Primary prophylaxis for children with severe congenital factor VII deficiency — Clinical and laboratory assessment

Kuperman, AA; Aa, Barg; Fruchtman, Yariv; Shaoul, Ety; Rosenberg, Nurit; Kenet, Gili

doi:10.1016/j.bcmd.2016.12.008

Cited by 10 publications

(8 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although this view is novel, to our knowledge, its elements are in good agreement with previous reports. All results of this study in its homogeneous model are well in line with previous reports on the sensitivity of the clotting cascade to coagulation factor deficiency (11,(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). The decrease in clotting sensitivity to coagulation factor deficiency with the increase in TF activation level is also well documented (34).…”

Section: Discussionsupporting

confidence: 91%

Sensitivity and Robustness of Spatially Dependent Thrombin Generation and Fibrin Clot Propagation

Kuprash

Shibeko

Vijay

et al. 2018

Biophysical Journal

View full text Add to dashboard Cite

Blood coagulation is a delicately regulated space-and time-dependent process that leads to the formation of fibrin clots preventing blood loss upon vascular injury. The sensitivity of the coagulation network was previously investigated without accounting for transport processes. To investigate its sensitivity to coagulation factor deficiencies in a spatial reactiondiffusion system, we combined an in vitro experimental design with a computational systems biology model. Clot formation in platelet-free plasma supplemented with phospholipids was activated with identical amounts of tissue factor (TF) either homogeneously distributed (concentration 5 pM, homogeneous model) or immobilized on the surface (surface density 100 pmole/m 2 , spatially heterogeneous model). Fibrin clot growth and thrombin concentration dynamic in space were observed using video microscopy in plasma of healthy donors or patients with deficiencies in factors (F) II, FV, FVII, FVIII, FIX, FX, or FXI. In the spatially heterogeneous model, near-activator thrombin generation was decreased in FV-, FVII-, and FX-deficient plasma. In the homogeneous model, clotting was not registered in these samples. The simulation and experiment data showed that the coagulation threshold depended on the TF concentration. Our data indicate that the velocity of spatial clot propagation correlates linearly with the concentration of thrombin at the clot wave front but not with the overall thrombin wave amplitude. Spatial clot growth in normal plasma at early stages was neither reaction nor diffusion limited but became diffusion limited later. In contrast, clot growth was always diffusion limited in FV-, FVII-, and FX-deficient plasma and reaction limited in FVIII-, FIX-, and FXI-deficient plasma. We conclude that robustness of the spatially heterogeneous coagulation system was achieved because of the combination of 1) a local high TF surface density that overcomes activation thresholds, 2) diffusion control being shared between different active factors, and 3) an early saturated stimulus-response dependence of fibrin clot formation by thrombin.

show abstract

Section: Discussionsupporting

confidence: 91%

Sensitivity and Robustness of Spatially Dependent Thrombin Generation and Fibrin Clot Propagation

Kuprash

Shibeko

Vijay

et al. 2018

Biophysical Journal

View full text Add to dashboard Cite

show abstract

“…Prophylaxis is warranted for patients with the most severe bleeding picture and should be prescribed from childhood or soon after the first bleeding event. 45,68 Effective prophylaxis schedules have been reported for rFVIIa 68,69 and pdFVII concentrates. 70…”

Section: Replacement Therapy and Prophylaxismentioning

confidence: 99%

Biochemical, molecular and clinical aspects of coagulation factor VII and its role in hemostasis and thrombosis

Bernardi

Mariani

2021

haematol

View full text Add to dashboard Cite

Activated factor VII (FVIIa), the first protease of clotting, expresses its physiological procoagulant potential only after complexing with tissue factor (TF) exposed to blood. Deep knowledge of the FVIIa-TF complex and F7 gene helps to understand the Janus-faced clinical findings associated to low or elevated FVII activity (FVIIc). Congenital FVII deficiency, the most frequent among the recessively inherited bleeding disorders, is caused by heterogeneous mutations in the F7 gene. Complete FVII deficiency causes perinatal lethality. A wide range of bleeding symptoms, from life-threatening intracranial hemorrhage to mild mucosal bleeding, is observed in patients with apparently modest differences in FVIIc levels. Though clinically relevant FVIIc threshold levels are still uncertain, effective management, including prophylaxis, has been devised, substantially improving the quality of life of patients. The exposure of TF in diseased arteries fostered investigation on the role of FVII in cardiovascular disease. FVIIc levels were found to be predictors of cardiovascular death and to be markedly associated to F7 gene variation. These genotype-phenotype relationships are among the most extensively investigated in humans. Genome-wide analyses extended association to numerous loci that, together with F7, explain >50% of FVII level plasma variance. However, the ability of F7 variation to predict thrombosis was not consistently evidenced in the numerous population studies. Main aims of this review are to highlight i) the biological and clinical information that distinguishes FVII deficiency from the other clotting disorders and ii) the impact exerted by genetically predicted FVII level variation on bleeding as well as on the thrombotic states.

show abstract

“…Short-term or intermittent prophylactic schedules can also be considered, particularly in conditions like menorrhagia or severe hemarthroses [16,20]. Early long-term primary prophylaxis in children with severe FVII deficiency with very high bleeding risk was proved to be safe and effective [50]. …”

Section: Replacement Therapymentioning

confidence: 99%

Factor VII Deficiency: Clinical Phenotype, Genotype and Therapy

Napolitano

Siragusa

Mariani

2017

JCM

View full text Add to dashboard Cite

Factor VII deficiency is the most common among rare inherited autosomal recessive bleeding disorders, and is a chameleon disease due to the lack of a direct correlation between plasma levels of coagulation Factor VII and bleeding manifestations. Clinical phenotypes range from asymptomatic condition—even in homozygous subjects—to severe life-threatening bleedings (central nervous system, gastrointestinal bleeding). Prediction of bleeding risk is thus based on multiple parameters that challenge disease management. Spontaneous or surgical bleedings require accurate treatment schedules, and patients at high risk of severe hemorrhages may need prophylaxis from childhood onwards. The aim of the current review is to depict an updated summary of clinical phenotype, laboratory diagnosis, and treatment of inherited Factor VII deficiency.

show abstract

Primary prophylaxis for children with severe congenital factor VII deficiency — Clinical and laboratory assessment

Cited by 10 publications

References 30 publications

Sensitivity and Robustness of Spatially Dependent Thrombin Generation and Fibrin Clot Propagation

Sensitivity and Robustness of Spatially Dependent Thrombin Generation and Fibrin Clot Propagation

Biochemical, molecular and clinical aspects of coagulation factor VII and its role in hemostasis and thrombosis

Factor VII Deficiency: Clinical Phenotype, Genotype and Therapy

Contact Info

Product

Resources

About