Potential Diagnostic Approaches for Prediction of Therapeutic Responses in Immune Thrombocytopenia

Abstract

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder in which, via unresolved mechanisms, platelets and megakaryocytes (MKs) are targeted by autoantibodies and/or T cells resulting in increased platelet destruction and impairment of MK function. Over the years, several therapeutic modalities have become available for ITP, however, therapeutic management has proven to be very challenging in several cases. Patients refractory to treatment can develop a clinically worsening disease course, treatment-induced toxicities and are predisposed to development of potentially life-endangering bleedings. It is therefore of critical importance to timely identify potential refractory patients, for which novel diagnostic approaches are urgently needed in order to monitor and predict specific therapeutic responses. In this paper, we propose promising diagnostic investigations into immune functions and characteristics in ITP, which may potentially be exploited to help predict platelet count responses and thereby distinguish therapeutic responders from non-responders. This importantly includes analysis of T cell homeostasis, which generally appears to be disturbed in ITP due to decreased and/or dysfunctional T regulatory cells (Tregs) leading to loss of immune tolerance and initiation/perpetuation of ITP, and this may be normalized by several therapeutic modalities. Additional avenues to explore in possible prediction of therapeutic responses include examination of platelet surface sialic acids, platelet apoptosis, monocyte surface markers, B regulatory cells and platelet microparticles. Initial studies have started evaluating these markers in relation to response to various treatments including glucocorticosteroids (GCs), intravenous immunoglobulins (IVIg) and/or thrombopoietin receptor agonists (TPO-RA), however, further studies are highly warranted. The systematic molecular analysis of a broad panel of immune functions may ultimately help guide and improve personalized therapeutic management in ITP.

The Use of Clinical Scores in the Management of Immune Thrombocytopenic Purpura in Children

“…The authors aimed to analyse how beneficial this score was in their population for predicting ITP duration <6 months in 3 age groups: <12 months, 1–8 years, and over 9 years old. The choice of 6 months as predictive threshold was based on previous studies that found a high percentage of spontaneous remission after 6 months from diagnosis ( 5 , 9 , 13 , 21 , 24 ).…”

“…While investigations into immune functions in ITP ( 7 , 8 ), aiming for a better prediction of platelet count responses have been exploited and included in nowadays ITP management ( 9 – 11 ), a lack of consensus among clinical scores and use in ITP monitoring still exists ( 10 ). Several clinical scores have been developed including a combination of different already known risk factors: age, gender, presence of a previous infections or vaccination, bleeding grade, type of onset, platelet count at diagnosis ( 1 , 12 – 16 ).…”

Platelets in ITP: Victims in Charge of Their Own Fate?

“…Interestingly, several miRNAs with significant immunological functions have been described to be up-or down regulated in ITP [81,[84][85][86]. Moreover, circulating miRNA levels have been observed to be increased or decreased after several ITP treatments, indicating that miRNA could be a possible biomarker for therapeutic response [30,87,88]. In this regard, one could hypothesize that PMP contents such as miRNAs might even differ between several subgroups of patients with ITP, including acute vs. chronic ITP and therapeutic responders vs. non-responders.…”

“…Most importantly, the likely possibility that platelets are not only the victims of the autoimmune response in ITP, but also immuno-modulating cells involved in promoting and sustaining their own destruction, is an important issue which warrants further investigation. More understanding of the role of platelets in the pathophysiology of ITP could help us with identification of new diagnostic biomarkers and predictors of therapeutic response [87]. Ultimately, this may lead to new platelet-directed therapeutic strategies for ITP.…”

Amifostine and rituximab in refractory immune thrombocytopaenia: A case series

“…With updated guidelines recommending deferral of splenectomy, refractory ITP has been redefined to include those who are non‐responsive to ≥2 lines of therapy, lack of response to any therapy, or bleeding associated with severe thrombocytopaenia [10]. In these cases, management can be challenging as alternative therapeutic options are associated with lower response rates, immunosuppressive complications, treatment‐specific toxicities and poor durability of response [11].…”