Study of Bone Marrow Response to Platelet Transfusion in Severe Traumatic Brain Injury Patients

Introduction: SevereTraumatic Brain Injury (TBI) patients are predisposed to secondary brain insults due to thrombocytopenia and coagulopathy, warranting platelet transfusion. Thrombopoietin (Tpo) has been shown to be a physiological regulator of thrombopoiesis. An inverse correlation between Tpo and the circulating platelet has been previously reported for several clinical conditions. Response pattern of Tpo to circulating platelets in TBI patients has not been studied yet. We hypothesised that in severe TBI patients thrombopoiesis response to TPO will be impaired

Methodology: Plasma Tpo levels were measured by enzyme-linked immunosorbent assay was measured 3 times i.e. Pre-platelet transfusion of platelets,24h and 48h post-transfusion in 100 severe (GSC≤8)TBI patients. Platelet transfusion response was evaluated and defined as a ≥20% increase in platelet count from baseline and patients were categorized as responders and non-responders to platelet transfusion.

Results: Platelet count was low at admission (89.4±31.1*10³ per cumm). Less than 2 units of random donor platelets(RDP) was given to 14% patients,67% patients required2-4 units of RDP and 19% required >4 units of RDP. TPO levels decreased 24h post transfusion compared to pre transfusion (Mean±SD)(127.8±90.2 vs. 142.2±82.6 pg/ml; P 0.07), but elevated at 48h (209.1±74.8 pg/ml; p Pre vs. 48h 0.05). On Average the platelet count improved after transfusion at 24h to 112.7±74.6pg/ml (p Pre vs. 24h 0.003) and continued to rise at 48 h (123.7±82.1 pg/ml; p Pre vs. 48h 0.02). Platelet count and TPO levels were found to be independent (rho -0.12, p 0.38). 62% showed a ≥20% increase in platelet count from baseline (Responders), 38% were non-responders. As significant increase in 24 h post transfusion Tpo levels were seen in responders [median (IQR)] [173.6(0-202.4) pg/ml vs. 164.3(137.1-203.7) pg/ml; p 0.04] compared to pre transfusion levels. Tpo levels in Non-responders did not vary post platelet transfusion [156(0-198.11) pg/ml vs. 158.88(0-198.11) pg/ml; p 0.97]. 28% of Non-responders had low (<81.25 pg/ml) and 2.8% had high (>237.7 pg/ml) pre transfusion Tpo levels. At 24 h post transfusion 26.6% had low and zero had High Tpo levels.

Conclusion: In the present study platelet transfusion response inversely correlates with Tpo levels, as 24h post platelet transfusion Tpo levels were transiently low but insignificant and elevated at 48h post transfusion. In non-responders, the post transfusion TPO levels were not sufficient to mitigate the low platelet counts. Hence, the possibility of transient bone marrow depression in severe TBI patients is suggested, which requires further analysis in a larger study cohort.