U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Thrombocytopenia 1(XLT; THC1)

MedGen UID:
326416
Concept ID:
C1839163
Disease or Syndrome
Synonyms: Thrombocytopenia, X-linked; THROMBOCYTOPENIA, X-LINKED, 1; X-linked thrombocytopenia with normal platelets
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Gene (location): WAS (Xp11.23)
 
Monarch Initiative: MONDO:0010743
OMIM®: 313900
Orphanet: ORPHA852

Disease characteristics

Excerpted from the GeneReview: WAS-Related Disorders
The WAS-related disorders, which include Wiskott-Aldrich syndrome, X-linked thrombocytopenia (XLT), and X-linked neutropenia (XLN), are a spectrum of disorders of hematopoietic cells, with predominant defects of platelets and lymphocytes. Wiskott-Aldrich syndrome usually presents in infancy. Affected males have thrombocytopenia with intermittent mucosal bleeding, bloody diarrhea, and intermittent or chronic petechiae and purpura; recurrent bacterial, viral, fungal, and/or opportunistic infections; and eczema. Approximately 25%-40% of those who survive the early complications develop one or more autoimmune conditions including hemolytic anemia, immune thrombocytopenic purpura, immune-mediated neutropenia, vasculitis, rheumatoid arthritis, and immune-mediated damage to the kidneys and liver. Individuals with a WAS-related disorder, particularly those who have been exposed to Epstein-Barr virus (EBV), are at increased risk of developing lymphomas, which often occur in unusual extranodal locations including the brain, lung, or gastrointestinal tract. Males with XLT have small platelet volume and thrombocytopenia. Severe disease-related events include severe bleeding episodes (14%), autoimmunity (12%), life-threatening infections (7%), and malignancy (5%). Males with XLN typically have congenital neutropenia associated with myelodysplasia, hyperactive neutrophils, increased myeloid cell apoptosis, and lymphoid cell abnormalities. [from GeneReviews]
Authors:
Sharat Chandra  |  Chinmayee B Nagaraj  |  Miao Sun, et. al.   view full author information

Additional descriptions

From OMIM
Hereditary nonsyndromic thrombocytopenia is characterized by decreased numbers of platelets and bleeding tendency (summary by Villa et al., 1995). Genetic Heterogeneity of Hereditary Thrombocytopenia Autosomal dominant forms of thrombocytopenia include THC2 (188000), caused by mutation in the ANKRD26 (610855) gene on chromosome 10p12; THC4 (612004), caused by mutation in the CYCS gene (123970) on chromosome 7p15; THC5 (616216), caused by mutation in the ETV6 gene (600618) on chromosome 12p13; THC6 (616937), caused by mutation in the SRC gene (190090) on chromosome 20q11; THC7 (619130), caused by mutation in the IKZF5 gene (606238) on chromosome 10q26; THC8 (620475), caused by mutation in the ACTB gene (102630) on chromosome 7p22; THC9 (620478), caused by mutation in the THPO gene (600044) on chromosome 3q27; and THC11 (620654), caused by mutation in the RAP1B gene (179530) on chromosome 12q14. Autosomal recessive forms include THC3 (273900), caused by mutation in the FYB gene (602731) on chromosome 5p13; THC10 (620484), caused by mutation in the PTPRJ gene (600925) on chromosome 11p11; THC12 (620757), caused by mutation in the GNE gene (603824) on chromosome 9p13; and THC13 (620776), caused by mutation in the GALE gene (606953) on chromosome 1p36.  http://www.omim.org/entry/313900
From MedlinePlus Genetics
X-linked thrombocytopenia is a bleeding disorder that primarily affects males. This condition is characterized by a blood cell abnormality called thrombocytopenia, which is a shortage in the number of blood cells involved in clotting (platelets). Affected individuals often have abnormally small platelets as well, a condition called microthrombocytopenia. X-linked thrombocytopenia can cause individuals to bruise easily or have episodes of prolonged bleeding following minor trauma or even in the absence of injury (spontaneous bleeding). Some people with this condition experience spontaneous bleeding in the brain (cerebral hemorrhage), which can cause brain damage that can be life-threatening.

Some people with X-linked thrombocytopenia also have patches of red, irritated skin (eczema) or an increased susceptibility to infections. In severe cases, additional features can develop, such as cancer or autoimmune disorders, which occur when the immune system malfunctions and attacks the body's own tissues and organs. It is unclear, however, if people with these features have X-linked thrombocytopenia or a more severe disorder with similar signs and symptoms called Wiskott-Aldrich syndrome.

Some people have a mild form of the disorder called intermittent thrombocytopenia. These individuals have normal platelet production at times with episodes of thrombocytopenia.  https://medlineplus.gov/genetics/condition/x-linked-thrombocytopenia

Clinical features

From HPO
Joint hemorrhage
MedGen UID:
5479
Concept ID:
C0018924
Pathologic Function
Hemorrhage occurring within a joint.
Epistaxis
MedGen UID:
4996
Concept ID:
C0014591
Pathologic Function
Epistaxis, or nosebleed, refers to a hemorrhage localized in the nose.
Congenital thrombocytopenia
MedGen UID:
124422
Concept ID:
C0272278
Disease or Syndrome
Thrombocytopenia with congenital onset.
Decreased mean platelet volume
MedGen UID:
853132
Concept ID:
C1096368
Finding
Average platelet volume below the lower limit of the normal reference interval.
Intermittent thrombocytopenia
MedGen UID:
374151
Concept ID:
C1839167
Finding
Reduced platelet count that occurs sporadically, i.e., it comes and goes.
Abnormality of the musculature
MedGen UID:
867380
Concept ID:
C4021745
Anatomical Abnormality
Abnormality originating in one or more muscles, i.e., of the set of muscles of body.
Eczematoid dermatitis
MedGen UID:
3968
Concept ID:
C0013595
Disease or Syndrome
Eczema is a form of dermatitis that is characterized by scaly, pruritic, erythematous lesions located on flexural surfaces.
Increased circulating IgE concentration
MedGen UID:
116018
Concept ID:
C0236175
Finding
An abnormally increased overall level of immunoglobulin E in blood.
Increased circulating IgA concentration
MedGen UID:
66800
Concept ID:
C0239984
Finding
An abnormally increased level of immunoglobulin A in blood.
Petechiae
MedGen UID:
10680
Concept ID:
C0031256
Disease or Syndrome
Petechiae are pinpoint-sized reddish/purple spots, resembling a rash, that appear just under the skin or a mucous membrane when capillaries have ruptured and some superficial bleeding into the skin has happened. This term refers to an abnormally increased susceptibility to developing petechiae.
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  
  • CROGVThrombocytopenia 1
Follow this link to review classifications for Thrombocytopenia 1 in Orphanet.

Professional guidelines

PubMed

Miklos E, Oliver TP, Adam K, Eva K, Balazs K, Eszter K, Anett P, Viktoria GK, Jozsef H, Peter R
Eur J Haematol 2024 Aug;113(2):183-189. Epub 2024 Apr 21 doi: 10.1111/ejh.14213. PMID: 38644361
Cao P, Xu W, Zhang L
Front Immunol 2022;13:928621. Epub 2022 Jun 13 doi: 10.3389/fimmu.2022.928621. PMID: 35769474Free PMC Article
Farge D, Debourdeau P, Beckers M, Baglin C, Bauersachs RM, Brenner B, Brilhante D, Falanga A, Gerotzafias GT, Haim N, Kakkar AK, Khorana AA, Lecumberri R, Mandala M, Marty M, Monreal M, Mousa SA, Noble S, Pabinger I, Prandoni P, Prins MH, Qari MH, Streiff MB, Syrigos K, Bounameaux H, Büller HR
J Thromb Haemost 2013 Jan;11(1):56-70. doi: 10.1111/jth.12070. PMID: 23217107

Recent clinical studies

Etiology

Corn PG, Heath EI, Zurita A, Ramesh N, Xiao L, Sei E, Li-Ning-Tapia E, Tu SM, Subudhi SK, Wang J, Wang X, Efstathiou E, Thompson TC, Troncoso P, Navin N, Logothetis CJ, Aparicio AM
Lancet Oncol 2019 Oct;20(10):1432-1443. Epub 2019 Sep 9 doi: 10.1016/S1470-2045(19)30408-5. PMID: 31515154Free PMC Article
Oshima K, Imai K, Albert MH, Bittner TC, Strauss G, Filipovich AH, Morio T, Kapoor N, Dalal J, Schultz KR, Casper JT, Notarangelo LD, Ochs HD, Nonoyama S
J Clin Immunol 2015 Jan;35(1):15-21. Epub 2014 Nov 12 doi: 10.1007/s10875-014-0105-5. PMID: 25388447
Lorusso V, Cinieri S, Giampaglia M, Ciccarese M, Tinelli A, Chiuri V, Manca C, Silvestris N, Gasparini G, Colucci G
Breast 2010 Jun;19(3):214-8. Epub 2010 Feb 18 doi: 10.1016/j.breast.2010.01.015. PMID: 20167491
Ghosh S, Mittal M, Jaganathan G
Indian J Med Sci 2001 Sep;55(9):495-500. PMID: 11887300
Lin SJ, Chao HC, Huang JL, Lin TY, Hsieh KH
Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi 1997 Nov-Dec;38(6):448-53. PMID: 9473817

Diagnosis

Udomkittivorakul N, Wattanasirichaigoon D, Manuyakorn W, Pongphitcha P, Khongkraparn A, Tunlayadechanont P, Sirachainan N
Platelets 2022 Jul 4;33(5):792-796. Epub 2021 Oct 27 doi: 10.1080/09537104.2021.1988549. PMID: 34705590
Zhang JW, Luo YX, Yang YL, Long B, Lu Y, Zhang XZ
Clin Lab 2018 Oct 31;64(11) doi: 10.7754/Clin.Lab.2018.180837. PMID: 30549999
Hoshino A, Shimizu M, Matsukura H, Sakaki-Nakatsubo H, Nomura K, Miyawaki T, Kanegane H
J Clin Immunol 2014 Jan;34(1):53-7. Epub 2013 Nov 12 doi: 10.1007/s10875-013-9964-4. PMID: 24217816
Balduini CL, Savoia A
Hum Genet 2012 Dec;131(12):1821-32. Epub 2012 Aug 11 doi: 10.1007/s00439-012-1215-x. PMID: 22886561
Ghosh S, Mittal M, Jaganathan G
Indian J Med Sci 2001 Sep;55(9):495-500. PMID: 11887300

Therapy

Seiler JA, Durrani AK, Ahmeti M
Am Surg 2023 Aug;89(8):3574-3575. Epub 2023 Mar 15 doi: 10.1177/00031348231161690. PMID: 36919894
Cao P, Xu W, Zhang L
Front Immunol 2022;13:928621. Epub 2022 Jun 13 doi: 10.3389/fimmu.2022.928621. PMID: 35769474Free PMC Article
Zhang Z, Wu B, Peng G, Xiao G, Huang J, Ding Q, Yang C, Xiong X, Ma H, Shi L, Yang J, Hong X, Wei J, Qin Y, Wan C, Zhong Y, Zhou Y, Zhao X, Leng Y, Zhang T, Wu G, Yao M, Zhang X, Yang K
Clin Cancer Res 2022 Aug 2;28(15):3268-3276. doi: 10.1158/1078-0432.CCR-22-0666. PMID: 35766967Free PMC Article
Corn PG, Heath EI, Zurita A, Ramesh N, Xiao L, Sei E, Li-Ning-Tapia E, Tu SM, Subudhi SK, Wang J, Wang X, Efstathiou E, Thompson TC, Troncoso P, Navin N, Logothetis CJ, Aparicio AM
Lancet Oncol 2019 Oct;20(10):1432-1443. Epub 2019 Sep 9 doi: 10.1016/S1470-2045(19)30408-5. PMID: 31515154Free PMC Article
Kakio Y, Uchida HA, Kitagawa M, Arata Y, Kato A, Inoue-Torii A, Hinamoto N, Ogawa-Akiyama A, Sugiyama H, Wada J
Acta Med Okayama 2018 Jun;72(3):301-307. doi: 10.18926/AMO/56077. PMID: 29926009

Prognosis

Chen B, Wu JX, Cheng SH, Wang LM, Rong WQ, Wu F, Wang SL, Jin J, Liu YP, Song YW, Ren H, Fang H, Tang Y, Li N, Li YX, Wang WH
Hepatology 2021 Nov;74(5):2595-2604. Epub 2021 Sep 16 doi: 10.1002/hep.31993. PMID: 34097307Free PMC Article
Mantadakis E, Sawalle-Belohradsky J, Tzanoudaki M, Kanariou M, Chatzimichael A, Albert MH
Pediatr Blood Cancer 2014 Dec;61(12):2305-6. Epub 2014 Aug 23 doi: 10.1002/pbc.25196. PMID: 25154619
Hoshino A, Shimizu M, Matsukura H, Sakaki-Nakatsubo H, Nomura K, Miyawaki T, Kanegane H
J Clin Immunol 2014 Jan;34(1):53-7. Epub 2013 Nov 12 doi: 10.1007/s10875-013-9964-4. PMID: 24217816
Ghosh S, Mittal M, Jaganathan G
Indian J Med Sci 2001 Sep;55(9):495-500. PMID: 11887300
Warkentin TE
Semin Hematol 1998 Oct;35(4 Suppl 5):9-16; discussion 35-6. PMID: 9855179

Clinical prediction guides

Cao P, Xu W, Zhang L
Front Immunol 2022;13:928621. Epub 2022 Jun 13 doi: 10.3389/fimmu.2022.928621. PMID: 35769474Free PMC Article
Corn PG, Heath EI, Zurita A, Ramesh N, Xiao L, Sei E, Li-Ning-Tapia E, Tu SM, Subudhi SK, Wang J, Wang X, Efstathiou E, Thompson TC, Troncoso P, Navin N, Logothetis CJ, Aparicio AM
Lancet Oncol 2019 Oct;20(10):1432-1443. Epub 2019 Sep 9 doi: 10.1016/S1470-2045(19)30408-5. PMID: 31515154Free PMC Article
Kakio Y, Uchida HA, Kitagawa M, Arata Y, Kato A, Inoue-Torii A, Hinamoto N, Ogawa-Akiyama A, Sugiyama H, Wada J
Acta Med Okayama 2018 Jun;72(3):301-307. doi: 10.18926/AMO/56077. PMID: 29926009
Lorusso V, Cinieri S, Giampaglia M, Ciccarese M, Tinelli A, Chiuri V, Manca C, Silvestris N, Gasparini G, Colucci G
Breast 2010 Jun;19(3):214-8. Epub 2010 Feb 18 doi: 10.1016/j.breast.2010.01.015. PMID: 20167491
Wiedemann GJ, Robins HI, Gutsche S, Mentzel M, Deeken M, Katschinski DM, Eleftheriadis S, Crahé R, Weiss C, Storer B, Wagner T
Eur J Cancer 1996 May;32A(5):888-92. doi: 10.1016/0959-8049(95)00622-2. PMID: 9081372

Recent systematic reviews

Cao P, Xu W, Zhang L
Front Immunol 2022;13:928621. Epub 2022 Jun 13 doi: 10.3389/fimmu.2022.928621. PMID: 35769474Free PMC Article
Nielson CM, Bylsma LC, Fryzek JP, Saad HA, Crawford J
Oncologist 2021 Sep;26(9):e1609-e1618. Epub 2021 Jun 9 doi: 10.1002/onco.13822. PMID: 33973301Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...