Molecular investigation of 41 patients affected by coagulation factor XI deficiency

Haemophilia ◽  
2017 ◽  
Vol 24 (2) ◽  
pp. e50-e55 ◽  
Author(s):  
V. Rimoldi ◽  
E. M. Paraboschi ◽  
M. Menegatti ◽  
F. Peyvandi ◽  
O. Salomon ◽  
...  
Keyword(s):  
Coagulation Factor ◽  
Factor Xi ◽  
Factor Xi Deficiency ◽  
Molecular Investigation

Platelets and Factor XI Bypass the Contact System of Blood Coagulation

1999 ◽  
Vol 82 (08) ◽  
pp. 234-242 ◽  
Author(s):  
Peter Walsh
Keyword(s):  
Blood Coagulation ◽  
Coagulation Factor ◽  
Bleeding Complications ◽  
Ashkenazi Jews ◽  
Factor Xi ◽  
Contact Phase ◽  
Platelet Factor ◽  
Proteolytic Activation ◽  
Factor Xi Deficiency ◽  
Plasma Factor

IntroductionFactor XI is a plasma glycoprotein (concentration ∼30 nM) that was first identified by Rosenthal et al1 as a plasma coagulation factor deficiency in patients with abnormal hemostasis, particularly common among Ashkenazi Jews.2,3 In spite of recent advances in our understanding of the structure of factor XI and its gene, the structure-function relationships of the protein, and the molecular genetics of factor XI deficiency, considerable confusion about the physiologic role and clinical relevance of factor XI has arisen from both clinical and biochemical observations. One problem arises from the fact that, until recently, the only known pathway for activation of factor XI involved proteolytic activation by factor XIIa and interactions with coagulation proteins of the contact phase of blood coagulation.4-7 The problem arose from the clinical observation that patients with deficiencies of factor XI are subject to bleeding complications, whereas patients with deficiencies of the contact proteins are not.2,3,8-13 A related unanswered question concerns the lack of correlation in many reported patients between plasma levels of factor XI and the severity of clinical bleeding manifestations.2,3,8,9,13-15 In addition, some patients with severe factor XI deficiency experience significant bleeding complications, whereas others appear to be hemostatically normal. These clinical and biochemical observations have motivated investigations focused on alternative mechanisms for activation of factor XI independent of contact phase protein.19-22 Additional studies have focused on the identification and characterization of platelet factor XI, which is postulated to be an alternative splicing product of the factor XI gene. Platelet factor XI is present in platelet membranes and might substitute for plasma factor XI in hemostasis and account for the absence of bleeding complications in some patients with severe plasma factor XI deficiency.14,16-18,23-26 Studies addressing these two important and related problems are presented and discussed in this chapter.

Asymptomatic Familial Factor XI Deficiency.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4449-4449
Author(s):  
Juan Herrada ◽  
Maria Chona Aloba ◽  
Dorothy M Adcock ◽  
Anuradha Gupta ◽  
Luis S. Noble ◽  
...  
Keyword(s):  
Reference Range ◽  
Conflicts Of Interest ◽  
Coagulation Factor ◽  
Normal Serum ◽  
Laboratory Evaluation ◽  
White Female ◽  
Factor Xii ◽  
Factor Xi ◽  
Factor Xi Deficiency ◽  
Family Medical History

Abstract Abstract 4449 Background Factor XI deficiency (known as Rosenthal syndrome or hemophilia C) is an autosomal disorder affecting both sexes which results in a bleeding disorder of variable severity. This condition is very uncommon among the non-Jewish population and consists mostly of sporadic cases, although an occasional familial cluster has been described (Bolton-Maggs et al. J Thromb Haemost 2004 Jun;2(6):918-24). We present two asymptomatic siblings with coagulation Factor XI deficiency. Case Report In February 2004 a healthy 33 year-old non-Jewish white female without personal or family medical history presented with an elevated partial thromboplastin time (PTT) incidentally found during a routine pre-operative evaluation. Her prothrombin time (PT) was normal. Her PTT was 45 seconds (reference interval 23-37 seconds), and normalized with 1:1 mixing studies of patient and normal plasma. Preliminary laboratory evaluation included negative tests for the presence of a Lupus Anticoagulant, a normal serum albumin level, and a normal urinalysis. Additional laboratory testing of coagulation and included FXI and XII activities, measured by means of a one stage APTT-based clotting assay using APTT reagent (Automated APTT, Trinity Biotech, Bray Ireland), congenitally depleted deficient plasma (HRF, Inc, Raleigh NC) using the MDA II Trinity Biotech, Bray Ireland). FXI was 46% (reference range 60-150) and FXII was 42% (reference range 50-150). In March 2004, a repeated the laboratory evaluation showed a FXI of 41% and a FXII of 46%. In April 2006, FXI was 49%, and FXII was 40%. Is to be noted that the patient never had abnormal bleeding episodes despite abdominal and breast surgical procedures. In 2009, her only brother (aged 29 and otherwise healthy) underwent hematological evaluation that showed normal levels of PT, PTT, platelet count, fibrinogen, and factor XII (88% activity). His factor XI was 51% (decreased activity). Conclusion Although modern laboratory methods are able to identify unusual coagulation defects, their clinical significance requires additional investigation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Hematological findings in Noonan syndrome

2003 ◽  
Vol 58 (1) ◽  
pp. 5-8 ◽  
Author(s):  
Débora R. Bertola ◽  
Jorge David A. Carneiro ◽  
Élbio Antônio D'Amico ◽  
Chong A. Kim ◽  
Lilian Maria José Albano ◽  
...  
Keyword(s):  
Platelet Count ◽  
Noonan Syndrome ◽  
Coagulation Factor ◽  
Invasive Procedure ◽  
Clinical Findings ◽  
Thrombin Time ◽  
Factor Xi ◽  
Factor Xi Deficiency ◽  
And Function

OBJECTIVE: Noonan syndrome is a multiple congenital anomaly syndrome, and bleeding diathesis is considered part of the clinical findings. The purpose of this study was to determine the frequency of hemostatic abnormalities in a group of Noonan syndrome patients. METHOD: We studied 30 patients with clinical diagnosis of Noonan syndrome regarding their hemostatic status consisting of bleeding time, prothrombin time, activated partial thromboplastin time and thrombin time tests, a platelet count, and a quantitative determination of factor XI. RESULTS: An abnormal laboratory result was observed in 9 patients (30%). Although coagulation-factor deficiencies, especially factor XI deficiency, were the most common hematological findings, we also observed abnormalities of platelet count and function in our screening. CONCLUSIONS: Hemostatic abnormalities are found with some frequency in Noonan syndrome patients (30% in our sample). Therefore, we emphasize the importance of a more extensive hematological investigation in these patients, especially prior to an invasive procedure, which is required with some frequency in this disorder.

Genetic analysis of a pedigree with hereditary coagulation factor XI deficiency

2019 ◽  
Vol 30 (8) ◽  
pp. 413-418
Author(s):  
Xingxing Zhou ◽  
Haiyue Zhang ◽  
Mingshan Wang ◽  
Shasha Luo ◽  
Siqi Liu ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Coagulation Factor ◽  
Factor Xi ◽  
Factor Xi Deficiency

scholarly journals Cys482Trp Missense Mutation in the Coagulation Factor XI Gene (F11) in a Korean Patient with Factor XI Deficiency

2014 ◽  
Vol 34 (4) ◽  
pp. 332-335
Author(s):  
Seung Jun Choi ◽  
Juwon Kim ◽  
Kyung-A Lee ◽  
Jong Rak Choi ◽  
Jongha Yoo
Keyword(s):  
Missense Mutation ◽  
Coagulation Factor ◽  
Factor Xi ◽  
Korean Patient ◽  
Factor Xi Deficiency

scholarly journals The Molecular Genetic Analysis of Coagulation Factor XI (FXI) Deficiency in Two Chinese Patients

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5033-5033
Author(s):  
Rong-Fu Zhou ◽  
Qian Li ◽  
Min Zhou
Keyword(s):  
Genetic Analysis ◽  
Conflicts Of Interest ◽  
Coagulation Factor ◽  
Chinese Patients ◽  
Compound Heterozygous ◽  
Factor Xi ◽  
Factor Xi Deficiency ◽  
Software Analysis ◽  
Prolonged Aptt ◽  
Compound Heterozygous Mutations

Abstract Objective: To investigate the molecular pathogenesis of two coagulation factor XI (FXI) deficiency patients. Methods: The diagnosis was validated by coagulant assays: APTT and correct test, PT, INR and coagulation factors activities. Coagulation factor activity were tested with clotting assay. The patients' DNA were extracted and all exons and flanking sequences of FXI gene were amplified using PCR. After purified, the products were sent for sequencing directly, the mutations were detected by comparing with wild sequences and analyzed using some bioinformatics software. Results: The two patients were diagnosed as coagulation factor XI deficiency due to prolonged APTT and low activities of coagulation factor FXI. The results of APTT, FXI:C was 88.1s, 1.1% and 107.1s, 3.8% , respectively. Genetic analysis found that compound heterozygous mutations g.1251-1G > A and g.1271delT in the first patient and the sequencing results of TA plasmid clones showed that the two mutations were located on different single strands of chromosomes. Double heterozygous mutations g.1070A >G and g.1446C > G were detected in the second patient, resulting in Lys357Arg and Cys482Stop. Software analysis indicated the mutations probably brought amino acid sequence changed, protein features affected and splice site changed. Conclusion: Compound heterozygous mutations g.1251-1G > A, g.1271delT and g.1070A > G , g.1446C > G had been identified in two coagulation factor XI deficiency patients, which might be the cause of their prolonged APTT and low FXI:C. To the best of our knowledge, the four mutations are reported for the first time in the literature. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

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