of 33 male endurance runners who were engaged in a 21.1 km run under competitive conditions. Blood samples were collected before the run, immediately after the run, and 3 hours after run completion. Samples were assessed for activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen, D-dimer, factor VIII (FVIII), von Willebrand factor antigen (VWF:Ag), endogenous thrombin potential (area under the curve of thrombin generation [TGA-AUC]), and peak thrombin generation (TGA-PK)...
August 17, 2018: Seminars in Thrombosis and Hemostasis
Adam Cuker, Joseph E Marturano, Maria E Carinato, Thomas J Lowery, Douglas B Cines
There is a clinical need for pragmatic approaches to measure integrated hemostatic reactions in whole blood rapidly, using small volumes of blood. The authors have applied T2 magnetic resonance (T2MR) to assess coagulation reactions based on partitioning of red blood cells and proteins that occurs during fibrin formation and platelet-mediated clot contraction. T2MR is amenable to measuring clotting times, individual coagulation factors, and platelet function. T2MR also revealed a novel "hypercoagulable" signature characterized by fibrin clots almost insusceptible to fibrinolysis that surround tessellated arrays of polyhedral erythrocytes ("third peak")...
August 17, 2018: Seminars in Thrombosis and Hemostasis
Laura P B Elbers, Alessandro Squizzato, Victor E A Gerdes
Lower levels of free thyroxine (whether this is endogenous or exogenous) lead to a hypocoagulable state, and higher levels of free thyroxine lead to a hypercoagulable state. In this narrative review, the effects of different levels of thyroid hormones on clinical end points are described. Hypothyroidism is associated with an increased bleeding risk, whereas hyperthyroidism leads to an increased risk of venous thrombosis. Besides, effects of thyroid hormone on the heart may indirectly influence hemostasis. Hyperthyroidism leads to a higher incidence of atrial fibrillation and atrial flutter, and, at least partly by that mechanism, a higher risk of cerebral arterial thrombosis...
July 25, 2018: Seminars in Thrombosis and Hemostasis
Beverley J Hunt
Extremes of body weight are not uncommon in the modern world and include anorexia nervosa (AN) and obesity. Both conditions are associated with increased morbidity and mortality: AN has the highest mortality rate of all mental illnesses and unfortunately obesity has reached epidemic proportions and is a well-recognized risk factor for cardiovascular disease including venous thromboembolism (VTE). This article summarizes the current understanding of hemostatic changes of these extremes of body weight. The hemostatic changes of AN have not been well described...
July 9, 2018: Seminars in Thrombosis and Hemostasis
Cho Yeow Koh, Cassandra M Modahl, Namrata Kulkarni, R Manjunatha Kini
Venomous and hematophagous animals use their venom or saliva for survival, to obtain food, and for self-defense. Venom and saliva from these animals are cocktails of bioactive molecules primarily composed of proteins and peptides. These molecules are called toxins because they cause unwanted consequences on prey. They exhibit unique, diverse, and specific biological activities that perturb normal physiological processes of their prey and host. However, the potential of toxins as inspirations for the development of therapeutic agents or pharmacological tools has also long been recognized...
June 28, 2018: Seminars in Thrombosis and Hemostasis
Jaime Francisco Borjas-Howard, Karina de Leeuw, Abraham Rutgers, Karina Meijer, Vladimir Ynse Ieuwe Gerardus Tichelaar
Despite an abundance of literature on the risk of a first venous thromboembolic event (VTE) in autoimmune diseases, specific recommendations about managing VTE in autoimmune diseases are lacking. This article aimed to collect evidence on the risk of recurrent VTE in patients with autoimmune diseases. The authors searched PubMed/Embase for studies including patients with VTE and autoimmune diseases as an exposure or studies including patients with autoimmune diseases in which recurrent VTE was one of the outcomes...
June 28, 2018: Seminars in Thrombosis and Hemostasis
Antonio Coppola, Annarita Tagliaferri, Cristina Santoro, Massimo Franchini
No abstract text is available yet for this article.
September 2018: Seminars in Thrombosis and Hemostasis
Shermarke Hassan, Karin Fijnvandraat, Johanna G van der Bom, Samantha C Gouw
Eradication of factor VIII (FVIII) specific neutralizing antibodies (also known as inhibitors) by the traditional method of immune tolerance induction (ITI) is costly and unsuccessful in one out of three patients. Furthermore, effective inhibitor prevention strategies are presently lacking. An overview is given in this narrative review of antidrug antibody prevention or eradication strategies that have been used in disorders beyond hemophilia A, with the aim of analyzing what we can learn from these strategies for hemophilia A...
September 2018: Seminars in Thrombosis and Hemostasis
Maurizio Margaglione, Mariano Intrieri
Over the past few decades, important knowledge on why inhibitors develop and better information about significant risk factors have become available. A series of both genetic and nongenetic factors are recognized and clinical score systems were proposed to quantify the risk for each patient. In addition, modulation of the immunological response was acknowledged to play a pivotal role in the occurrence of inhibitors. However, with the exception of mutation testing in severe hemophilia B patients, no single risk factor or clinical score is currently utilized in clinical practice...
September 2018: Seminars in Thrombosis and Hemostasis
Cristina Santoro, Gabriele Quintavalle, Giancarlo Castaman, Erminia Baldacci, Antonietta Ferretti, Federica Riccardi, Annarita Tagliaferri
Hemophilia B (HB) is an X-linked bleeding disorder caused by deficiency of factor IX (FIX). Patients with the severe form (FIX <1%) account approximately for 30 to 45% of persons with HB and usually suffer from recurrent joint, soft-tissue, and muscle bleeds. The availability of safe plasma-derived and recombinant products has virtually abolished the risk of viral infections and the adoption of prophylactic regimens has attenuated the impact of hemophilic arthropathy. Therefore, the development of an inhibitor against FIX is currently the most serious complication that can still occur in the new generations of HB patients...
September 2018: Seminars in Thrombosis and Hemostasis
Man-Chiu Poon, Roseline d'Oiron
Glanzmann's thrombasthenia (GT) and Bernard-Soulier's syndrome (BSS) are well-understood congenital bleeding disorders, showing defect/deficiency of platelet glycoprotein (GP) IIb/IIIa (integrin αIIbβ3) and GPIb-IX-V complexes respectively, with relevant clinical, laboratory, biochemical, and genetic features. Following platelet transfusion, affected patients may develop antiplatelet antibodies (to human leukocyte antigen [HLA], and/or αIIbβ3 in GT or GPIb-IX in BSS), which may render future platelet transfusion ineffective...
September 2018: Seminars in Thrombosis and Hemostasis
Sandrine Delignat, Julie Rayes, Jules Russick, Srinivas V Kaveri, Sebastien Lacroix-Desmazes
The immunogenicity of therapeutic factor VIII (FVIII) in patients with hemophilia A has been puzzling scientific and clinical communities for more than 3 decades. Indeed, the development of inhibitory antibodies to FVIII remains a major clinical challenge and is associated with enormous societal costs. Thus, the reasons for which a presumably innocuous, short-lived, intravenously administered glycoprotein triggers such a deleterious, long-lasting neutralizing immune response is an enigma. This review does not pretend to bring an answer to this challenging question...
September 2018: Seminars in Thrombosis and Hemostasis
Antonio Coppola, Massimo Franchini, Giancarlo Castaman, Elena Santagostino, Cristina Santoro, Rita Carlotta Santoro, Massimo Morfini, Giovanni Di Minno, Angiola Rocino
The development of neutralizing antibodies (inhibitors) against infused factor VIII currently represents the main complication of replacement therapy in patients with severe hemophilia A. Inhibitors, indeed, particularly high-titer inhibitors (>5 BU/mL), greatly complicate the management of bleeding, exposing patients to an increased morbidity and mortality risk, thus representing a significant burden for physicians of Hemophilia Treatment Centers (HTCs). Although bypassing agents (i.e., activated prothrombin complex concentrate [APCC] and recombinant activated factor VII [rFVIIa]) are available for the treatment and prevention of bleeding in inhibitor patients, their efficacy, safety, and cost-benefit outcomes are poorly known in the long term and should be further improved...
September 2018: Seminars in Thrombosis and Hemostasis
Amal Abdi, Silvia Linari, Lisa Pieri, Jan Voorberg, Karin Fijnvandraat, Giancarlo Castaman
Nonsevere hemophilia A (NSHA) is an inherited X-linked bleeding disorder, caused by mutations of the F8 gene, leading to decreases of clotting factor VIII (FVIII) levels to 1 to 40 IU/dL. Desmopressin is the first therapeutic option for NSHA, but 40 to 50% of patients fail to attain adequate postinfusion FVIII levels. Thus, in these cases, FVIII concentrates remain the mainstay of treatment. The development of neutralizing FVIII antibodies (inhibitors) is a major challenge with replacement therapy. In contrast to severe disease, NSHA patients have a lifelong risk of inhibitor development...
September 2018: Seminars in Thrombosis and Hemostasis
Assaf Arie Barg, Tami Livnat, Gili Kenet
Hemophilia A (HA) and hemophilia B (HB) are rare congenital severe bleeding disorders, that may be controlled by proper administration of adequate prophylaxis with factor VIII (FVIII), and factor IX (FIX) concentrates, respectively, to prevent joint damage due to recurrent bleeding. However, approximately 30% of patients develop inhibitory antibodies that render factor replacement therapy ineffective. Due to the high variability of patients' bleeding tendency, there is a need to "individually tailor treatment" for this unique group of patients...
September 2018: Seminars in Thrombosis and Hemostasis
Andrea Messori
A discussion of the main pharmacoeconomic issues related to inhibitors in hemophilia A cannot be separated from an analysis of the most relevant clinical questions. In the field of inhibitors, the clinical evidence includes several controversial topics, such as high-titer versus low-titer inhibitors, the influence of factor VIII products on inhibitor risk, effectiveness of different immune tolerance induction (ITI) treatments, the role of bypassing agents, and development of new non-factor-VIII compounds. In terms of pharmacoeconomic data, numerous cost estimates have been reported in these fields, but this information is strongly influenced by the wide between-country differences in unit costs...
September 2018: Seminars in Thrombosis and Hemostasis
Massimo Franchini, Giuseppe Marano, Carlo Mengoli, Vanessa Piccinini, Simonetta Pupella, Stefania Vaglio, Giancarlo Maria Liumbruno
The most worrying complication of replacement therapy for severe hemophilia A and B is currently the occurrence of inhibitory alloantibodies against infused factor VIII and factor IX, respectively. Inhibitors compromise the management of hemorrhage in affected patients, with a considerable increase in complications, disability, and costs. While these alloantibodies have been extensively studied in the past years in hemophilia A and B, those occurring in patients with other inherited bleeding disorders are less well characterized and still poorly understood, mostly due to the rarity of these hemorrhagic conditions...
September 2018: Seminars in Thrombosis and Hemostasis
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