Approval of the first protease-activated receptor antagonist: Rationale, development, significance, and considerations of a novel anti-platelet agent
Twenty-three years after the discovery of the first thrombin receptor, now known as protease-activated receptor 1 (PAR1), the first drug targeting this receptor is available for human use. The PAR1 inhibitor, vorapaxar (Zontivity, MSD), was recently approved by the FDA for use in the USA for the prevention of thrombotic cardiovascular events in patients with a history of myocardial infarction or peripheral artery disease. In this review, we detail the rationale, development, as well as the clinical significance and considerations of vorapaxar, the original PAR antagonist and the latest anti-platelet agent in the pharmaco-a...
Source: Blood Reviews - November 6, 2014 Category: Hematology Authors: Shauna L. French, Jane F. Arthur, Huyen A. Tran, Justin R. Hamilton Source Type: research
Lifting the mantle: unveiling new treatment approaches in relapsed or refractory mantle cell lymphoma
The management of relapsed/refractory mantle cell lymphoma (MCL) remains a clinical challenge. A standard second-line treatment for relapsed/refractory MCL does not exist. Management of relapsed/refractory MCL requires an individualized treatment approach, incorporating factors such as: functional status, prior treatments, response to prior therapies, and disease biology. Generally, there are two categories of salvage therapy; the first, non-cross-resistant cytotoxic chemotherapeutic agents and, the second, pathway-targeted agents. (Source: Blood Reviews)
Source: Blood Reviews - November 1, 2014 Category: Hematology Authors: Alberto Mussetti, Anita Kumar, Parastoo B. Dahi, Miguel-Angel Perales, Craig S. Sauter Tags: Review Source Type: research
Is there a rationale for treatment of chronic liver disease with antithrombotic therapy?
Recent advances in the understanding of the coagulopathy in chronic liver disease have provided a strong support for anticoagulation as a new therapeutic paradigm for patients with cirrhosis. Laboratory studies indicate that the net effect of changes in hemostasis in many patients with chronic liver disease is a hypercoagulable status. In turn, clinical thrombosis is increasingly recognized as a complication of liver disease. When occurring within the liver, thrombosis may even progress the disease course. (Source: Blood Reviews)
Source: Blood Reviews - November 1, 2014 Category: Hematology Authors: Greg C.G. Hugenholtz, Patrick G. Northup, Robert J. Porte, Ton Lisman Tags: Review Source Type: research
Platelet secretion: from haemostasis to wound healing and beyond
Upon activation, platelets secret more than 300 active substances from their intracellular granules. Platelet dense granule components, such as ADP and polyphosphates, contribute to haemostasis and coagulation, but also play a role in cancer metastasis. α-granules contain multiple cytokines, mitogens, pro- and anti-inflammatory factors and other bioactive molecules that are essential regulators in the complex microenvironment of the growing thrombus but also contribute to a number of disease processes. (Source: Blood Reviews)
Source: Blood Reviews - October 31, 2014 Category: Hematology Authors: Ewelina M. Golebiewska, Alastair W. Poole Tags: Review Source Type: research
“No donor”? Consider a haploidentical transplant
Haploidentical stem cell transplantation (HaploSCT) is an attractive option for patients requiring a hematopoietic stem cell transplant who do not have an HLA-matched donor, because it is cheaper, can be performed faster, and may extend transplantation to virtually all patients in need. Significant advances have been made in the recent decade with dramatic improvement in treatment outcomes. Historically, overcoming the HLA-incompatibility barrier has been a significant limitation to the expansion of this form of transplant. (Source: Blood Reviews)
Source: Blood Reviews - September 30, 2014 Category: Hematology Authors: Stefan O. Ciurea, Ulas D. Bayraktar Tags: REVIEW Source Type: research
Corrigendum to “Von Willebrand factor and ADAMTS13 in arterial thrombosis: A systematic review and meta-analysis” [Blood Rev 28 (2014) 167–178]
The authors would like to make a correction in the abovementioned article. For the meta-analysis the authors used data from the previously published ATTAC study (T.N. Bongers et al., Atherosclerosis 2009, 207) on the association between ADAMTS13 levels and coronary heart disease (CHD). The originally reported OR for CHD in individuals with ADAMTS13 levels in the lowest tertile compared to individuals in the highest tertile was 8.2 (95% CI 4.5–14.7). Recently this OR was corrected to 5.20 (95% CI 2.67–10.13) after re-analysis of the data on CHD. (Source: Blood Reviews)
Source: Blood Reviews - September 29, 2014 Category: Hematology Authors: Michelle A.H. Sonneveld, Moniek P.M. de Maat, Frank W.G. Leebeek Tags: Corrigendum Source Type: research
Global characteristics of childhood acute promyelocytic leukemia
Acute promyelocytic leukemia (APL) comprises approximately 5–10% of childhood acute myeloid leukemia (AML) cases in the US. While variation in this percentage among other populations was noted previously, global patterns of childhood APL have not been thoroughly characterized. In this comprehensive review of childhood APL, we examined its geographic pattern and the potential contribution of environmental factors to observed variation. In 142 studies (spanning >60 countries) identified, variation was apparent—de novo APL represented from 2% (Switzerland) to >50% (Nicaragua) of childhood AML in different geographic regio...
Source: Blood Reviews - September 29, 2014 Category: Hematology Authors: L. Zhang, A. Samad, M.S. Pombo-de-Oliveira, G. Scelo, M.T. Smith, J. Feusner, J.L. Wiemels, C. Metayer Tags: REVIEW Source Type: research
The development of potential antibody-based therapies for myeloma
With optimal target antigen selection antibody-based therapeutics can be very effective agents for hematologic malignancies, but none have yet been approved for myeloma. Rituximab and brentuximab vedotin are examples of success for the naked antibody and antibody–drug conjugate classes, respectively. Plasma cell myeloma is an attractive disease for antibody-based targeting due to target cell accessibility and the complementary mechanism of action with approved therapies. Initial antibodies tested in myeloma were disappointing. (Source: Blood Reviews)
Source: Blood Reviews - September 26, 2014 Category: Hematology Authors: Daniel W. Sherbenou, Christopher R. Behrens, Yang Su, Jeffrey L. Wolf, Thomas G. Martin, Bin Liu Tags: REVIEW Source Type: research
The double-edged sword: Neurotoxicity of chemotherapy
The number of available therapies for hematologic malignancies continues to grow at a rapid pace. Unfortunately, many of these treatments carry both central and peripheral nervous system toxicities, potentially limiting a patient's ability to tolerate a full course of treatment. Neurotoxicity with chemotherapy is common and second only to myelosuppression as a reason to limit dosing. This review addresses the neurotoxicity of newly available therapeutic agents including brentuximab vedotin and blinatumomab as well as classic ones such as methotrexate, vinca alkaloids and platinums. (Source: Blood Reviews)
Source: Blood Reviews - September 26, 2014 Category: Hematology Authors: Rajiv S. Magge, Lisa M. DeAngelis Tags: REVIEW Source Type: research
All in The Family: Clueing Into The Link Between Metabolic Syndrome and Hematologic Malignancies
Metabolic syndrome constitutes a constellation of findings including central obesity, insulin resistance/type 2 diabetes mellitus (DM), dyslipidemia and hypertension. Metabolic syndrome affects 1 in 4 adults in the United States and is rapidly rising in prevalence, largely driven by the dramatic rise in obesity and insulin resistance/DM. Being central to development of metabolic syndrome and its other related diseases, much focus has been placed on identifying the mitogenic effects of obesity and insulin resistance/DM as mechanistic clues of the link between metabolic syndrome and cancer. (Source: Blood Reviews)
Source: Blood Reviews - September 25, 2014 Category: Hematology Authors: Reem Karmali, Andrew Dalovisio, Jeffrey A. Borgia, Parameswaran Venugopal, Brian W. Kim, Kelly Grant Szymanski, Parameswaran Hari, Hillard Lazarus Tags: Review Source Type: research
Cerebral venous thrombosis—A primer for the haematologist
Cerebral venous thrombosis (CVT) is a condition that can affect all age groups and can often be difficult to diagnose and treat. The difficulties in diagnosis are mainly due to the non-specific presenting features of CVT, which can range from isolated headache and visual or auditory problems, to serious symptoms such as hemiparesis and coma. Therefore, it can present to various specialists including general physicians, obstetricians and neurologists. In recent years, more widespread use of cerebral imaging has led to the diagnosis being made more often. (Source: Blood Reviews)
Source: Blood Reviews - September 20, 2014 Category: Hematology Authors: Sofia E. Thorell, Adrian R. Parry-Jones, Martin Punter, Robert Hurford, Jecko Thachil Tags: Review Source Type: research
De novo thrombotic microangiopathy after non-renal solid organ transplantation
This article presents the first literature review on TMA following non-renal solid organ transplantation (SOT). Ischemia–reperfusion, immunosuppressive drugs, acute interfering disease and a relative deficiency of the von Willebrand factor (vWF) cleaving protease (ADAMTS13) appear to play a major role in its pathogenesis. De novo TMA occurs in 4.0% of liver and 2.3% of lung transplant recipients, whereas the incidence remains unknown after intestinal transplantation. (Source: Blood Reviews)
Source: Blood Reviews - September 19, 2014 Category: Hematology Authors: Annelies Verbiest, Jacques Pirenne, Daan Dierickx Tags: REVIEW Source Type: research
Pathogenesis of non-antibody mediated transfusion-related acute lung injury from bench to bedside
Transfusion-related acute lung injury (TRALI) is a major cause of transfusion-related mortality. Causative factors are divided in antibody mediated TRALI and non-antibody mediated TRALI. Antibody mediated TRALI is caused by passive transfusion of cognate antibodies and non-antibody mediated TRALI is caused by transfusion of aged cellular blood products. This review focuses on mechanisms in non-antibody mediated TRALI which includes soluble mediators accumulating during storage of red blood cells (RBCs) and platelets (PLTs), as well as changes in morphology and function of aged PLTs and RBCs. (Source: Blood Reviews)
Source: Blood Reviews - September 19, 2014 Category: Hematology Authors: Anna L. Peters, Maike E. van Hezel, Nicole P. Juffermans, Alexander P.J. Vlaar Tags: REVIEW Source Type: research
Drug resistance-related microRNAs in hematological malignancies: Translating basic evidence into therapeutic strategies
Systemic chemotherapy has been used as the first-line therapy for patients with hematological malignancies. Despite the enormous progress in anti-tumor efficacy achieved during the last decades, the development of multidrug resistance (MDR) remains a major challenge in the successful treatment of hematological malignancies. Extensive investigations have discovered diverse mechanisms underlying MDR. More recently, increasing evidence demonstrates that miRNAs play a key regulatory role in MDR in hematological malignancies through modulating drug transporter-related proteins, cell cycle-related proteins, drug targets, autopha...
Source: Blood Reviews - September 17, 2014 Category: Hematology Authors: Lingling Xie, Rongrong Jing, Jing Qi, Zenghua Lin, Shaoqing Ju Tags: Review Source Type: research
Fibrinolysis and the control of blood coagulation
Fibrin plays an essential role in hemostasis as both the primary product of the coagulation cascade and the ultimate substrate for fibrinolysis. Fibrinolysis efficiency is greatly influenced by clot structure, fibrinogen isoforms and polymorphisms, the rate of thrombin generation, the reactivity of thrombus-associated cells such as platelets, and the overall biochemical environment. Regulation of the fibrinolytic system, like that of the coagulation cascade, is accomplished by a wide array of cofactors, receptors, and inhibitors. (Source: Blood Reviews)
Source: Blood Reviews - September 14, 2014 Category: Hematology Authors: John C. Chapin, Katherine A. Hajjar Tags: Review Source Type: research
