Glanzmann's thrombasthenia is an abnormality of the
platelets
Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby i ...
. It is an extremely rare
coagulopathy
Coagulopathy (also called a bleeding disorder) is a condition in which the blood's ability to coagulate (form clots) is impaired. This condition can cause a tendency toward prolonged or excessive bleeding (bleeding diathesis), which may occur sp ...
(bleeding disorder due to a
blood
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in th ...
abnormality), in which the platelets contain defective or low levels of
glycoprotein IIb/IIIa (GpIIb/IIIa), which is a receptor for
fibrinogen
Fibrinogen (factor I) is a glycoprotein complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted enzymatically by thrombin to fibrin and then to a fibrin-based blood ...
. As a result, no
fibrinogen
Fibrinogen (factor I) is a glycoprotein complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted enzymatically by thrombin to fibrin and then to a fibrin-based blood ...
bridging of platelets to other platelets can occur, and the
bleeding time
Bleeding time is a medical test done on someone to assess their platelets function. It involves making a patient bleed, then timing how long it takes for them to stop bleeding using a stopwatch or other suitable devices.
The term template bleed ...
is significantly prolonged.
Signs and symptoms
Characteristically, there is increased
mucosal
A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It is ...
bleeding
Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vag ...
:
*
heavy menstrual bleeding
Heavy menstrual bleeding (HMB), previously known as menorrhagia or hypermenorrhea, is a menstrual period with excessively heavy flow. It is a type of abnormal uterine bleeding (AUB).
Abnormal uterine bleeding can be caused by structural abnorma ...
* easy bruising
*
nosebleeds
A nosebleed, also known as epistaxis, is bleeding from the nose. Blood can flow down into the stomach, and cause nausea and vomiting. In more severe cases, blood may come out of both nostrils. Rarely, bleeding may be so significant that low blo ...
* Bleeding from the
gums
The gums or gingiva (plural: ''gingivae'') consist of the mucosal tissue that lies over the mandible and maxilla inside the mouth. Gum health and disease can have an effect on general health.
Structure
The gums are part of the soft tissue l ...
* gastrointestinal bleeding
*
postpartum
The postpartum (or postnatal) period begins after childbirth and is typically considered to end within 6 weeks as the mother's body, including hormone levels and uterus size, returns to a non-pregnant state. The terms puerperium, puerperal perio ...
bleeding
* increased postoperative bleeding.
The bleeding tendency is variable but may be severe.
Bleeding into the joints, particularly spontaneous bleeds, are very rare, in contrast to the
hemophilia
Haemophilia, or hemophilia (), is a mostly hereditary, inherited genetic disorder that impairs the body's ability to coagulation, make blood clots, a process needed to hemostasis, stop bleeding. This results in people bleeding for a longer ti ...
s. Platelet numbers and morphology are normal. Platelet
aggregation
Aggregation may refer to:
Business and economics
* Aggregation problem (economics)
* Purchasing aggregation, the joining of multiple purchasers in a group purchasing organization to increase their buying power
* Community Choice Aggregation, the ...
is normal with
ristocetin
Ristocetin is a glycopeptide 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 so ...
, but impaired with other agonists such as
ADP
Adp or ADP may refer to:
Aviation
* Aéroports de Paris, airport authority for the Parisian region in France
* Aeropuertos del Perú, airport operator for airports in northern Peru
* SLAF Anuradhapura, an airport in Sri Lanka
* Ampara Air ...
,
thrombin
Thrombin (, ''fibrinogenase'', ''thrombase'', ''thrombofort'', ''topical'', ''thrombin-C'', ''tropostasin'', ''activated blood-coagulation factor II'', ''blood-coagulation factor IIa'', ''factor IIa'', ''E thrombin'', ''beta-thrombin'', ''gamma- ...
,
collagen, or
epinephrine
Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...
.
Cause
Glanzmann's thrombasthenia can be inherited in an
autosomal
An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosomal (sex chromosome) pairs, which may have different structures. The DNA in autosomes ...
recessive
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and ...
manner
[Kaushansky K, Lichtman M, Beutler E, Kipps T, Prchal J, Seligsohn U. (2010; edition 8: pages 1933-1941) ''Williams Hematology''. McGraw-Hill.][ or acquired as an ]autoimmune disorder
An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...
.
The bleeding tendency in Glanzmann's thrombasthenia is variable, some individuals having minimal bruising, while others have frequent, severe, potentially fatal hemorrhage
Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vag ...
s. 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 bleeding. Unidentified factors other than the platelet defect itself may have important roles.
Pathophysiology
Glanzmann's thrombasthenia is associated with abnormal integrin αIIbβ3, formerly known as glycoprotein IIb/IIIa (GpIIb/IIIa), which is an integrin
Integrins are transmembrane receptors that facilitate cell-cell and cell-extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, ...
aggregation receptor on platelets
Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby i ...
. This receptor is activated when the platelet is stimulated by ADP, epinephrine
Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...
, collagen, or thrombin. GpIIb/IIIa is essential to blood coagulation
Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechani ...
since the activated receptor has the ability to bind fibrinogen
Fibrinogen (factor I) is a glycoprotein complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted enzymatically by thrombin to fibrin and then to a fibrin-based blood ...
(as well as von Willebrand factor
Von Willebrand factor (VWF) () is a blood glycoprotein involved in hemostasis, specifically, platelet adhesion. It is deficient and/or defective in von Willebrand disease and is involved in many other diseases, including thrombotic thrombocytop ...
, fibronectin
Fibronectin is a high-molecular weight (~500-~600 kDa) glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. Fibronectin also binds to other extracellular matrix proteins such as collagen ...
, and vitronectin
Vitronectin (VTN or VN) is a glycoprotein of the hemopexin family which is abundantly found in serum, the extracellular matrix and bone. In humans it is encoded by the ''VTN'' gene.
Vitronectin binds to integrin alpha-V beta-3 and thus promotes ...
), which is required for fibrinogen-dependent platelet-platelet interaction (aggregation). Understanding of the role of GpIIb/IIIa in Glanzmann's thrombasthenia led to the development of GpIIb/IIIa inhibitors In medicine, glycoprotein IIb/IIIa inhibitors, also GpIIb/IIIa inhibitors, is a class of antiplatelet agents.
Several GpIIb/IIIa inhibitors exist:
* abciximab (abcixifiban) (ReoPro)
* eptifibatide (Integrilin)
* tirofiban (Aggrastat)
* roxifiba ...
, a class of powerful antiplatelet agent
An antiplatelet drug (antiaggregant), also known as a platelet agglutination inhibitor or platelet aggregation inhibitor, is a member of a class of pharmaceuticals that decrease platelet aggregation and inhibit thrombus formation. They are effect ...
s.
Diagnosis
Light transmission aggregometry
Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ...
is widely accepted as the gold standard diagnostic tool for assessing platelet function, and a result of absent aggregation with any agonist except ristocetin is highly specific for Glanzmann's thrombasthenia. Following is a table comparing its result with other platelet aggregation disorders:
Treatment
Therapy involves both preventive measures and treatment of specific bleeding episodes.
* Dental hygiene lessens gingiva
The gums or gingiva (plural: ''gingivae'') consist of the mucosal tissue that lies over the mandible and maxilla inside the mouth. Gum health and disease can have an effect on general health.
Structure
The gums are part of the soft tissue l ...
l bleeding
* Avoidance of antiplatelet agents such as aspirin
Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat in ...
and other anti-inflammatory drugs ( NSAIDs) such as ibuprofen
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used for treating pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus ...
and naproxen
Naproxen is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain, menstrual cramps, inflammatory diseases such as rheumatoid arthritis, gout and fever. It is taken orally. It is available in immediate and delayed release formula ...
, and anticoagulants
* Iron or folate
Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...
supplementation may be necessary if excessive or prolonged bleeding has caused anemia
* Hepatitis B
Hepatitis B is an infectious disease caused by the '' Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection.
Many people have no symptoms during an initial infection. F ...
vaccine
* Antifibrinolytic drugs such as tranexamic acid
Tranexamic acid (TXA) is a medication used to treat or prevent excessive blood loss from major trauma, postpartum bleeding, surgery, tooth removal, nosebleeds, and heavy menstruation. It is also used for hereditary angioedema. It is taken ...
or ε-aminocaproic acid (Amicar)
* Desmopressin
Desmopressin, sold under the trade name DDAVP among others, is a medication used to treat diabetes insipidus, bedwetting, hemophilia A, von Willebrand disease, and high blood urea levels. In hemophilia A and von Willebrand disease, it should onl ...
(DDAVP) does not normalize the bleeding time
Bleeding time is a medical test done on someone to assess their platelets function. It involves making a patient bleed, then timing how long it takes for them to stop bleeding using a stopwatch or other suitable devices.
The term template bleed ...
in Glanzmann's thrombasthenia but anecdotally improves hemostasis
In biology, hemostasis or haemostasis is a process to prevent and stop bleeding, meaning to keep blood within a damaged blood vessel (the opposite of hemostasis is hemorrhage). It is the first stage of wound healing. This involves coagulation, wh ...
* Hormonal contraceptive
Hormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The origin ...
s to control excessive menstrual bleeding
* Topical agents such as gelfoam
Embolization refers to the passage and lodging of an embolus within the bloodstream. It may be of natural origin (pathological), in which sense it is also called embolism, for example a pulmonary embolism; or it may be artificially induced (t ...
, fibrin sealant
Fibrin glue (also called fibrin sealant) is a surgical formulation used to create a fibrin clot for hemostasis, cartilage repair surgeries or wound healing. It contains separately packaged human fibrinogen and human thrombin.
Medical uses
This g ...
s, polyethylene glycol
Polyethylene glycol (PEG; ) is a polyether compound derived from petroleum with many applications, from industrial manufacturing to medicine. PEG is also known as polyethylene oxide (PEO) or polyoxyethylene (POE), depending on its molecular w ...
polymers, custom dental splints
* Platelet transfusions (only if bleeding is severe; risk of platelet alloimmunization
Alloimmunity (sometimes called isoimmunity) is an immune response to nonself antigens from members of the same species, which are called alloantigens or isoantigens. Two major types of alloantigens are blood group antigens and histocompatibility a ...
)
* Recombinant Recombinant may refer to:
* Recombinant organism – an organism that contains a different combination of alleles from either of its parents.
* Recombinant DNA – a form of artificial DNA sequence
* Recombinant protein - artificially produced (and ...
factor VIIa
Coagulation factor VII (, formerly known as proconvertin) is one of the proteins that causes blood to clot in the coagulation cascade, and in humans is coded for by the gene ''F7''. It is an enzyme of the serine protease class. Once bound to tiss ...
, AryoSeven
Recombinant factor VIIa also known as eptacog alfa (INN), and sold under the brand name NovoSeven among others, is a form of blood factor VII that has been manufactured via recombinant technology. It is administered intravenously (IV).
Medic ...
or NovoSeven FDA approved this drug for the treatment of the disease in July 2014.
* Hematopoietic stem cell transplantation
Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produ ...
(HSCT) for severe recurrent hemorrhages
Eponym
It is named after Eduard Glanzmann
Eduard Model Accessories is a Czech manufacturer of plastic models and finescale model accessories.
Formed in 1989 in the city of Most, Eduard began in a rented cellar as a manufacturer of photoetched brass model components. Following the succ ...
(1887-1959), the Swiss pediatrician who originally described it.
History
The subsequent studies, following Eduard Glanzmann's description of hemorrhagic symptoms and "weak platelets" demonstrated that these patients have prolonged bleeding times and their platelets failed to aggregate in response to activation. In the mid-1970s, Nurden and Caen and Phillips and colleagues discovered that thrombasthenic platelets are deficient in integrins αIIbβ3.
See also
* Platelet
Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby i ...
* Coagulation
Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanis ...
* Bernard-Soulier syndrome
References
External links
{{Cell surface receptor deficiencies
Autosomal recessive disorders
Coagulopathies
Rare diseases