Correcting the hemophilic imbalance

Lane, David A.

doi:10.1182/blood-2016-11-748822

Cited by 5 publications

(5 citation statements)

References 9 publications

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“…On the other hand, TP53 mutations in Shwachman-Diamond are controversial in that the mutations do not augur for transformation (Xia et al, 2018 ). Furthermore, the prevalence of mutations in TP53 and in other genes such RUNX1 in Fanconi anemia or dyskeratosis congenita appears to be much less than that of CSF3R in SCN (Chao et al, 2017 ; Lane, 2017 ; Kirschner et al, 2018 ). Despite this, modified Moran model might be applicable to other bone marrow failure syndromes that are associated with leukemia transformation.…”

Section: Discussionmentioning

confidence: 99%

Application of the Moran Model in Estimating Selection Coefficient of Mutated CSF3R Clones in the Evolution of Severe Congenital Neutropenia to Myeloid Neoplasia

2020

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Section: Discussionmentioning

confidence: 99%

Application of the Moran Model in Estimating Selection Coefficient of Mutated CSF3R Clones in the Evolution of Severe Congenital Neutropenia to Myeloid Neoplasia

2020

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“…1). [46][47][48] APC is activated from its precursor, protein C, by thrombin bound to thrombomodulin on the endothelial cell surface. 46 Once formed, APC exerts its anticoagulant activity by proteolytically inactivating FVIIIa and activated factor V (FVa).…”

Section: Anti-activated Protein Cmentioning

confidence: 99%

Nonfactor Therapies: New Approaches to Prophylactic Treatment of Haemophilia

Chowdary

2021

Hamostaseologie.

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For several decades, the treatment of haemophilia has relied on factor replacement therapy, which restores haemostasis by replacing the missing coagulation factor. In recent years, novel alternative therapies for the treatment of haemophilia in patients with and without inhibitors have been developed. These emergent therapies promote haemostasis by mimicking coagulation factors or inhibiting natural anticoagulants. They provide a less invasive route of administration (i.e. subcutaneous) and some offer reduced frequency of dosing (i.e. every 2 weeks, monthly) compared with the majority of factor replacement therapies, and thus have the potential to simplify treatment, increase adherence and subsequently improve outcomes for patients. Their introduction has transformed the care of haemophilia patients with inhibitors to factor VIII, with similar expectation for haemophilia B patients with inhibitors. However, these therapies also come with several new challenges including their limitation to prophylactic treatment, the observed increased incidence of thrombosis, or their impact on the natural history of the disease and potential disruption of existing treatment guidelines like the use of immune tolerance induction. Moreover, questions remain regarding the long-term impact of non-replacement therapies on joint health as well as the optimal strategy to manage breakthrough bleeds in patients with inhibitors.

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“…However, several lines of evidence have demonstrated that the hemostatic balance may also be restored by inhibiting/reducing the natural anticoagulants even without replacing the missing procoagulant. 26 Clinical evidence has been provided by the observation that coinheritance of thrombophilic risk factors can moderate the clinical phenotype of severe hemophilia A. 27,28 Thrombin generation is increased in the plasma of individuals with coinheritance of hemophilia and some thrombophilias (eg, protein C deficiency).…”

Section: Agents That Alter the Hemostatic Balancementioning

confidence: 99%

Novel therapeutics for hemophilia and other bleeding disorders

Callaghan

Sidonio

Pipe

2018

Blood

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Hemophilia and von Willebrand disease are the most common congenital bleeding disorders. Treatment of these disorders has focused on replacement of the missing coagulation factor to prevent or treat bleeding. New technologies and insights into hemostasis have driven the development of many promising new therapies for hemophilia and von Willebrand disease. Emerging bypass agents including zymogen-like factor IXa and Xa molecules are in development and a bispecific antibody, emicizumab, demonstrated efficacy in a phase 3 trial in people with hemophilia A and inhibitors. Tissue factor pathway inhibitor, the protein C/S system, and antithrombin are targets of novel compounds in development to alter the hemostatic balance and new approaches using modified factor VIII molecules are being tested for prevention and eradication of inhibitor antibodies in hemophilia A. The first recombinant von Willebrand factor (VWF) product has been approved and has unique VWF multimer content and does not contain factor VIII. These new approaches may offer better routes of administration, improved dosing regimens, and better efficacy for prevention and treatment of bleeding in congenital bleeding disorders.

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Correcting the hemophilic imbalance

Cited by 5 publications

References 9 publications

Application of the Moran Model in Estimating Selection Coefficient of Mutated CSF3R Clones in the Evolution of Severe Congenital Neutropenia to Myeloid Neoplasia

Application of the Moran Model in Estimating Selection Coefficient of Mutated CSF3R Clones in the Evolution of Severe Congenital Neutropenia to Myeloid Neoplasia

Nonfactor Therapies: New Approaches to Prophylactic Treatment of Haemophilia

Novel therapeutics for hemophilia and other bleeding disorders

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