Glanzmann's thrombasthenia
Encyclopedia
Glanzmann's thrombasthenia is an abnormality of platelets. It is an extremely rare coagulopathy
(disorder of the blood
), in which the platelets lack glycoprotein IIb/IIIa (GpIIb/IIIa). As a result, no fibrinogen
bridging of platelets to other platelets can occur, and the bleeding time is significantly prolonged.
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 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 platelets to be activated 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.
manner or acquired as an autoimmune disorder.
bleeding
:
The bleeding tendency is variable but may be severe.
Platelet numbers and morphology are normal. Platelet aggregation is normal with ristocetin
, but impaired with other agonists such as ADP, thrombin
, collagen or epinephrine.
Coagulopathy
Coagulopathy is a condition in which the blood’s ability to clot is impaired. This condition can cause prolonged or excessive bleeding, which may occur spontaneously or following an injury or medical and dental procedures.The normal clotting process depends on the interplay of various proteins in...
(disorder of the blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
), in which the platelets lack glycoprotein IIb/IIIa (GpIIb/IIIa). As a result, no fibrinogen
Fibrinogen
Fibrinogen is a soluble plasma glycoprotein, synthesised by the liver, that is converted by thrombin into fibrin during blood coagulation. This is achieved through processes in the coagulation cascade that activate the zymogen prothrombin to the serine protease thrombin, which is responsible for...
bridging of platelets to other platelets can occur, and the bleeding time is significantly prolonged.
Pathophysiology
Glycoprotein IIb/IIIa (GpIIb/IIIa) is an integrinIntegrin
Integrins are receptors that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the ECM. They also play a role in cell signaling and thereby regulate cellular shape, motility, and the cell cycle....
aggregation receptor on platelets. This receptor is activated when the platelet is stimulated by ADP, epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...
, collagen or thrombin. GpIIb/IIIa is essential to blood coagulation since the activated receptor has the ability to bind fibrinogen
Fibrinogen
Fibrinogen is a soluble plasma glycoprotein, synthesised by the liver, that is converted by thrombin into fibrin during blood coagulation. This is achieved through processes in the coagulation cascade that activate the zymogen prothrombin to the serine protease thrombin, which is responsible for...
(as well as fibronectin
Fibronectin
Fibronectin is a high-molecular weight glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. In addition to integrins, fibronectin also binds extracellular matrix components such as collagen, fibrin and heparan sulfate proteoglycans...
and vitronectin
Vitronectin
Vitronectin also known as VTN is a protein that in humans is encoded by the VTN gene.The protein encoded by this gene is a member of the pexin family...
), which is required for fibrinogen-dependent platelet-platelet interaction (aggregation.)
In contrast, Glanzmann's thrombasthenia has normal glycoprotein Ib
Glycoprotein Ib
Glycoprotein Ib , also known as CD42,is a component of the GPIb-V-IX complex on platelets. The GPIb-V-IX complex binds von Willebrand factor, allowing platelet adhesion and platelet plug formation at sites of vascular injury....
receptors, the role of which is to enable platelets to be activated by contact with the von Willebrand factor
Von Willebrand factor
von Willebrand factor is a blood glycoprotein involved in hemostasis. It is deficient or defective in von Willebrand disease and is involved in a large number of other diseases, including thrombotic thrombocytopenic purpura, Heyde's syndrome, and possibly hemolytic-uremic syndrome...
-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.
Cause
Glanzmann's thrombasthenia can be inherited in an autosomal recessiveRecessive
In genetics, the term "recessive gene" refers to an allele that causes a phenotype that is only seen in a homozygous genotype and never in a heterozygous genotype. Every person has two copies of every gene on autosomal chromosomes, one from mother and one from father...
manner or acquired as an autoimmune disorder.
Clinical features
Characteristically, there is increased mucosalMucocutaneous zone
A mucocutaneous zone is a region of the body in which mucosa transitions to skin. Mucocutaneous zones occur in animals, at the body orifices.In humans, mucocutaneous zones are found at the lips, nostrils, conjunctivae, urethra, vagina , foreskin , and anus.At a mucocutaneous zone, epithelium...
bleeding
Bleeding
Bleeding, technically known as hemorrhaging or haemorrhaging is the loss of blood or blood escape from the circulatory system...
:
- epistaxis
- menorrhagiaMenorrhagiaMenorrhagia is an abnormally heavy and prolonged menstrual period at regular intervals. Causes may be due to abnormal blood clotting, disruption of normal hormonal regulation of periods or disorders of the endometrial lining of the uterus...
- increased bleeding post-operatively.
The bleeding tendency is variable but may be severe.
Platelet numbers and morphology are normal. Platelet aggregation is normal with ristocetin
Ristocetin
Ristocetin is an antibiotic, obtained from Amycolatopsis lurida, previously used to treat staphylococcal infections. It is no longer used clinically because it caused thrombocytopenia and platelet agglutination. It is now used solely to assay those functions in vitro in the diagnosis of conditions...
, but impaired with other agonists such as ADP, thrombin
Thrombin
Thrombin is a "trypsin-like" serine protease protein that in humans is encoded by the F2 gene. Prothrombin is proteolytically cleaved to form thrombin in the first step of the coagulation cascade, which ultimately results in the stemming of blood loss...
, collagen or epinephrine.