PB0750 - Changes to platelet quality and function in Waldenstrӧm Macroglobulinaemia

Background: Platelet glycoprotein (GP) receptors are essential for initiating platelet adhesion, activation and aggregation. Reduced levels can occur when thrombopoiesis is disturbed, or coincident with bleeding in patients with thrombocytopenia, trauma or haematological malignancies. Both GPVI and GPIbα are metalloproteolytically shed from activated or aged platelets. Waldenström Macroglobulinaemia (WM) is a B-cell lymphoma with common symptoms including bleeding/bruising and thrombocytopenia. WM is treated with Bruton’s tyrosine kinase inhibitors (BTKis) and chemotherapies, which can exacerbate bleeding. Platelet function and quality are under-investigated in WM.

Aims: To evaluate platelet quality and function, and clotting potential in WM.

Methods: Relative platelet receptor levels, reticulated platelets and platelet activation were measured by whole blood or PRP flow cytometry in 16 WM patients compared with 66 healthy donors (HD). Blood was enumerated by automated analyser; metalloproteolytically-shed soluble GPVI was measured by ELISA; whole blood clotting potential was evaluated using ROTEM.

Results: WM blood displayed significantly reduced platelets (**p < 0.01) bearing less GPVI (**p < 0.01), GPIbα (*p < 0.05) and reticulation (*p < 0.05), and increased tetraspanin CD9 (***p < 0.001) and P-selectin (*p < 0.05) compared with HDs. Plasma soluble GPVI was within HD ranges. Samples from WM patients displayed normal ROTEM parameters in intrinsic and extrinsic clotting assays but markedly reduced thrombus size (****p < 0.0001) compared to HD values in FIBTEM. When recalcified (NATEM), WM patient blood formed thrombi 58% faster (****p < 0.0001), that were enlarged 22% (****p < 0.0001) over HDs.

Conclusion(s): WM patient platelets bore reduced levels of key receptors governing platelet function. Reductions may be due to changes in platelet maturation/production as GPVI shedding was not evident and reticulated platelets were reduced. Global clotting capacity was normal, however the relative contributions of platelets and plasma components were abnormal, consistent with deranged haemostatic regulatory capacity in WM. Future work will assess the utility of these measurements in stratifying patients for bleeding risk.