Setting the stage for individualized therapy in hemophilia: What role can pharmacokinetics play?
Replacement therapy with clotting factor concentrates (CFC) is the mainstay of treatment in hemophilia. Its widespread application has led to a dramatic decrease in morbidity and mortality in patients, with concomitant improvement of quality of life. However, dosing is challenging and costs are high. This review discusses benefits and limitations of pharmacokinetic (PK)-guided dosing of replacement therapy as an alternative for current dosing regimens. Dosing of CFC is now primarily based on body weight and based on its in vivo recovery (IVR). (Source: Blood Reviews)
Source: Blood Reviews - February 4, 2018 Category: Hematology Authors: H.C.A.M. Hazendonk, I. van Moort, R.A.A. Math ôt, K. Fijnvandraat, F.W.G. Leebeek, P.W. Collins, M.H. Cnossen, for the OPTI-CLOT study group Tags: Review Source Type: research
Consequences of dysregulated complement regulators on red blood cells
The complement system represents the first line of defense that is involved in the clearance of pathogens, dying cells and immune complexes via opsonization, induction of an inflammatory response and the formation of a lytic pore. Red blood cells (RBCs) are very important for the delivery of oxygen to tissues and are continuously in contact with complement proteins in the blood plasma. To prevent complement activation on RBCs, various complement regulatory proteins can be found in plasma and on the cell membrane. (Source: Blood Reviews)
Source: Blood Reviews - February 4, 2018 Category: Hematology Authors: Astrid J.F. Thielen, Sacha Zeerleder, Diana Wouters Tags: Review Source Type: research
Setting the stage for individualized therapy in hemophilia: What role can pharmacokinetics play?
Replacement therapy with clotting factor concentrates (CFC) is the mainstay of treatment in hemophilia. Its widespread application has led to a dramatic decrease in morbidity and mortality in patients, with concomitant improvement of quality of life. However, dosing is challenging and costs are high. This review discusses benefits and limitations of pharmacokinetic (PK)-guided dosing of replacement therapy as an alternative for current dosing regimens. Dosing of CFC is now primarily based on body weight and based on its in vivo recovery (IVR). (Source: Blood Reviews)
Source: Blood Reviews - February 4, 2018 Category: Hematology Authors: H.C.A.M. Hazendonk, I. van Moort, R.A.A. Math ôt, K. Fijnvandraat, F.W.G. Leebeek, P.W. Collins, M.H. Cnossen, for the OPTI-CLOT study group Tags: Review Source Type: research
Consequences of dysregulated complement regulators on red blood cells
The complement system represents the first line of defense that is involved in the clearance of pathogens, dying cells and immune complexes via opsonization, induction of an inflammatory response and the formation of a lytic pore. Red blood cells (RBCs) are very important for the delivery of oxygen to tissues and are continuously in contact with complement proteins in the blood plasma. To prevent complement activation on RBCs, various complement regulatory proteins can be found in plasma and on the cell membrane. (Source: Blood Reviews)
Source: Blood Reviews - February 4, 2018 Category: Hematology Authors: Astrid J.F. Thielen, Sacha Zeerleder, Diana Wouters Tags: Review Source Type: research
Cardiovascular, pulmonary, and metabolic toxicities complicating tyrosine kinase inhibitor therapy in chronic myeloid leukemia: Strategies for monitoring, detecting, and managing
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm, the incidence of which increases with age. Tyrosine kinase inhibitors (TKIs) are the mainstay of CML treatment, including imatinib, nilotinib, dasatinib, bosutinib, and ponatinib. Beyond matching patient disease profiles with TKI specificity, differences in the efficacy and toxicity profiles and a patient's comorbid risk factors should be considered when selecting the most appropriate agent. Our objectives are to review the incidence and severity of cardiovascular, metabolic, and pulmonary disorders associated with these TKIs, highlighting differences in adve...
Source: Blood Reviews - February 3, 2018 Category: Hematology Authors: Bruno C. Medeiros, Jennifer Possick, Michael Fradley Tags: Review Source Type: research
Direct oral anticoagulant use in patients with thrombophilia, antiphospholipid syndrome or venous thrombosis of unusual sites: A narrative review
Direct oral anticoagulants (DOACs) are indicated in the treatment and prevention of venous thromboembolism (VTE). However, the use of DOACs in unusual VTE, including cerebral venous thrombosis (CVT) and splanchnic venous thrombosis (SVT), and in patients with biological thrombophilia including minor thrombophilia (Factor V Leiden and prothrombin G20210A), major innate thrombophilia (protein C and S deficiency, and antithrombin) and major acquired thrombophilia (antiphospholipid syndrome [APS]), remains controversial due to the paucity of available data. (Source: Blood Reviews)
Source: Blood Reviews - February 2, 2018 Category: Hematology Authors: Laurent Bertoletti, Ygal Benhamou, Yannick B éjot, Sylvestre Marechaux, Saida Cheggour, Boris Aleil, Nicolas Lellouche, Jean-Guillaume Dillinger, Aurélien Delluc Tags: Review Source Type: research
The pathobiology of primary testicular diffuse large B-cell lymphoma: Implications for novel therapies
Primary testicular lymphomas (PTL) are the most prevalent type of testicular cancer arising in men over the age of 60. PTL accounts for approximately 1 –2% of all non-Hodgkin lymphomas and most present with localized disease but despite this, outcome is poor. The majority of cases represent an extranodal manifestation of diffuse large B-cell lymphoma (DLBCL), known as primary testicular DLBCL (PT-DLBCL). Gene expression profiling has established that over 75% of PT-DLBCLs resemble the activated B-cell-like (ABC) or non-germinal center subtype of nodal DLBCL. (Source: Blood Reviews)
Source: Blood Reviews - December 20, 2017 Category: Hematology Authors: David D.W. Twa, Anja Mottok, Kerry J. Savage, Christian Steidl Tags: Review Source Type: research
Reintroduction of anticoagulant therapy after intracranial haemorrhage: If and when?
Intracranial haemorrhage is a devastating complication of anticoagulation. In surviving patients, physicians will be faced with the dilemma of if and when treatment should be reintroduced. There is little evidence to support this decision making and guidelines refrain from making specific recommendations. Existing data relates almost exclusively to vitamin K antagonists and is entirely retrospective.There appears to be an overall benefit to reintroducing anticoagulation in most patients; although, this may not be advocated in those at the highest risk of recurrent bleeding. (Source: Blood Reviews)
Source: Blood Reviews - December 20, 2017 Category: Hematology Authors: Martin Scott, Ryan Low, Dawn Swan, Jecko Thachil Tags: Review Source Type: research
The pathobiology of primary testicular diffuse large B-cell lymphoma: Implications for novel therapies
Primary testicular lymphomas (PTL) are the most prevalent type of testicular cancer arising in men over the age of 60. PTL accounts for approximately 1 –2% of all non-Hodgkin lymphomas and most present with localized disease but despite this, outcome is poor. The majority of cases represent an extranodal manifestation of diffuse large B-cell lymphoma (DLBCL), known as primary testicular DLBCL (PT-DLBCL). Gene expression profiling has established that over 75% of PT-DLBCLs resemble the activated B-cell-like (ABC) or non-germinal center subtype of nodal DLBCL. (Source: Blood Reviews)
Source: Blood Reviews - December 20, 2017 Category: Hematology Authors: David D.W. Twa, Anja Mottok, Kerry J. Savage, Christian Steidl Tags: Review Source Type: research
Reintroduction of anticoagulant therapy after intracranial haemorrhage: If and when?
Intracranial haemorrhage is a devastating complication of anticoagulation. In surviving patients, physicians will be faced with the dilemma of if and when treatment should be reintroduced. There is little evidence to support this decision making and guidelines refrain from making specific recommendations. Existing data relates almost exclusively to vitamin K antagonists and is entirely retrospective.There appears to be an overall benefit to reintroducing anticoagulation in most patients; although, this may not be advocated in those at the highest risk of recurrent bleeding. (Source: Blood Reviews)
Source: Blood Reviews - December 20, 2017 Category: Hematology Authors: Martin Scott, Ryan Low, Dawn Swan, Jecko Thachil Tags: Review Source Type: research
Dueling for dual inhibition: Means to enhance effectiveness of PI3K/Akt/mTOR inhibitors in AML
The phosphatidylinositol 3-kinase/protein kinase B (Akt)/mechanistic target of rapamycin (PI3K/Akt/mTOR) pathway is amplified in 60 –80% of patients with acute myelogenous leukemia (AML). Since this complex pathway is crucial to cell functions such as growth, proliferation, and survival, inhibition of this pathway would be postulated to inhibit leukemia initiation and propagation. Inhibition of the mTORC1 pathway has met with limited success in AML due to multiple resistance mechanisms including direct insensitivity of the mTORC1 complex, feedback activation of the PI3k/Akt signaling network, insulin growth factor-1 (IGF...
Source: Blood Reviews - December 1, 2017 Category: Hematology Authors: Lauren Herschbein, Jane L. Liesveld Tags: Review Source Type: research
Clinical, laboratory and imaging findings in Castleman's disease – The subtype decides
Castleman's disease (CD) is a rare lymphoproliferative disorder with its distinct unicentric (uCD) and multicentric (mCD) entities. The present work aimed at characterizing CD in more detail. From the 775 articles found by a PubMed search, 1133 cases were extracted. Two own cases were included. UCD was identified in 719 (42% males) and mCD in 416 (63% males) cases. Age in uCD was 34 ±17 and in mCD 48±18years. The hyaline-vascular type predominated in uCD and the plasma cell type in mCD. Clinical symptoms were more common in mCD. (Source: Blood Reviews)
Source: Blood Reviews - November 29, 2017 Category: Hematology Authors: Michael Haap, Julia Wiefels, Marius Horger, Annika Hoyer, Karsten M üssig Tags: Review Source Type: research
