Articles & Papers

One of the main goals of Glanzmann’s Research Foundation is to increase awareness of Glanzmann’s Thrombasthenia. We do this by making scientific research available to GT patients and their healthcare providers. The Foundation continues to share new research with our community as it becomes available.

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SSRI Bleeding Problems Are Real, But Rare

Published Online:26 Dec 2017

While selective serotonin reuptake inhibitors (SSRIs) remain the most commonly prescribed class of antidepressants, many physicians and patients express concerns about the risks of bleeding associated with these medications. It is thought that this risk is due to reduction in platelets’ serotonin, which impairs their role in clotting (Anglin et al. 2014). There is also evidence that SSRI use increases gastric acidity, promoting gastritis and peptic ulcers and associated gastrointestinal (GI) bleeding (Andrade and Sharma 2016).

Influence of antidepressants on hemostasis

Dialogues Clin Neurosci. 2007 Mar; 9(1): 47–59

Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), are widely used for the treatment of depression and anxious disorders. The observation that depression is an independent risk factor for cardiovascular mortality and morbidity in patients with ischemic heart disease, the assessment of the central role of serotonin in pathophysiological mechanisms of depression, and reports of cases of abnormal bleeding associated with antidepressant therapy have led to investigations of the influence of antidepressants on hemostasis markers. In this review, we summarize data regarding modifications of these markers, drawn from clinical studies and case reports. We observed an association between the type of antidepressant drug and the number of abnormal bleeding case reports, with or without modifications of hemostasis markers. Drugs with the highest degree of serotonin reuptake inhibition – fluoxetine, paroxetine, and sertraline – are more frequently associated with abnormal bleeding and modifications of hemostasis markers. The most frequent hemostatic abnormalities are decreased platelet aggregability and activity, and prolongation of bleeding time. Patients with a history of coagulation disorders, especially suspected or documented thrombocytopenia or platelet disorder, should be monitored in case of prescription of any serotonin reuptake inhibitor (SRI). Platelet dysfunction, coagulation disorder, and von Willebrand disease should be sought in any case of abnormal bleeding occurring during treatment with an SRI. Also, a non-SSRI antidepressant should be favored over an SSRI or an SRI in such a context. Considering the difficulty in performing platelet aggregation tests, which are the most sensitive in SRI-associated bleeding, and the low sensitivity of hemostasis tests when performed in case of uncomplicated bleeding in the general population, establishing guidelines for the assessment of SRI-associated bleeding complications remains a challenge.

An abnormal platelet membrane glycoprotein pattern in three cases of Glanzmann’s thrombasthenia.

British Journal of Haematology. 1974;28(2):253-260. PMID: 4473996.

Eduard Glanzmann was a Swiss pediatrician who in 1918 reported an inherited platelet functional disorder associated with a defective clot retraction. The clinical phenotype of this autosomal recessive bleeding disorder, later known as Glanzmann thrombasthenia (GT), was largely defined in the 1960s with major contributions from Jacques Caen in Paris and Marjorie Zucker in New York. My involvement in platelet research began in Oxford in 1968. Our project at that time was to define the components of the platelet “glycocalyx”, a carbohydrate-rich layer first highlighted on platelets by an electron microscopes, Olaf Behnke, in Copenhagen. I applied cytochemical techniques to identify negatively charged elements digested from this surface layer and separated by polyacrylamide gel electrophoresis (PAGE). Use of the detergent sodium dodecyl sulfate (SDS) and SDS-PAGE soon enabled the separation of the major intrinsic membrane glycoproteins (GP). Teams led by Ralph Nachman (New York) and David Phillips (Memphis) highlighted three major bands termed GPI (a sialic acid rich GP), GPII and GPIII. I continued my research in London and identified these GP in a range of mammals. However, I quickly realized that inherited platelet disorders held the key to identifying their function.

Eptacog alfa activated: a recombinant product to treat rare congenital bleeding disorders

2015 June 29

Glanzmann’s thrombasthenia (GT) and congenital factor VII deficiency (FVII CD) are rare autosomal recessive bleeding disorders: GT is the most frequent congenital platelet function disorder, and FVII CD is the most common factor-deficiency disease after haemophilia. The frequency of these disorders in the general population ranges from 1:500,000 to 1:2,000,000. Because GT and FVII CD are both rare, registries are the only approach possible to allow the collection and analysis of sufficient observational data. Recombinant activated factor VII (rFVIIa, eptacog alfa activated) is indicated for the treatment of acute bleeding episodes and for surgery coverage in patients with GT who are refractory to platelets and have antiplatelet or anti-human leukocyte antigen (HLA) antibodies, and for the prevention and treatment of bleeding in patients with FVII CD. This article summarises published data on the mechanism of action and use of rFVIIa in these disorders from two international, prospective, observational registries: the Glanzmann’s Thrombasthenia Registry (GTR) for GT; and the Seven Treatment Evaluation Registry (STER) for FVII CD. Haemostatic effectiveness rates with rFVIIa were high across all patients with GT and those with FVII CD, and treatment with rFVIIa in the GTR and STER registries was well tolerated. The GTR and the STER are the largest collections of data in GT and FVII CD, respectively, and have expanded our knowledge of the management of these two rare bleeding disorders.

Eptacog Alfa (Activated) Is Physically and Chemically Stable over 24 Hours when Administered as Bolus Injections in an Automated Infusion Pump

Published online 2019 Feb 6

Eptacog alfa (activated) is a recombinant activated factor VII (rFVIIa) used for the treatment and prevention of bleeding episodes in patients with congenital hemophilia with inhibitors. Frequent dosing requirements make the use of an automated bolus infusion pump a promising alternative to manual administration.

Description and Clinical Management of Patients With Glanzmann’s Thrombasthenia in a University Hospital, a Referral Center Specialized in Hemostasis, in Bogotá, Colombia

Published: June 04, 2022

Glanzmann’s thrombasthenia (GT) is an autosomal recessive disorder of platelets caused by a deficiency in the glycoprotein IIb-IIIa. Bleeding from the skin, mucous membranes, and ecchymosis are symptoms manifested starting in early childhood. There may also be major bleeding conditions as a result of surgical procedures or trauma. The treatment is based on platelet transfusions, antifibrinolytic agents, and recombinant activated factor VII (rFVIIa).

Glanzmann’s Thrombasthenia: How Listening to the Patient Is Sometimes the Simple Key to Good Medicine!

Case Report | Open Access Volume 2020 | Article ID 4862987

Glanzmann’s thrombasthenia is a rare clotting disorder caused by impaired platelet function. Lack of awareness of the appropriate management of rare medical conditions may lead to patient dissatisfaction and potentially poor treatment outcome. Case Report. A 78-year-old male with a history of Glanzmann’s thrombasthenia was admitted to the trauma service following a fall in which he sustained a facial laceration as well as maxillary sinus and nasal fractures. He received DDAVP 20 mcg and tranexamic acid upon presentation to the emergency department (ED). In the ED, the patient requested administration of platelet transfusion but was refused due to a normal platelet count. During the course of his hospital stay, he complained of epistaxis and was noted to have a downtrending hemoglobin from 11.0 g/dl to 9.0 g/dl. The patient and his family were not comfortable when the discharge plan was finalized and demanded platelet transfusion (due to history of needing platelets in association with injuries or procedures in the past) was refused by the primary team as they continued to state that his platelet count is normal. On hospital day 3, hematology was consulted as the patient and his family were extremely angry and hematology recommended platelet transfusion. Further clinical information was not available as the patient was transferred to another facility per family request as they wanted to be at a center which had the patient’s primary hematologist. Discussion. A delay in specialist consultation resulted in patient dissatisfaction and extended the length of stay. Patients with rare medical conditions and potential for major complications should be managed aggressively with appropriate specialist consultation to promote patient satisfaction and improve the overall quality of care. This case shows that as physicians it our duty to listen to our patient’s concerns and involve them in the medical decision-making to provide optimal patient-centered care.

Glanzmann’s Thrombasthenia: You Are Not Alone

Whether you are newly diagnosed with Glanzmann’s Thrombasthenia (GT) or have been diagnosed for some time, it is common to go through many ups and downs. We want to share information that you should know and some resources about this condition that can help you on your path to improved health and quality of life. When you are first given a new diagnosis, one as rare as GT, it is understandable to have many emotions or feel overwhelmed. The good thing is that you’re not alone. There are other people who have the same condition and lead full lives. They have had their lives enriched by becoming closer to other people who are traveling on a similar path. With the care of an experienced team, you will find support from your health care providers as well as from the vibrant and caring bleeding disorders community. You can be involved in this community and build meaningful relationships with your new extended family.

Disease Burden in Patients with Glanzmann Thrombasthenia: Perspectives from the Glanzmann Thrombasthenia Patient/Caregiver Questionnaire

Blood (2019) 134 (Supplement_1): 3456.

Glanzmann thrombasthenia (GT) is a rare bleeding disorder (~1:1,000,000) caused by impaired function of platelet glycoprotein IIb/IIIa responsible for aggregation. This novel survey was designed to identify the burden of GT through better understanding of the management of the disorder and its psychosocial impact on patients and caregivers.

Screening and Management of Bleeding Disorders in Adolescents With Heavy Menstrual Bleeding

ACOG Committee on Adolescent Health Care – Committee Opinion | Number 785 | VOL. 134, NO. 3, SEPTEMBER 2019

Heavy menstrual bleeding is defined as excessive menstrual blood loss that interferes with a woman’s physical, social, emotional, or material quality of life. If obstetrician–gynecologists suspect that a patient has a bleeding disorder, they should work in coordination with a hematologist for laboratory evaluation and medical management. Evaluation of adolescent girls who present with heavy menstrual bleeding should include assessment for anemia from blood loss, including serum ferritin, the presence of an endocrine disorder leading to anovulation, and evaluation for the presence of a bleeding disorder. Physical examination of the patient who presents with acute heavy menstrual bleeding should include assessment of hemodynamic stability, including orthostatic blood pressure and pulse measurements. The first-line approach to acute bleeding in the adolescent is medical management; surgery should be reserved for those who do not respond to medical therapy. Use of antifibrinolytics such as tranexamic acid or aminocaproic acid in oral and intravenous form may be used to stop bleeding. Nonmedical procedures should be considered when there is a lack of response to medical therapy, if the patient is clinically unstable despite initial measures, or when severe heavy bleeding warrants further investigation, such as an examination under anesthesia. After correction of acute heavy menstrual bleeding, maintenance hormonal therapy can include combined hormonal contraceptives, oral and injectable progestins, and levonorgestrel-releasing intrauterine devices. Obstetrician–gynecologists can provide important guidance to premenarchal and postmenarchal girls and their families about issues related to menses and should counsel all adolescent patients with a bleeding disorder about safe medication use and future surgical considerations.

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