Recombinant activated factor VII: 30 years of research and innovation
Recombinant activated factor VII (rFVIIa) was initially developed to treat bleeding episodes in patients with congenital haemophilia and inhibitors. The story of its development began in the 1970s, when FVIIa was identified as one of the activated coagulation factors that has minimal potential for inducing thromboembolic side-effects. Extensive research over the last 30 years has greatly increased our knowledge of the characteristics of FVII, its activation, and the mechanisms by which rFVIIa restores haemostasis. (Source: Blood Reviews)
Source: Blood Reviews - June 1, 2015 Category: Hematology Authors: Ulla Hedner Source Type: research
Recombinant activated factor VII in the treatment of bleeds and for the prevention of surgery-related bleeding in congenital haemophilia with inhibitors
This article attempts to review in detail the extensive evidence of rFVIIa in congenital haemophilia patients with inhibitors. (Source: Blood Reviews)
Source: Blood Reviews - June 1, 2015 Category: Hematology Authors: Elena Santagostino, Miguel Escobar, Margareth Ozelo, Luigi Solimeno, Per Arkhammar, Hye Youn Lee, Gabriela Rosu, Paul Giangrande Source Type: research
The use of recombinant activated factor VII in patients with acquired haemophilia
Acquired haemophilia (AH) is a rare, often severe bleeding disorder characterised by autoantibodies to coagulation factor VIII (FVIII). Observational studies offer crucial insight into the disease and its treatment. Recombinant activated factor VII (rFVIIa, eptacog alfa activated) was available on an emergency and compassionate use basis from 1988 to 1999 at sites in Europe and North America. In 1996, rFVIIa was approved in Europe for the treatment of AH; it was licensed for this indication in the United States in 2006. (Source: Blood Reviews)
Source: Blood Reviews - June 1, 2015 Category: Hematology Authors: Andreas Tiede, Kagehiro Amano, Alice Ma, Per Arkhammar, Soraya Benchikh el Fegoun, Anders Rosholm, Stephanie Seremetis, Francesco Baudo Source Type: research
Eptacog alfa activated: a recombinant product to treat rare congenital bleeding disorders
Glanzmann's thrombasthenia (GT) and congenital factor VII deficiency (FVII CD) are rare autosomal recessive bleeding disorders: GT is the most frequent congenital platelet function disorder, and FVII CD is the most common factor-deficiency disease after haemophilia. The frequency of these disorders in the general population ranges from 1:500,000 to 1:2,000,000. Because GT and FVII CD are both rare, registries are the only approach possible to allow the collection and analysis of sufficient observational data. (Source: Blood Reviews)
Source: Blood Reviews - June 1, 2015 Category: Hematology Authors: Giovanni Di Minno Source Type: research
Safety update on the use of recombinant activated factor VII in approved indications
This updated safety review summarises the large body of safety data available on the use of recombinant activated factor VII (rFVIIa) in approved indications: haemophilia with inhibitors, congenital factor VII (FVII) deficiency, acquired haemophilia and Glanzmann's thrombasthenia. Accumulated data up to 31 December 2013 from clinical trials as well as post-marketing data (registries, literature reports and spontaneous reports) were included. Overall, rFVIIa has shown a consistently favourable safety profile, with no unexpected safety concerns, in all approved indications. (Source: Blood Reviews)
Source: Blood Reviews - June 1, 2015 Category: Hematology Authors: Ellis J Neufeld, Claude Négrier, Per Arkhammar, Soraya Benchikh el Fegoun, Mette Duelund Simonsen, Anders Rosholm, Stephanie Seremetis Source Type: research
Lyse or not to lyse: clinical significance of red blood cell autoantibodies
Autoimmune hemolytic anemia (AIHA) is a rare autoimmune disease characterized by a hemolytic anemia caused by autoantibodies against red blood cells (RBCs). These autoantibodies are routinely detected via the Direct Antiglobulin Test (DAT). As expected, the DAT score correlates with the presence of clinical symptoms, but this correlation is far from perfect. Regularly, strongly positive DAT scores are encountered with no sign of hemolysis, while severe hemolysis can be seen even in patients with a negative DAT score. (Source: Blood Reviews)
Source: Blood Reviews - May 7, 2015 Category: Hematology Authors: Elisabeth M. Meulenbroek, Diana Wouters, Sacha S. Zeerleder Tags: Review Source Type: research
Platelets and physics: How platelets “feel” and respond to their mechanical microenvironment
During clot formation, platelets are subjected to various different signals and cues as they dynamically interact with extracellular matrix proteins such as von Willebrand factor (vWF), fibrin(ogen) and collagen. While the downstream signaling of platelet-ligand interactions is well-characterized, biophysical cues, such as hydrodynamic forces and mechanical stiffness of the underlying substrate, also mediate these interactions and affect the binding kinetics of platelets to these proteins. Recent studies have observed that, similar to nucleated cells, platelets mechanosense their microenvironment and exhibit dynamic physio...
Source: Blood Reviews - May 7, 2015 Category: Hematology Authors: Yongzhi Qiu, Jordan Ciciliano, David R. Myers, Reginald Tran, Wilbur A. Lam Tags: Review Source Type: research
Managing Critically Ill Hematology Patients: Time to Think Differently
The number of patients living with hematological malignancies (HMs) has increased steadily over time. This is the result of intensive and effective treatments that also increase the probability of infiltrative, infectious or toxic life threatening event. Over the last two decades, the number of patients with HMs admitted to the ICU increased and their mortality has dropped sharply. ICU patients with HMs require an extensive diagnostic workup and the optimal use of ICU treatments to identify the reason for ICU admission and the nature of the complication that explains organ dysfunctions. (Source: Blood Reviews)
Source: Blood Reviews - April 26, 2015 Category: Hematology Authors: Elie Azoulay, Frédéric Pène, Michael Darmon, Etienne Lengliné, Dominique Benoit, Marcio Soares, Francois Vincent, Fabrice Bruneel, Pierre Perez, Virginie Lemiale, Djamel Mokart, Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique (Grr Tags: Review Source Type: research
From evidence to clinical practice in blood and marrow transplantation
Clinical practice in the field of blood and marrow transplantation (BMT) has evolved over time, as a result of thousands of basic and clinical research studies. While it appears that scientific discovery and adaptive clinical research may be well integrated in case of BMT, there is lack of sufficient literature to definitively understand the process of translation of evidence to practice and if it may be selective . In this review, examples from BMT and other areas of medicine are used to highlight the state of and potential barriers to evidence uptake. (Source: Blood Reviews)
Source: Blood Reviews - April 19, 2015 Category: Hematology Authors: Nandita Khera Tags: Review Source Type: research
Antithrombotic Drugs, Patient Characteristics, and Gastrointestinal Bleeding: Clinical Translation and Areas of Research
Gastrointestinal bleeding (GIB) is a potentially fatal and avoidable medical condition that poses a burden on global health care costs. Current understanding of the roles of platelet activation and thrombin generation/activity in vascular medicine has led to the development of effective antithrombotic treatments. However, in parallel with a sustained coronary and cerebral flow patency, the increasingly intensive treatment with warfarin; direct oral anticoagulant drugs [DOACs], and/or with aspirin ±clopidogrel (or ±prasugrel or ±ticagrelor), has increased the burden of GIBs related to the use of antithrombotic agents. (S...
Source: Blood Reviews - March 30, 2015 Category: Hematology Authors: Alessandro Di Minno, Gaia Spadarella, Domenico Prisco, Antonella Scalera, Elena Ricciardi, Giovanni Di Minno Source Type: research
Strategies targeting apoptosis proteins to improve therapy of chronic lymphocytic leukemia
This article reviews the strategies targeting proteins that directly regulate the mitochondrial pathway of apoptosis and caspase activation: (i) inhibiting the expression or activity of prosurvival proteins of the Bcl-2 and IAP (inhibitor of apoptosis protein) families which are overexpressed in CLL cells and (ii) upregulating proapoptotic BH3-only members of the Bcl-2 family (which are antagonists of the prosurvival members). (Source: Blood Reviews)
Source: Blood Reviews - March 30, 2015 Category: Hematology Authors: Samaher Besbes, Massoud Mirshahi, Marc Pocard, Christian Billard Source Type: research
Cereblon binding molecules in multiple myeloma
Immunomodulation is an established treatment strategy in multiple myeloma with thalidomide and its derivatives lenalidomide and pomalidomide as its FDA approved representatives. Just recently the method of action of these cereblon binding molecules was deciphered and results from large phase 3 trials confirmed the backbone function of this drug family in various combination therapies. This review details the to-date knowledge concerning mechanism of IMiD action, clinical applications and plausible escape mechanisms in which cells may become resistant/refractory to cereblon binding molecule based treatment. (Source: Blood Reviews)
Source: Blood Reviews - March 27, 2015 Category: Hematology Authors: K.M. Kortüm, Y.X. Zhu, C.X. Shi, P. Jedlowski, A.K. Stewart Tags: REVIEW Source Type: research
The history, function and clinical application of cereblon binding molecules in multiple myeloma
Immunomodulation is an established treatment strategy in Multiple Myeloma with Thalidomide and its derivatives Lenalidomide and Pomalidomide as its FDA approved representatives. Just recently the method of action of these cereblon binding molecules was deciphered and results from large phase 3 trials confirmed the backbone function of this drug family in various combination therapies. This review details the to-date knowledge concerning mechanism of IMiD action, clinical applications and plausible escape mechanisms in which cells may become resistant/refractory to cereblon binding molecule based treatment. (Source: Blood Reviews)
Source: Blood Reviews - March 27, 2015 Category: Hematology Authors: K.M. Kortüm, Y.X. Zhu, C.X. Shi, P. Jedlowski, A.K. Stewart Tags: Review Source Type: research
Haemophilia Gene Therapy: Progress and challenges
Current treatment for haemophilia entails life-long intravenous infusion of clotting factor concentrates. This is highly effective at controlling and preventing haemorrhage and its associated complications. Clotting factor replacement therapy is, however, demanding, exceedingly expensive and not curative. In contrast, gene therapy for haemophilia offers the potential of a cure as a result of continuous endogenous expression of biologically active factor VIII (FVIII) or factor IX (FIX) proteins following stable transfer of a normal copy of the respective gene. (Source: Blood Reviews)
Source: Blood Reviews - March 26, 2015 Category: Hematology Authors: Elsa Lheriteau, Andrew M. Davidoff, Amit C. Nathwani Tags: Review Source Type: research
Waldenström Macroglobulinemia: What a Hematologist Needs to Know
Waldenström Macroglobulinemia (WM) is a distinct hematologic malignancy characterized by a lymphoplasmacytic bone marrow infiltration and the presence of immunoglobulin (Ig)M monoclonal protein. Patients typically present at an advanced age, and a substantial proportion are asymptomatic at diagnosis. A unifying diagnosis of WM may be missed by an unsuspecting hematologist, as symptomatic patients present with a multitude of non-specific manifestations. Although constitutional and neuropathy-related symptoms predominate, concomitant IgM-induced hyperviscosity-associated features can provide useful diagnostic clues. (Source: Blood Reviews)
Source: Blood Reviews - March 24, 2015 Category: Hematology Authors: Prashant Kapoor, Jonas Paludo, Nishanth Vallumsetla, Philip R. Greipp Source Type: research
