In Non-Selected Patients Treated for Influenza, Oseltamivir, a Glycosialidase Inhibitor, Demonstrates Improvement in Platelet Counts Compared to Time of Dosing, but Not over Baseline Levels

Background:

Severe thrombocytopenia can cause morbidity or mortality in many patients, especially those with hematologic cancers or who are treated with chemotherapy. Safer and more rational treatment options are critically needed. Platelet aging and clearance, and therefore the quantity of circulating platelets, is intimately tied to the loss of sialic acid on the platelet surface. Platelets lose surface sialic acid gradually as they circulate and age through cleavage by sialidases. In vitro desialylation of the platelet could be circumvented with a sialidase inhibitor. Oseltamivir phosphate (Tamiflu) is an FDA-approved antiviral sialidase inhibitor and has been prescribed worldwide for the treatment of patients with influenza. Multiple case reports have shown a significant improvement in platelet quantity in patients with thrombocytopenia who were treated with oseltamivir. We here investigated the in vivo effect of oseltamivir treatment on platelet counts in a historical cohort.

Methods:

We performed a retrospective observational study in 52 patients treated at the Medical College of Wisconsin. All patients received one treatment course of 75 mg oseltamivir phosphate between October 2004 and February 2017 due to suspicion of influenza. Excluded patients included those who received a different dose of oseltamivir and those who received multiple treatment courses during this time. Constraints in patient platelet count availability at various time-points around dosing led us to divide our two time-point comparison analysis into four groups: (1) baseline (defined as 30 days prior to dosing) vs. 30 days post-treatment, (2) baseline vs. 100 days post-treatment, (3) first day of treatment vs. 30 days post-treatment and (4) first day of treatment vs. 100 days post-treatment. Data were analyzed using paired t-testing after normalizing with a logarithmic scale. Statistical analyses were done with significance level of p<0.05.

Results:

The mean patient age was 61 years old (range 25-88 years old) and 59.6% were male. Treatment courses ranged from 1 to 15 doses over 1 to 14 days with an average treatment course of 4.3 doses over 3.9 days (median of 4 doses over 3 days). There were a total of 26 patients in Group 1, 24 patients in Group 2, 32 patients in Group 3, and 32 patients in Group 4. Some patients had data for multiple time-points and are therefore represented in more than one group.

In Groups 3 and 4, the difference in platelet count was statistically significant (p<0.05) between the first day of oseltamivir administration and 30 days or 100 days after the last dose. About 72% of patients (23 out of 32) in Group 3 experienced a 2-fold increase in platelet count at 30 days following termination of treatment and 84% of patients (27 out of 32) in Group 4 experienced a 2.1-fold increase in platelet count at 100 days following termination of treatment.

In Groups 1 and 2, where end-points were compared to 30 days prior to oseltamivir administration (baseline), platelet counts were also increased, but were not found to be statistically significant. About 65% of patients (17 out of 26) in Group 1 experienced a 1.1-fold increase in platelet count 30 days following termination of treatment. About 63% of patients (15 out of 24) in Group 2 experienced a 2.5-fold increase in platelet count 100 days following termination of treatment.

Conclusions:

Multiple published case reports have pointed to improvements in thromobocytopenia following dosing of oseltamivir for the treatment of influenza. Our data also shows significant increases in platelet counts when 30 day and 100 day post-treatment levels are compared to levels on the first day of treatment. However, our analysis does not indicate that treatment with oseltamivir significantly increases a patient's platelet count over baseline (defined as 30 days prior to dosing). To our knowledge, this is the only data to look at platelet counts both at the time of drug administration as well as at baseline to assess effect. Platelet counts may be decreased at the time of drug dosing due to concomitant illness, in particular, influenza. Whether there is an independent effect of oseltamivir on platelet clearance will require a controlled study. We plan further research to clarify potential therapeutic application of this commonly available sialidase inhibitor in patients with chronically low platelets.