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Factor XI (FXI) deficiency (hemophilia C or Rosenthal disease) was first described in the 1950s in a multigenerational family experiencing bleeding related to surgery and dental procedures. Managing patients with FXI deficiency presents several challenges, including a lack of correlation of bleeding symptoms with FXI activity levels, the large volume of fresh frozen plasma required to achieve hemostatic FXI levels, lack of availability of FXI concentrate in certain regions of the world, and the inherent thrombotic risk associated with replacement therapy. This article summarizes presentation, diagnosis, and management of patients with FXI deficiency in a variety of clinical settings.

Background: Factor XI deficiency (Hemophilia C) is a rare bleeding disorder that was first described in 1953 by Rosenthal et al. in patients who experienced severe bleeding after dental extractions. The estimated prevalence is about 1 in 1 million with increased prevalence among Ashkenazi Jews (8-9%). Patients are generally classified into three categories based on the factor XI levels: severe (40%). Distinct from hemophilia A and B, FXI deficiency usually presents as post-traumatic bleeding and rarely manifests as spontaneous bleeding. Aims: To report a case of severe Hemophilia C in a 70-year-old woman. Methods: A 70-year-old woman was referred to Fundação Hemominas Juiz de Fora, Brazil due to gingivorrhagia and recurrent epistaxis. She reports having already received blood transfusions due to massive bleeding after surgeries, including cholecystectomy, cesarean section and hysterectomy. The patient is the sixth daughter of a seven children family. Her mother, three siblings and one nephew also have coagulation disorders, unknown Jewish descendancy. Results: The laboratory study showed normal whole blood count, screening tests for coagulation disorders showed normal platelet count and an increase of activated partial thromboplastin time (aTTP). A plasma dosage of coagulation factors was performed, with results shown in Table 1. With the reduction of factor XI activity levels (3.59%), the increase of aTTP and the normality of other tests, the diagnosis of Hemophilia C was established. A family study was performed with heredogram, shown in Figure 1. Conclusion: Hemophilia C is a rare bleeding disorder with a wide variability in clinical presentation. Adequate diagnosis is essential to minimize severe hemorrhagic conditions, specially in surgical procedures. Family screening is recommended if a member has FXI deficiency and prevalence may vary in Brazil due to the wide miscegenation.

 Hemophilia C or factor XI deficiency is a rare clotting disorder with prevalence of only 1 per 1 million. A 24-year-old male with multiple abdominal surgeries complicated by wound infections and poor healing was admitted to plastic surgery service for an elective abdominoplasty. Hematology was consulted for increased intraoperative and postoperative bleeding. Laboratory workup showed high-normal activated plasma thromboplastin time of 31 s (reference: 23 - 34 s), prothrombin time (PT) of 15 s (reference: 11.8 - 14.3 s) and internationalized normal ratio (INR) of 1.2. Patient had normal factors VIII, IX, XIII levels and normal von Willebrand's factor level. The factor XI level came back at 0.28 (0.44 - 1.43 U/mL) diagnostic for intermediate factor XI deficiency. Factor XI is responsible for thrombin generation after clotting is initiated as well as clot stabilization. The confirmatory test is factor XI assay. The management of factor-XI deficiency is based on history of bleeding and nature of the procedure. J Hematol. 2019;8(3):144-147 doi: https://doi.org/10.14740/jh522 Â

Objective Rosenthal's disease (RD) is a rare constitutional hemorrhagic disorder defined by factor XI deficiency. It is clinically characterized by the presence of minimal haemorrhage. We report the first observation of RD in Togo. Observation Mrs. G. A., 45 years old with no particular pathological antecedents, was referred for anemia in a context of chronic epistaxis. It was a spontaneous anterior exteriorization epistaxis often of great abundance, rocking and which evolved episodically. The patient received several transfusions for anemia. The ear-nose-throat examination was normal and a sinus CT scan found only an inflammatory process of the right maxillary sinus. The blood count showed microcytic severe anemia (2,2g/dl). Hemostasis tests showed a prolonged aPTT (57,9 seconds). Clinical examination documented an anemic syndrome with dry skin. Iron deficiency was found. The hemostasis balance confirmed aPTT elongation. Coagulation factors activity showed normal VIII and IX level, but moderate decrease of factor XI (32%). The family survey was not possible (orphan patient). It is recommended the setting under fresh frozen plasma (FFP) in case of a new episode. Follow-up is in progress. Conclusion In the event of any hemorrhagic syndrome, the isolated elongation of the aPTT must lead to a systematic analysis of intrinsic pathway factors

Factor XI deficiency is a hemorrhage disorder which can be either autosomal recessive or/and autosomal codominant and effects both women and men. Factor XI deficiency is uncommon in non-Jewish general population and average frequency of disorder is 1/1 million. Clinical phenotype is nonhomogeneous and bleeding risk depends on individual’s reaction against hemostatic variances. There is a poor relation between the Factor XI plasma level and bleeding tendency. In case of Factor XI deficiency, uncommon, unlike hemophilia A and B, spontaneous hemorrhage, surgical or trauma sequent are at risk. Hemarthrosis and intramuscular bleeding are common in hemophilia A and B but not typically seen in Factor XI deficiency disorders. Common symptoms are easy bruising and nosebleed. History of the disorder mostly indicates the findings about the difficulty in staunching. In this case, after detecting the activated partial thromboplastin time length before the operation due to build upon mandibula, management of patients, having Factor XI deficiency hemophilia C which is a cause of rare seen hemorrhage disorder, are presented in terms of bleeding diathesis. © Faktör XI eksikliği kadınları ve erkekleri etkileyen otozomal resesif geçişli aynı zamanda otozomal dominant geçiş de gösterebilen bir kanama bozukluğudur. Yahudi olmayan genel popülasyonda Faktör XI eksikliği yaygın değildir ve yaklaşık görülme sıklığı 1/1 milyondur. Klinik fenotipi heterojendir ve kanama riski bireyin hemostatik değişikliklere verdiği cevaba göre değişmektedir. Faktör XI’in plazma düzeyi ile kanama eğilimi arasında zayıf bir ilişki vardır. Faktör XI eksikliğinde hasta hemofili A ve B’ye benzemeyen şekilde yaygın olmamakla birlikte spontan kanama ve cerrahi ya da travmayı takip eden kanamalar için risk altındadır. Hemartroz ve kas içi kanama hemofili A ve B’de yaygındır ancak Faktör XI eksikliği olanlarda tipik olarak görülmez. Yaygın görülen semptomlar kolay morarma ve burun kanamasıdır. Sıklıkla öyküde kanamanın zor durduğuna yönelik bulgular görülmektedir. Bu olguda mandibula üzerinde kitle nedeni ile operasyon öncesi incelemelerinde aktive parsiyel tromboplastin zamanı uzunluğu tespit edilerek nadir görülen bir kanama bozukluğu nedeni olan Faktör XI eksikliği hemofili C tanısı alan olgunun kanama diyatezi açısından yönetimi sunulmuştur.

We report a case of clot formation in the cardiopulmonary bypass in a patient with type C hemophilia after receiving FXI concentrate. Caution is warranted when using FXI concentrate in cardiac surgery.

Introduction: Hemophilia is a genetic bleeding disorder caused by deficiency of clotting factor VIII (Hemophilia A) or Factor IX (Christmas disease) or Factor XI (Hemophilia C). Hemophilia is a X linked recessive trait with defective F8 an F9 genes in long arm of X chromosome. Hemophilia can also be acquired due to development of antibodies directed against the clotting factors. Aim: To compare the prevalence of Hemophilia A and Hemophilia B. Materials and Methods: The present study is done over a period of two years i.e., from 2016 to 2018. During the above period 130 cases were studied. Among these 112 cases (86.1%) were Hemophilia A and 18 cases (13.8%) were Hemophilia B. Requirement of materials: Capillary tubes, Blotting paper, Blood samples, Sprit and cotton. Results: In the present study we registered 130 cases of Hemophilia. Among these 112 cases (86.1%) were Hemophilia A and 18 cases (13.8%) were Hemophilia B. Keywords: Blood sample, Hemophilia A, Hemophilia B, Kadapa

RESUMOA hemofilia é uma doença hemorrágica hemofilia hereditária ligada ao cromossomo X, caracterizada pela deficiência ou anormalidade da atividade coagulante do fator VIII (hemofilia A), do fator IX (B) ou mesmo do fator XI (hemofilia C). Esta doença é causada pela deficiência quantitativas dos fatores de coagulação, podendo causar sangramento espontâneo ou mesmo induzido por cirurgia ou trauma. A hemofilia C foi descrita em 1953, após vários membros de famílias de descendentes judaica (judeus Ashkenazi, descendentes de judeus que abandonaram Jerusalém e migraram para a Polônia e Báltico durante o primeiro século), terem surgidos com hemorragias excessiva ao serem submetidos a amigdalatomia e exodontias. A deficiência deste fator, é hereditária, resultante de uma mutação em um gene autossômico recessivo presente no cromossomo 4. Embora o diagnostico precoce seja de difícil execução, pois o paciente não apresenta sangramento espontâneo como em outros hemofilia, uma rigorosa anamnese deve ser realizada para que se possa tomar todas as medidas preventivas, evitando possíveis riscos ao paciente. O objetivo deste trabalho é realizar uma revisão de literatura sobre os cuidados necessários que o cirurgião – dentista deve ter frente a um paciente portador de hemofilia C. Para que o mesmo possa indicar e realizar corretamente o tratamento odontológico e evite possíveis riscos. Palavras-chaves: Hemofilia; Hemofilia C; Atendimento odontológico; Fator XI. ABSTRACTHemophilia is a hereditary hemorrhagic disease linked to the X chromosome, characterized by the deficiency or abnormality of factor VIII (hemophilia A), factor IX (hemophilia B) or even factor XI (hemophilia C) factor VIII coagulant activity. This disease is caused by the quantitative deficiency of coagulation factors, which can cause spontaneous bleeding or even induced by surgery or trauma. Haemophilia C was described in 1953 after several members of families of Jewish descent (Ashkenazi Jews, descendants of Jews who left Jerusalem and migrated to Poland and the Baltic during the first century), have arisen with excessive hemorrhages when undergoing tonsilatomy and Exodontia. The deficiency of this factor is hereditary, resulting from a mutation in an autosomal recessive gene present in chromosome 4. Although the early diagnosis is difficult to perform, since the patient does not present spontaneous bleeding as in other haemophilia, a rigorous anamnesis should be performed for That all preventive measures can be taken, avoiding possible risks to the patient. The objective of this work is to carry out a review of the literature on the necessary care that the dental surgeon must have in front of a patient with hemophilia C. In order that he may indicate and correctly perform the dental treatment and avoid possible risks. Key words: Hemophilia; Hemophilia C; Dental care; Fact

Intraoperative coagulopathies can be complex and difficult to treat. Its management is further obfuscated in patients withpre-existing bleeding disorders. Hemophilia C, is an autosomal recessive bleeding disorder. Like in most hemophilias, thebleeding tendency is variable depending on the activity level of factor XI. However, because hemophilia C is less commonthan other coagulopathies, it is usually recognized only after inappropriate bleeding often overcorrected with blood products,exposing the patient to further risks. The purpose of this report is to describe the role of rotational thromboelastometryinthe anesthetic management of a patient with hemophilia C undergoing debulking of a recurrent intra-abdominaland retroperitoneal liposarcoma.

This chapter outlines the pathophysiology, clinical presentation, inheritance, and incidence of factor XI deficiency. The chapter describes the interaction with pregnancy and discusses the medical and anesthetic management of pregnant women with factor XI deficiency, including treatment of acute hemorrhage.

Orthotopic liver transplantation for other diseases typically results in a coincidental cure for hemophilia A and B; however, long-term outcomes of liver transplant in hemophilia C are not very well described. Herein, the authors report a patient of severe congenital factor XI (FXI) deficiency who received an orthotopic liver transplant. The authors discuss the perioperative management and long-term outcomes. The normalization of his FXI levels confirms that the liver is the most clinically relevant site of synthesis of FXI.

SummaryBackground Factor XI (FXI) is a key component of the intrinsic pathway of coagulation. It can be activated by either FXIIa or thrombin and amplifies thrombin generation during clot formation. Congenital FXI deficiency in humans (known as hemophilia C) is associated with bleeding after hemostatic challenge. However, to date there are no reports of excess bleeding in FXI deficient mice. Objectives To determine if the absence of FXI in mice prolongs bleeding in different models. Methods We assessed the hemostatic capacity of FXI-/- mice in 3 different bleeding models: tail bleeding, surgical bleeding, and saphenous vein bleeding. Results We found that tail bleeding and surgical bleeding of FXI-/- mice were similar to wild-type mice. However, FXI-/- mice had an impaired hemostatic capacity in the saphenous vein bleeding model compared with wild-type controls. Conclusions Our results indicate that FXI-/- mice have a mild hemostatic defect after injury to the saphenous vein but not after transection of the tail or vessels in the abdominal wall. This article is protected by copyright. All rights reserved.

Factor XI (FXI) deficiency is a rare bleeding disorder, resulting in a wide range of bleeding manifestations, from asymptomatic bleeding to injury-related bleeding. First in this review, we give an overview of the basic pathophysiology, clinical manifestations, and management of FXI deficiency. Finally, we describe 34 members of 16 FXI-deficient kindreds from south Italy, diagnosed and followed at the Haemophilia, Haemostasis and Thrombosis Centre of Pugliese-Ciaccio Hospital, Catanzaro, during the past 20 years. In our patients, bleeding tendency did not appear to be correlated with FXI levels. Furthermore, we describe 24 pregnancies in 11 patients with FXI deficiency. In all the pregnancies, no bleeding manifestations were reported.

Le deficit constitutionnel en facteur XI (FXI) est un deficit rare de la coagulation, mais son incidence est particulierement elevee parmi les Juifs Ashkenazes. Le deficit en FXI, y compris dans les formes severes, constitue une pathologie moderee de l'hemostase ; en effet, il n'y a pas ou peu de saignements spontanes mais post-traumatiques ou chirurgicaux en particulier au niveau des tissus a haute activite fibrinolytique. Le traitement des hemorragies au cours des deficits en FXI repose sur la substitution par du PFC ou des concentres de FXI. La faible correlation entre le phenotype hemorragique et le taux de FXI, la variabilite des saignements y compris chez un meme individu, et les complications potentielles des traitements, rendent sa prise en charge delicate. Cette revue rapporte les principales donnees sur la structure et le role du FXI dans la coagulation, la physiopathologie, l'epidemiologie et la genetique de son deficit ainsi que l'expression clinique, le diagnostic biologique et la prise en charge de ce deficit.

Hemophilia C or Factor XI deficiency is a hypocoagulable state leading to increased bleeding diathesis. Acute coronary syndrome can be manifested with chest pain and require a coronography to investigate the reason of the symptoms. This type of procedure requires the use of heparin and the possible need for oral antiplatelets especially if a stent was deployed. The use of anticoagulants or antiplatelets to prevent stent clotting becomes a challenge in patients with hypocoagulable state including patients with Hemophilia C. We will summarize in our review the approach taken in similar cases described in literature.

It has been suggested that persons with factor XI deficiency can have a normal activated partial thromboplastin time (aPTT). This notion is based on limited data, especially in children. Because of the central role the aPTT plays in diagnostic algorithms for bleeding disorders, it is important to know if a normal aPTT eliminates the need for factor XI activity testing. Our institutional database contains seven children with factor XI deficiency, of whom four have a normal aPTT. This supports the hypothesis that children with factor XI deficiency can have a normal aPTT. Clinicians may wish to consider this evidence when evaluating children with abnormal bleeding.

Introduction Hemophilia is a genetic disorder that results in either an inactive or inadequate supply of a plasma protein needed for normal blood clotting. The two most common forms are hemophilia A and B, caused by a defect or deficiency in clotting factors VIII and IX, respectively. Both types are X-linked recessive disorders characterized by prolonged bleeding and hemorrhages, typically into joints and soft tissues. Hemophilia C is an autosomal recessive defect that results in a deficiency of factor XI. Marked by bleeding in mucous membranes, hemophilia C exhibits a somewhat different clinical pattern of hemorrhaging than hemophilia A or B but similar to that in von Willebrand disease. This review will focus on hemophilia A and B. Hemophilia has served as a model for the treatment of chronic illness through the comprehensive approach to care. If a child who has hemophilia is managed appropriately with early factor replacement therapy and attempts to avoid the long-term consequences of bleeding, the prospects for a long, full, and healthy life are very good. Epidemiology/Genetic Transmission The incidence of hemophilia A and B is about 15 to 20 per 100 000 males born worldwide and occurs in all races and socioeconomic groups. Hemophilia A, also known as "classical hemophilia," accounts for about 80% of cases of hemophilia, occurs in one of 10 000 male births, and affects about 17 500 individuals in North America.

espanolLa displasia fibrosa es una enfermedad osea benigna que cambia el tejido oseo normal por una proliferacion de tejido conectivo. Se piensa que la alteracion del gen Gsalfa es la principal razon de la enfermedad. La hemofilia C es una enfermedad sanguinea, hereditaria rara, que provoca hemorragias en pacientes afectos. Es autonomica recesiva, por lo que hombres y mujeres pueden estar afectos. Paciente de 13 anos que desarrolla una displasia fibrosa en maxilar superior derecho que empieza con dolor durante la masticacion de alimentos duros. Presenta abombamiento de vestibulo y enrojecimiento de paladar derecho. Presenta un deficit discreto de factor XI (heterocigoto). Por ello, necesita una preparacion especial antes de extirpar la lesion debido a su deficit. Se ha descubierto que la razon de la displasia fibrosa es la mutacion del gen Gs? (GNAS1) que esta en el cromosoma 20q. La causa de la hemofilia C es el deficit del factor XI debido a una mutacion del gen FXI en el cromosoma 4. Quizas estas dos raras enfermedades tengan una relacion, porque ambas se presentan en el mismo paciente. EnglishFibrous dysplasia is a benign bone disease that changes normal bone tissue for a proliferation of connective fibrous tissue. It is thought that an alteration of the Gsalpha gene is the main cause of the disease. Hemophilia C is a rare inherited blood disease leading to abnormal hemorrhages in affected patients. They have a factor XI deficiency. It is the least drequent of all hemophilias. It is a recesive autosomal disease, affecting both men and woman. A 13 year-old patient developed fibrous dysplasia in right upper maxila. The patient started with pain on chewing hard food. She had vestibular swelling and reddening of the right side of the palate. She had a discrete factor XI deficiency (heterozygotic). She needed special preparation before the lesion could be removed because of her deficiency. It has been discovered that the mutation of gene Gsalpha (GNAS1) is the reason for fibrous dysplasia. This gene is a chromosome 20q. The cause of hemophilia C is a factor XI deficiency due to a mutation in the FXI gene in chromosome 4. Perhaps these two rare diseases are related, because both are unusual diseases and both are in the same patient.

Congenital factor XI deficiency (also known as the Rosenthal syndrome or hemophilia C) manifests as minor bleeding, usually after trauma or surgery. We report a case in which bilateral knee hemarthrosis was the first manifestation. The patient presented at 32 years of age with a 2-year history of mechanical pain and intermittent swelling in both knees. Knee aspiration recovered blood-tinged fluid. The laboratory workup showed severe factor XI deficiency. Replacement therapy with fresh frozen plasma was effective. Tests in the family showed factor XI deficiency in the patient's sister.

A 39-year-old male developed severely prolonged bleeding after periodontal surgery because of a previously undetected clotting Factor XI deficiency (Hemophilia C). Diagnosis and treatment of this bleeding disorder are discussed.

Factor XI deficiency (also called Hemophilia C) rarely occurs among ethnicities other than Ashkenazi Jews. A boy was scheduled for frontoethmoidectomy due to bilateral chronic rhinosinusitis. He was incidentally found to have factor XI deficiency due to prolonged aPTT on preoperative laboratory finding. His medical history reveals frequent epistaxis 2 or 3 times per day and his factor XI and XII activity were 17% (normal; 60-140%) and 34% (normal; 60-140%), respectively on furthermore laboratory evaluation. He was diagnosed as hereditary factor XI deficiency. He underwent the operation with administration of the fresh frozen plasma without complication.

Summary1. A third type of hemophilia characterized by a deficiency in a plasma thromboplastin factor other than anti-hemophilic globulin and plasma thromboplastin component (PTC) has been identifie...

The different radiologic features of hemophiliac joint and bone changes are well known and described in the literature (1, 5). The most common manifestation of hemophilia is crippling joint deformity. The classic and typical joint and bone changes are usually seen only in authentic hemophilia or hemophilia A and in Christmas disease or hemophilia B. In cases of hemophilia C there are only minimal and slight changes in the bones and joints. In extensive hemophiliac arthropathies, the pediatrician and the orthopedic surgeon usually deal with the therapeutic problems. A hemophiliac patient has been followed for eleven years at the University of Chicago Hospitals. The first episode of bleeding was at the age of thirteen months, and at that time the diagnosis of hemophilia A was made. The patient's family moved to Illinois in 1955 when he was nine years old, and he has been followed by us ever since. In the past twelve years he has had 32 admissions to our hospital with different complications of hemophilia su...