| Glanzmann's thrombasthenia |
| Classification and external resources |
| ICD-10 |
D69.1 |
| ICD-9 |
287.1 |
| OMIM |
187800 273800 |
| DiseasesDB |
5224 |
| MedlinePlus |
001305 |
| eMedicine |
med/872 |
| MeSH |
D013915 |
Glanzmann's thrombasthenia is an abnormality of platelets.[1] It is an extremely rare coagulopathy (bleeding disorder due to a blood abnormality), in which the platelets contain defective or low levels of glycoprotein IIb/IIIa (GpIIb/IIIa), which is a receptor for fibrinogen. As a result, no fibrinogen bridging of platelets to other platelets can occur, and the bleeding time is significantly prolonged.
Contents
- 1 Pathophysiology
- 2 Cause
- 3 Clinical features
- 4 Treatment
- 5 Eponym
- 6 See also
- 7 References
- 8 External links
Pathophysiology
Glycoprotein IIb/IIIa (GpIIb/IIIa), also known as αIIbβ3, is an integrin aggregation receptor on platelets. This receptor is activated when the platelet is stimulated by ADP, epinephrine, collagen, or thrombin. GpIIb/IIIa is essential to blood coagulation since the activated receptor has the ability to bind fibrinogen (as well as von Willebrand factor, fibronectin, and vitronectin), which is required for fibrinogen-dependent platelet-platelet interaction (aggregation).
In contrast, Glanzmann's thrombasthenia has normal glycoprotein Ib receptors, the role of which is to enable platelet activation by contact with the von Willebrand factor-collagen complex that is exposed when the endothelial blood vessel lining is damaged.
Understanding of the role of GpIIb/IIIa in Glanzmann's thrombasthenia led to the development of GpIIb/IIIa inhibitors, a class of powerful antiplatelet agents.[2]
Cause
Glanzmann's thrombasthenia can be inherited in an autosomal recessive manner[2][3] or acquired as an autoimmune disorder.[3][4]
The bleeding tendency in Glanzmann's thrombasthenia is variable,[3] some individuals having minimal bruising, while others have frequent, severe, potentially fatal hemorrhages. Moreover, platelet αIIbβ3 levels correlate poorly with hemorrhagic severity, as virtually undetectable αIIbβ3 levels can correlate with negligible bleeding symptoms, and 10%–15% levels can correlate with severe hemorrhage.[5] Unidentified factors other than the platelet defect itself may have important roles.[3]
Clinical features
Characteristically, there is increased mucosal bleeding:[3]
- menorrhagia
- easy bruising
- epistaxis
- gingival bleeding
- gastrointestinal bleeding
- postpartum bleeding
- increased bleeding post-operatively.
The bleeding tendency is variable but may be severe. Hemarthrosis, particularly spontaneous, is very rare, in contrast to the hemophilias.
Platelet numbers and morphology are normal. Platelet aggregation is normal with ristocetin, but impaired with other agonists such as ADP, thrombin, collagen or epinephrine.
Laboratory findings in various platelet and coagulation disorders (V - T)
| Condition |
Prothrombin time |
Partial thromboplastin time |
Bleeding time |
Platelet count |
| Vitamin K deficiency or warfarin |
Prolonged |
Normal or mildly prolonged |
Unaffected |
Unaffected |
| Disseminated intravascular coagulation |
Prolonged |
Prolonged |
Prolonged |
Decreased |
| Von Willebrand disease |
Unaffected |
Prolonged or unaffected |
Prolonged |
Unaffected |
| Hemophilia |
Unaffected |
Prolonged |
Unaffected |
Unaffected |
| Aspirin |
Unaffected |
Unaffected |
Prolonged |
Unaffected |
| Thrombocytopenia |
Unaffected |
Unaffected |
Prolonged |
Decreased |
| Liver failure, early |
Prolonged |
Unaffected |
Unaffected |
Unaffected |
| Liver failure, end-stage |
Prolonged |
Prolonged |
Prolonged |
Decreased |
| Uremia |
Unaffected |
Unaffected |
Prolonged |
Unaffected |
| Congenital afibrinogenemia |
Prolonged |
Prolonged |
Prolonged |
Unaffected |
| Factor V deficiency |
Prolonged |
Prolonged |
Unaffected |
Unaffected |
| Factor X deficiency as seen in amyloid purpura |
Prolonged |
Prolonged |
Unaffected |
Unaffected |
| Glanzmann's thrombasthenia |
Unaffected |
Unaffected |
Prolonged |
Unaffected |
| Bernard-Soulier syndrome |
Unaffected |
Unaffected |
Prolonged |
Decreased or unaffected |
| Factor XII deficiency |
Unaffected |
Prolonged |
Unaffected |
Unaffected |
| C1INH deficiency |
Unaffected |
Shortened |
Unaffected |
Unaffected |
Treatment
Therapy involves both preventive measures and treatment of specific bleeding episodes.[3]
- Dental hygiene lessens gingival bleeding[6]
- Avoidance of antiplatelet agents such as aspirin and other anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen, and anticoagulants
- Iron or folate supplementation may be necessary if excessive or prolonged bleeding has caused anemia
- Hepatitis B vaccine
- Antifibrinolytic drugs such as tranexamic acid or ε-aminocaproic acid (Amicar)
- Desmopressin (DDAVP) does not normalize the bleeding time in Glanzmann's thrombasthenia but anecdotally improves hemostasis
- Hormonal contraceptives to control excessive menstrual bleeding
- Topical agents such as gelfoam, fibrin sealants, polyethylene glycol polymers, custom dental splints
- Platelet transfusions (only if bleeding is severe; risk of platelet alloimmunization)
- Recombinant factor VIIa
- Hematopoietic stem cell transplantation (HSCT) for severe recurrent hemorrhages
Eponym
It is named after Eduard Glanzmann (1887-1959), the Swiss pediatrician who originally described it.[7][8][9]
See also
References
- ^ "Glanzmann thrombasthenia" at Dorland's Medical Dictionary
- ^ a b Seligsohn U (2002). "Glanzmann thrombasthenia: a model disease which paved the way to powerful therapeutic agents" (PDF). Pathophysiol. Haemost. Thromb. 32 (5-6): 216–7. doi:10.1159/000073569. PMID 13679645.
- ^ a b c d e f Kaushansky K, Lichtman M, Beutler E, Kipps T, Prchal J, Seligsohn U. (2010; edition 8: pages 1933-1941) Williams Hematology. McGraw-Hill.ISBN 978-0071621519
- ^ Tholouli E, Hay CR, O'Gorman P, Makris M (2004). "Acquired Glanzmann's thrombasthenia without thrombocytopenia: a severe acquired autoimmune bleeding disorder". Br. J. Haematol. 127 (2): 209–13. doi:10.1111/j.1365-2141.2004.05173.x. PMID 15461628.
- ^ Nurden, A. T. (2006). "Glanzmann thrombasthenia". Orphanet Journal of Rare Diseases 1: 10. doi:10.1186/1750-1172-1-10. PMC 1475837. PMID 16722529. edit
- ^ F.Z. Elmouatarif, B. Badre, S. Elarabi (2013). "Thrombasthénie de Glanzmann". Le courrier du dentiste.
- ^ synd/1289 at Who Named It?
- ^ Glanzmann, WE (1918). "Hereditäre hämorrhägische Thrombasthenie. Ein Beitrag zur Pathologie der Blutplättchen.[Hereditary haemorrhagic thrombasthenia. A contribution to the pathology of platelets] (German)". Jahrbuch für Kinderheilkunde [Yearbook of Pediatrics] 88 (1-42): 113–141.
- ^ Kannan, M.; Saxena, R. (2009). "Glanzmann's thrombasthenia: an overview". Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis 15 (2): 152–165. doi:10.1177/1076029608326165. PMID 18930954. edit
External links
- Internet database of mutations giving rise to Glanzmann's thrombasthenia: [1]
|
Pathology: hematology, hematologic diseases of RBCs and megakaryocytes / MEP (D50-69,74, 280-287)
|
|
Red
blood cells |
| ↑ |
|
|
| ↓ |
| Anemia |
| Nutritional |
- Micro-: Iron deficiency anemia
- Macro-: Megaloblastic anemia
|
|
Hemolytic
(mostly Normo-) |
| Hereditary |
- enzymopathy: G6PD
- glycolysis
- hemoglobinopathy: Thalassemia
- Sickle-cell disease/trait
- HPFH
- membrane: Hereditary spherocytosis
- Minkowski-Chauffard syndrome
- Hereditary elliptocytosis
- Southeast Asian ovalocytosis
- Hereditary stomatocytosis
|
|
| Acquired |
- Drug-induced autoimmune
- Drug-induced nonautoimmune
- Hemolytic disease of the newborn
|
|
|
Aplastic
(mostly Normo-) |
- Hereditary: Fanconi anemia
- Diamond–Blackfan anemia
- Acquired: PRCA
- Sideroblastic anemia
- Myelophthisic
|
|
| Blood tests |
- MCV
- Normocytic
- Microcytic
- Macrocytic
- MCHC
|
|
|
| Other |
- Methemoglobinemia
- Sulfhemoglobinemia
- Reticulocytopenia
|
|
|
|
Coagulation/
coagulopathy |
| ↑ |
Hyper-
coagulability |
- primary: Antithrombin III deficiency
- Protein C deficiency/Activated protein C resistance/Protein S deficiency/Factor V Leiden
- Prothrombin G20210A
- Sticky platelet syndrome
- acquired:Thrombocytosis
- DIC
- Congenital afibrinogenemia
- Purpura fulminans
- autoimmune
|
|
|
| ↓ |
Hypo-
coagulability |
| Thrombocytopenia |
- Thrombocytopenic purpura: ITP
- TM
- Heparin-induced thrombocytopenia
- May-Hegglin anomaly
|
|
| Platelet function |
- adhesion
- aggregation
- Glanzmann's thrombasthenia
- platelet storage pool deficiency
- Hermansky–Pudlak syndrome
- Gray platelet syndrome
|
|
| Clotting factor |
- Hemophilia
- von Willebrand disease
- Hypoprothrombinemia/II
- XIII
- Dysfibrinogenemia
|
|
|
|
|
|
|
cell/phys (coag, heme, immu, gran), csfs
|
rbmg/mogr/tumr/hist, sysi/epon, btst
|
drug (B1/2/3+5+6), btst, trns
|
|
|
|
|
Genetic disorder, membrane: cell surface receptor deficiencies
|
|
G protein-coupled receptor
(including hormone) |
| Class A |
- TSHR (Congenital hypothyroidism 1)
- LHCGR (Male-limited precocious puberty)
- FSHR (XX gonadal dysgenesis)
- EDNRB (ABCD syndrome, Waardenburg syndrome 4a, Hirschsprung's disease 2)
- AVPR2 (Nephrogenic diabetes insipidus 1)
- PTGER2 (Aspirin-induced asthma)
|
|
| Class B |
- PTH1R (Jansen's metaphyseal chondrodysplasia)
|
|
| Class C |
- CASR (Familial hypocalciuric hypercalcemia)
|
|
| Class F |
- FZD4 (Familial exudative vitreoretinopathy 1)
|
|
|
Enzyme-linked receptor
(including
growth factor) |
| RTK |
- ROR2 (Robinow syndrome)
- FGFR1 (Pfeiffer syndrome, KAL2 Kallmann syndrome)
- FGFR2 (Apert syndrome, Antley–Bixler syndrome, Pfeiffer syndrome, Crouzon syndrome, Jackson–Weiss syndrome)
- FGFR3 (Achondroplasia, Hypochondroplasia, Thanatophoric dysplasia, Muenke syndrome)
- INSR (Donohue syndrome
- Rabson–Mendenhall syndrome)
- NTRK1 (Congenital insensitivity to pain with anhidrosis)
- KIT (KIT Piebaldism, Gastrointestinal stromal tumor)
|
|
| STPK |
- AMHR2 (Persistent Mullerian duct syndrome II)
- TGF beta receptors: Endoglin/Alk-1/SMAD4 (Hereditary hemorrhagic telangiectasia)
- TGFBR1/TGFBR2 (Loeys-Dietz syndrome)
|
|
| GC |
- GUCY2D (Leber's congenital amaurosis 1)
|
|
|
| JAK-STAT |
- Type I cytokine receptor: GH (Laron syndrome)
- CSF2RA (Surfactant metabolism dysfunction 4)
- MPL (Congenital amegakaryocytic thrombocytopenia)
|
|
| TNF receptor |
- TNFRSF1A (TNF receptor associated periodic syndrome)
- TNFRSF13B (Selective immunoglobulin A deficiency 2)
- TNFRSF5 (Hyper-IgM syndrome type 3)
- TNFRSF13C (CVID4)
- TNFRSF13B (CVID2)
- TNFRSF6 (Autoimmune lymphoproliferative syndrome 1A)
|
|
| Lipid receptor |
- LRP: LRP2 (Donnai–Barrow syndrome)
- LRP4 (Cenani–Lenz syndactylism)
- LRP5 (Worth syndrome, Familial exudative vitreoretinopathy 4, Osteopetrosis 1)
- LDLR (LDLR Familial hypercholesterolemia)
|
|
| Other/ungrouped |
- Immunoglobulin superfamily: AGM3, 6
- Integrin: LAD1
- Glanzmann's thrombasthenia
- Junctional epidermolysis bullosa with pyloric atresia
EDAR (EDAR Hypohidrotic ectodermal dysplasia)
- PTCH1 (Nevoid basal cell carcinoma syndrome)
- BMPR1A (BMPR1A Juvenile polyposis syndrome)
- IL2RG (X-linked severe combined immunodeficiency)
|
|
- See also
- cell surface receptors
- B structural
- perx
- skel
- cili
- mito
- nucl
- sclr
- DNA/RNA/protein synthesis
- membrane
- transduction
- trfk
|
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