Acquired Glanzmann thrombasthenia: From antibodies to anti-platelet drugs

Nurden, Alan T.

doi:10.1016/j.blre.2019.03.004

Cited by 20 publications

(28 citation statements)

References 174 publications

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“…Acquired GT is found in some unusual ITP patients and can cause hemorrhagic complications, despite normal platelet count . Other frequently associated underlying disorders include lymphoproliferative diseases and Evans syndrome . Treatment for acquired GT, as for ITP, needs to be individualized.…”

Section: Resultsmentioning

confidence: 99%

“…Patients’ response may range from spontaneous remission to death as a result of devastating bleeding . Therefore, recognizing such condition, which can be difficult when masked by thrombocytopenia, is of clinical importance . The utility of platelet function testing, together with specialized platelet antibody assays, are vital for diagnosis.…”

Section: Resultsmentioning

confidence: 99%

“…23,24 Other frequently associated underlying disorders include lymphoproliferative diseases and Evans syndrome. 4,5,23,24 Treatment for acquired GT, as for ITP, needs to be individualized.…”

Section: Re Sults and Discussionmentioning

confidence: 99%

“…The severity generally correlates with the degree of thrombocytopenia and patient's age . Notable exceptions exist if patient's antiplatelet autoantibodies have inhibitory functional effects on fibrinogen‐integrin α IIb β 3 or von Willebrand factor‐glycoprotein (GP) Ib interaction, causing moderate to severe bleeding phenotype, irrespective to the platelet counts, from acquired Glanzmann thrombasthenia (GT) or acquired Bernard‐Soulier syndrome, respectively …”

Section: Introductionmentioning

confidence: 99%

“…3 Notable exceptions exist if patient's antiplatelet autoantibodies have inhibitory functional effects on fibrinogen-integrin α IIb β 3 or von Willebrand factor-glycoprotein (GP) Ib interaction, causing moderate to severe bleeding phenotype, irrespective to the platelet counts, from acquired Glanzmann thrombasthenia (GT) or acquired Bernard-Soulier syndrome, respectively. 4,5 Several pathways have been postulated in the pathogenesis of ITP, including autoantibodies against platelet membrane GP complexes, 6 B-cell clonality, 7 T regulatory cell dysfunction 8 , and T lymphocyte-mediated cytotoxicity. 9 More recently, anti-GPIbα 10 and CD8 + T-cell mediated platelet desialylation 11 has been implicated in ITP.…”

Section: Introductionmentioning

confidence: 99%

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Acquired Glanzmann thrombasthenia associated with platelet desialylation

Zheng

Perdomo

Leung

et al. 2020

Journal of Thrombosis and Haemostasis

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Background The notable discrepancy between platelet count and bleeding manifestations in immune thrombocytopenia (ITP) patients with acquired Glanzmann thrombasthenia (GT) has been described. Objectives We aimed to examine the mechanisms responsible for thrombocytopenia and the bleeding phenotype in a patient with acquired GT. Patient, methods, and results A patient with primary ITP underwent splenectomy due to steroid intolerance. Despite platelet count normalization, bleeding continued. Platelet aggregometry was abnormal with all agonists except for ristocetin. Flow cytometry demonstrated the presence of antiplatelet antibody, which caused dose‐dependent inhibition of fibrinogen and PAC‐1 binding, induction of neuraminidase‐1 expression as well as platelet desialylation in donor platelets. Indirect monoclonal antibody immobilization of platelet specific antigen assay (MAIPA) confirmed specificity to αIIbβ3 only, corroborated by binding on Chinese hamster ovary (CHO) cells expressing human glycoprotein αIIbβ3 but not GP Ib/IX. Both desialylation and neuraminidase expression were observed with plasma adsorbed on Ib/IX CHO cells and with the immunoglobulin G (IgG) fraction. Desialylation was inhibited in the presence of anti‐Fc‐gamma receptor IIa (FcγRIIa) antibody. A nonobese diabetic/severe combined immunodeficient ITP murine model was established, which showed rapid hepatic donor platelet clearance in the presence of patient IgG. Treatment of mice with the neuraminidase inhibitor oseltamivir significantly reduced antibody‐induced platelet destruction. Conclusions We report the first case of a patient with acquired GT due to ITP with FcγRIIa mediated platelet desialylation, independent of platelet activation. Treatment with neuraminidase inhibitor may prevent platelet clearance by anti‐αIIbβ3 antibodies.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Re Sults and Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Acquired Glanzmann thrombasthenia associated with platelet desialylation

Zheng

Perdomo

Leung

et al. 2020

Journal of Thrombosis and Haemostasis

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Bleeding and Clotting Disorders

Napeñas¹,

Patton²

2021

Burket's Oral Medicine

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Dental health care workers are increasingly called upon to provide quality dental care to individuals whose bleeding and clotting mechanisms have been altered by inherited or acquired diseases. This provides an opportunity for the dentist who is trained in the recognition of oral and systemic signs of altered hemostasis to assist in the diagnosis of the underlying condition. A number of dental procedures result in the risk of bleeding that can have serious consequences, such as severe hemorrhage or possibly death, for the patient with a bleeding disorder. Safe dental care may require consultation with the patient's physician, systemic management, and dental treatment modifications.Of the inherited coagulopathies, von Willebrand's disease (vWD) is the most common. It results from deficiency of von Willebrand's factor (vWF) and affects about 0.8 to 1% of the population. 1 Hemophilia A, caused by coagulation factor (F) VIII deficiency, is the next most common, followed by hemophilia B, a F IX deficiency. The age-adjusted prevalence of hemophilia in six surveillance states in 1994 was 13.4 cases in 100,000 males (10.5 for hemophilia A and 2.9 for hemophilia B). 2 Application to the US population resulted in an estimated national prevalence of 13,320 cases of hemophilia A and 3,640 cases of hemophilia B, with an incidence rate of 1 per 5,032 live male births. Hemophilia A was predominant, accounting for 79% of all hemophiliacs, and prevalence of disease severity was 43% severe (< 1% F VIII), 26% moderate (1-5% F VIII), and 31% with mild (6-30% F VIII) disease. 2 Acquired coagulation disorders can result from drug actions or side effects, or underlying systemic disease. A stratified household sample of 4,163 community residents aged 65 years or older living in a five-county area of North Carolina revealed 51.7% to be taking one or more medications (aspirin, warfarin, dipyridamole, nonsteroidal anti-inflammatory drugs

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Acquired Glanzmann thrombasthenia: a rare disorder

et al. 2020

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Qualitative platelet function defects may be congenital, e.g., Glanzmann thrombasthenia, or acquired. Acquired platelet function disorders are more common than reported. Glanzmann thrombasthenia, an inherited platelet function disorder, is caused by mutations in the ITGA2B and ITGB3 genes encoding the αIIbβ3 integrin. An acquired form of GT is also seen, which is caused by antibodies to platelet integrin αIIbβ3. This affects fibrinogen binding and blocks platelet aggregation. These patients have low platelet count with a moderate-to-severe bleeding tendency, while some patients may have normal platelet counts. It is commonly found in association with autoimmune disorders, hematological malignancies, and infections. Glanzmann thrombasthenia-like state can also be seen in immune thrombocytopenic purpura (ITP) due to presence of antibodies to αIIbβ3. These patients present with severe bleeding even with mild thrombocytopenia. We describe a patient of ITP with borderline low platelet count and severe bleeding, who posed a diagnostic challenge. However, an accurate diagnosis and suitable management helped to avoid catastrophic bleeding.

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Acquired Glanzmann thrombasthenia: From antibodies to anti-platelet drugs

Cited by 20 publications

References 174 publications

Acquired Glanzmann thrombasthenia associated with platelet desialylation

Acquired Glanzmann thrombasthenia associated with platelet desialylation

Bleeding and Clotting Disorders

Acquired Glanzmann thrombasthenia: a rare disorder

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