Epidemiological perspective of chronic immune thrombocytopenia

Sammanfattning: This thesis deals with different aspects of immune thrombocytopenia disease (ITP), what happens before diagnosis, characteristics of patients at treatment start and outcomes potentially related to the disease and treatment, such as thrombosis and cancer. In study one we investigate the risk of infections prior to the diagnosis of ITP. There are some infections causing secondary ITP and there is an association with infection and risk of autoimmune disease. With information from national health registries we were able to compare the amount of diagnosis of infection and anti-infective drugs within five years before diagnosis of ITP in 1087 patients with primary chronic ITP (cITP) to the general population. Our hypothesis turned out to be right and the patients with ITP were more likely to have had an infection diagnosis, Standardized Incidence Ratio (SIR) 8.74(7.47-10-18) and anti-infective drugs SIR 1.37(1.25-1.50) compared with persons of the same age and sex in the general population. In addition, we estimated the incidence of ITP in Sweden to 2.3 per 100 000. In study two we investigated characteristics at treatment start in patients with (cITP). We wanted to know how the patients’ characteristics influence start and type of treatment. We found that patients start treatment at low platelet counts, median 12(IQR 5-27). This finding supports the recommendation to treat in order to avoid symptoms and not aim for a normal platelet count, in order to avoid unnecessary potential harm from the treatment. Moreover, we confirm that the most common first treatment is corticosteroids followed by diverse treatment used as second line treatment and refractory treatment. During the last four years of the study splenectomy was less common and the time to splenectomy delayed. Comorbidity influenced treatment start and type of treatment. Patients with diabetes were less likely to receive corticosteroids. In the third study underlying risk factors for arterial thrombosis and venous thromboembolism were evaluated. In collaboration with a research group at the university of Toulouse a cohort study was performed using the same variables and analysis in both countries. The incidence rate of arterial thrombosis in France was 15(13.4-16.7) and in Sweden 14.7(12.4-17.5) and for venous thromboembolism in France 6.9(5.9-8.1) and 6.5(5.1-8.1) in Sweden per 1000 person-years, 95% CI. The impact of baseline risk factors was similar as well. In study four we studied the risk of cancer in patients with ITP. Molecular evidence suggests that the dysfunctional immune system related to autoimmune disease may increase the risk of certain cancers. A risk of haematological malignancies has been reported in studies of patients with ITP but the risk of solid tumours warrants further attention and those performed have reported contradictory results. We compared the rate of cancer in patients with ITP to the general population in a matched cohort study. We found a slightly increased risk of overall cancer HR 1.37(1.27-1.48), more pronounced in men, an increased risk of liver cancer 3.83(2.46-5.97) and an increased risk of skin cancer after 10 years of follow up, 1.52(1.05-2.19). We confirmed the increased risk of haematological malignancies. The risk of hematologic malignancies was increased in all time intervals and follow a trend with the highest risk, 9-fold, following the year of diagnosis of ITP to down to twofold higher 10-20 years after diagnosis We conclude that treating clinicians should have a high index of suspicion of cancer when treating these patients.