Low Concentrations of Recombinant Factor VIIa May Improve the Impaired Thrombin Generation of Glanzmann Thrombasthenia Patients

Levy‐Mendelovich, Sarina; Levy, Tamara; Budnik, Ivan; Barg, Assaf Arie; Rosenberg, Nurit; Seligsohn, Uri; Kenet, Gili; Livnat, Tami

doi:10.1055/s-0038-1676348

Cited by 12 publications

(9 citation statements)

References 45 publications

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“…While the use of platelets have remained standard for both treatment of bleeding and prophylaxis, the use of factor VII either in isolation or in combination with other agents has been shown to be equally efficacious [ 9 , 13 ]. It is especially effective in cases with platelet refractoriness such as in the presence of platelet antibodies [ 5 , 14 ].…”

Section: Discussionmentioning

confidence: 99%

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

Jayakrishnan

Limonnik

Shah

et al. 2020

Case Reports in Medicine

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Introduction. 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.

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Section: Discussionmentioning

confidence: 99%

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

Jayakrishnan

Limonnik

Shah

et al. 2020

Case Reports in Medicine

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“…Although platelets from these patients have impaired aggregation, they are still able to adhere and likely provide some surface for coagulation factor complex formation. Therefore, rFVIIa may function by enhancing platelet surface thrombin generation in vivo (44). Moreover, RASGRP2 mutant platelets typically have normal or only minimally reduced response to thrombin (11,13) and therefore may benefit from increased thrombin generation not only due to fibrin formation (45) but also via thrombin receptor signaling.…”

Section: Discussionmentioning

confidence: 99%

Impaired hemostatic activity of healthy transfused platelets in inherited and acquired platelet disorders: Mechanisms and implications

et al. 2019

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Platelet transfusions can fail to prevent bleeding in patients with inherited platelet function disorders (IPDs), such as Glanzmann’s thrombasthenia (GT; integrin αIIbβ3 dysfunction), Bernard-Soulier syndrome [BSS; glycoprotein (GP) Ib/V/IX dysfunction], and the more recently identified nonsyndromic RASGRP2 variants. Here, we used IPD mouse models and real-time imaging of hemostatic plug formation to investigate whether dysfunctional platelets impair the hemostatic function of healthy donor [wild-type (WT)] platelets. In Rasgrp2−/− mice or mice with platelet-specific deficiency in the integrin adaptor protein TALIN1 (“GT-like”), WT platelet transfusion was ineffective unless the ratio between mutant and WT platelets was ~2:1. In contrast, thrombocytopenic mice or mice lacking the extracellular domain of GPIbα (“BSS-like”) required very few transfused WT platelets to normalize hemostasis. Both Rasgrp2−/− and GT-like, but not BSS-like, platelets effectively localized to the injury site. Mechanistic studies identified at least two mechanisms of interference by dysfunctional platelets in IPDs: (i) delayed adhesion of WT donor platelets due to reduced access to GPIbα ligands exposed at sites of vascular injury and (ii) impaired consolidation of the hemostatic plug. We also investigated the hemostatic activity of transfused platelets in the setting of dual antiplatelet therapy (DAPT), an acquired platelet function disorder (APD). “DAPT” platelets did not prolong the time to initial hemostasis, but plugs were unstable and frequent rebleeding was observed. Thus, we propose that the endogenous platelet count and the ratio of transfused versus endogenous platelets should be considered when treating select IPD and APD patients with platelet transfusions.

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“…FEIBA is a drug accomplished from plasma, containing a mixture of activated and non-activated FX, FIX, FVII, and prothrombin (139). Recombinant factor VIIa (rFVIIa), known as eptacog alfa (Novo-Seven ® ) is indicated for bleeding episodes and peri-operative management of HA or HB with inhibitors, congenital Factor VII (FVII) deficiency, and Glanzmann's thrombasthenia refractory to platelet transfusions, with or without antibodies to platelets and for the treatment of bleeding episodes and peri-operative management in adults with acquired hemophilia (140,141). The understanding of the coagulation cascade explains why no bypass agent can generate hemostasis as efficiently as substitute therapy with factor VIII and factor IX.…”

Section: Bypass Agentsmentioning

confidence: 99%

Current therapeutic approaches in the management of hemophilia—a consensus view by the Romanian Society of Hematology

et al. 2021

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Hemophilia A (HA) and hemophilia B (HB) are rare disorders, being caused by the total lack or under-expression of two factors from the coagulation cascade coded by genes of the X chromosome. Thus, in hemophilic patients, the blood does not clot properly. This results in spontaneous bleeding episodes after an injury or surgical intervention. A patient-centered regimen is considered optimal. Age, pharmacokinetics, bleeding phenotype, joint status, adherence, physical activity, personal goals are all factors that should be considered when individualizing therapy. In the past 10 years, many innovations in the diagnostic and treatment options were presented as being either approved or in development, thus helping clinicians to improve the standard-of-care for patients with hemophilia. Recombinant factors still remain the standard of care in hemophilia, however they pose a challenge to treatment adherence because they have short halflife, which where the extended half-life (EHL) factors come with the solution, increasing the half-life to 96 hours. Gene therapies have a promising future with proven beneficial effects in clinical trials. We present and critically analyze in the current manuscript the pros and cons of all the major discoveries in the diagnosis and treatment of HA and HB, as well as identify key areas of hemophilia research where improvements are needed.

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Low Concentrations of Recombinant Factor VIIa May Improve the Impaired Thrombin Generation of Glanzmann Thrombasthenia Patients

Cited by 12 publications

References 45 publications

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

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

Impaired hemostatic activity of healthy transfused platelets in inherited and acquired platelet disorders: Mechanisms and implications

Current therapeutic approaches in the management of hemophilia—a consensus view by the Romanian Society of Hematology

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