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Blood Coagul Fibrinolysis 2022 Aug 10. Epub 2022 Aug 10.

UR14ES11 Tunis Medical University of Tunis, University of Tunis El Manar.

Factor XI (FXI) deficiency is a rare inherited bleeding disorder that is highly prevalent in Ashkenazi Jewish ancestry but sporadically observed in most ethnic groups. It is heterogeneous both in clinical presentation and in genetic causality. Although a large spectrum of mutations associated with this disorder has been reported in several populations, genetic data of FXI deficiency in Tunisia are poorly described. Read More

Genes (Basel) 2022 Jul 25;13(8). Epub 2022 Jul 25.

Gansu Key Laboratory of Herbivorous Animal Biotechnology, Faculty of Animal Science and Technology, International Wool Research Institute, Gansu Agricultural University, Lanzhou 730070, China.

Lymphatic enhancer factor 1 () and distal-less homeobox 3 () are the transcription factors involved in regulating hair follicle development in mice, goats, and other animals. Their deletion can lead to hair follicle deficiency. In this study, hematoxylin-eosin staining (HE), real-time quantitative PCR (RT-qPCR), immunohistochemistry, and immunofluorescence were used to analyze the expression, location, and biological functions of and in the lateral skin of Gansu Alpine Merino aged 1, 30, 60, and 90 days. Read More

Front Neurol 2022 5;13:935604. Epub 2022 Jul 5.

Department of Neurology, The First Hospital of Jilin University, Changchun, China.

Methylmalonic acidemia is a severe heterogeneous disorder of methylmalonate and cobalamin (Cbl; vitamin B12) metabolism with poor prognosis. Around 90% of reported patients with methylmalonic acidemia (MMA) are severe infantile early onset, while cases with late-onset MMA have been rarely reported. Few reported late-onset MMA patients presented with atypical clinical symptoms, therefore, often misdiagnosed if without family history. Read More

J Neurosurg Case Lessons 2021 Dec 13;2(24):CASE21333. Epub 2021 Dec 13.

Department of Neurosurgery, IRCCS Neuromed, Pozzilli (IS), Italy.

Background: Factor XI deficiency, also known as hemophilia C, is a rare inherited bleeding disorder that may leave routine coagulation parameters within normal range. Depending on the mutation subtype, prolonged activated partial thromboplastin time may occasionally be found. The disease has an autosomal transmission, with an estimated prevalence in the general population of approximately 1 in 1 million. Read More

Acta Haematol 2022 Jul 18. Epub 2022 Jul 18.

Objectives: Three variations including a novel F11 gene variation were detected in two unrelated Chinese families with coagulation factor XI deficiency and their possible pathogenesis were elucidated.

Methods: The genomic DNA of the probands' pedigrees was extracted, and all exons and flanking sequences of F11 gene were subjected to PCR amplification and Sanger sequencing. ClustalX-2. Read More

Tunis Med 2022 Janvier;100(1):60-65

Introduction: Factor XI deficiency is a rare coagulation disorder with variable bleeding manifestations.

Aim: To evaluate the correlation between the degree of factorXI deficiency and the clinical expression of the disease.

Methods: Retrospective study, spanning 10 years from January 1, 2010 to December 31, 2019, concerning patients followed at the Hemophilia Center at Aziza Othmana Hospital in Tunis. Read More

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2022 Jun;39(6):646-650

School of Basic Medical Science, Henan University of Science and Technology, Luoyang, Henan 471023, China.

γ-glutamyl carboxylase (GGCX), also known as vitamin K-dependent glutamyl carboxylase, catalyzes the posttranslational modification of specific glutamate residues in vitamin K-dependent proteins (VKDPs), and participates multiple biological functions including blood coagulation, bone metabolism, vascular calcification, and cell proliferation. It has been reported originally that GGCX pathogenic variation causes blood coagulation deficiency, which is called as vitamin K-dependent coagulation factor deficiency 1 (VKCFD1). Recently, it has been found that GGCX gene variation results in multiple clinical phenotypes, including dermatological, ophthalmological, skeletal or cardiac abnormalities. Read More

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2022 Jun;39(6):597-601

Department of Hematology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China.

Objective: To investigate the molecular pathogenesis of two coagulation factor Ⅺ (FⅪ) deficiency patients.

Methods: Coagulant assays: activated partial thromboplastin time (APTT), normal pooled-plasma corrected APTT test, PT, PT-INR and one-stage assay of coagulation factors activities were validated to diagnose coagulation factor Ⅺ deficiency. The patients' DNA samples were extracted and all exons and flanking sequences of F11 gene were amplified using PCR. Read More

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2022 Jun;39(6):592-596

Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.

Objective: To explore the molecular mechanisms of a Chinese pedigree with hereditary factor Ⅺ (FⅪ) deficiency.

Methods: All of the 15 exons, flanking sequences of the FⅪ gene and the corresponding mutation sites of family members were analyzed by the Sanger sequencing, followed by the extraction of the peripheral blood genomic DNA. And all the results were verified by the reverse sequencing. Read More

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2022 Jun;38(6):481-486

Department of Infectious Diseases, the Chaohu Affiliated Hospital of Anhui Medical University, Chaohu 238000; Department of Infectious Diseases, the First Affiliated Hospital of Anhui Medical University, Hefei 230022; Anhui Center for Surveillance of Bacterial Resistance, Hefei 230022; Institute of Bacterial Resistance, Anhui Medical University, Hefei 230022, China. *Corresponding author, E-mail:

Objective To explore the biological function and mechanisms of LAMTOR2 during Klebsiella pneumoniae(K. pneumoniae) induced liver sepsis by establishing late endosomal/lysosomal adaptor 2(LAMTOR2) gene liver conditional knockout mouse model infected by K. pneumoniae. Read More

J Med Case Rep 2022 Jun 11;16(1):235. Epub 2022 Jun 11.

Department of Allergy and Clinical Immunology, Iran University of Medical Sciences, 1445613131, Tehran, Iran.

Background: Progressive multifocal leukoencephalopathy is a rare demyelinating disease that is often secondary to lytic destruction of oligodendrocytes and, to a lesser extent, to astrocytes' response to human neurotrophic John Cunningham polyomavirus. Any underlying congenital disorder of primary or secondary immunodeficiency may predispose to virus infection and possible invasion of the brain. We present the first reported case of progressive multifocal leukoencephalopathy due to a mutation in the RAC2 gene. Read More

Blood Cells Mol Dis 2022 May 25;96:102677. Epub 2022 May 25.

Division of Hematology, the Second Affiliated Hospital of Shantou University Medical College, China; Department of Clinical Laboratory Medicine, the Second Affiliated Hospital of Shantou University Medical College, China. Electronic address:

Objective: In order to clarify the interaction mechanism, the phenotype and abnormal gene loci of FXI, FXII, and PS were investigated in this study.

Methods: Chinese pedigree with hereditary combined deficiency of coagulation factor (F) XI, FXII, and PS was enrolled in our study. Activated partial thromboplastin time (APTT), partial thromboplastin time (PT), FXI:C, FXII:C, and protein S (PS):C were determined using the one-stage coagulation method. Read More

J Clin Invest 2022 06;132(11)

Department of Experimental Therapeutics.

Poly(ADP-ribose) polymerase inhibitors (PARP inhibitors) have had an increasing role in the treatment of ovarian and breast cancers. PARP inhibitors are selectively active in cells with homologous recombination DNA repair deficiency caused by mutations in BRCA1/2 and other DNA repair pathway genes. Cancers with homologous recombination DNA repair proficiency respond poorly to PARP inhibitors. Read More

Genes (Basel) 2022 Apr 28;13(5). Epub 2022 Apr 28.

Vetsuisse Faculty, University of Zürich, Winterthurerstrasse 260, CH-8057 Zurich, Switzerland.

Hereditary factor XI (FXI) deficiency is characterized as an autosomal mild to moderate coagulopathy in humans and domestic animals. Coagulation testing revealed FXI deficiency in a core family of Maine Coon cats (MCCs) in the United States. Factor XI-deficient MCCs were homozygous for a guanine to adenine transition resulting in a methionine substitution for the highly conserved valine-516 in the FXI catalytic domain. Read More

Clin Case Rep 2022 Apr 25;10(4):e05710. Epub 2022 Apr 25.

Division of Hematology/Oncology Department of Internal Medicine Harbor-UCLA Medical Center Torrance California USA.

Factor VII and XI deficiencies are rare bleeding disorders typically associated with mild or provoked bleeding. This case report describes a patient with factor VII and XI deficiencies with an unprovoked episode of lower extremity hematoma causing compartment syndrome requiring multiple surgeries, extensive transfusion of blood products, and ultimately amputation. Read More

Virchows Arch 2022 Jul 26;481(1):13-21. Epub 2022 Apr 26.

Department of Pathology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi Province, People's Republic of China.

The molecular subtyping of triple-negative breast cancer (TNBC) is critical to guiding individualized patient treatment. In this study, we sought to characterize the clinicopathologic features of TNBC subtypes and to identify correlates of patient survival in an effort to provide a robust foundation for treatment planning. We additionally assessed PD-L1 expression in Chinese TNBC patients and evaluated the relationship between such expression and immunotherapeutic treatment outcomes. Read More

Thromb Res 2022 06 14;214:23-28. Epub 2022 Apr 14.

Department of Molecular Hematology, Sanquin Research, Amsterdam, the Netherlands; Department of Experimental Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands. Electronic address:

Background: Thrombin-mediated activation of FXI supports clot stability and protects the clot from fibrinolysis. This generally poor activation could be enhanced to stimulate coagulation, which might serve patients experiencing bleeding, for example due to FXI deficiency.

Objectives: To establish a reliable assay that can monitor FXI-thrombin binding and is suitable for high throughput screening. Read More

J Cardiovasc Dev Dis 2022 Apr 15;9(4). Epub 2022 Apr 15.

Department of Anesthesiology, The University of Arizona College of Medicine, Tucson, AZ 85724, USA.

Severe congenital Factor XI (FXI) deficiency (<20% normal activity) can be associated with significant bleeding disorders, and there has been great concern for severe bleeding following cardiac surgery requiring cardiopulmonary bypass (CPB) in this patient population. Over the past four decades remarkably different approaches to this problem have been taken, including the administration of blood volumes of fresh frozen plasma, administration of activated recombinant Factor VII, and diminutive administration of heparin. We describe a case wherein the patient was assessed in the perioperative period with a point-of-care, viscoelastic hemostasis device (ROTEM), with changes in the intrinsic/Factor XII-dependent coagulation pathway determined before, during, and after CPB. Read More

Placenta 2022 04 22;121:145-154. Epub 2022 Mar 22.

Central Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China. Electronic address:

Introduction: Preeclampsia (PE) is one of the main causes of maternal, fetal, and neonatal mortality. So far, the underlying mechanism of this pregnancy-specific syndrome remains unelucidated. The expression of Follistatin (FST) decreased in maternal serum (especially early onset severe PE) and placental trophoblasts of PE patients. Read More

Rev Esp Enferm Dig 2022 Aug;114(8):504-505

Gastroenterology, Hospital Universitario Río Hortega, España.

We present the case of a 73-year-old woman with no relevant medical history. She was admitted for a 3-month intermittent melena. The physical exam was unremarkable. Read More

Saudi J Anaesth 2022 Jan-Mar;16(1):111-113. Epub 2022 Jan 4.

Department of Anesthesiology, Resuscitation and Pain Management, Puerta de Hierro Hospital, Majadahonda, Majadahonda, Madrid, Spain.

Coagulation alterations might represent a problem in obstetric anesthesia considering that they may contraindicate neuraxial techniques and worsen a case of uterine atony with more severe bleeding if they are not correctly recognized and treated. We report the case of a parturient diagnosed with severe factor XI deficiency during the delivery progress. In this case, non-steroidal anti-inflammatory drugs and neuraxial techniques were avoided and intravenous patient-controlled analgesia with boluses of remifentanil was used for pain management. Read More

Clin Rheumatol 2022 Jul 6;41(7):1979-1987. Epub 2022 Mar 6.

Department of Rheumatology & Immunology, the First Affiliated Hospital of Anhui Medical University, No. 218, Ji-xi Road, Hefei, 230022, Anhui, China.

Objectives: To explore the synergistic effect of vitamin D deficiency and sarcopenia on vertebral osteoporostic fracture (VF) in patients with rheumatoid arthritis (RA).

Methods: A total of 188 patients with RA and 158 control subjects were enrolled. Bone mineral density (BMD) at the total hip, neck of femur, lumbar vertebra 1-4, and skeletal muscle mass was measured by dual energy X-ray absorptiometry (DXA) and biological electrical impedance, respectively. Read More

Pharmacol Res 2022 04 4;178:106155. Epub 2022 Mar 4.

Traditional Chinese Medicine Resource and Technology Center, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Department of Pharmacy, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China; Shanghai Key Laboratory for Pharmaceutical Metabolite Research, Shanghai 200433, China. Electronic address:

The XELOX chemotherapy protocol that includes capecitabine and oxaliplatin is the routine treatment for colorectal cancer (CRC), but it can cause chemotherapy-related adverse events such as thrombocytopenia (TCP). To identify predictive biomarkers and clarify the mechanism of TCP susceptibility, we conducted integrative analysis using normal colorectal tissue (CRT), plasma, and urine samples collected before CRC patients received adjuvant XELOX chemotherapy. RNA-sequencing and DNA methylation arrays were performed on CRT samples, while liquid chromatography-mass spectrometry was performed on CRT, plasma, and urine samples. Read More

Hamostaseologie 2022 Feb 23;42(1):65-72. Epub 2022 Feb 23.

Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.

Blood coagulation is essential to maintain the integrity of a closed circulatory system (hemostasis), but also contributes to thromboembolic occlusion of vessels (thrombosis). Thrombosis may cause deep vein thrombosis, pulmonary embolism, myocardial infarction, peripheral artery disease, and ischemic stroke, collectively the most common causes of death and disability in the developed world. Treatment for the prevention of thromboembolic diseases using anticoagulants such as heparin, coumarins, thrombin inhibitors, or antiplatelet drugs increase the risk of bleeding and are associated with an increase in potentially life-threatening hemorrhage, partially offsetting the benefits of reduced coagulation. Read More

Am J Clin Pathol 2022 07;158(1):132-141

Diagnostic Haemostasis Laboratory, Westmead, Australia.

Objectives: To advance knowledge in using the ex vivo method to identify factor sensitivity of the activated partial thromboplastin time (APTT), using data from a hemophilia and reference hemostasis laboratory; to evaluate application of inclusion and exclusion criteria to eliminate data outliers; and to discuss outcomes with reference to comparable studies.

Methods: An ex vivo, retrospective analysis was performed on patient samples with conjointly ordered APTT and intrinsic pathway factors (VIII, IX, XI, XII) for application to a large network of laboratories. The relationship between factor levels and APTT, before and after application of exclusion criteria, is demonstrated. Read More

Haemophilia 2022 Mar 5;28(2):301-307. Epub 2022 Feb 5.

Unité d'Hémostase Clinique, Hôpital Cardiologique Louis Pradel, Hospices Civils de Lyon, Bron, France.

Background: In patients with FXI deficiency, the risk of surgery-related bleeding is poorly correlated with plasma FXI activity (FXI:C); the latter can therefore not be used as a reliable predictor of bleeding in surgeries.

Objectives: The aim of this retrospective study was to determine whether thrombin generation assay (TGA) could be used to evaluate the risk of surgery-related bleeding in FXI-deficient patients. TGA parameters were compared to FXI:C values, haemostatic treatments and surgical outcomes. Read More

World J Clin Cases 2022 Jan;10(1):242-248

Department of Anesthesiology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.

Background: Factor XI (FXI) deficiency, also known as hemophilia C, is a rare bleeding disorder of unpredictable severity that correlates poorly with FXI coagulation activity. This often poses great challenges in perioperative hemostatic management. Thromboelastography (TEG) is a method for testing blood coagulation using a viscoelastic hemostatic assay of whole blood to assess the overall coagulation status. Read More

TH Open 2021 Oct 23;5(4):e557-e569. Epub 2021 Nov 23.

Research Department of Structural and Molecular Biology, University College London, Darwin Building, Gower Street, London, United Kingdom.

Coagulation factor X (FX), often termed as Stuart-Prower factor, is a plasma glycoprotein composed of the γ-carboxyglutamic acid (GLA) domain, two epidermal growth factor domains (EGF-1 and EGF-2), and the serine protease (SP) domain. FX plays a pivotal role in the coagulation cascade, activating thrombin to promote platelet plug formation and prevent excess blood loss. Genetic variants in FX disrupt coagulation and lead to FX or Stuart-Prower factor deficiency. Read More

TH Open 2021 Oct 1;5(4):e543-e556. Epub 2021 Nov 1.

Research Department of Structural and Molecular Biology, University College London, London, United Kingdom.

Coagulation Factor XI (FXI) is a plasma glycoprotein composed of four apple (Ap) domains and a serine protease (SP) domain. FXI circulates as a dimer and activates Factor IX (FIX), promoting thrombin production and preventing excess blood loss. Genetic variants that degrade FXI structure and function often lead to bleeding diatheses, commonly termed FXI deficiency. Read More

J Thromb Haemost 2022 04 8;20(4):833-844. Epub 2022 Feb 8.

Department of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands.

Background: Patients with rare inherited bleeding disorders (RBDs) exhibit hemorrhagic symptoms, varying in type and severity, often requiring only on-demand treatment. Prolonged bleeding after invasive procedures is common. Adequate peri-procedural therapy may reduce this bleeding risk. Read More