Simone A Brysland, Dipti Talaulikar, Sarah M Hicks, James I Hearn, Sidra Asad Ali, Muhammad Gohar Maqbool, Mridula Mokoonlall, Vijay Bhoopalan, Amandeep Kaur, Yee Lin Thong, Robert K Andrews, James C Whisstock, Philip J Crispin, Elizabeth E Gardiner
{"title":"瓦尔登斯特伦巨球蛋白血症淋巴瘤患者的血小板和凝血功能受损。","authors":"Simone A Brysland, Dipti Talaulikar, Sarah M Hicks, James I Hearn, Sidra Asad Ali, Muhammad Gohar Maqbool, Mridula Mokoonlall, Vijay Bhoopalan, Amandeep Kaur, Yee Lin Thong, Robert K Andrews, James C Whisstock, Philip J Crispin, Elizabeth E Gardiner","doi":"10.1182/bloodadvances.2024014190","DOIUrl":null,"url":null,"abstract":"<p><p>Clinical features in patients with the B-cell lymphoma, Waldenström Macroglobulinaemia (WM), include cytopenias, IgM-mediated hyperviscosity, fatigue, bleeding and bruising. Therapeutics such as Bruton's tyrosine kinase inhibitors (BTKis) exacerbate bleeding risk. Abnormal haemostasis arising from platelet dysfunction, altered coagulation or vascular impairment have not been investigated in WM patients. To evaluate haemostatic dysfunction in samples from WM patients. Whole blood (WB) samples were collected from 14 WM patients not receiving therapy, 5 patients receiving BTKis and 15 healthy donors (HDs). Platelet receptor levels and reticulation were measured by flow cytometry, plasma thrombin generation ± platelets by FRET assay, WB clotting potential by rotational thromboelastometry (ROTEM), and plasma soluble glycoprotein VI (sGPVI) and serum thrombopoietin (TPO) by ELISA. Donor platelet spreading, aggregation and ability to accelerate thrombin generation in the presence of WM-derived IgM were assessed. WM platelet receptor levels, responses to physiological agonists and plasma sGPVI were within normal ranges. WM platelets had reduced reticulation (p=0.0012) while serum TPO levels were increased (p=0.0040). WM plasma displayed slower thrombin generation (p=0.0080) and WM platelets contributed less to endogenous thrombin potential (ETP, p=0.0312). HD plasma or platelets incubated with IgM (50-60 mg/mL) displayed reduced spreading (p=0.0002), aggregation (p<0.0001) and ETP (p=0.0081). Alterations to thrombin potential and WB coagulation were detected in WM samples. WM IgM significantly impaired haemostasis in vitro. Platelet and coagulation properties are disturbed in well-managed WM patients.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":null,"pages":null},"PeriodicalIF":7.4000,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Waldenström Macroglobulinaemia lymphoma patients have impaired platelet and coagulation function.\",\"authors\":\"Simone A Brysland, Dipti Talaulikar, Sarah M Hicks, James I Hearn, Sidra Asad Ali, Muhammad Gohar Maqbool, Mridula Mokoonlall, Vijay Bhoopalan, Amandeep Kaur, Yee Lin Thong, Robert K Andrews, James C Whisstock, Philip J Crispin, Elizabeth E Gardiner\",\"doi\":\"10.1182/bloodadvances.2024014190\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Clinical features in patients with the B-cell lymphoma, Waldenström Macroglobulinaemia (WM), include cytopenias, IgM-mediated hyperviscosity, fatigue, bleeding and bruising. Therapeutics such as Bruton's tyrosine kinase inhibitors (BTKis) exacerbate bleeding risk. Abnormal haemostasis arising from platelet dysfunction, altered coagulation or vascular impairment have not been investigated in WM patients. To evaluate haemostatic dysfunction in samples from WM patients. Whole blood (WB) samples were collected from 14 WM patients not receiving therapy, 5 patients receiving BTKis and 15 healthy donors (HDs). Platelet receptor levels and reticulation were measured by flow cytometry, plasma thrombin generation ± platelets by FRET assay, WB clotting potential by rotational thromboelastometry (ROTEM), and plasma soluble glycoprotein VI (sGPVI) and serum thrombopoietin (TPO) by ELISA. Donor platelet spreading, aggregation and ability to accelerate thrombin generation in the presence of WM-derived IgM were assessed. WM platelet receptor levels, responses to physiological agonists and plasma sGPVI were within normal ranges. WM platelets had reduced reticulation (p=0.0012) while serum TPO levels were increased (p=0.0040). WM plasma displayed slower thrombin generation (p=0.0080) and WM platelets contributed less to endogenous thrombin potential (ETP, p=0.0312). HD plasma or platelets incubated with IgM (50-60 mg/mL) displayed reduced spreading (p=0.0002), aggregation (p<0.0001) and ETP (p=0.0081). Alterations to thrombin potential and WB coagulation were detected in WM samples. WM IgM significantly impaired haemostasis in vitro. 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Waldenström Macroglobulinaemia lymphoma patients have impaired platelet and coagulation function.
Clinical features in patients with the B-cell lymphoma, Waldenström Macroglobulinaemia (WM), include cytopenias, IgM-mediated hyperviscosity, fatigue, bleeding and bruising. Therapeutics such as Bruton's tyrosine kinase inhibitors (BTKis) exacerbate bleeding risk. Abnormal haemostasis arising from platelet dysfunction, altered coagulation or vascular impairment have not been investigated in WM patients. To evaluate haemostatic dysfunction in samples from WM patients. Whole blood (WB) samples were collected from 14 WM patients not receiving therapy, 5 patients receiving BTKis and 15 healthy donors (HDs). Platelet receptor levels and reticulation were measured by flow cytometry, plasma thrombin generation ± platelets by FRET assay, WB clotting potential by rotational thromboelastometry (ROTEM), and plasma soluble glycoprotein VI (sGPVI) and serum thrombopoietin (TPO) by ELISA. Donor platelet spreading, aggregation and ability to accelerate thrombin generation in the presence of WM-derived IgM were assessed. WM platelet receptor levels, responses to physiological agonists and plasma sGPVI were within normal ranges. WM platelets had reduced reticulation (p=0.0012) while serum TPO levels were increased (p=0.0040). WM plasma displayed slower thrombin generation (p=0.0080) and WM platelets contributed less to endogenous thrombin potential (ETP, p=0.0312). HD plasma or platelets incubated with IgM (50-60 mg/mL) displayed reduced spreading (p=0.0002), aggregation (p<0.0001) and ETP (p=0.0081). Alterations to thrombin potential and WB coagulation were detected in WM samples. WM IgM significantly impaired haemostasis in vitro. Platelet and coagulation properties are disturbed in well-managed WM patients.
期刊介绍:
Blood Advances, a semimonthly medical journal published by the American Society of Hematology, marks the first addition to the Blood family in 70 years. This peer-reviewed, online-only, open-access journal was launched under the leadership of founding editor-in-chief Robert Negrin, MD, from Stanford University Medical Center in Stanford, CA, with its inaugural issue released on November 29, 2016.
Blood Advances serves as an international platform for original articles detailing basic laboratory, translational, and clinical investigations in hematology. The journal comprehensively covers all aspects of hematology, including disorders of leukocytes (both benign and malignant), erythrocytes, platelets, hemostatic mechanisms, vascular biology, immunology, and hematologic oncology. Each article undergoes a rigorous peer-review process, with selection based on the originality of the findings, the high quality of the work presented, and the clarity of the presentation.