Thrombocytopenia, or low platelet (PLT) count, is a common hematologic abnormality that may be associated with risk of severe bleeding. Understanding the cause of thrombocytopenia can be a clinical puzzle for clinicians. While the PLT count is the most important parameter to diagnose thrombocytopenia, it doesn’t provide information regarding the underlying cause of low platelet count, which makes the differential diagnosis unclear. It is merely a snapshot in time, reflecting PLT quantity and not the mechanism responsible for the low count.
Possible causes of thrombocytopenia may include decreased platelet production or increased platelet consumption. Clinicians must determine the cause of thrombocytopenia because low platelet counts can be associated with spontaneous bleeding, even without injury. Patients with thrombocytopenia therefore must be carefully monitored and treated based upon the underlying cause.
Rapid assessment of platelet production may aid clinicians in distinguishing between thrombocytopenia due to platelet destruction (such as immune thrombocytopenia [ITP]) and low platelet count due to aplastic disorders or other bone marrow failure syndromes.
Assessing the cause of thrombocytopenia
Determining the cause of thrombocytopenia may require additional laboratory tests and potentially invasive procedures. It is virtually impossible for the clinician to differentially diagnose thrombocytopenia from CBC results alone.
One non-invasive method of understanding the underlying cause of thrombocytopenia is to measure the immature platelet fraction (IPF), which indicates the presence of immature platelets in the peripheral blood.
The IPF is the automated measurement of reticulated, or immature, platelets. It reflects the presence of nucleic acid material in the cell by using a combination of fluorescent stains, flow cytometry and algorithms to separate immature from mature platelets. The more immature the platelet, the more it fluoresces, thus allowing an accurate immature platelet count without requiring a separate reticulated platelet test performed by traditional flow cytometry.
Using this test, physicians have immediate access to relevant data specific to platelet maturity for better patient management. For example, thrombocytopenic samples with low to normal IPF are often consistent with a platelet production disorder. This could be due to conditions such as aplastic anemia, leukemia, and bone marrow suppression, or the effect of drugs.
On the other hand, thrombocytopenic samples with higher than normal IPF are often consistent with platelet destruction disorders like immune thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), disseminated intravascular coagulation (DIC), the effect of drugs or other causes.
Using IPF as a screening tool
The value of IPF has been proven as a screening tool for the clinician in the differential diagnosis of thrombocytopenia. IPF is most effective when the measurement is used serially and interpreted in conjunction with the platelet count.1 IPF can also be used as an early indicator of bone marrow recovery in patients who are undergoing a stem cell transplant or chemotherapy. In fact, IPF has been found to show recovery faster than absolute neutrophil recovery.2
Because immature platelets are usually larger in size, some technologies use the MPV, or mean platelet volume, as an indication of platelet immaturity. However, MPV may not be an accurate indication of immaturity because of interference from giant platelets, platelet clumps, microerythrocytes, and cell fragments. Due to these interferences, MPV is not necessarily the best method for assessing the immaturity of platelets.
In summary, IPF provides an automated, direct cellular measurement of thrombopoietic activity in bone marrow. Used in conjunction with platelet count and other patient information, IPF may help the clinician assess the mechanism of newly identified thrombocytopenias. Therefore, IPF is a valuable laboratory parameter that may provide clinicians with the missing piece to the thrombocytopenia puzzle.
- Psaila B, Bussell JB, Frelinger AL, et al. Differences in platelet function in patients with acute myeloid leukemia and myelodysplasia compared to equally thrombocytopenic patients with immune thrombocytopenia. J Thrombosis Hemostasis. 2011;9(11):2302-2310.
- Zucker, M., Murphy CA, Rachel JM,et al. Immature Platelet Fraction as a predictor of platelet recovery following hematopoietic progenitor cell transplantation. Laboratory Hematology. 2006;12(3):125-130.