Factor X Deficiency

Menegatti, Marzia; Peyvandi, Flora

doi:10.1055/s-0029-1225763

Cited by 128 publications

(133 citation statements)

References 46 publications

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“…A comparison of the most and least common symptoms among those with severe deficient RBDs is shown in Table 2. [9][10][11][12][13][14][15][16] Heterozygous individuals commonly do not manifest a bleeding tendency. Mucocutaneous and surgical associated bleeding were reported in 20% of patients, whereas post-traumatic hemarthrosis and hematomas are rarely reported in FVII and FX deficiencies.…”

Section: Clinical Symptomsmentioning

confidence: 99%

Rare bleeding disorders: diagnosis and treatment

Palla

Peyvandi

Shapiro

2015

Blood

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265

258

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Despite the worldwide prevalence of rare bleeding disorders (RBDs), knowledge of these conditions and their management is suboptimal; health care professionals often have little diagnostic and treatment experience with variable access to diagnostic modalities required for accurate identification. Therefore, patients often experience morbidity and mortality due to delayed diagnosis. As RBDs represent a small potential commercial market, few, if any, specific therapies exist for these conditions. As a result, affected individuals commonly face delayed diagnosis, incomplete laboratory evaluation, and limited treatment options. Standardization and customization of coagulation assays, full genome sequencing, and global clotting assays will significantly improve diagnosis of patients with RBDs. In addition, new therapeutic modalities, both recombinant and plasma derived, are emerging, at least in developed countries. Registries and clinical trials have demonstrated decreased bleeding and improved outcomes when patients are appropriately diagnosed and properly treated. Expansion and harmonization of international registries has been initiated to correlate genotype, laboratory, and clinical phenotypes including bleeding severity to improve the diagnosis and therapeutic approach. This review focuses on the latest advances in our understanding, diagnosis, and treatment of RBDs.

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Section: Clinical Symptomsmentioning

confidence: 99%

Rare bleeding disorders: diagnosis and treatment

Palla

Peyvandi

Shapiro

2015

Blood

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265

258

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“…17 Bleeding related to severe coagulation factor deficiency is tolerable for FXIII, 18 less tolerable for FV, 19 and severe for FX. 20 Near-complete reductions in FVII 21 and FII 22 are not observed in humans, suggesting that their absence is not physiologically tolerated.…”

Section: Bleeding Disorder Of Hemophilia Cmentioning

confidence: 99%

Inhibition of Factor XIa as a New Approach to Anticoagulation

Schumacher

Luettgen

Quan

et al. 2010

ATVB

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Abstract-The dose-limiting issue with available anticoagulant therapies is bleeding. Is there an approach that could provide antithrombotic protection with reduced bleeding? One hypothesis is that targeting proteases upstream from the common pathway provides a reduction in thrombin sufficient to impede occlusive thrombosis yet allows enough thrombin generation to support hemostasis. The impairment of intrinsic coagulation by selective inhibition of factor XI (FXI) leaves the extrinsic and common pathways of coagulation intact, making FXI a drug target. This concept is supported by the observation that human deficiency in FXI results in a mild bleeding disorder compared with other coagulation factor deficiencies, and that elevated levels of FXI are a risk factor for thromboembolic disease. Moreover, FXI knockout mice have reduced thrombosis with little effect on hemostasis. The results from genetic models have been supported by studies using neutralizing antibodies, peptide inhibitors, and small-molecule inhibitors. These agents impede thrombosis without affecting bleeding time in a variety of experimental animals, including primates. Together, these data strongly support FXIa inhibition as a viable method to increase the ratio of benefit to risk in an antithrombotic drug. (Arterioscler Thromb Vasc Biol. 2010;30:388-392.)Key Words: intrinsic pathway Ⅲ coagulation Ⅲ factor XI Ⅲ thrombosis The Need for Improved Anticoagulant TherapyHemostasis is an adaptive process that maintains blood in a fluid state and preserves vasculature integrity. Thrombosis is a maladaptive process of vascular occlusion and remains a primary cause of cardiovascular morbidity and mortality. Antithrombotic therapy is effective for the prevention and treatment of thromboembolic disease. However, the established oral anticoagulant warfarin has numerous limitations, including lack of reversibility, a steep dose response, food and multiple drug-drug interactions, need for monitoring, and a narrow therapeutic index. The availability of newer oral anticoagulants, such as direct and selective inhibitors of factor Xa (FXa) and thrombin, has overcome many of these liabilities; however, dose-dependent bleeding continues to be observed. 1,2 An overlap of antithrombotic benefit and a disruption of hemostasis are not unexpected given that both processes involve interactions between the vessel wall, platelets, blood coagulation, and fibrinolysis. Improving the risk to benefit ratio remains a viable goal for antithrombotic drug See accompanying article on page 369discovery. This requires selecting a molecular target that defines a difference between hemostasis and thrombosis. Selecting such a target derives from the detailed study of human physiology and animal models. A good example is the inhibition of blood coagulation FXIa as a novel mechanism for preventing and treating thromboembolic diseases. Role of FXIa in Blood CoagulationBlood coagulation is the coordinated activation of plasma proteases, their cofactors, and platelets. The end product is the pr...

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“…Heterozygous cases might be identified incidentally by laboratory tests performed preoperatively or for another purpose. 79 In the NARBDR, most bleeding symptoms in factor X deficiency were mucocutaneous, including easy bruising, followed by musculoskeletal bleeding. Intracranial bleeding occurred in 15% of the homozygous cohort, of which 54% had a factor X level <0.01 U/ mL.…”

Section: Factor X Deficiencymentioning

confidence: 99%

Evaluating for Suspected Child Abuse: Conditions That Predispose to Bleeding

Carpenter¹,

Abshire²,

Anderst³

et al. 2013

Pediatrics

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Child abuse might be suspected when children present with cutaneous bruising, intracranial hemorrhage, or other manifestations of bleeding. In these cases, it is necessary to consider medical conditions that predispose to easy bleeding/bruising. When evaluating for the possibility of bleeding disorders and other conditions that predispose to hemorrhage, the pediatrician must consider the child’s presenting history, medical history, and physical examination findings before initiating a laboratory investigation. Many medical conditions can predispose to easy bleeding. Before ordering laboratory tests for a disease, it is useful to understand the biochemical basis and clinical presentation of the disorder, condition prevalence, and test characteristics. This technical report reviews the major medical conditions that predispose to bruising/bleeding and should be considered when evaluating for abusive injury.

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Factor X Deficiency

Cited by 128 publications

References 46 publications

Rare bleeding disorders: diagnosis and treatment

Rare bleeding disorders: diagnosis and treatment

Inhibition of Factor XIa as a New Approach to Anticoagulation

Evaluating for Suspected Child Abuse: Conditions That Predispose to Bleeding

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