DOCSLIB.ORG

Platelet Function Disorder Panel Please Complete All Pages of the of Disorders of Platelet Function

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Platelet Function Disorder Panel Please Complete All Pages of the of Disorders of Platelet Function Shipping requirements Gresele P. 2014. Diagnosis of inherited platelet function disorders: guidance for the SSC of the ISTH. J Thromb and Haemost. 13:314-322. Ship on an ice pack or at room Hinckley J, Di Paola J. 2014. Genetic basis of congenital platelet disorders. temperature. Protect from freezing. Hematology Am Soc Hematol Educ Program. Dec5;(1): 3337-42. Place the specimen and the requisition Platelet Function Israels SJ, El-Ekiaby M, Quiroga T, Mezzano D. 2010. Inherited disorders of platelet into plastic bags and seal. Insert into function and challenges to diagnosis of mucocutaneous bleeding. Haemophilia. a Styrofoam container, seal and place 16 (Suppl 5):152-9. into a sturdy cardboard box, and Johnson B, Lowe GC et al. 2016. Whole exome sequencing identifies genetic tape securely. Ship the package in variants in inherited thrombocytopenia with secondary qualitative function Disorder Panel defects. Haematologica. 101(10):1170-1179. ORDER SHIP compliance with your overnight carrier guidelines. Label with the following Kunicki TJ, Williams SA, Nugent DJ. 2012. Genetic variants that affect platelet address: function. Current Opin Hematol.19:371-9. Client Services/Diagnostic Laboratory Lentaigne C, Freson K et al. 2016. Inherited platelet disorders: toward DNA-based BloodCenter of Wisconsin diagnosis. Blood. 127(23):2814-2823. 638 N. 18th St. Maclachlan A, Watson SP, Morgan NV. 2017. Inherited platelet disorders: Insight Milwaukee, WI 53233 from platelet genomics using next-generation sequencing. Platelets. Jan ;28(1);14- 19. Mumford AD, Nisar S et al. 2013. Platelet dysfunction associated with the novel platelet syndrome, FLI1-Paris Trousseau thrombocytopenia, and Trp29Cys thromboxane A₂ receptor variant. J Thromb Haemost. Mar;11(3):547-54. BloodCenter of Wisconsin offers a specifically Required forms a number of platelet-type bleeding disorders. Additional genes Nurden AT, Nurden P. 2011. Advances in our understanding of the molecular basis designed Platelet Function Disorder Panel Please complete all pages of the of disorders of platelet function. J Thromb Haemost. 9 Suppl 1:76-91. in this panel are associated with syndromes that have defective (test code 4835) optimized for detection of platelet function as a common finding among other non- requisition form. Clinical history Nurden AT, Nurden P. 2015. Inherited disorders of platelet function: selected (including patient’s ethnicity, clinical updates. J Thromb Haemost. Volume 13(Suppl1): S2- S9. germline variants in 31 genes known to cause hematologic features. diagnosis, family history and relevant Paterson AD, Rommens JM, et al. 2010. Persons with Quebec platelet disorder inherited platelet function disorders. This panel evaluates for single nucleotide variants and small laboratory findings) is necessary for have a tandem duplication of PLAU, the urokinase plasminogen activator gene. deletions and duplications, which are most commonly optimal interpretation of genetic test Blood.115:1264-6. responsible for genetic disease. However, large deletions and ORDER results and recommendations. ClinicalSHIP Rao AK. 2013. Inherited platelet function disorders: overview and disorders of Inherited platelet function disorders are a heterogeneous group duplications, also referred to as copy number variants (CNV), are and laboratory history can either be granules, secretion, and signal transduction. Hematol Oncol Clin North Am. Jun; of bleeding disorders of variable severity caused by defects in also known cause of genetic disorders, but can escape detection 27(3):585-611. recorded on the requisition form or platelet adhesion, glycoprotein expression, receptor function, by next-generation sequence analysis. Further testing with clinical and laboratory reports can be Rehm HL, Bale SJ et al. 2013. Working Group of the American College of Medical signaling pathways, aggregation, cytoskeleton proteins, secretion, the BloodCenter of Wisconsin custom designed, high-density Genetics and Genomics Laboratory Quality Assurance Committee. ACMG clinical granular contents and abnormalities in procoagulant activity. submitted with the sample. laboratory standards for next-generation sequencing. Genet Med.15:733-747. gene-focused array, aCGH Deletion/Duplication Analysis, allows These disorders are typically associated with normal platelet for the possible detection of large deletions and duplications Richards S, Aziz N A et al.2015. Standards and guidelines for the interpretation of counts and characterized by bleeding symptoms which may sequence variants: a joint consensus recommendation of the American College within a single exon of a given gene, encompassing one or CPT Codes/Billing/Turnaround time of Medical Genetics and Genomics and the Association for Molecular Pathology. include epistaxis, extensive bruising, menorrhagia in women, more exons, or affecting an entire gene. This testing may be and the possibility of life-threatening excessive bleeding when Test Code: 4835 Genet Med.17:405-424. warranted when results of sequence analysis do not fully explain Saultier P,Vidal, L.et al. 2017. Macrothrombocytopenia and dense granule challenged by surgery, injury, or childbirth. a clinical phenotype, or when a suspected disorder is known to CPT codes: 81404, 81479 deficiency associated with FLI1 variants: ultrastructural and pathogenic features. The diagnosis of a specific platelet function disorder may be be caused by deletions or duplications. Specifically, the Quebec Haematologica.102:1006-1016. Turnaround time: 21 days difficult to establish based solely on functional studies, especially Platelet Disorder is associated with a heterozygous 78-kb tandem Stevenson WS, Rabbolini DJ et al. 2015. Paris-Trousseau thrombocytopenia is The CPT codes provided are subject to change as more in patients with milder disorders, as these assays are often duplication of the PLAU gene, which will be detected by aCGH phenocopied by the autosomal recessive inheritance of a DNA-binding domain and not by the Platelet Function Disorder Panel. Please refer to information becomes available. CPT codes are provided only as mutation in FLI1. Blood. Oct 22;126(17); 2027-30. technically challenging, difficult to interpret, and typically require guidance to assist clients with billing. immediate testing on fresh patient platelets due to limited sample the aCGH Deletion/Duplication Analysis test description for more Songdej N, Rao AK. 2017. Inherited platelet dysfunction and hematopoietic information about specific genes included in this array. transcription factor mutations. Platelets Jan; 28(1):20-26. stability. Advances in genetic testing through next-generation For additional information related to shipping, billing or pricing, sequencing allow for identification of underlying genetic please contact, BloodCenter Client Services: (414) 937-6396 or Watson SP, Lowe M et al. 2013. Genotyping and phenotyping of platelet function For broader evaluation of unspecified platelet problems, disorders. J Thromb Haemost. 11(suppl.1):351-363. defects for platelet function disorders that have overlapping both the Platelet Function Disorder Panel and the Inherited 800-245-3117, Option 1, or [email protected]. clinical and laboratory findings. Accurate diagnosis provides Westbury SK, Mumford AD. 2016. Genomics of platelet disorders. Hemophilia. Thrombocytopenia Panel can be ordered together as the 22(Suppl.5): 20-24. information about the phenotype and prognosis, guides medical Comprehensive Platelet Disorder Panel. For broader evaluation management decisions, assists with the identification of affected References Zhou Y, Zhang J. 2014. Arthrogryposis–renal dysfunction–cholestasis (ARC) of unspecified bleeding disorders, the Platelet Function Disorder syndrome: from molecular genetics to clinical features. Italian J Pediatrics. 40:77. family members, and allows for accurate genetic recurrence risk Panel and Coagulation Disorder Panel can be ordered together as Cox K, Price V, Kahr WHA. 2011. Inherited platelet disorders: a clinical approach to assessment. the Comprehensive Bleeding Disorder Panel. diagnosis and management. Expert Rev Hematol. Aug;4(4):455-72. Variants in several different genes known to cause syndromic or Faioni EM, Razzari C et al. 2014. Bleeding diathesis and gastro-duodenal ulcers Refer to the table inside for further information about each in inherited cytosolic phospholipase-A2 alpha deficiency. Thromb Haemost. non-syndromic platelet function disorders may be inherited in gene in the Platelet Function Disorder Panel, including the Dec;112(6):1182-9. an autosomal recessive or autosomal dominant manner. More clinical phenotype, OMIM numbers and inheritance pattern. Freson K, Wijgaerts A, Van Geet C. 2014. Update on the causes of platelet disorders common and many rare types of inherited platelet function and functional consequences. John Wiley & Sons Ltd, Int. Jnl. Lab. Hem. 36, disorders will be identified with this panel, including Glanzmann 313–325. thrombasthenia, Bernard-Soulier syndrome, familial platelet disorder with associated myeloid malignancy (FPDMM), Scott syndrome, leukocyte integrity adhesion deficiency type III, gray © Copyright 2017 r0818 BloodCenter of Wisconsin, Inc. , Part of Versiti. All rights reserved. Platelet Function Disorder Panel: gene, clinical phenotype, OMIM number and inheritance pattern. Platelet Function Disorder Panel: gene, clinical phenotype, OMIM number and inheritance pattern. Gene Clinical Phenotype Phenotype/Gene Inheritance Gene Clinical Phenotype Phenotype/Gene Inheritance
Load more

Recommended publications
  • MYH9-Related Platelet Disorders
    Reprinted with permission from Thieme Medical Publishers (Semin Thromb Hemost 2009;35:189-203) Homepage at www.thieme.com MYH9-Related Platelet Disorders Karina Althaus, M.D.,1 and Andreas Greinacher, M.D.1 ABSTRACT Myosin heavy chain 9 (MYH9)-related platelet disorders belong to the group of inherited thrombocytopenias. The MYH9 gene encodes the nonmuscle myosin heavy chain IIA (NMMHC-IIA), a cytoskeletal contractile protein. Several mutations in the MYH9 gene lead to premature release of platelets from the bone marrow, macro- thrombocytopenia, and cytoplasmic inclusion bodies within leukocytes. Four overlapping syndromes, known as May-Hegglin anomaly, Epstein syndrome, Fechtner syndrome, and Sebastian platelet syndrome, describe different clinical manifestations of MYH9 gene mutations. Macrothrombocytopenia is present in all affected individuals, whereas only some develop additional clinical manifestations such as renal failure, hearing loss, and presenile cataracts. The bleeding tendency is usually moderate, with menorrhagia and easy bruising being most frequent. The biggest risk for the individual is inappropriate treatment due to misdiagnosis of chronic autoimmune thrombocytopenia. To date, 31 mutations of the MYH9 gene leading to macrothrombocytopenia have been identified, of which the upstream mutations up to amino acid 1400 are more likely associated with syndromic manifestations than the downstream mutations. This review provides a short history of MYH9-related disorders, summarizes the clinical and laboratory character- istics, describes a diagnostic algorithm, presents recent results of animal models, and discusses aspects of therapeutic management. KEYWORDS: MYH9 gene, nonmuscle myosin IIA, May-Hegglin anomaly, Epstein syndrome, Fechtner syndrome, Sebastian platelet syndrome, macrothrombocytopenia The correct diagnosis of hereditary chronic as isolated platelet count reductions or as part of thrombocytopenias is important for planning appropri- more complex clinical syndromes.
    [Show full text]
  • 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.
    [Show full text]
  • Gri Trombosit Sendromu
    Cukurova Medical Journal Cukurova Med J 2017;42(2):360-362 ÇUKUROVA ÜNİVERSİTESİ TIP FAKÜLTESİ DERGİSİ DOI: 10.17826/cutf.322967 OLGU SUNUMU / CASE REPORT Gray platelet syndrome Gri trombosit sendromu Fatima Ayaz1, Saeed Bin Ayaz2, Sunila Tashfeen2, Muhammad Furrukh1 1Benazir Bhutto Hospital, Rawalpindi, Punjab, Pakistan 2Combined Military Hospital, Okara, Punjab, Pakistan Cukurova Medical Journal 2017;42(2):360-362 Abstract Öz Gray platelet syndrome (GPS) is an autosomal recessive Gri trombosit (platelet) sendromu (GPS), trombositopeni disorder characterized by thrombocytopenia and defective ve ışık mikroskopunda soluk görünen kusurlu platelets that appear pale on light microscope. Patients trombositlerle karakterize, otozomal resesif geçişli bir present with easy bruisability, nose bleeds, menorrhagia hastalıktır. Hastalarda kolay morarma, burun kanaması, and prolonged bleeding. There is no specific treatment for menoraji ve uzun kanamalar görülmektedir. GPS için GPS and the management includes anticipating risks and spesifik bir tedavi bulunmamaktadır dolayısı ile hastalığa preventing bleeding by avoiding drugs that impair platelet karşı, riskleri öngörmek ve kanamanın önlenmesi function. We present here report of a case who presented için trombosit fonksiyonunu bozan ilaçlardan kaçınmak with repeated episodes of abnormal bleeding and was gerekmektedir. Bu olgu sunumunda, tekrarlayan anormal found to have GPS. kanama atakları olan ve GPS bulgusu bulunan bir vaka sunulmaktadır. Key words: Bleeding disorder, gray platelet syndrome, Anahtar
    [Show full text]
  • Platelet Function Disorders
    TREATMENT OF HEMOPHILIA APRIL 2008 • NO 19 PLATELET FUNCTION DISORDERS Second Edition Anjali A. Sharathkumar Amy Shapiro Indiana Hemophilia and Thrombosis Center Indianapolis, U.S.A. Published by the World Federation of Hemophilia (WFH), 1999; revised 2008. © World Federation of Hemophilia, 2008 The WFH encourages redistribution of its publications for educational purposes by not-for-profit hemophilia organizations. In order to obtain permission to reprint, redistribute, or translate this publication, please contact the Communications Department at the address below. This publication is accessible from the World Federation of Hemophilia’s website at www.wfh.org. Additional copies are also available from the WFH at: World Federation of Hemophilia 1425 René Lévesque Boulevard West, Suite 1010 Montréal, Québec H3G 1T7 CANADA Tel. : (514) 875-7944 Fax : (514) 875-8916 E-mail: [email protected] Internet: www.wfh.org The Treatment of Hemophilia series is intended to provide general information on the treatment and management of hemophilia. The World Federation of Hemophilia does not engage in the practice of medicine and under no circumstances recommends particular treatment for specific individuals. Dose schedules and other treatment regimes are continually revised and new side effects recognized. WFH makes no representation, express or implied, that drug doses or other treatment recommendations in this publication are correct. For these reasons it is strongly recommended that individuals seek the advice of a medical adviser and/or consult printed instructions provided by the pharmaceutical company before administering any of the drugs referred to in this monograph. Statements and opinions expressed here do not necessarily represent the opinions, policies, or recommendations of the World Federation of Hemophilia, its Executive Committee, or its staff.
    [Show full text]
  • Hemophilia Update 2015
    J. Martin Johnston, MD Pediatric Project ECHO 7 December 2018 Objectives Review history and physical exam as they relate to a potential bleeding disorder Discuss step-wise laboratory evaluation: screening labs and follow-ups Review some common congenital and acquired bleeding disorders, and their management Objectives Review history and physical exam as they relate to a potential bleeding disorder Discuss step-wise laboratory evaluation: screening labs and follow-ups Review some common congenital and acquired bleeding disorders, and their management Objectives Review history and physical exam as they relate to a potential bleeding disorder Discuss step-wise laboratory evaluation: screening labs and follow-ups Review some common congenital and acquired bleeding disorders, and their management The chief complaint “Easy” bruising Nosebleeds Petechiae Menorrhagia Bleeding after Circumcision Tonsillectomy/adenoidectomy, tooth extraction Mild (head) trauma The problem…. • Everyone bleeds. • All bleeding eventually stops. The bleeding history Birth/neonatal Tooth eruption/shedding Bruising Nosebleeds Surgeries? (don’t forget circumcision!) Orthopedic hx (traumas, joints) Menstruation Family history How much bleeding is too much? Neonatal ICH, needle/heel sticks, post-circumcision How much bleeding is too much? Neonatal ICH, needle/heel sticks, post-circumcision Infant Petechiae, chest/back/buttock bruising Consider NAT How much bleeding is too much? Neonatal ICH, needle/heel sticks, post-circumcision Infant
    [Show full text]
  • Comprehensive Platelet Disorder Panel
    References Mumford AD, Nisar S et al. 2013. Platelet dysfunction associated with the novel Trp29Cys thromboxane A₂ receptor variant. J Thromb Haemost. Mar;11(3):547-54. Albers CA, Paul DS et al. 2012. Compound inheritance of a low-frequency regulatory SNP and a rare null mutation in exon-junction complex subunit RBM8A Noris P, Biino G et al. 2014. Platelet diameters in inherited thrombocytopenias: causes TAR syndrome. Nat Genet. 2012 Feb 26; 44(4):435-9. analysis of 376 patients with all known disorders. Blood. Aug 7; 124(6):e4-e10. Comprehensive Ali S, Ghosh K et al. 2016. Congenital macrothrombocytopenia is a heterogeneous Noris P, Favier R et al. 2013. ANKRD26-related thrombocytopenia and myeloid disorder in India. Haemophilia. Jul; 22(4):570-82. malignancies. Blood .122:1987-1989. Balduini CL, Pecci A, Savoia A. 2011. Recent advances in the understanding and Nurden AT, Nurden P. 2011. Advances in our understanding of the molecular basis management of MYH9-related inherited thrombocytopenias. Br J Haematol. of disorders of platelet function. J Thromb Haemost. 9 Suppl 1:76-91. Jul;154(2):161-174. Nurden AT, Nurden P. 2015. Inherited disorders of platelet function: selected Platelet Disorder Balduini CL, Melazzini F, Pecci A. 2017. Inherited thrombocytopenias-recent updates. J Thromb Haemost. Volume 13(Suppl1): S2- S9. advances in clinical and molecular aspects. Platelets. Jan;28(1):3-13. Ok Bozkaya I, Yarali N et al. Severe Clinical Course in a Patient with Congenital Bastida JM, Del Rey M et al. 2016. Wiskott-Aldrich syndrome in a child presenting Amegakaryocytic Thrombocytopenia Due to a Missense Mutation of the c-MPL with macrothrombocytopenia.
    [Show full text]
  • Gray Platelet Syndrome
    Gray platelet syndrome Description Gray platelet syndrome is a bleeding disorder associated with abnormal platelets, which are small blood cells involved in blood clotting. People with this condition tend to bruise easily and have an increased risk of nosebleeds (epistaxis). They may also experience abnormally heavy or extended bleeding following surgery, dental work, or minor trauma. Women with gray platelet syndrome often have irregular, heavy periods ( menometrorrhagia). These bleeding problems are usually mild to moderate, but they have been life-threatening in a few affected individuals. A condition called myelofibrosis, which is a buildup of scar tissue (fibrosis) in the bone marrow, is another common feature of gray platelet syndrome. Bone marrow is the spongy tissue in the center of long bones that produces most of the blood cells the body needs, including platelets. The scarring associated with myelofibrosis damages bone marrow, preventing it from making enough blood cells. Other organs, particularly the spleen, start producing more blood cells to compensate; this process often leads to an enlarged spleen (splenomegaly). Frequency Gray platelet syndrome appears to be a rare disorder. About 60 cases have been reported worldwide. Causes Gray platelet syndrome can be caused by mutations in the NBEAL2 gene. Little is known about the protein produced from this gene. It appears to play a role in the formation of alpha-granules, which are sacs inside platelets that contain growth factors and other proteins that are important for blood clotting and wound healing. In response to an injury that causes bleeding, the proteins stored in alpha-granules help platelets stick to one another to form a plug that seals off damaged blood vessels and prevents further blood loss.
    [Show full text]
  • Thrombocytopathies: Not Just Aggregation Defects—The Clinical Relevance of Procoagulant Platelets
    Journal of Clinical Medicine Review Thrombocytopathies: Not Just Aggregation Defects—The Clinical Relevance of Procoagulant Platelets Alessandro Aliotta 1,† , Debora Bertaggia Calderara 1,† , Maxime G. Zermatten 1, Matteo Marchetti 1,2 and Lorenzo Alberio 1,* 1 Hemostasis and Platelet Research Laboratory, Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), CH-1010 Lausanne, Switzerland; [email protected] (A.A.); [email protected] (D.B.C.); [email protected] (M.G.Z.); [email protected] (M.M.) 2 Service de Médecine Interne, Hôpital de Nyon, CH-1260 Nyon, Switzerland * Correspondence: [email protected] † These authors contributed equally to this work. Abstract: Platelets are active key players in haemostasis. Qualitative platelet dysfunctions result in thrombocytopathies variously characterized by defects of their adhesive and procoagulant activation endpoints. In this review, we summarize the traditional platelet defects in adhesion, secretion, and aggregation. In addition, we review the current knowledge about procoagulant platelets, focusing on their role in bleeding or thrombotic pathologies and their pharmaceutical modulation. Procoagulant activity is an important feature of platelet activation, which should be specifically evaluated during the investigation of a suspected thrombocytopathy. Citation: Aliotta, A.; Bertaggia Keywords: thrombocytopathy; platelet disorders; procoagulant platelets; activation endpoints Calderara, D.; Zermatten, M.G.; Marchetti, M.; Alberio, L. Thrombocytopathies: Not Just Aggregation Defects—The Clinical 1. Introduction Relevance of Procoagulant Platelets. J. Clin. Med. 2021, 10, 894. https:// Platelets or thrombocytes are small (2–5 µm) discoid anucleated cells produced by doi.org/10.3390/jcm10050894 megakaryocytes. They are released in the blood stream where they circulate for 7–10 days to be eventually cleared by the spleen and the liver [1].
    [Show full text]
  • Platelet Phenotyping and Function Testing in Thrombocytopenia
    Journal of Clinical Medicine Review Platelet Phenotyping and Function Testing in Thrombocytopenia Kerstin Jurk 1,* and Yavar Shiravand 2 1 Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany 2 Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy; [email protected] * Correspondence: [email protected]; Tel.: +49-6131-178278 Abstract: Patients who suffer from inherited or acquired thrombocytopenia can be also affected by platelet function defects, which potentially increase the risk of severe and life-threatening bleeding complications. A plethora of tests and assays for platelet phenotyping and function analysis are available, which are, in part, feasible in clinical practice due to adequate point-of-care qualities. However, most of them are time-consuming, require experienced and skilled personnel for platelet handling and processing, and are therefore well-established only in specialized laboratories. This review summarizes major indications, methods/assays for platelet phenotyping, and in vitro function testing in blood samples with reduced platelet count in relation to their clinical practicability. In addition, the diagnostic significance, difficulties, and challenges of selected tests to evaluate the hemostatic capacity and specific defects of platelets with reduced number are addressed. Keywords: thrombocytopenia; bleeding; platelet function tests; platelet disorders; platelet count; flow cytometry Citation: Jurk, K.; Shiravand, Y. 1. Introduction Platelet Phenotyping and Function Platelet bleeding disorders are a heterogeneous group in terms of frequency and bleed- Testing in Thrombocytopenia. J. Clin. ing severity. They are characterized by qualitative/function and/or quantitative/number Med. 2021, 10, 1114.
    [Show full text]
  • 2020.03.23.20041467V1.Full.Pdf
    medRxiv preprint doi: https://doi.org/10.1101/2020.03.23.20041467; this version posted March 27, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . Novel manifestations of immune dysregulation and granule defects in gray platelet syndrome Matthew C Sims*1,2,3, Louisa Mayer*1,2, Janine H Collins*1,2,4, Tadbir K Bariana*1,4,5, Karyn Megy1,2,6, Cecile Lavenu-Bombled7, Denis Seyres1,2,6, Laxmikanth Kollipara8, Frances S Burden1,2,6, Daniel Greene1,6,9, Dave Lee10, Antonio Rodriguez-Romera1,2, Marie-Christine Alessi11, William J Astle2,9, Wadie F Bahou12, Loredana Bury13, Elizabeth Chalmers14, Rachael Da Silva10, Erica De Candia15,16, Sri V V Deevi1,6, Samantha Farrow1,2,6, Keith Gomez5, Luigi Grassi1,2,6, Andreas Greinacher17, Paolo Gresele13, Dan Hart18, Marie-Françoise Hurtaud7, Anne M Kelly1, Ron Kerr19, Sandra Le Quellec20, Thierry Leblanc7, Eva B Leinøe21, Rutendo Mapeta1,6, Harriet McKin- ney1,2,6, Alan D Michelson22, Sara Morais23,24, Diane Nugent25, Sofia Papadia1,2,6, Soo J Park26, John Pasi18, Gian Marco Podda27, Man-Chiu Poon28, Rachel Reed10, Mallika Sekhar29, Hanna Shalev30, Suthesh Sivapalaratnam1,4, Orna Steinberg-Shemer31,32, Jonathan C Stephens1,6, Robert C Tait33, Ernest Turro1,2,6,9, John K M Wu34, Barbara Zieger35, NIHR BioResource6, Taco W Kuijpers36,37, Anthony D Whetton10, Albert Sickmann8,38,39, Kathleen Freson40, Kate Downes1,6, Wendy N Erber41,42, Mattia Frontini1,2,43, Paquita Nurden44, Willem H Ouwehand1,2,6,45, Remi Favier**7,46, and Jose A Guerrero**1,2 1 Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; 2 National Health Service Blood and Transplant, Cambridge Biomedical Campus, Cambridge, UK; NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
    [Show full text]
  • Chronic Thrombocytopenia As the Initial Manifestation of STIM1
    Chronic Thrombocytopenia as the Initial Manifestation of STIM1-Related Disorders Anjali Sura, MD,a Joseph Jacher, MS,b Erin Neil, DO,c Kathryn McFadden, MD,d Kelly Walkovich, MD,e Mark Hannibal, MD, PhDb Pediatric thrombocytopenia has a wide differential diagnosis, and recently, abstract genetic testing to identify its etiology has become more common. We present a case of a 16-year-old boy with a history of chronic moderate thrombocytopenia, who later developed constitutional symptoms and bilateral hand edema with cold exposure. Laboratory evaluation revealed evidence both of inflammation and elevated muscle enzymes. These abnormalities persisted over months. His thrombocytopenia was determined to be immune mediated. Imaging revealed lymphadenopathy and asplenia, Divisions of aPediatric Rheumatology, bPediatric Genetics, and a muscle biopsy was consistent with tubular aggregate myopathy. cPediatric Neurology, and ePediatric Hematology-Oncology d Ophthalmology evaluation noted photosensitivity, pupillary miosis, and iris and Department of Pathology, University of Michigan, Ann Arbor, Michigan hypoplasia. Genetic testing demonstrated a pathogenic variant in STIM1 consistent with autosomal dominant Stormorken syndrome. Our case is novel Mr Jacher, Ms Sura, Ms Neil, Mr Hannibal, Ms McFadden, and Ms Walkovich all participated in because of the overlap of phenotypes ascribed to both gain-of-function and literature review, drafted the initial manuscript, and loss-of-function pathogenic variants in STIM1, thereby blurring the then reviewed and revised the manuscript; and all distinctions between these previously described syndromes. Pediatricians authors approved the final manuscript as submitted and agree to be accountable for all aspects of should consider checking muscle enzymes when patients present with the work.
    [Show full text]
  • The Role of Genetic Mutations in Gene NBEAL2 in Gray Platelet Syndrome
    ARC Journal of Hematology Volume 5, Issue 1, 2020, PP 1-4 www.arcjournals.org The Role of Genetic Mutations in Gene NBEAL2 in Gray Platelet Syndrome Shahin Asadi* Medical Genetics-Harvard University, Director of the Division of Medical Genetics and Molecular Optogenetic Research, Division of Medical Genetics and Molecular Pathology Research, Harvard University, Boston Children's Hospital *Corresponding Author: Shahin Asadi, Medical Genetics-Harvard University. Director of the Division of Medical Genetics and Molecular Optogenetic Research. Division of Medical Genetics and Molecular Pathology Research, Harvard University, Boston Children's Hospital, Email: [email protected] Abstract : Gray platelet syndrome (GPS) is a rare inherited bleeding disorder characterized by macro thrombocytopenia , myelofibrosis, splenomegaly and typical gray appearance of platelets on Wright stained peripheral blood smear. GPS is caused by mutations in the NBEAL2 gene. Absence or marked reduction of alpha -granules in platelets underlies the disorder. Alpha-granules are the most abundant vesicles in platelets and store proteins that promote platelet adhesiveness and wound healing when secreted during platelet activation. Keywords: Gray Platelet Syndrome, Hematology Disorder, NBEAL2 gene. 1. OVERVIEW OF GRAY PLATELET SYNDROME Gray platelet syndrome is a bleeding disorder associated with abnormal platelets that are involved in blood clotting. The skin of people with this syndrome is easily bruised and may increase the risk of nasal bleeding [1]. 2. CLINICAL SIGNS AND SYMPTOMS OF GRAY PLATELET SYNDROME Patients with GD may also experience abnormal or severe bleeding after surgery, dental work or minor skin damage. Women with gray platelet Figure1: Schematic view of the cellular structure of syndrome often experience irregular periods blood platelets (menorrhagia) of menstruation.
    [Show full text]