A pathological condition of mind glanzmann body: As for all medicines, data on the use of NovoSeven are continuously monitored. International non-proprietary name INN or common name. Chrigel Glanzmann Although access to this website is not restricted, the glznzmann found here is intended for use by medical providers. Related Topics in Platelet Disorders. Content is updated monthly with systematic literature reviews and conferences.
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Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. This article has been cited by other articles in PMC. Spontaneous mucocutaneous bleeding is common and can lead to fatal bleeding episodes.
Control and prevention of bleeding among patients with GT is imperative, and remains challenging. Local measures, including anti-fibrinolytic therapy, with or without platelet transfusions, used to be the mainstay of therapy. However, in recent years the use of recombinant factor VIIa rFVIIa has increased significantly, with excellent response rates in treating and preventing hemorrhage among GT patients.
Gene therapy and stem cell transplantation offer a potential cure of this disease, but both are costly and remain experimental at this point. This manuscript offers a comprehensive review of our understanding of GT and the available treatment options.
Keywords: Glanzmann, thrombasthenia, treatment Introduction Platelets are a central component of many restorative physiological processes, including hemostasis. During hemostasis, damaged subendothelium releases adhesive proteins ie, collagen and thromboplastin and fibrinogen, which bind with aggregated platelets at the site of injury, forming a platelet plug. Platelets then provide a surface and phospholipid source for attachment of coagulation cofactors. Subsequent activation of the coagulation pathways prompts fibrin attachment to activated platelets, creating a thrombus.
Any disruption in platelet function, whether acquired or inherited, will generate bleeding. Acquired platelet disorders are more likely to be encountered in clinical practice than their inherited counterpart, and often result from the initiation of medications or underlying medical conditions. In contrast, inherited platelet disorders are rare, and until recently, have been under less scrutiny. Eduard Glanzmann was a Swiss pediatrician who first discovered the condition of thrombasthenia in Noting a familial pattern and symptoms manifesting in children, he considered a possible hereditary component.
The disease also served as a template for understanding processes of platelet aggregation as well as targets for therapeutic measures. These subunits are non-covalently linked, allowing for duplex signaling between the cell membrane and extracellular matrix, while instituting intracellular signaling pathways. Missense mutations have been further studied, and display interruption in integrin maturation or subunit formation.
Phedel, and ITGB3 p. Early work by George et al failed to correlate the subtype of GT with severity of bleeding. According to one study, the disease has a high prevalence among the French Gypsy Manouche community, with approximately cases of in France from that origin. The inflated number among these population groups illustrates a founder effect.
The majority of patients will be diagnosed before the age of 5, with recurring episodes of epistaxis and gingival bleeding being among the most common manifestations.
The most common cause of epistaxis in any child is digital manipulation; however, in patients with GT, severe bleeding can occur in this highly vascularized area, which can be fatal. While fatal bleeding episodes can occur at any point in the lifespan of a patient with GT, the prevalence of severe bleeding does decrease with age. Excessive bleeding during circumcision has been noted, and is often the reason for investigation and diagnosis of GT in males.
In some cases, women have not been diagnosed until menarche, when severe blood loss due to menorrhagia has required transfusion, as reported in a study by George et al. Labor and delivery is of special concern, as women are at increased risk for severe or fatal hemorrhage during this time.
One must remember to include GT in the differential diagnosis, carefully analyzing the medical history eg, asking about unprovoked bruising or bleeding episodes, or episodes of severe bleeding after minor trauma , family history eg, inquiring about possible consanguinity , and clinical presentation eg, examining for purpura and ecchymoses.
When considering a diagnosis of GT, selecting the appropriate laboratory evaluation is essential. For example, a normal platelet count on a routine blood smear does not rule out a diagnosis of GT, as patients with GT usually show no abnormalities in the platelet count. The complete blood count may be entirely normal, or may reveal iron deficiency. The prothrombin time and activated partial thromboplastin time will also be normal.
However, the bleeding time will be prolonged, which warrants further investigation. Light transmission aggregometry LTA is widely accepted as the gold standard diagnostic tool for assessing platelet function. Centrifuged platelet-rich plasma samples are monitored before and after the addition of an agonist ADP, collagen, epinephrine, arachidonic acid, ristocetin, thrombin receptor activating peptide, and thromboxane A2 mimetic , assessing shape change, lag phase, percent of aggregation, slope of aggregation, and deaggregation.
This test is highly specific for GT, as platelet aggregation fails to occur with any agonist, except ristocetin, where the reaction is preserved. Although this test yields specific data, LTA is very time consuming and personnel dependent, requiring the use of experienced laboratories.
It is also more difficult to obtain platelet-rich plasma in patients with thrombocytopenia and in pediatric patients under the testing guidelines. As citrated whole blood flows at a high shear stress rate through these cartridges, platelets bind, creating a platelet plug.
Overall, the diagnosis of GT includes the presence of normal platelet count typically on the lower end of normal , prolonged bleeding time, and prolonged PFA time. Platelets fail to aggregate under the conditions utilized in LTA, which is uniquely indicative of GT.
Treatment All patients with GT require management by a specialist, and should be registered with a hour center capable of handling diagnosis and treatment. Patient education As patients will likely receive transfusions of blood products at least once in their lifetime, all patients should receive immunization against hepatitis B. Patients should also be advised to avoid contact sports as well as the use of aspirin and non-steroidal anti-inflammatory drugs. Women in particular, due to the consequences of menorrhagia, need monitoring for iron deficiency, and should be placed on iron supplementation if necessary.
General treatment concepts The current standard of treatment of bleeding episodes in patients with GT is the use of local measures alone or in conjunction with anti-fibrinolytic therapy first, followed by platelet transfusion, and rFVIIa if bleeding persists. If HLA-matched platelets are not available, patients should receive leukocyte-reduced platelets, as this has been shown to reduce the rate of HLA immunization.
Patients with severe bleeding episodes should continue to receive platelet transfusions for 48 hours after the cessation of bleeding, and until wound healing has occurred in patients undergoing surgery. The PFA assay time will normalize with adequate transfusions. Anti-fibrinolytic drugs work particularly well for mucocutaneous bleeding, and have been shown to successfully decrease bleeding during dental procedures, in combination with local measures.
Local measures include compression, gelatin sponges, fibrin sealants, and topical thrombin. These agents, used alone or as adjunctive therapy with rFVIIa, have proven to be useful and safe agents in minimizing or resolving bleeding in patients with GT in multiple settings. As both agents can be given orally or intravenously, they have been used successfully for the treatment of epistaxis, gingival bleeding, and menorrhagia, and also as prophylaxis prior to dental extractions and other minor surgical procedures.
The use of anti-fibrinolytics in cases of hematuria should be avoided due to the risk of clots in the urinary tract, and should be used with caution in patients undergoing procedures carrying a high risk of thrombosis.
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