Fxi deficiency

Hemophilia C is a rare bleeding disorder characterized by a deficiency in clotting factor XI (fXI) and has no standard of care for preoperative optimization before cardiac surgery. Normalization of fXI levels in patients with hemophilia C can be achieved with fresh frozen plasma (FFP), which sometimes results in allergic reactions. We present a case of a patient with hemophilia C requiring coronary artery bypass grafting surgery who developed an allergic reaction to FFP. Our report underscores the balance between thrombosis and bleeding risks when devising a perioperative plan for patients with hemophilia C...

BACKGROUND: Congenital factor XI deficiency is a coagulopathy probably underestimated that confers antithrombotic protection. Characterization of genetic defects in F11 is mainly focused on the identification of single nucleotide variants and small insertion/deletions, as they represent up to 99% of the alterations accounting for factor deficiency, with only 3 gross gene defects of structural variants (SVs) having been described. OBJECTIVE: To identify and characterize SVs affecting F11...

BACKGROUND: Current assays that monitor thrombin generation in plasma rely on fluorogenic substrates to follow the kinetics of zymogen activation, which may be complicated by substrate cleavage from other proteases. In addition, these assays depend on activation following cleavage at the R320 site of prothrombin and fail to report cleavage at the alternative R271 site that leads to shedding of the auxiliary Gla and kringle domains of prothrombin. OBJECTIVE: To develop a plasma assay that directly monitors prothrombin activation independent of fluorogenic substrate hydrolysis...

INTRODUCTION: Whilst the introduction of direct oral anticoagulants (DOACs) has improved the prevention of thromboembolic events, there is still a need for safer anticoagulants. This is particularly so, for specific populations of patients, such as those with an increased bleeding risk or those with severely reduced kidney function. People with Factor XI (FXI) deficiency are at reduced risk of thromboembolic events, without an increased risk of spontaneous bleeding. FXI inhibition, therefore, presents the ideal target for novel anticoagulants...

Anticoagulation therapy is a mainstay of the treatment of thrombotic disorders; however, conventional anticoagulants trade antithrombotic benefits for bleeding risk. Factor (f) XI deficiency, known as hemophilia C, rarely causes spontaneous bleeding, suggesting that fXI plays a limited role in hemostasis. In contrast, individuals with congenital fXI deficiency display a reduced incidence of ischemic stroke and venous thromboembolism, indicating that fXI plays a role in thrombosis. For these reasons, there is intense interest in pursuing fXI/factor XIa (fXIa) as targets for achieving antithrombotic benefit with reduced bleeding risk...

BACKGROUND: During plasma contact activation, factor XII (FXII) binds to surfaces through its heavy chain and undergoes conversion to the protease FXIIa. FXIIa activates prekallikrein and factor XI (FXI). Recently, we showed that the FXII first epidermal growth factor-1 (EGF1) domain is required for normal activity when polyphosphate is used as a surface. OBJECTIVES: The aim of this study was to identify amino acids in the FXII EGF1 domain required for polyphosphate-dependent FXII functions...

Factor XI/XIa (FXI/FXIa) represents a potential target for improved precision in anticoagulation because it is involved primarily in thrombus formation and plays a much smaller role in clotting and hemostasis. This suggests that the inhibition of FXI/XIa could prevent pathologic thrombi from forming, but largely preserve a patient's ability to clot in response to bleeding or trauma. This theory is supported by observational data showing that patients with congenital FXI deficiency have lower rates of embolic events without an increase in spontaneous bleeding...

FXI deficiency is a rare bleeding disorder characterized by a decreased level or activity of factor. Pregnant women are at increased risk of uterine bleeding during childbirth. Neuroaxial analgesia may increase the risk of epidural hematoma in these patients. However, there is no consensus on the anesthetic management. We present the clinical case of a 36-year-old woman with a personal history of factor XI deficiency, pregnant with 38 weeks gestation who is scheduled to perform birth induction. Pre-induction factor levels were measured...

PURPOSE OF REVIEW: Factor XI (FXI) inhibitors were developed to address unmet needs and limitations of current anticoagulants and are currently being studied in several indications. In this paper, we review the rationale for the development of these agents and summarize what clinicians should know about drugs that target FXI. RECENT FINDINGS: Patients with FXI deficiency may have a lower risk of venous thromboembolism and cardiovascular events and have a variable but generally mild bleeding diathesis...

Factor XI (FXI) deficiency is an autosomal bleeding disorder characterized by injury-related hemorrhage, mostly associated with surgical procedures at sites noted for high fibrinolytic activity. Severe FXI deficiency is defined when the FXI level is lower than 15-20 IU/dL. Perioperative prophylactic treatment for high-bleeding-risk surgery in patients with severe FXI deficiency is based on fresh frozen plasma (FFP) transfusions or FXI concentrate (where available). Exposure to FFP and to FXI concentrate may lead to the development of inhibitory antibodies against FXI...

BACKGROUND: Factor (F) XI deficiency is associated with increased bleeding risk in some individuals. Neither FXI levels nor clinical clotting assays predict the bleeding risk. Compared with controls, FXI-deficient bleeders have reduced clot formation, decreased fibrin network density, and increased susceptibility to fibrinolysis. Tissue factor pathway inhibitor (TFPI) was recently implicated as a modifying factor in individuals with bleeding of unknown cause. OBJECTIVES: To determine the potential of TFPI in modifying the bleeding risk in FXI-deficient individuals...

Factor XI (FXI) deficiency is a rare bleeding disorder of unpredictable severity that correlates poorly with FXI coagulation activity and that poses great challenges for perioperative hemostatic management and the dialysis methods potentially available to new end-stage renal disease (ESRD) patients. We describe an individual with both ESRD and severe FXI deficiency, who successfully underwent peritoneal dialysis (PD) after emergency abdominal surgery. In the traditional concept, recent abdominal surgery is a contraindication to PD, especially for patients with bleeding risk...

Thrombin generation (TG) assays serve as valuable tools to study the amplifying roles of intrinsic pathway factors in human coagulation and provide functional insight into the increased bleeding observed in individuals deficient in factors (F) XI, IX or VIII. Mice are used extensively in hemostasis research due to the availability of coagulation factor deficient mice. However, phenotypic differences between mouse and human TG have become apparent. Herein, we describe a novel, calibrated mouse whole blood (WB) TG assay used to assess the amplifying roles of intrinsic pathway factors in mouse coagulation...

Thrombophilia leads to an increased risk of venous thromboembolism. Widely accepted risk factors for thrombophilia comprise deficiencies of protein C, protein S, and antithrombin, as well as the factor V "Leiden" mutation, the prothrombin G20210A mutation, dysfibrinogenemia, and, albeit less conclusive, increased levels of factor VIII. Besides these established markers of thrombophilia, risk factors of unclear significance have been described in the literature. These inherited risk factors include deficiencies or loss-of-activity of the activity of ADAMTS13, heparin cofactor II, plasminogen, tissue factor pathway inhibitor (TFPI), thrombomodulin, protein Z (PZ), as well as PZ-dependent protease inhibitor...

Factor XI (FXI) deficiency is an autosomally inherited milder bleeding disorder which may predispose to a potential risk of life-threatening bleeding during childbirth or surgery. Unfortunately, data regarding obstetric and perioperative management of this condition are scarce, with limited cases reviewed in the last decade. Therefore, the present study aimed to expand this database and identify factors associated with increased bleeding risk. We performed a retrospective chart review of patients with FXI deficiency who underwent childbirth or other surgical procedures between August 2011 to April 2021 within a single academic health system and identified 198 patients who underwent 252 procedures, including 143 vaginal deliveries, 63 cesarean (C-sections) and 46 other surgical procedures...

Calibrated Automated Thrombography (CAT) is a versatile and sensitive method for analyzing coagulation reactions culminating in thrombin generation (TG). Here, we present a CAT method for analyzing TG in murine whole blood by adapting the CAT assay used for measuring TG in human plasma. The diagnostically used artificial and physiologic factor XII (FXII) contact activators kaolin, ellagic acid and polyphosphate (polyP) stimulated TG in murine blood in a dose-dependent manner resulting in a gradual increase in endogenous thrombin potential and peak thrombin, with shortened lag times and times to peak...

Rare bleeding disorders (RBDs), including factor (F) I, FII, FV, FVII, combined FV and FVIII (CF5F8), FXI, FXIII and vitamin-K dependent coagulation factors (VKCF) deficiencies, are a heterogeneous group of hemorrhagic disorder with a variable bleeding tendency. RBDs are due to mutation in underlying coagulation factors genes, except for CF5F8 and VKCF deficiencies. FVII deficiency is the most common RBD with >330 variants in the F7 gene, while only 63 variants have been identified in the F2 gene. Most detected variants in the affected genes are missense (>50% of all RBDs), while large deletions are the rarest, having been reported in FVII, FX, FXI and FXIII deficiencies...

Inherited bleeding disorders are characterized by a diverse clinical phenotype within and across specific diagnoses. von Willebrand disease (VWD), hemophilia A, and hemophilia B comprise 95 to 97% of inherited bleeding disorders, with the remaining 3 to 5% attributed to rare bleeding disorders, including congenital fibrinogen disorders, factor deficiencies (affecting FII, FV, FV + FVIII, FVII, FX, FXI, and FXIII), and platelet function defects. The pregnancy, birth, and the puerperium may be adversely influenced in the setting of an inherited bleeding disorder depending on its type and clinical phenotype...

INTRODUCTION: Hereditary factor XI (FXI) deficiency is a rare coagulation disorder that may result in excessive bleeding requiring intervention to restore haemostasis. AIM: The aim of this review was to report the current knowledge of the worldwide incidence and prevalence of FXI deficiency. METHODS: A targeted PubMed search using terms related to FXI deficiency was conducted to identify studies published from April 2002 through April 2022...

Bleeding is the dominant adverse event of anticoagulation and often discourages many patients and physicians from starting treatment with anticoagulant drugs. The fact that factor (F)XI deficiency is associated with a mild bleeding phenotype and that FXI knockdown or inhibition in different animal models reduced the occurrence of thrombotic events in response to injury suggests that FXI is more important for the coagulation propagation and thrombotic process than for the overall hemostasis. The aim of this review is to summarize clinical pharmacology and evidence from phase 2 clinical trials on efficacy and safety of drugs directed against FXI for the treatment and prevention of thrombosis...