Assessment of IPF% as a Predictive Biomarker and its use in Predicting Platelet Recovery in Thrombocytopenic Patients


1.  University Hospital Waterford

Thrombocytopenia,  a  reduction  of  circulating  platelets,  can  be  caused  by  decreased  platelet production or increased platelet destruction. A biomarker which can rapidly assess the aetiology of  thrombocytopenia  would  be  beneficial  to  clinicians.  Sysmex  XN  analysers  can  measure reticulated  platelets,  expressed  as  immature  platelet  fraction  (IPF%).  This  parameter  may  also predict  platelet  recovery  allowing  for  justification  of  platelet  transfusions  prophylactically.  A normal reference range for IPF% of 1.1-8.5%was established using healthy controls (n=100). 87 thrombocytopenic  patients  were  included  over  a  13-month  period.  Patients  were  divided  into two  groups;  decreased  platelet  production  (n=53)  and  increased  platelet  destruction  (n=34). IPF% was significantly higher in those with increased platelet destruction (p<0.05). Patients with immune  thrombocytopenia  purpura  (ITP)  had  a  significantly  higher  IPF%  (13.7%)  than  aplastic anaemia   (1.9%)   and   control   patients   (3.8%)   (p<0.05).   ROC   curve   analysis  determined a diagnostic  cut  off  point  of  6.8%  with  a  sensitivity  of  87%  and  specificity  of  92.9%.  14  patients were  followed  daily  for  platelet  recovery  through  platelet  count  and  IPF%.  Platelet  recovery occurred  within  two  days  of  an  increase  in  IPF%  of  2.1%  or  greater from  platelet  nadir (sensitivity 92%, specificity 96%, p<0.05). IPF% measured on the Sysmex XN analysers could be a useful  clinical  parameter  in  the  evaluation  of  patients  presenting  with  thrombocytopenia potentially  avoiding  invasive  procedures  such  as  bone  marrow  examination.  IPF%  can  also predict  platelet  recovery  leading  to  rationalisation  of  prophylactic  platelet  transfusions.  This rapid,  inexpensive  parameter  should  be  implemented  into  routine  full  blood  count  analysis allowing for thorough evaluationof thrombocytopenic patients.
The main causes of thrombocytopenia can be divided into two groups; a failure in the productions of platelets (e.g. aplastic anaemia) and increased peripheral platelet destruction (e.g. ITP).  Patients with haematological malignancies more commonly present with thrombocytopenia than any other cohort. Early identification of the cause of thrombocytopenia is important to provide timely intervention to decrease the risk of life-threatening bleeding.  Such intervention includes platelet transfusion support. The main reason for justification of platelet transfusion to thrombocytopenic patients is platelet count in correlation with clinical evaluation of the patient. Sysmex XN analysers allow for the measurement of immature platelet fraction (IPF%), differentiating mature from immature platelets. IPF% has the ability to distinguish between the causes of thrombocytopenia, differentiating decreased platelet production from increased platelet destruction. IPF% also has the ability to predict platelet recovery, reducing unnecessary platelet transfusions in patients where the platelet count would recover without intervention.
IPF% is available as a parameter on the Sysmex XN haematology analysers and measure on K2EDTA samples. 87 thrombocytopenic patients were included over a 13-month period. Patients were divided into two groups; decreased platelet production (n=53) and increased platelet destruction (n=34). Patients with normal FBC parameters (n=100) were included to establish a reference range for IPF%, represented using the 2.5thand 97.5thpercentile. Comparison of IPF% amongst each group was carried out using Mann-Whitney U test. Reproducibility of IPF% was assessed by coefficient of variation (CV%) analysis. 14 patients were followed daily through platelet count and IPF% to determine the ability of IPF% to predict platelet recovery. ROC curve analysis was performed to determine the diagnostic cut off point of IPF% in differentiating between ITP and aplastic anaemia. ROC curve analysis was also used to determine the optimal value of IPF% for the prediction of platelet recovery.
IPF% as a Diagnostic Marker
IPF% was assessed in patients with ITP, aplastic anaemia and a control group. A statistically significant different in IPF% between ITP and AA patients (p<0.05) and the control group (p<0.05) was found. ROC curve analysis determined a cut of point of 6.8% for differentiating ITP from AA with a sensitivity of 87% and specificity of 92.9%. (Figure 1)(Table 1)
IPF% in Predicting Platelet Recovery
To determine the sensitivity and specificity of IPF% in predicting imminent platelet recovery, ROC curve analysis was used. The increase in IPF% for ROC curve analysis was defined as the increase in IPF% from platelet nadir to the peak IPF% prior to platelet recovery.  An increase of 2.1% was found to have a sensitivity and specificity of 92% and 96% respectively in predicting platelet recovery within 2 days of increase in IPF%. (Figure 2)
IPF% results, easily available on the Sysmex XN analysers, could be a useful clinical parameter in the evaluation of patients presenting with thrombocytopenia potentially avoiding invasive procedures such as bone marrow examination. IPF% can also predict platelet recovery leading to rationalisation of prophylactic platelet transfusions. This rapid, inexpensive parameter should be implemented into routine full blood count analysis allowing for thorough evaluation of thrombocytopenic patients.
The data in this poster was presented at EHA 2021. Published with permission from the Copyright owner.
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