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Gray platelet syndrome(GPS)

MedGen UID:
82900
Concept ID:
C0272302
Disease or Syndrome
Synonyms: BLEEDING DISORDER, PLATELET-TYPE, 4; GPS; Marked decrease or absence of alpha-granules and of platelet-specific alpha-granule proteins; Platelet alpha-granule deficiency
SNOMED CT: Platelet granule defect (51720005); Platelet alpha granule deficiency (51720005); Gray platelet syndrome (51720005); Deficient alpha granule syndrome (51720005)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): NBEAL2 (3p21.31)
 
Monarch Initiative: MONDO:0007686
OMIM®: 139090
Orphanet: ORPHA721

Definition

The gray platelet syndrome (GPS) is a rare inherited disorder characterized by mild to moderate bleeding tendency, moderate thrombocytopenia, and a marked decrease or absence of platelet alpha-granules and of the proteins contained in alpha-granules. The platelets are enlarged, but not giant, and have a gray appearance on light microscopy of Wright-stained peripheral blood smears due to decreased granules. Many patients with gray platelet syndrome develop a stable myelofibrosis (summary by Nurden and Nurden, 2007). Cases suggesting autosomal dominant and autosomal recessive inheritance have been described, indicating that GPS is probably a genetically heterogeneous disorder with more than one molecular cause. [from OMIM]

Additional description

From MedlinePlus Genetics
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).  https://medlineplus.gov/genetics/condition/gray-platelet-syndrome

Clinical features

From HPO
Epistaxis
MedGen UID:
4996
Concept ID:
C0014591
Pathologic Function
Epistaxis, or nosebleed, refers to a hemorrhage localized in the nose.
Menorrhagia
MedGen UID:
44358
Concept ID:
C0025323
Pathologic Function
Prolonged and excessive menses at regular intervals in excess of 80 mL or lasting longer than 7 days.
Myelofibrosis
MedGen UID:
10146
Concept ID:
C0026987
Neoplastic Process
Replacement of bone marrow by fibrous tissue.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Prolonged bleeding time
MedGen UID:
56231
Concept ID:
C0151529
Finding
Prolongation of the time taken for a standardized skin cut of fixed depth and length to stop bleeding.
Abnormal bleeding
MedGen UID:
264316
Concept ID:
C1458140
Pathologic Function
An abnormal susceptibility to bleeding, often referred to as a bleeding diathesis. A bleeding diathesis may be related to vascular, platelet and coagulation defects.
Abnormal number of alpha granules
MedGen UID:
868468
Concept ID:
C4022862
Anatomical Abnormality
A deviation from the normal count of alpha granules per thrombocyte.
Reduced quantity of Von Willebrand factor
MedGen UID:
893065
Concept ID:
C4023022
Finding
Decreased quantity of von Willebrand factor.
Impaired thrombin-induced platelet aggregation
MedGen UID:
868748
Concept ID:
C4023153
Finding
Abnormal response to thrombin or thrombin mimetics as manifested by reduced or lacking aggregation of platelets upon addition of thrombin (or thrombin mimetics).
Reduced von Willebrand factor activity
MedGen UID:
870263
Concept ID:
C4024701
Finding
Decreased activity of von Willebrand factor. Von Willebrand factor mediates the adhesion of platelets to the collagen exposed on endothelial cell surfaces.
Impaired collagen-induced platelet aggregation
MedGen UID:
870264
Concept ID:
C4024703
Finding
Abnormal response to collagen or collagen-mimetics as manifested by reduced or lacking aggregation of platelets upon addition collagen or collagen-mimetics.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Bruising susceptibility
MedGen UID:
140849
Concept ID:
C0423798
Finding
An ecchymosis (bruise) refers to the skin discoloration caused by the escape of blood into the tissues from ruptured blood vessels. This term refers to an abnormally increased susceptibility to bruising. The corresponding phenotypic abnormality is generally elicited on medical history as a report of frequent ecchymoses or bruising without adequate trauma.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVGray platelet syndrome
Follow this link to review classifications for Gray platelet syndrome in Orphanet.

Professional guidelines

PubMed

Bottega R, Pecci A, De Candia E, Pujol-Moix N, Heller PG, Noris P, De Rocco D, Podda GM, Glembotsky AC, Cattaneo M, Balduini CL, Savoia A
Haematologica 2013 Jun;98(6):868-74. Epub 2012 Oct 25 doi: 10.3324/haematol.2012.075861. PMID: 23100277Free PMC Article
Köhler M
Thromb Haemost 1988 Aug 30;60(1):123-4. PMID: 3187941

Recent clinical studies

Etiology

Brambilla M, Becchetti A, Rovati GE, Cosentino N, Conti M, Canzano P, Giesen PLA, Loffreda A, Bonomi A, Cattaneo M, De Candia E, Podda GM, Trabattoni D, Werba PJ, Campodonico J, Pinna C, Marenzi G, Tremoli E, Camera M
Arterioscler Thromb Vasc Biol 2023 Oct;43(10):2042-2057. Epub 2023 Aug 17 doi: 10.1161/ATVBAHA.123.319099. PMID: 37589138Free PMC Article
Sims MC, Mayer L, Collins JH, Bariana TK, Megy K, Lavenu-Bombled C, Seyres D, Kollipara L, Burden FS, Greene D, Lee D, Rodriguez-Romera A, Alessi MC, Astle WJ, Bahou WF, Bury L, Chalmers E, Da Silva R, De Candia E, Deevi SVV, Farrow S, Gomez K, Grassi L, Greinacher A, Gresele P, Hart D, Hurtaud MF, Kelly AM, Kerr R, Le Quellec S, Leblanc T, Leinøe EB, Mapeta R, McKinney H, Michelson AD, Morais S, Nugent D, Papadia S, Park SJ, Pasi J, Podda GM, Poon MC, Reed R, Sekhar M, Shalev H, Sivapalaratnam S, Steinberg-Shemer O, Stephens JC, Tait RC, Turro E, Wu JKM, Zieger B; NIHR BioResource, Kuijpers TW, Whetton AD, Sickmann A, Freson K, Downes K, Erber WN, Frontini M, Nurden P, Ouwehand WH, Favier R, Guerrero JA
Blood 2020 Oct 22;136(17):1956-1967. doi: 10.1182/blood.2019004776. PMID: 32693407Free PMC Article
Nurden AT, Nurden P
J Thromb Haemost 2015 Jun;13 Suppl 1:S2-9. doi: 10.1111/jth.12898. PMID: 26149024
Salles II, Feys HB, Iserbyt BF, De Meyer SF, Vanhoorelbeke K, Deckmyn H
Blood Rev 2008 May;22(3):155-72. Epub 2008 Jan 3 doi: 10.1016/j.blre.2007.11.002. PMID: 18180086
Nurden AT
J Thromb Haemost 2005 Aug;3(8):1773-82. doi: 10.1111/j.1538-7836.2005.01428.x. PMID: 16102044

Diagnosis

Collins JH, Mayer L, Guerrero Lopez JA
J Thromb Haemost 2023 Jun;21(6):1409-1419. Epub 2023 Apr 5 doi: 10.1016/j.jtha.2023.03.032. PMID: 37028650
Chen CH, Lo RW, Urban D, Pluthero FG, Kahr WH
Platelets 2017 Mar;28(2):147-154. Epub 2017 Feb 22 doi: 10.1080/09537104.2017.1280599. PMID: 28277061
Jurk K
Hamostaseologie 2017 Aug 7;37(3):208-210. Epub 2016 Sep 21 doi: 10.5482/HAMO-16-07-0023. PMID: 27656707
Michelson AD
Blood 2013 Jan 10;121(2):250. doi: 10.1182/blood-2012-09-455550. PMID: 23427340
Bain BJ, Bhavnani M
Am J Hematol 2011 Dec;86(12):1027. Epub 2011 Jul 28 doi: 10.1002/ajh.22055. PMID: 21800352

Therapy

Brambilla M, Becchetti A, Rovati GE, Cosentino N, Conti M, Canzano P, Giesen PLA, Loffreda A, Bonomi A, Cattaneo M, De Candia E, Podda GM, Trabattoni D, Werba PJ, Campodonico J, Pinna C, Marenzi G, Tremoli E, Camera M
Arterioscler Thromb Vasc Biol 2023 Oct;43(10):2042-2057. Epub 2023 Aug 17 doi: 10.1161/ATVBAHA.123.319099. PMID: 37589138Free PMC Article
Valera MC, Kemoun P, Cousty S, Sie P, Payrastre B
J Oral Pathol Med 2013 Feb;42(2):115-24. Epub 2012 May 15 doi: 10.1111/j.1600-0714.2012.01151.x. PMID: 22583386
Wilcox DA, White GC 2nd
J Thromb Haemost 2003 Nov;1(11):2300-11. doi: 10.1046/j.1538-7836.2003.00476.x. PMID: 14629461
Köhler M, Hellstern P, Morgenstern E, Mueller-Eckhardt C, Berberich R, Meiser RJ, Scheffler P, Wenzel E
Blut 1985 Jun;50(6):331-40. doi: 10.1007/BF00320926. PMID: 3159448
Raccuglia G
Am J Med 1971 Dec;51(6):818-28. doi: 10.1016/0002-9343(71)90311-1. PMID: 5129551

Prognosis

Di Buduo CA, Alberelli MA, Glembostky AC, Podda G, Lev PR, Cattaneo M, Landolfi R, Heller PG, Balduini A, De Candia E
Sci Rep 2016 Mar 18;6:23213. doi: 10.1038/srep23213. PMID: 26987485Free PMC Article
Nurden AT, Nurden P
J Thromb Haemost 2015 Jun;13 Suppl 1:S2-9. doi: 10.1111/jth.12898. PMID: 26149024
Glembotsky AC, Marta RF, Pecci A, De Rocco D, Gnan C, Espasandin YR, Goette NP, Negro F, Noris P, Savoia A, Balduini CL, Molinas FC, Heller PG
J Thromb Haemost 2012 Aug;10(8):1653-61. doi: 10.1111/j.1538-7836.2012.04805.x. PMID: 22672365
Kahr WH, Hinckley J, Li L, Schwertz H, Christensen H, Rowley JW, Pluthero FG, Urban D, Fabbro S, Nixon B, Gadzinski R, Storck M, Wang K, Ryu GY, Jobe SM, Schutte BC, Moseley J, Loughran NB, Parkinson J, Weyrich AS, Di Paola J
Nat Genet 2011 Jul 17;43(8):738-40. doi: 10.1038/ng.884. PMID: 21765413Free PMC Article
Nurden AT, Nurden P, Bermejo E, Combrié R, McVicar DW, Washington AV
Thromb Haemost 2008 Jul;100(1):45-51. doi: 10.1160/TH08-02-0067. PMID: 18612537Free PMC Article

Clinical prediction guides

Delage L, Carbone F, Riller Q, Zachayus JL, Kerbellec E, Buzy A, Stolzenberg MC, Luka M, de Cevins C, Kalouche G, Favier R, Michel A, Meynier S, Corneau A, Evrard C, Neveux N, Roudières S, Pérot BP, Fusaro M, Lenoir C, Pellé O, Parisot M, Bras M, Héritier S, Leverger G, Korganow AS, Picard C, Latour S, Collet B, Fischer A, Neven B, Magérus A, Ménager M, Pasquier B, Rieux-Laucat F
Nat Commun 2023 Jun 22;14(1):3728. doi: 10.1038/s41467-023-39295-7. PMID: 37349339Free PMC Article
Sims MC, Mayer L, Collins JH, Bariana TK, Megy K, Lavenu-Bombled C, Seyres D, Kollipara L, Burden FS, Greene D, Lee D, Rodriguez-Romera A, Alessi MC, Astle WJ, Bahou WF, Bury L, Chalmers E, Da Silva R, De Candia E, Deevi SVV, Farrow S, Gomez K, Grassi L, Greinacher A, Gresele P, Hart D, Hurtaud MF, Kelly AM, Kerr R, Le Quellec S, Leblanc T, Leinøe EB, Mapeta R, McKinney H, Michelson AD, Morais S, Nugent D, Papadia S, Park SJ, Pasi J, Podda GM, Poon MC, Reed R, Sekhar M, Shalev H, Sivapalaratnam S, Steinberg-Shemer O, Stephens JC, Tait RC, Turro E, Wu JKM, Zieger B; NIHR BioResource, Kuijpers TW, Whetton AD, Sickmann A, Freson K, Downes K, Erber WN, Frontini M, Nurden P, Ouwehand WH, Favier R, Guerrero JA
Blood 2020 Oct 22;136(17):1956-1967. doi: 10.1182/blood.2019004776. PMID: 32693407Free PMC Article
Pluthero FG, Di Paola J, Carcao MD, Kahr WHA
Platelets 2018 Sep;29(6):632-635. Epub 2018 Jun 5 doi: 10.1080/09537104.2018.1478405. PMID: 29869935
Nurden AT, Nurden P
J Thromb Haemost 2015 Jun;13 Suppl 1:S2-9. doi: 10.1111/jth.12898. PMID: 26149024
Larocca LM, Heller PG, Podda G, Pujol-Moix N, Glembotsky AC, Pecci A, Alberelli MA, Balduini CL, Landolfi R, Cattaneo M, De Candia E
Platelets 2015;26(8):751-7. Epub 2015 Mar 25 doi: 10.3109/09537104.2014.994093. PMID: 25806575

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