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Glanzmann thrombasthenia 2(GT2; BDPLT23)

MedGen UID:
1782592
Concept ID:
C5543273
Disease or Syndrome
Synonym: BLEEDING DISORDER, PLATELET-TYPE, 23
 
Gene (location): ITGB3 (17q21.32)
 
Monarch Initiative: MONDO:0031009
OMIM®: 619267

Definition

Glanzmann thrombasthenia-2 (GT2) is an autosomal recessive bleeding disorder characterized by failure of platelet aggregation and by absent or diminished clot retraction. The abnormalities are related to quantitative or qualitative abnormalities of the GPIIb (607759)/IIIa platelet surface fibrinogen receptor complex resulting from mutations in the GPIIIa gene (Rosenberg et al., 1997). For a general phenotypic description and a discussion of genetic heterogeneity of Glanzmann thrombasthenia, see 273800. [from OMIM]

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.
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.
Prolonged bleeding after dental extraction
MedGen UID:
369536
Concept ID:
C1969572
Pathologic Function
Prolonged bleeding post dental extraction sufficient to require medical intervention.
Prolonged bleeding after surgery
MedGen UID:
867284
Concept ID:
C4021646
Pathologic Function
Bleeding that persists longer than the normal time following a surgical procedure.
Decreased platelet glycoprotein IIb-IIIa
MedGen UID:
892761
Concept ID:
C4021767
Finding
Decreased cell membrane concentration of glycoprotein IIb-IIIa.
Impaired ristocetin-induced platelet aggregation
MedGen UID:
868749
Concept ID:
C4023154
Pathologic Function
Abnormal response to ristocetin as manifested by reduced or lacking aggregation of platelets upon addition of ristocetin.
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.
Impaired epinephrine-induced platelet aggregation
MedGen UID:
870285
Concept ID:
C4024727
Finding
Abnormal response to epinephrine as manifested by reduced or lacking aggregation of platelets upon addition of epinephrine.
Impaired ADP-induced platelet aggregation
MedGen UID:
870824
Concept ID:
C4025282
Finding
Abnormal platelet response to ADP as manifested by reduced or lacking aggregation of platelets upon addition of ADP.
Impaired clot retraction
MedGen UID:
1376447
Concept ID:
C4476985
Finding
Platelets contain contractile proteins (actin and myosin) that induce clot retraction. As the platelets contract, they pull on the surrounding fibrin strands, squeezing serum form the mass, compacting the clot and drawing the ruptured edges of the blood vessel more closely together. Clot retraction is directly proportional to the platelet count and inversely proportional to the fibrinogen concentration.
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.

Professional guidelines

PubMed

Fiore M, d'Oiron R, Pillois X, Alessi MC
Br J Haematol 2018 Apr;181(2):173-182. Epub 2018 Apr 2 doi: 10.1111/bjh.15087. PMID: 29611179
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Int J Lab Hematol 2017 Apr;39(2):e41-e44. Epub 2016 Nov 3 doi: 10.1111/ijlh.12603. PMID: 27808476
Poon MC, Di Minno G, d'Oiron R, Zotz R
Transfus Med Rev 2016 Apr;30(2):92-9. Epub 2016 Jan 30 doi: 10.1016/j.tmrv.2016.01.001. PMID: 26968829

Recent clinical studies

Etiology

Hussain S, Ali Zaidi SA, Sawani S, Moiz B
J Pak Med Assoc 2024 Feb;74(2):378-383. doi: 10.47391/JPMA.9378. PMID: 38419241
Wiegering V, Sauer K, Winkler B, Eyrich M, Schlegel PG
Hamostaseologie 2013;33(4):305-12. Epub 2013 Jul 18 doi: 10.5482/HAMO-12-08-0014. PMID: 23868573
Toogeh G, Sharifian R, Lak M, Safaee R, Artoni A, Peyvandi F
Am J Hematol 2004 Oct;77(2):198-9. doi: 10.1002/ajh.20159. PMID: 15389911
Bellucci S, Caen J
Blood Rev 2002 Sep;16(3):193-202. doi: 10.1016/s0268-960x(02)00030-9. PMID: 12163005
Blanchette VS, Sparling C, Turner C
Baillieres Clin Haematol 1991 Apr;4(2):291-332. doi: 10.1016/s0950-3536(05)80162-3. PMID: 1912663

Diagnosis

Miller JL
Semin Thromb Hemost 2009 Mar;35(2):224-32. Epub 2009 Apr 30 doi: 10.1055/s-0029-1220330. PMID: 19408195
Blanchette VS, Sparling C, Turner C
Baillieres Clin Haematol 1991 Apr;4(2):291-332. doi: 10.1016/s0950-3536(05)80162-3. PMID: 1912663
O'Brien JR
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Caen JP
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Quick AJ
Am J Med Sci 1966 Feb;251(2):156-60. doi: 10.1097/00000441-196602000-00005. PMID: 5904734

Therapy

Gandhi PS, Zivkovic M, Østergaard H, Bonde AC, Elm T, Løvgreen MN, Schluckebier G, Johansson E, Olsen OH, Olsen EHN, de Bus IA, Bloem K, Alskär O, Rea CJ, Bjørn SE, Schutgens RE, Sørensen B, Urbanus RT, Faber JH
Nat Cardiovasc Res 2024 Feb;3(2):166-185. Epub 2024 Feb 8 doi: 10.1038/s44161-023-00418-4. PMID: 39196196Free PMC Article
Ganapule A, Jain P, Abubacker FN, Korula A, Abraham A, Mammen J, George B, Mathews V, Srivastava A, Viswabandya A
Blood Coagul Fibrinolysis 2017 Mar;28(2):171-175. doi: 10.1097/MBC.0000000000000524. PMID: 27273143
Franchini M, Crestani S, Frattini F, Sissa C, Bonfanti C
J Thromb Thrombolysis 2015 Feb;39(2):235-40. doi: 10.1007/s11239-014-1114-1. PMID: 25015059
Nurden AT, Nurden P
Semin Vasc Med 2003 May;3(2):123-30. doi: 10.1055/s-2003-40670. PMID: 15199475
Blanchette VS, Sparling C, Turner C
Baillieres Clin Haematol 1991 Apr;4(2):291-332. doi: 10.1016/s0950-3536(05)80162-3. PMID: 1912663

Prognosis

Nakajima Y, Yada K, Ogiwara K, Furukawa S, Shimonishi N, Shima M, Nogami K
Pediatr Int 2021 Feb;63(2):160-167. Epub 2020 Dec 5 doi: 10.1111/ped.14378. PMID: 32640065
Zhou L, Jiang M, Shen H, You T, Ding Z, Cui Q, Ma Z, Yang F, Xie Z, Shi H, Su J, Cao L, Lin J, Yin J, Dai L, Wang H, Wang Z, Yu Z, Ruan C, Xia L
Clin Genet 2018 Aug;94(2):213-220. Epub 2018 May 22 doi: 10.1111/cge.13366. PMID: 29675921Free PMC Article
Wiegering V, Sauer K, Winkler B, Eyrich M, Schlegel PG
Hamostaseologie 2013;33(4):305-12. Epub 2013 Jul 18 doi: 10.5482/HAMO-12-08-0014. PMID: 23868573
Almeida AM, Khair K, Hann I, Liesner R
Br J Haematol 2003 May;121(3):477-81. doi: 10.1046/j.1365-2141.2003.04286.x. PMID: 12716372
Brown CH 3rd, Weisberg RJ, Natelson EA, Alfrey CP Jr
Transfusion 1975 Mar-Apr;15(2):124-31. doi: 10.1046/j.1537-2995.1975.15275122805.x. PMID: 1167989

Clinical prediction guides

Xie Z, Jiang J, Cao L, Jiang M, Yang F, Ma Z, Wang Z, Ruan C, Liu H, Zhou L
Clin Genet 2021 Aug;100(2):213-218. Epub 2021 May 5 doi: 10.1111/cge.13975. PMID: 33928629
Tadokoro S, Nakazawa T, Kamae T, Kiyomizu K, Kashiwagi H, Honda S, Kanakura Y, Tomiyama Y
Blood 2011 Jan 6;117(1):250-8. Epub 2010 Oct 12 doi: 10.1182/blood-2009-10-246751. PMID: 20940419
Toogeh G, Sharifian R, Lak M, Safaee R, Artoni A, Peyvandi F
Am J Hematol 2004 Oct;77(2):198-9. doi: 10.1002/ajh.20159. PMID: 15389911
Brown CH 3rd, Weisberg RJ, Natelson EA, Alfrey CP Jr
Transfusion 1975 Mar-Apr;15(2):124-31. doi: 10.1046/j.1537-2995.1975.15275122805.x. PMID: 1167989
Quick AJ
Am J Clin Pathol 1975 Jul;64(1):87-94. doi: 10.1093/ajcp/64.1.87. PMID: 1080353

Recent systematic reviews

Saultier P, Grino M, Falaise C, Voisin S, Lavenu-Bombled C, Ibrahim-Kosta M, Petit A, Boutroux H, Desprez D, Fiore M, d'Oiron R, Alessi MC
Haemophilia 2025 Jan;31(1):7-15. Epub 2024 Nov 27 doi: 10.1111/hae.15130. PMID: 39604156Free PMC Article
Punt MC, Schuitema PCE, Bloemenkamp KWM, Kremer Hovinga ICL, van Galen KPM
Haemophilia 2020 Mar;26(2):216-227. Epub 2020 Jan 31 doi: 10.1111/hae.13927. PMID: 32004416Free PMC Article

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