| 1. |
- Askmyr, Maria K, et al.
(författare)
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Towards a better understanding and new therapeutics of osteopetrosis.
- 2008
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Ingår i: British journal of haematology. - : Wiley. - 1365-2141 .- 0007-1048. ; 140:6, s. 597-609
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Forskningsöversikt (refereegranskat)abstract
- Lack of or dysfunction in osteoclasts result in osteopetrosis, a group of rare but often severe, genetic disorders affecting skeletal tissue. Increase in bone mass results in skeletal malformation and bone marrow failure that may be fatal. Many of the underlying defects have lately been characterized in humans and in animal models of the disease. In humans, these defects often involve mutations in genes expressing proteins involved in the acidification of the osteoclast resorption compartment, a process necessary for proper bone degradation. So far, the only cure for children with severe osteopetrosis is allogeneic hematopoietic stem cell (HSC) transplantation but without a matching donor this form of therapy is far from optimal. The characterization of the genetic defects opens up the possibility for gene replacement therapy as an alternative. Accordingly, HSC-targeted gene therapy in a mouse model of infantile malignant osteopetrosis was recently shown to correct many aspects of the disease.
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| 2. |
- Ljung, Rolf
(författare)
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Intracranial haemorrhage in haemophilia A and B.
- 2008
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 140:4, s. 378-384
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Forskningsöversikt (refereegranskat)abstract
- In countries with a good standard of health care, intracranial haemorrhage (ICH) during the neonatal period affects 3.5-4.0% of all haemophilia boys, which is considerably (40-80 times) higher than expected in the normal population. ICHs are also frequent after the neonatal period, affecting 3-10% of the haemophilia population who are mainly treated on demand. The risk is higher in inhibitor patients. Spontaneous haemorrhage is reported more frequently than trauma-induced haemorrhage in most studies. The prevalence of ICH in patients treated with a prophylactic regimen is not known. Although more frequent in younger patients, a substantial proportion of ICH occur in adults, suggesting that general risk factors because of age, such as hypertension, are increasingly important as the haemophiliac gets older. Some studies have reported a substantial proportion of ICH affecting patients with milder forms of haemophilia. The risk of ICH has to be considered when discussing treatment strategies for haemophilia patients.
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| 3. |
- Olsson, Martin L, et al.
(författare)
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Modifying the red cell surface: towards an ABO-universal blood supply
- 2008
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 140:1, s. 3-12
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Forskningsöversikt (refereegranskat)abstract
- Eliminating the risk for ABO-incompatible transfusion errors and simplifying logistics by creating a universal blood inventory is a challenging idea. Goldstein and co-workers pioneered the field of enzymatic conversion of blood group A and B red blood cells (RBCs) to O (ECO). Using alpha-galactosidase from coffee beans to produce B-ECO RBCs, proof of principle for this revolutionary concept was achieved in clinical trials. However, because this enzyme has poor kinetic properties and low pH optimum the process was not economically viable. Conversion of group A RBCs was only achieved with the weak A(2) subgroup with related enzymes having acidic pH optima. More recently, the identification of entirely new families of bacterial exoglycosidases with remarkably improved kinetic properties for cleaving A and B antigens has reinvigorated the field. Enzymatic conversion of groups A, B and AB RBCs with these novel enzymes resulting in ECO RBCs typing as O can now be achieved with low enzyme protein consumption, short incubation times and at neutral pH. Presently, clinical trials evaluating safety and efficacy of ECO RBCs are ongoing. Here, we review the status of the ECO technology, its impact and potential for introduction into clinical component preparation laboratories.
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| 4. |
- Vlachos, Adrianna, et al.
(författare)
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Diagnosing and treating Diamond Blackfan anaemia : results of an international clinical consensus conference
- 2008
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 142:6, s. 859-876
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Forskningsöversikt (refereegranskat)abstract
- Diamond Blackfan anaemia (DBA) is a rare, genetically and clinically heterogeneous, inherited red cell aplasia. Classical DBA affects about seven per million live births and presents during the first year of life. However, as mutated genes have been discovered in DBA, non-classical cases with less distinct phenotypes are being described in adults as well as children. In caring for these patients it is often difficult to have a clear understanding of the treatment options and their outcomes because of the lack of complete information on the natural history of the disease. The purpose of this document is to review the criteria for diagnosis, evaluate the available treatment options, including corticosteroid and transfusion therapies and stem cell transplantation, and propose a plan for optimizing patient care. Congenital anomalies, mode of inheritance, cancer predisposition, and pregnancy in DBA are also reviewed. Evidence-based conclusions will be made when possible; however, as in many rare diseases, the data are often anecdotal and the recommendations are based upon the best judgment of experienced clinicians. The recommendations regarding the diagnosis and management described in this report are the result of deliberations and discussions at an international consensus conference.
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| 5. |
- Ljung, Rolf
(författare)
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The risk associated with indwelling catheters in children with haemophilia.
- 2007
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 138:5, s. 580-586
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Forskningsöversikt (refereegranskat)abstract
- Infections are the most frequent complications associated with the use of central venous lines (CVLs) in children with haemophilia. Several retrospective studies that include data from a substantial number of patients have reported approximately 0.2-0.3 infections per 1000 catheter-days (mainly Port-A-Cath). Some studies have shown a much higher frequency of infections, 1-2/1000 catheter-days. The most plausible explanations, for the difference seen in frequency of infections with Port-A-Caths, are probably related to the protocol used for the device care and the quality of education and the compliance of the users, whether these are parents or health-care professionals. The figures are low for clinically apparent thrombosis in the larger series on record, but routine venograms were not performed in most of these series. In studies, where this has been performed, a high frequency of abnormalities (> 50%) on venograms have been seen in some series but not in others. Despite obvious potential risks with CVLs, they are useful in many cases and facilitate the treatment of a serious disorder. With careful guidelines and surveillance protocols, the risk of complications should be reduced in the future.
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| 6. |
- Ljung, Rolf C.R.
(författare)
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How I manage patients with inherited haemophilia A and B and factor inhibitors
- 2018
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048. ; 180:4, s. 501-510
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Forskningsöversikt (refereegranskat)abstract
- Development of inhibitors to coagulation factor VIII or IX is still the most challenging complication in haemophilia care. 'Bypassing agents' may be used to treat a bleed but the eradication of the inhibitor by immune tolerance induction (ITI) is the main objective in the treatment of a patient with haemophilia who has developed neutralizing antibodies. Several options exist for ITI and the patient may be at 'good' or 'bad risk' for successful outcome with different regimens. This paper offers a review of current regimens to be considered in the treatment of a bleed in a patient with an inhibitor but the main focus is the aspects of different choices in the management of the child or the adult with severe or mild forms of haemophilia A or B, who has developed an inhibitor. There are also some final outlooks on new and emerging treatment possibilities.
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| 7. |
- Ljung, Rolf, et al.
(författare)
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The current status of prophylactic replacement therapy in children and adults with haemophilia.
- 2015
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048. ; 169:6, s. 777-786
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Forskningsöversikt (refereegranskat)abstract
- Initiating prophylactic treatment at an early age is considered to be the optimal form of therapy for a child with haemophilia A or B. The pioneering long term experiences of prophylactic treatment from Sweden and The Netherlands demonstrated the benefit of prophylaxis in retrospective and observational studies. Decades later, these benefits were confirmed in a randomized controlled study in USA. We review the current status of prophylactic replacement therapy of haemophilia in children, adolescents, adults and the elderly. Prophylaxis should begin at an early age and there are arguments for continuing it into adulthood. The dose of prophylaxis is dependent on the goal of treatment, economic resources and venous access and should be tailored individually. Starting the first exposures to clotting factor concentrates as prophylactic treatment, instead of on-demand in response to a bleed, may decrease the frequency of inhibitors in patients with haemophilia A. Novel longer-acting products are being introduced that could be helpful for patients with difficult venous access and enable higher trough levels.
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| 8. |
- Olsson, Linda, et al.
(författare)
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Ikaros and leukaemia.
- 2015
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048. ; 169:4, s. 479-491
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Forskningsöversikt (refereegranskat)abstract
- The IKZF1 gene at 7p12.2 codes for IKAROS (also termed IKZF1), an essential transcription factor in haematopoiesis involved primarily in lymphoid differentiation. Its importance is underlined by the fact that deregulation of IKAROS results in leukaemia in both mice and men. During recent years, constitutional as well as acquired genetic changes of IKZF1 have been associated with human disease. For example, certain germline single nucleotide polymorphisms in IKZF1 have been shown to increase the risk of some disorders and abnormal expression and somatic rearrangements, mutations and deletions of IKZF1 (ΔIKZF1) have been detected in a wide variety of human malignancies. Of immediate clinical importance is the fact that ΔIKZF1 occurs in 15% of paediatric B-cell precursor acute lymphoblastic leukaemia (BCP ALL) and that the presence of ΔIKZF1 is associated with an increased risk of relapse and a poor outcome; in some studies such deletions have been shown to be an independent risk factor also when minimal residual disease data are taken into account. However, cooperative genetic changes, such as ERG deletions and CRLF2 rearrangements, may modify the prognostic impact of ΔIKZF1, for better or worse. This review summarizes our current knowledge of IKZF1 abnormalities in human disease, with an emphasis on BCP ALL.
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| 9. |
- Storry, Jill, et al.
(författare)
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Genetic basis of blood group diversity.
- 2004
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048. ; 126:6, s. 759-771
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Forskningsöversikt (refereegranskat)
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| 10. |
- Yazdanbakhsh, Karina, et al.
(författare)
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The role of T cells and myeloid-derived suppressor cells in refractory immune thrombocytopenia
- 2023
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Ingår i: British Journal of Haematology. - 0007-1048. ; 203:1, s. 54-61
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Forskningsöversikt (refereegranskat)abstract
- Immune thrombocytopenia (ITP) is characterized by a dysregulated immune response against platelets, affecting both their destruction and production. A role for an abnormal T-cell compartment has been established in ITP pathogenesis and treatments that increase platelet counts in patients with ITP have shown improvements in T-cell profiles. On the other hand, patients who were refractory to treatment appear to retain the T-cell abnormalities as before. Myeloid-derived suppressive cells (MDSCs) are also emerging as key contributors to the immune pathology of ITP and response to treatment. In this review, we will discuss how various treatments affect the T-cell and MDSC compartments in ITP. The review will focus on studies that have examined the underlying mechanisms and/or genetic basis responsible for refractoriness to a given treatment and highlight remaining challenges in identifying factors and mechanisms to predict response to treatment.
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