Risk Factors for Systemic Lupus Erythematous (SLE) In Patients with Immune Thrombocytopenia (ITP)
The authors looked at clinical features in ITP patients who later went on to develop systemic lupus erythematous (SLE) to try to determine if there are any identifiable risk factors common to this group of patients that could be used in future to predict which ITP patients may develop SLE with a low platelet count. Between August 2001 – November 2018, 130 patients with ITP were enrolled into the study. Participants required a normal bone marrow examination and a negative antibody-nuclear antibody (ANA) test at the time of their ITP diagnosis and were followed for at least one year within a hospital in South Korea. Participants were excluded from the study if within a year after their ITP diagnosis they developed SLE.
Participants were more likely to be female (69%), over the age of 50 years. The average platelet count at the time of ITP diagnosis was 13,000 µL, with two-thirds of participants reporting severe thrombocytopenia (under 20,000). Out of the 130 participants, only 10 went on to develop SLE. When comparing this subgroup to those that did not develop SLE, a number of risk factors were identified.
Individuals diagnosed with ITP were more likely to also develop SLE if they were younger adults, many were female, and had a platelet count less than 10,000. The presence at ITP diagnosis of skin bleeding, internal bleeding, lymphocytopenia (low white cell count), anemia (low red cell count), and an ANA positive test were also more common in those who went on to later develop SLE. There were no differences in treatment response or megakaryocyte counts (the cells that produce platelets) between those who developed SLE and those who did not.
Comments from PDSA Medical Advisors
In some cases, a low platelet count may be diagnosed as ITP when in fact it is ITP but part of another condition altogether; this is considered secondary ITP. SLE is one of many known secondary causes of a low platelet count that is immune-mediated. It may take years for SLE to either develop or become apparent in patients who have a low platelet count and “ITP.”
The study focused on 130 patients with ITP followed at a single center and only included participants who were diagnosed with SLE one year or more after their diagnosis of ITP. Some of the findings common among ITP patients who later developed SLE have previously been reported such as a positive ANA titre (blood test) and being a younger woman.
Using Recombinant Human Thrombopoietin (rhTPO) To Glucocorticoids in The Treatment of Patients with Immune Thrombocytopenia (ITP)
In this study, the authors assessed the value of treating ITP patients with a combination of both steroids and a recombinant human thrombopoietin receptor agonist (rhTPO), specifically looking at how the combination improve immune function and coagulation (blood clotting). Using data from 87 ITP patient charts admitted to a single hospital in China; 42 were assigned to a control group were treated with steroids alone, while 45 were assigned to the study group where they received both steroids and rhTPO at the same time.
Results revealed that ITP patients receiving both a steroid and a rhTPO had a more effective and quicker response rate in terms of elevating their overall platelet counts to over 50,000 and required less platelet transfusions. The group receiving both therapies also demonstrated a better immune response compared to ITP patients who were only receiving a steroid for treatment. Treatment with both agents did not have a significant beneficial effect on coagulation.
In follow-up three months post treatment in both the control and study group, more ITP patients in the study group had a continued response, compared to the control group, however this was not statistically significant, meaning it is not clear that the combination therapy was the cause of the extended treatment response.
Overall, combination treatment with rhTPO and steroids enhances the therapeutic effect and is in many ways is more efficient than treated with steroids alone.
Comments from PDSA Medical Advisors
This study result is not a surprise. Both steroids and rhTPO (a Chinese form of thrombopoietin which was approved in China over 10 years ago) have been tried and are true treatments of ITP. Having a better response to two treatments vs one is not surprising and probably would have been true even if they compared steroids plus rhTPO to rhTPO.
Therefore the “immediate” results with a better acute response were expected. The main outcome of particular interest is whether the combination would have any curative effect. Given the overall sample size, having less than 100 patients, it was not surprising to demonstrate a statistically significant increase in the long-term response rate. There is a tendency for combination treatment to be more curative. No unexpected serious adverse events occurred.
Other studies of combination treatments such as dexamethasone and a TPO agent (usually eltrombopag) usually show increases in long-term responses but not by very much, so larger numbers were required to see this effect. Why the combination therapy approach should produce more of a curative effect, above and beyond a better immediate response is not clear.