Reversal of Glanzmann thrombasthenia platelet phenotype after imatinib treatment in a pediatric chronic myeloid leukemia patient

Chauhan, Richa; Sazawal, Sudha; Singh, Kanwaljeet; Nair, Rathish; Chhikara, Sunita; Deka, Roopam; Chaubey, Rekha; Veetil, Karthika Kundil; Dange, Prasad; Mahapatra, Manoranjan; Saxena, Renu

doi:10.1080/09537104.2017.1384539

Cited by 6 publications

(5 citation statements)

References 11 publications

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“…Several mechanisms of projecting GT phenotype in CML, such as defects in a signaling pathway vital for α IIb β 3 activation [5], defects in activation-dependent inside-out signaling [6], dysfunction in the phosphatidylinositol-3 kinase (PI3 kinase)/Rap1/ α IIb β 3 pathway [7], poor platelet aggregation attributed to dysregulated tyrosine kinase activity associated with BCR-ABL [8], and reduced α IIb β 3 on platelets [9] have been described. In CML, the platelet dysfunction is believed to have originated from a clonal expansion of dysfunctional megakaryocytes.…”

Section: Discussionmentioning

confidence: 99%

“…Although bleeding diathesis attributed to defective platelet function is not uncommon in CML, typical GT (e.g., a defect in platelet aggregation) has not been reported earlier in adult CML. A singular case was reported in the literature by Chauhan et al of pediatric CML associated with a GT-like defect [9] due to dysfunctional circulating platelets.…”

Section: Discussionmentioning

confidence: 99%

“…The concordance of hematoma formation with signs and symptoms of MPN suggests bleeding secondary to MPN. Moreover, basic coagulation profile, platelet aggregation studies, and autoantibodies to platelet glycoprotein are recommended to identify the cause of bleeding in CML patients [9]. Successful treatment of underlying CML reduces the risk of life-threatening bleeding diathesis.…”

Section: Discussionmentioning

confidence: 99%

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An Unusual Cause of Bleeding in a Patient with Chronic Myeloid Leukemia Chronic Phase

Kartthik

Mandal

Abdullah

2019

Case Reports in Hematology

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Chronic myelogenous leukemia (CML) is a clonal myeloproliferative neoplasm (MPN) characterized by dysregulated and uncontrolled proliferation of mature and maturing granulocytes with normal differentiation. A genetic hallmark of CML is the presence of the fusion gene product BCR-ABL. Bleeding diathesis in CML patients is rare (<10%) and primarily caused by acquired platelet dysfunction. We report a rare case of an adult CML chronic phase patient who presented with spontaneous muscle hematoma due to acquired Glanzmann’s thrombasthenia (GT). On laboratory workup, a GT was confirmed along with the diagnosis of CML in chronic phase. The muscle hematoma was completely resolved following imatinib therapy. The present case demonstrates that bleeding is a complication of MPNs and highlights the importance of both acquired GT diagnosis to determine the cause of bleeding in CML and of prompt treatment with imatinib to reverse this condition.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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An Unusual Cause of Bleeding in a Patient with Chronic Myeloid Leukemia Chronic Phase

Kartthik

Mandal

Abdullah

2019

Case Reports in Hematology

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“…Bleeding is caused by a reduced plasma concentration of large Von Willebrand (VW) factor multimers, indicating a diagnosis of acquired VW-syndrome, which resolves after initiation of CML treatment. Platelet function abnormalities like Glanzmann thrombasthenia in CML at diagnosis have also been described in the literature [82].…”

Section: Clinical Features and Hematological Findingsmentioning

confidence: 87%

Definition, Epidemiology, Pathophysiology, and Essential Criteria for Diagnosis of Pediatric Chronic Myeloid Leukemia

Suttorp

Millot

Sembill

et al. 2021

Cancers

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Depending on the analytical tool applied, the hallmarks of chronic myeloid leukemia (CML) are the Philadelphia Chromosome and the resulting mRNA fusion transcript BCR-ABL1. With an incidence of 1 per 1 million of children this malignancy is very rare in the first 20 years of life. This article aims to; (i) define the disease based on the WHO nomenclature, the appropriate ICD 11 code and to unify the terminology, (ii) delineate features of epidemiology, etiology, and pathophysiology that are shared, but also differing between adult and pediatric patients with CML, iii) give a short summary on the diseases to be considered as a differential diagnosis of pediatric CML, (iv) to describe the morphological, histopathological and immunophenotypical findings of CML in pediatric patients, (v) illustrate rare but classical complications resulting from rheological problems observed at diagnosis, (vi) list essential and desirable diagnostic criteria, which hopefully in the future will help to unify the attempts when approaching this rare pediatric malignancy.

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“…Acquired Glanzmann thrombasthenia is usually associated with anti‐αIIbβ3 autoAbs concomitant with autoimmune diseases or lymphoproliferative disorders, although an exceptional case with leukemia has been reported . We reviewed 33 aGT cases reported in the literature so far and summarized the reported status of anti‐αIIbβ3 Abs and αIIbβ3 expression (Table ).…”

Section: Discussionmentioning

confidence: 99%

A unique phenotype of acquired Glanzmann thrombasthenia due to non‐function‐blocking anti‐αIIbβ3 autoantibodies

Akuta

Kashiwagi

Yujiri

et al. 2019

Journal of Thrombosis and Haemostasis

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Acquired Glanzmann thrombasthenia (aGT) is generally caused by function‐blocking antibodies (Abs). We demonstrated a unique aGT case due to marked reduction of αIIbβ3 with anti‐αIIbβ3 Abs. The anti‐αIIbβ3 Abs of the patient did not inhibit platelet function but reduced surface αIIbβ3. Internalization of αIIbβ3 induced by the Abs binding may be responsible for the phenotype. Summary BackgroundAcquired Glanzmann thrombasthenia (aGT) is a bleeding disorder generally caused by function‐blocking anti‐αIIbβ3 autoantibodies. AimWe characterize an unusual case of aGT caused by marked reduction of surface αIIbβ3 with non‐function‐blocking anti‐αIIbβ3 antibodies (Abs). MethodsA 72‐year‐old male suffering from immune thrombocytopenia since his 50s showed exacerbation of bleeding symptom despite mild thrombocytopenia. Platelet aggregation was absent with all agonists but ristocetin. Analysis of αIIbβ3 expression and genetic analysis were performed. We also analyzed effects of anti‐αIIbβ3 Abs of the patient on platelet function and αIIbβ3 expression. ResultsSurface αIIbβ3 expression was markedly reduced to around 5% of normal, whereas his platelets contained αIIbβ3 to the amount of 40–50% of normal. A substantial amount of fibrinogen was also detected in his platelets. There were no abnormalities in ITGA2B and ITGB3 cDNA. These results indicated that reduced surface αIIbβ3 expression caused a GT phenotype, and active internalization of αIIbβ3 was suggested. Anti‐αIIbβ3 IgG Abs were detected in platelet eluate and plasma. These Abs did not inhibit PAC‐1 binding, indicating that the Abs were non‐function‐blocking. Surface αIIbβ3 expression of a megakaryocytic cell line and cultured megakaryocytes tended to be impaired by incubation with the patient's Abs. After 2 years of aGT diagnosis, his bleeding symptom improved and surface αIIbβ3 expression was recovered to 20% of normal with reduction of anti‐αIIbβ3 Abs. ConclusionWe demonstrated a unique aGT phenotype due to marked reduction of surface αIIbβ3. Internalization induced by anti‐αIIbβ3 Abs may be responsible in part for the phenotype.

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Reversal of Glanzmann thrombasthenia platelet phenotype after imatinib treatment in a pediatric chronic myeloid leukemia patient

Cited by 6 publications

References 11 publications

An Unusual Cause of Bleeding in a Patient with Chronic Myeloid Leukemia Chronic Phase

An Unusual Cause of Bleeding in a Patient with Chronic Myeloid Leukemia Chronic Phase

Definition, Epidemiology, Pathophysiology, and Essential Criteria for Diagnosis of Pediatric Chronic Myeloid Leukemia

A unique phenotype of acquired Glanzmann thrombasthenia due to non‐function‐blocking anti‐αIIbβ3 autoantibodies

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