Hemophilia Testing Algorithm

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Hemophilia Testing Algorithm Symptomatic male Hemophilia A Hemophilia B F8A / Coagulation Factor VIII F_9 / Coagulation Factor IX Activity Assay, Plasma Activity Assay, Plasma Activity decreased? Activity decreased? YES YES Hemophilia A diagnosis ■ Vitamin K antagonist (ie, warfarin) ■ Child/adolescent? NO F8 genetic testing has been performed on a family member and the specific mutation is known? YES NO YES NO ■ Retest when >4 weeks after antagonist treatment is complete ■ Adjust decreased activity levels for age ■ If known mutation is an Intron 1 Inversion Severe hemophilia: Moderate/mild If the activity assays mutation, order F81B / Hemophilia A activity <1% hemophilia: are normal, consider an F8 Gene, Intron 1 Inversion Known activity 1% alternate bleeding disorder: Mutation, Whole Blood* to 55% ALBLD / Bleeding Diathesis NO Is activity still decreased? YES Hemophilia B diagnosis ■ If known mutation is an Intron 22 Profile, Limited, Plasma inversion, order F822B / Hemophilia A F8INV / Hemophilia A F9 genetic testing has been performed F8 Gene, Intron 22 Inversion Known F8 Gene, Intron 1 and on a family member and the specific Mutation, Whole Blood* 22 Inversion Mutation mutation is known? ■ If known mutation is a point mutation Analysis, Whole Blood or deletion/duplication, contact a Laboratory Genetic Counselor to discuss YES NO targeted familial mutation testing FIXKM / Hemophilia B, NGSF9 / Hemophilia B, Inversion found Inversion not found F9 Gene Known F9 Gene, Next-Generation Mutation, Whole Blood* Sequencing, Varies F8NGS / Hemophilia A, F8 Gene, Next-Generation Sequencing, Varies Mutation found Mutation not found Contact a Laboratory Genetic Counselor Mutation found Mutation not found to discuss send-out for large deletion/ duplication analysis of F9 gene Contact a Laboratory Genetic Counselor to discuss send-out testing for large deletion/duplication analysis of F8 gene** *Send copy of known familial mutation with sample for testing to be performed **If all testing is normal, consider possibility that family member has alternate bleeding disorder © Mayo Foundation for Medical Education and Research (MFMER). All rights reserved. 12/2019.

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Familial Multiple Coagulation Factor Deficiencies
Journal of Clinical Medicine Article Familial Multiple Coagulation Factor Deficiencies (FMCFDs) in a Large Cohort of Patients—A Single-Center Experience in Genetic Diagnosis Barbara Preisler 1,†, Behnaz Pezeshkpoor 1,† , Atanas Banchev 2 , Ronald Fischer 3, Barbara Zieger 4, Ute Scholz 5, Heiko Rühl 1, Bettina Kemkes-Matthes 6, Ursula Schmitt 7, Antje Redlich 8 , Sule Unal 9 , Hans-Jürgen Laws 10, Martin Olivieri 11 , Johannes Oldenburg 1 and Anna Pavlova 1,* 1 Institute of Experimental Hematology and Transfusion Medicine, University Clinic Bonn, 53127 Bonn, Germany; [email protected] (B.P.); [email protected] (B.P.); [email protected] (H.R.); [email protected] (J.O.) 2 Department of Paediatric Haematology and Oncology, University Hospital “Tzaritza Giovanna—ISUL”, 1527 Sofia, Bulgaria; [email protected] 3 Hemophilia Care Center, SRH Kurpfalzkrankenhaus Heidelberg, 69123 Heidelberg, Germany; ronald.fi[email protected] 4 Department of Pediatrics and Adolescent Medicine, University Medical Center–University of Freiburg, 79106 Freiburg, Germany; [email protected] 5 Center of Hemostasis, MVZ Labor Leipzig, 04289 Leipzig, Germany; [email protected] 6 Hemostasis Center, Justus Liebig University Giessen, 35392 Giessen, Germany; [email protected] 7 Center of Hemostasis Berlin, 10789 Berlin-Schöneberg, Germany; [email protected] 8 Pediatric Oncology Department, Otto von Guericke University Children’s Hospital Magdeburg, 39120 Magdeburg, Germany; [email protected] 9 Division of Pediatric Hematology Ankara, Hacettepe University, 06100 Ankara, Turkey; Citation: Preisler, B.; Pezeshkpoor, [email protected] B.; Banchev, A.; Fischer, R.; Zieger, B.; 10 Department of Pediatric Oncology, Hematology and Clinical Immunology, University of Duesseldorf, Scholz, U.; Rühl, H.; Kemkes-Matthes, 40225 Duesseldorf, Germany; [email protected] B.; Schmitt, U.; Redlich, A.; et al.
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Intracerebral Bleeding in Young Infants Due to Rare Etiologies–A
eona f N tal l o B a io n l r o u g y o J Tewari et al., J Neonatal Biol 2016, 5:2 Journal of Neonatal Biology DOI: 10.4172/2167-0897.1000221 ISSN: 2167-0897 Case Report Open access Intracerebral Bleeding in Young Infants due to Rare Etiologies–A Report of two Cases Vishal Vishnu Tewari1*, Kunal Tewari2 and Ritu Mehta3 1Department of Pediatrics, Army Hospital (Referral and Research), New Delhi, India 2Department of Anaesthesia, Classified Specialist Anesthesia, Base Hospital, New Delhi, India 3Department of Pathology, All India Institute of Medical Sciences, New Delhi, India *Corresponding author: Vishal Vishnu Tewari, Department of Pediatrics, Army Hospital, New Delhi, India,Tel: +91-8826118889, E-mail: [email protected] Rec date: April 29, 2016; Acc date: May 16, 2016; Pub date: May 23, 2016 Copyright: © 2016 Tewari VV, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Neonates and young infants are physiologically encumbered by an inadequate hemostatic mechanism. They may also have inherited or acquired bleeding disorders which may have a catastrophic presentation with intracerebral hemorrhage. The need to reach an accurate diagnosis is paramount in order to provide accurate therapy and genetic counseling. We report two infants who presented with unprovoked life threatening massive intracerebral hemorrhage. The first infant was diagnosed and managed for congenital factor V deficiency while the second infant had Glanzmann thrombasthenia. Keywords: Intracerebral bleeding; Congenital factor V deficiency; disorder in the family.
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Diagnosis of Inherited Platelet Disorders on a Blood Smear
Journal of Clinical Medicine Article Diagnosis of Inherited Platelet Disorders on a Blood Smear Carlo Zaninetti 1,2,3 and Andreas Greinacher 1,* 1 Institut für Immunologie und Transfusionsmedizin, Universitätsmedizin Greifswald, 17489 Greifswald, Germany; [email protected] 2 University of Pavia, and IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy 3 PhD Program of Experimental Medicine, University of Pavia, 27100 Pavia, Italy * Correspondence: [email protected]; Tel.: +49-3834-865482; Fax: +49-3834-865489 Received: 19 January 2020; Accepted: 12 February 2020; Published: 17 February 2020 Abstract: Inherited platelet disorders (IPDs) are rare diseases featured by low platelet count and defective platelet function. Patients have variable bleeding diathesis and sometimes additional features that can be congenital or acquired. Identification of an IPD is desirable to avoid misdiagnosis of immune thrombocytopenia and the use of improper treatments. Diagnostic tools include platelet function studies and genetic testing. The latter can be challenging as the correlation of its outcomes with phenotype is not easy. The immune-morphological evaluation of blood smears (by light- and immunofluorescence microscopy) represents a reliable method to phenotype subjects with suspected IPD. It is relatively cheap, not excessively time-consuming and applicable to shipped samples. In some forms, it can provide a diagnosis by itself, as for MYH9-RD, or in addition to other first-line tests as aggregometry or flow cytometry. In regard to genetic testing, it can guide specific sequencing. Since only minimal amounts of blood are needed for the preparation of blood smears, it can be used to characterize thrombocytopenia in pediatric patients and even newborns further.
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Approach to Bleeding Diathesi
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TPA-2012-2ING:Layout 1
106 Original Article DOI: 10.4274/tpa.823 Glanzmann thrombasthenia: Cerrahpaşa Medical Faculty experience Büşra Kutlubay, Gül Nihal Özdemir, Gülen Tüysüz, Hilmi Apak, Tiraje Celkan İstanbul University Cerrahpaşa Medical Faculty, Department of Pediatrics, Division of Pediatric Hematology-Oncology, İstanbul, Turkey Sum mary Aim: Glazmann thrombasthenia is a rare autosomal recessive disease characterized by a defect in platelet aggregation. Herein, we report the management of children with Glazmann thrombasthenia followed up at Cerrahpasa Medical Faculty Pediatric Hematology Department. Material and Method: The files of nineteen patients (42% girls, 58% boys; median age: 10 months) were retrospectively reviewed. Results: The median age of onset of bleeding symptoms was 9 months (2 weeks-24 months). All patients presented with easy bruising and mucosal bleeding. Fourteen patients’ parents were consanguineous. In 15 patients, flow cytometry was performed. According to this, 7 patients had type I, 6 patients had type II and 2 patients had type III disease. Nine patients were treated with thrombocyte transfusion, tranexamic acid, recombinant active factor VII and fibrin glue as a single or combined therapy; none of them had a major bleeding complication. Conclusions: Bleeding control during invasive procedures may be challenging in children with Glazmann thrombasthenia; local treatments, DDAVP, steroid and antifibrinolytics may be used with success. (Turk Arch Ped 2012; 47: 106-8) Key words: Glanzmann thrombasthenia, thrombocyte function disorder Introduction test, GT platelets do not aggregate following interaction with any substance except for ristocetin. In addition to Glanzmann thrombasthenia (GT) was described by Dr. aggregometer, low than normal levels of glycoprotein (GP) IIb- Eduard Glanzmann in 1918 for the first time as abnormal clot IIIa can be determined with flow cytometer using CD41 and retraction and defects in platelets (1).
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Pathophysiology of Bleeding Diathesis in Haemophilia-A
The Egyptian Journal of Medical Human Genetics 19 (2018) 285–295 Contents lists available at ScienceDirect The Egyptian Journal of Medical Human Genetics journal homepage: www.sciencedirect.com Review Pathophysiology of bleeding diathesis in haemophilia-A: A sequential and critical appraisal of non-FVIII related haemostatic dysfunctions and their therapeutic implications ⇑ Umma A. Ibrahim a, Sagir G. Ahmed b, a Department of Paediatrics, Bayero University, PMB 3011, Kano, Kano State, Nigeria b Department of Haematology, Aminu Kano Teaching Hospital, PMB 3452, Kano, Kano State, Nigeria article info abstract Article history: Haemophilia-A is characterized by deficiency of FVIII, but the bleeding diathesis is not a mere reflection Received 29 December 2017 low FVIII activity. The pathophysiology of haemophilic bleeding diathesis is a complex interplay between Accepted 14 January 2018 defective procoagulant function and up-regulated fibrinolysis. Moreover, haemophilic bleeding diathesis Available online 1 February 2018 is frequently compounded by treatment-related and infective complications such as FVIII inhibitors, hep- atitis, HIV infection, non-steroidal anti-inflammatory drugs (NSAID) induced gastritis, and infective Keywords: mucosal injuries such as H pylori gastritis and intestinal and urinary helminthiasis. Hence, pathophysi- Haemophilia ology of haemophilic bleeding is multi-factorial, encompassing both FVIII and non-FVIII haemostatic Bleeding diathesis defects. Currently available literature on pathophysiologic roles of non-FVIII haemostatic defects in hae- Pathophysiology Targeted therapy mophilia is fragmented. This articles is aimed at providing a composite and comprehensive review of the Non-FVIII therapy roles of non-FVIII haemostatic defects and their therapeutic implications in haemophilic bleeding diathe- FVIII by-pass sis, which will enable a holistic approach towards clinical management of the bleeding diathesis.
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Inheritance of Factor VII and Protein S Deficiency Together with Factor V
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TEG-Platelet Mapping-Guided Evaluation of Anti-Phospholipid Carrier with Unusual Clinical Presentation and Paradoxical Laboratory Findings
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An Approach to the Management of Bleeding Disorders
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Non-Criteria Manifestations of Juvenile Antiphospholipid Syndrome
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