Waldenström Macroglobulinaemia (WM) is a B-cell lymphoma with clinical features including thrombocytopenia, IgM-mediated hyperviscosity, bleeding and bruising. Treatment of WM patients with Bruton’s tyrosine kinase inhibitors (BTKis) may exacerbate bleeding risk. Abnormal haemostasis may result from platelet dysfunction and altered coagulation, however the extent of dysregulation of these processes in WM patients is unknown.

 

To evaluate haemostatic and platelet dysfunction in WM patients. 

 

Platelet receptor levels in samples from 19 clinically annotated WM patients or healthy donors (HDs) were measured by flow cytometry. Thrombin generation in plasma ± platelets was measured by fluorescence resonance energy transfer assay. Whole blood clotting potential was evaluated by rotational thromboelastometry (ROTEM). Levels of plasma soluble GPVI (sGPVI) and serum thrombopoietin (TPO) were measured by enzyme-linked immunosorbent assays. 

 

WM platelets had reduced levels of GPIbα (p=0.0153), GPVI (p=0.0347) and reticulation (p=0.0005), and increased overall sialylation (p=0.0079) and tetraspanin CD9 levels (p<0.0001). WM plasma displayed significantly reduced thrombin generation potential (p=0.0408) and WM platelets contributed less to thrombus initiation (p=0.0208) and rate (p<0.0001) by ROTEM, but displayed normal responses to agonists, except in the presence of BTKis. Plasma sGPVI were within normal ranges and TPO levels were increased (p<0.0001).

 

The impaired haemostatic potential in WM samples was independent of BTKi therapy. Reduced platelet GPIbα and GPVI may arise from altered megakaryocyte maturation and thrombopoiesis, associated with bone marrow malignancy. Monitoring platelet and coagulation properties may help stratify WM patients for bleeding risk.


Simone A Brysland, Philip J Crispin, Dipti Talaulikar, Elizabeth E Gardiner
 
 

1.     Department of Cancer Biology and Therapeutics, John Curtin School of Medical Research, The Australian National University, Canberra, 2601, ACT. 

Department of Haematology, Canberra Health Services, Garran, ACT 2605