Waldenström Macroglobulinaemia lymphoma patients have impaired platelet and coagulation function.

Abstract

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.