Life-threatening hemorrhage secondary to acquired deficiency of coagulation factors VIII and XI related to systemic lupus erythematosus: case report / Hemorragia severa secundaria a deficiencia adquirida de factores VIII y XI de la coagulación relacionada con lupus eritematoso sistémico: reporte de caso

ABSTRACT In patients with autoimmune diseases, the simultaneous occurrence of lupus anticoagulant and blood coagulation factors inhibitors is infrequent and is associated with hemorrhagic events. In these cases, the initial approach requires a thorough interpretation of coagulation laboratory tests and mixing studies to reach a definitive diagnosis. We report the case of a patient with systemic lupus erythematosus and Sjögren's syndrome who presented with hemorrhagic diathesis caused by circulating inhibitors against factors VIII and XI coexisting with lupus anticoagulant. The inhibitors eradication was made with rituximab, achieving good results.

RESUMEN La ocurrencia simultánea de anticoagulante lúpico e inhibidores circulantes contra los factores de la coagulación es infrecuente en los pacientes con enfermedad autoinmune, y está relacionada con eventos hemorrágicos. El abordaje inicial requiere una adecuada interpretación de los tiempos de coagulación y prueba de mezcla con plasma para alcanzar el diagnóstico definitivo. Se reporta el caso de una paciente con lupus eritematoso sistémico y síndrome de Sjögren, quien se presentó con trastorno hemorrágico amenazante de la vida ocasionado por inhibidores circulantes contra los factores VIII y XI de la coagulación en coexistencia con anticoagulante lúpico. El tratamiento de erradicación de los inhibidores se realizó con rituximab, con buenos resultados.

Carrier frequency of autosomal recessive disorders (BC, BLAD, FXID and CVM) in Holstein cows in Jalisco, Mexico

The hereditary autosomal recessive disorders bovine citrullinemia (BC), bovine leukocyte adhesion deficiency (BLAD), factor XI deficiency (FXID), and complex vertebral malformation (CVM) have affected dairy cattle breeding significantly around the world. This study examined the carrier frequency of BC, BLAD, FXID, and CVM autosomal recessive disorders in Bos taurus Holstein cows bred in the Altos Norte region of the state of Jalisco, Mexico. We extracted DNA from 408 random samples of peripheral blood, and then used polymerase chain reaction (PCR) to identify insertion mutations for FXID, and PCR with restriction fragment length polymorphism (PCR-RFLP) for CVM, BC and BLAD. We visualized the PCR products using agarose gel electrophoresis stained with GelRed®. We found that 100% of wild-type (N/N) allele homozygous animals for genes CD18, ASS, and FXI were free of the mutations for BLAD, BC and FXID respectively. For gene SLC35A3 we estimated total carrier frequency of 10.3% and allele frequency of 5%.(AU)

Perfil demográfico y epidemiológico de pacientes con Hemofilia y von Willebrand atendidos en el Área de Estomatología del Hospital de Especialidades Carlos Andrade Marín / Demographic and epidemiological profile of patients with Hemophilia and von Willebrand treated in the Stomatology Area of the Carlos Andrade Marín Specialties Hospital

INTRODUCCIÓN. Las alteraciones hereditarias de la hemostasia son patologías raras, dentro de estas se encuentran: Hemofilia A, Hemofilia B y von Willebrand. La hemofilia es un trastorno hereditario, ligado al cromosoma X, causado por ausencia o actividad reducida del factor VIII o IX. La enfermedad de von Willebrand es causada por la deficiencia del factor VIII. OBJETIVO. Determinar el perfil demográfico y epidemiológico de pacientes con Hemofilia y von Willebrand. MATERIALES Y MÉTODOS. Estudio observacional, descriptivo, transversal. La población de estudio fueron 133719 con una muestra de 144 pacientes, los criterios de inclusión fueron: pacientes de ambos sexos entre 2 a 88 años de edad, con diagnóstico de Hemofilia A, B, von Willebrand. Atendidos en la consulta externa del Área de Estomatología del Hospital de Especialidades Carlos Andrade Marín, en el periodo 2015-2018. Datos obtenidos del sistema AS400, analizados en el programa International Business Machines Statistical Package for the Social Sciences, Versión 22.0. RESULTADOS. El 77,0% (111; 144) perteneció al género masculino. El rango de edad fue entre 23 y 33 años con 24,0% (34; 144). Tuvieron Hemofilia A 62,0% (93; 144); Hemofilia B 6,0% (9; 144); von Willerbrand 28,0% (42; 144). El 50,0% (77; 144) recibieron tratamientos odontológicos; preventivos 15,0% (21; 144) y curativos 13,0% (18; 144); siendo la mayor patología caries dental. CONCLUSIÓN. Se determinó el perfil demográfico y epidemiológico de los pacientes con Hemofilia y von Willebrand que permitió brindar un tratamiento integral, interdisciplinario y oportuno.

INTRODUCTION. Hereditary abnormalities of hemostasis are rare pathologies, within these are: Hemophilia A, Hemophilia B and von Willebrand. Hemophilia is an inherited disorder, linked to the X chromosome, caused by absence or reduced activity of factor VIII or IX. Von Willebrand's disease is caused by factor VIII deficiency. OBJECTIVE. Determine the demographic and epidemiological profile of patients with hemophilia and von Willebrand. MATERIALS AND METHODS. Observational, descriptive, cross-sectional study. The study population was 133719 with a sample of 144 patients, the inclusion criteria were: patients of both sexes between 2 and 88 years of age, with a diagnosis of Hemophilia A, B, von Willebrand. Attended in the external consultation of the Stomatology Area of the Carlos Andrade Marín Specialty Hospital, in the period 2015-2018. Data obtained from the AS400 system, analyzed in the International Business Machines Statistical Package for the Social Sciences program, Version 22.0. RESULTS 77,0% (111; 144) belonged to the male gender. The age range was between 23 and 33 years with 24,0% (34; 144). They had hemophilia at 62,0% (93; 144); Hemophilia B 6,0% (9; 144); von Willerbrand 28,0% (42; 144). 50,0% (77; 144) received dental treatments; preventive 15,0% (21; 144) and curative 13,0% (18; 144); being the biggest dental caries pathology. CONCLUSION. The demographic and epidemiological profile of patients with Hemophilia and von Willebrand was determined, which allowed to provide a comprehensive, interdisciplinary and timely treatment.

Research progress on the inhibitors against factor XI / 药学学报

The incidence of thrombotic diseases has increased in the past decade, a factor endangering human health. Currently, antithrombotic drugs used in the clinic have side effects such as inducing bleeding. Data from clinical observation indicate that congenital deficiency of factor XI (FXI) gene decreases the incidence of stroke and deep venous thrombosis, without causing spontaneous bleeding. This unique property of FXI makes it a potential new target for antithrombotic drugs development. Many studies have focused on the discovery of novel inhibitors targeting FXI. This review summarizes the research progress in searching for the inhibitors against FXI.

Impact of Rare Bleeding Disorders during Pregnancy on Maternal and Fetal Outcomes: Review of 29 Pregnancies at a Single Center / Impacto de distúrbios hemorrágicos raros durante a gestação na mãe e no feto: revisão de 29 gestações em um único centro

ABSTRACT Objective: This study aims to give information about the relationship between different types of factor deficiencies and maternal/obstetric outcomes. Methods We retrospectively reviewed the medical records of eight women with factor deficiency disorders. The demographic and clinical features of the patients after their last pregnancies were registered retrospectively. Results: There were 29 pregnancies among the 8 patients. The spontaneous abortion rate was relatively high in two patients with factor XIII deficiency (80% and 57.1%) compared with the other factor deficiency groups. There were 16 births, which included 1 set of twins, and 2 deaths (1 stillbirth and 1 postpartum exitus occurred in the same patient). Intrauterine growth restriction was noted in five cases; four of these occurred in factor X deficiency cases. The mean decrease in hemoglobin level of all patients after birth was 1.7 g/dL (range, 0.2-3.6 g/dL). Red blood cell transfusion was required only in one case of factor XIII deficiency. Conclusions: There is currently no consensus on the pregnancy management of women with factor deficiencies because of the limited knowledge due to the rarity of such disorders. Labor should be managed in a dedicated unit with a team consisting of an obstetrician, a hematologist, an anesthesiologist, a midwife, and a pediatrician to minimalize the complications.

RESUMO Objetivo: O presente estudo objetiva fornecer informações sobre a relação entre diferentes tipos de deficiências de fator e resultados obstétricos e maternais. Métodos Análise retrospectiva de registros médicos de oito mulheres com deficiências de fator. Dados demográficos e clínicos das pacientes após sua última gestação foram obtidos. Resultados: Vinte e nove gestações ocorreram entre as oito pacientes. As taxas de abortos espontâneos foram relativamente altas em duas pacientes com deficiência de fator XIII (80% e 57,1%) se comparadas aos demais grupos de deficiências de fator. Ocorreram dezesseis nascimentos, sendo que um deles foi o de um par de gêmeos, e dois óbitos (um natimorto e um pós-parto na mesma paciente). Restrição de crescimento intrauterino foi identificada em cinco casos, sendo quatro destes com deficiência de fator X. A principal baixa em nível de hemoglobina entre todas as pacientes após o parto foi de 1,7 g/dL (variação, 0,2-3,6 g/dL). Transfusão de hemácias foi necessária apenas em um caso com deficiência de fator XIII. Conclusão: Não há consenso atualmente para o manejo de gestantes com deficiências de fator em função do conhecimento limitado, dada a raridade de tais condições. O parto deve ocorrer em uma unidade específica com uma equipe composta de obstetra, hematologista, anestesista, parteira, e pediatra para minimizar as complicações

Factor XI deficiency and orthognathic surgery: a case report on anesthesia management

Factor XI deficiency (Hemophilia C) is a very rare autosomal recessive bleeding disorder. Patients with factor XI deficiency do not typically show any spontaneous bleeding or specific symptoms. Sometimes those who have this disorder are identified during special situations such as trauma or surgery. Orthognathic surgery is particularly associated with a high bleeding risk. Therefore, great care must be taken when treating patients with bleeding disorders such as factor XI deficiency. There are a few reports that address the management of patients with bleeding disorders during orthognathic surgery. The current report describes a patient with factor XI deficiency who underwent Le Fort I osteotomy together with bilateral sagittal split osteotomy. The patient's condition was assessed using both rotation thromboelastometry (ROTEM™) and noninvasive measurements of total hemoglobin (SpHb) using Masimo Radical 7 (Masimo Co. CA, USA).

Research progress on factor XI as a novel target for antithrombotic therapy / 中国药理学通报

Thromboembolic diseases are major health problems worldwide,and remain the leading cause of mortality and disabil-ity at present.Bleeding is the most important complication of an-tithrombotic therapy for thromboembolism,therefore research and development of new antithrombotic drugs with lowered bleeding risk is a significant medical need.The data that elevated plasma levels of FXI are associated with thromboembolic diseases,se-vere FXI deficiency reduced incidence of DVT and ischemic stroke,and FXI deficiency or inhibition in animals shows protec-tive effects against thrombus formation supporting FXI as a novel antithrombotic target with lowered bleeding risk.This paper re-views the progress on FXI as a novel antithrombotic target and the inhibitors target FXI.

Correção endovascular de aneurisma de aorta abdominal e artéria ilíaca comum esquerda em paciente com hemofilia C grave / Endovascular repair of abdominal aortic aneurysm and left common iliac artery in a patient with severe hemophilia C

A deficiência do fator XI, também conhecida como hemofilia C, é uma doença hematológica hereditária rara, que se manifesta clinicamente com hemorragia persistente após cirurgias, traumas, menorragias e extrações dentárias. Neste artigo, relatou-se a correção endovascular de um paciente com aneurisma de aorta e de artéria ilíaca comum esquerda em um paciente portador de deficiência major do fator XI (atividade do fator XI inferior a 20%). O procedimento foi realizado com sucesso, com o manuseio do distúrbio da coagulação por meio da infusão de plasma fresco no pré-operatório imediato e no pós-operatório, e controle laboratorial da coagulação do paciente.

Factor XI deficiency, also known as hemophilia C, is a rare hereditary blood disease that manifests with persistent bleeding after surgery, trauma, menorrhagia, and dental extractions. This article reports an endovascular repair of a patient diagnosed with an aortic and left common iliac aneurysm, with severe factor XI deficiency (factor XI activity below 20%). The procedure was successfully performed with management of the coagulation disorder by preoperative and postoperative infusion of plasma and laboratory control of the coagulation.

A Novel Missense Mutation Asp506Gly in Exon 13 of the F11 Gene in an Asymptomatic Korean Woman with Mild Factor XI Deficiency / 대한진단검사의학회지

Factor XI (FXI) deficiency is a rare autosomal recessive coagulation disorder most commonly found in Ashkenazi and Iraqi Jews, but it is also found in other ethnic groups. It is a trauma or surgery-related bleeding disorder, but spontaneous bleeding is rarely seen. The clinical manifestation of bleeding in FXI deficiency cases is variable and seems to poorly correlate with plasma FXI levels. The molecular pathology of FXI deficiency is mutation in the F11 gene on the chromosome band 4q35. We report a novel mutation of the F11 gene in an 18-year-old asymptomatic Korean woman with mild FXI deficiency. Pre-operative laboratory screen tests for lipoma on her back revealed slightly prolonged activated partial thromboplastin time (45.2 sec; reference range, 23.2-39.4 sec). Her FXI activity (35%) was slightly lower than the normal FXI activity (reference range, 50-150%). Direct sequence analysis of the F11 gene revealed a heterozygous A to G substitution in nucleotide 1517 (c.1517A>G) of exon 13, resulting in the substitution of aspartic acid with glycine in codon 506 (p.Asp506Gly). To the best of our knowledge, the Asp506Gly is a novel missense mutation, and this is the first genetically confirmed case of mild FXI deficiency in Korea.

A Case of Abdominal Aortic Aneurysm in Association with Congenital Factor XI Deficiency / 日本心臓血管外科学会雑誌

Congenital factor XI deficiency is a rare intrinsic coagulation factor. We treated a 67-year-old man with abdominal aortic aneurysm, in whom activated partial thromboplastin time (APTT) found to be prolonged preoperatively. After fresh frozen plasma (FFP) was given before surgery, aneurysm was successfully replaced by a woven Dacron graft. No bleeding tendency was noted during the operation and FFP was also administered during and after surgery. The patient recovered without incident and left the hospital 13 days after the operation. Since several days are required to determine factor XI activity, APTT is useful as a parameter of coagulation factor activity in the perioperative period.

Anesthetic experience of a patient with hereditary factor XI deficiency (Hemophilia C) : A case report / 대한마취과학회지

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.

Isolation and purification of human plasma coagulation Factor Ⅺ / 中国输血杂志

Objective To concentrate coagulation Factor Ⅺ(FⅪ)from human plasma.Methods FⅪwas isolated and purified from human plasma via two-step chromatography,including CM-Sepharose fast flow ion exchange and Heparin CL-6B affinity chromatography.Results The recovery rate of FⅪ was(21.02?5.04)%,the specific clotting activity of purified FⅪ was(17.59?1.96) U/mg,and the purification factor was(1162.29?129.64) fold(n=7).Conclusion The two-step chromatography is effective in concentrating FⅨ.

Factor XI deficiency in Indian Bos taurus, Bos indicus, Bos taurus x Bos indicus crossbreds and Bubalus bubalis

We investigated the occurrence of Factor XI (FXI) deficiency syndrome in the following Indian dairy animals: Bos taurus Holstein-Friesian and Jersey cattle, Bos indicus Indian cattle breeds, B. taurus x B. indicus crossbreds and the river buffalo Bubalus bubalis. Factor XI deficiency is an autosomal recessive bleeding disorder known to affect Holstein cattle worldwide. A total of 1001 dairy animals, mainly bulls, were genotyped to detect the mutation within exon 12 of the gene encoding for factor XI. Two Holstein bulls were detected as heterozygous (carrier) for FXI deficiency, giving a carrier frequency of 0.6 percent in Indian Holstein cattle. None of the other cattle or buffalo breeds was found to be a carrier for FXI. Sequence comparison between normal and heterozygous animals revealed that there is a 77 base pair insertion fragment (AT (A)29 TAAAG (A)27 GAATTATTAATTCT) within exon 12 of the FXI gene. Both sequences were submitted to the National Center for Biotechnology Information (NCBI) GenBank and assigned the accession numbers DQ438908 for normal Holstein Friesian animals and DQ438909 for heterozygous Holstein Friesian animals.

Simulation of normal, carrier and affected controls for large-scale genotyping of cattle for factor XI deficiency

An insertion mutation within exon 12 of the factor XI gene has been described in Holstein cattle. This has opened the prospect for large-scale screening of cattle using the polymerase chain reaction (PCR) technique for the rapid identification of heterozygous animals. To facilitate such a screening process, the mutant and normal alleles of factor XI gene, represented by 244- and 320-bp PCR amplified fragments, were individually cloned in Escherichia coli using a multicopy plasmid cloning vehicle to generate pFXI-N and pFXI-M, respectively. The authenticity of the inserts was confirmed by nucleotide sequencing. A nested PCR method was developed, by which PCR amplicons generated from primers with annealing sites on the recombinant plasmids and by flanking the insert were used as templates for amplification of the diagnostic products using factor XI gene-specific primers. An equimolar mixture of both PCR amplicons, originating from pFXI-N and pFXI-M, constituted the carrier control while the individual amplicons were the affected and normal controls. The controls were used as references for in-gel comparison to screen a population of 307 cattle and 259 water buffaloes; the frequency of the mutant allele was found to be 0. No DNA size standards were required in this study. The simulated control DNA samples representing normal, carrier and affected cattle have the potential to help in large-scale screening of a cattle population for individuals that are carriers or affected by factor XI deficiency.

Successful Management of a Patient with Factor XI Deficiency and Unstable Angina by Percutaneous Coronary Intervention

Factor XI deficiency is a very rare congenital coagulation disorder. Bleeding complications should be considered when treating a patient with unstable angina and congenital coagulation disorder during and after percutaneous coronary intervention (PCI). Thrombotic complications can develop after fresh frozen plasma (FFP) transfusion and drug-eluting stent (DES) implantation. We report here on the successful management of a patient having unstable angina with factor XI deficiency, and this patient was treated with PCI under intravascular guidance and with the aid of FFP and hemostatic devices.

Three Cases of Factor XI Deficiency / 대한소아혈액종양학회지

Factor XI deficiency is a very rare autosomal recessive coagulation factor deficiency, comprising 1/million in ethnic groups other than Ashkenazi Jews. The clinical manifestations are extremely variable, and generally milder than those of hemophilia A and B. We describe herewith 3 children with factor XI deficiency, who were found to have prolonged aPTT in routine laboratory studies, or in evaluation of intermittent epistaxis.

Two Cases of Factor XI Deficiency in Sisters

We experienced two cases of factor XI deficiency in a 5 yearr 7 month-old girl, whose chief complaint was coke-colored gross hematuria, and her 9-year-old elder sister. The laboratory findings were prolonged aPTT and prominent deficiency of factor XI. The gross hematuria of the index case was identified due to acute poststreptococcal glomerulonephritis. So we report two cases of factor XI deficiency with a brief review of the related literature.