Internal quality control (IQC) is essential to good laboratory practice. IQC for certain tests are, however, limited due to inherent problems in providing stabilized IQC material, as applicable to many whole-blood and cell-based systems. Paradigmatic in the hemostasis field is platelet function testing, where IQC processes remain at their infancy, despite such tests being undertaken for decades. One example is the PFA-100, a popular primary hemostasis screening system used to evaluate pre-surgical bleeding risk, screen for possible von Willebrand disease and/or platelet function disorders, and assess desmopressin and anti-platelet therapy; whatever application, laboratories are required to ensure instruments are in optimal working condition, but currently available IQC is limited. Accordingly, a novel test process for IQC of the PFA-100 is explored as an example of potential development. In brief, IQC test systems were prepared to yield prolonged PFA closure times (CTs) (‘pathological QC’) after the addition of normal whole blood (which provided ‘normal QC’). Inter-run test systems coefficients of variation (CVs; range 3.1%-26.2%) were typically similar or better than normal baseline CTs (16.1%-19.2%). There was no evidence of deterioration in CTs over time, indicating at least several years test system stability, and Levey-Jennings plots, typically applied to IQC monitoring, could also be devised. This provides the first evidence of feasibility, or proof of concept, for IQC testing for the PFA-100 incorporating pathological test findings and Levey-Jennings plots. Such a concept is also potentially more broadly applicable to other platelet function, or whole blood or cell-based test systems.