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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
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
Bellucci S, Caen J
Blood Rev 2002 Sep;16(3):193-202. doi: 10.1016/s0268-960x(02)00030-9. PMID: 12163005

Recent clinical studies

Etiology

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
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
Haghighi A, Borhany M, Ghazi A, Edwards N, Tabaksert A, Haghighi A, Fatima N, Shamsi TS, Sayer JA
Clin Genet 2016 Feb;89(2):187-92. Epub 2015 Jul 15 doi: 10.1111/cge.12622. PMID: 26096001Free 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
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

Lobo V, Shetty S, Kulkarni B, Butera D, Magalhaes GS, Ghosh K
Ann Hematol 2012 Jun;91(6):917-21. Epub 2011 Dec 21 doi: 10.1007/s00277-011-1390-1. PMID: 22183252
Agarwal MB, Agarwal UM, Viswanathan C, Bhave AA, Billa V
Indian Pediatr 1992 Jul;29(7):837-41. PMID: 1428131
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
Lancet 1990 Mar 24;335(8691):711-3. doi: 10.1016/0140-6736(90)90815-m. PMID: 1969070
Caen JP
Baillieres Clin Haematol 1989 Jul;2(3):609-25. doi: 10.1016/s0950-3536(89)80036-8. PMID: 2673430

Therapy

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
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
Di Minno G
Blood Rev 2015 Jun;29 Suppl 1:S26-33. doi: 10.1016/S0268-960X(15)30005-9. PMID: 26073366
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
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

Friend BD, Roach GD, Kempert PH, Moore TB
J Pediatr Hematol Oncol 2020 Aug;42(6):e521-e526. doi: 10.1097/MPH.0000000000001646. PMID: 31693514
Guillet B, Bayart S, Pillois X, Nurden P, Caen JP, Nurden AT
J Thromb Haemost 2019 Dec;17(12):2211-2215. Epub 2019 Sep 29 doi: 10.1111/jth.14622. PMID: 31565851
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
Iqbal I, Farhan S, Ahmed N
J Coll Physicians Surg Pak 2016 Aug;26(8):647-50. PMID: 27539755
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

Clinical prediction guides

Shapiro A
Thromb Res 2020 Dec;196:590-602. Epub 2019 Jul 19 doi: 10.1016/j.thromres.2019.07.014. PMID: 31420204
Iqbal I, Farhan S, Ahmed N
J Coll Physicians Surg Pak 2016 Aug;26(8):647-50. PMID: 27539755
Di Minno G
Blood Rev 2015 Jun;29 Suppl 1:S26-33. doi: 10.1016/S0268-960X(15)30005-9. PMID: 26073366
Léticée N, Kaplan C, Lémery D
Eur J Obstet Gynecol Reprod Biol 2005 Aug 1;121(2):139-42. doi: 10.1016/j.ejogrb.2005.02.011. PMID: 16054952
Seligsohn U, Peretz H
Haemostasis 1994 Mar-Apr;24(2):81-5. doi: 10.1159/000217088. PMID: 7959366

Recent systematic reviews

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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