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• W2105320555 abstract "Primary immune thrombocytopenia (ITP) is characterized by isolated thrombocytopenia, which is associated with an increased risk for bleeding (Fogarty, 2009) (Nørgaard et al, 2011). However, patients with chronic ITP (cITP) may, paradoxically, also have an increased risk for both venous thromboembolism (VTE) (Severinsen et al, 2011), (Sarpatwari et al, 2010), and arterial thrombosis (AT) (Aledort et al, 2004), (Nørgaard et al, 2012) possibly due to a high proportion of large and immature platelets (Rand & Dean, 1998) that are more thrombogenic or because patients with cITP have a high prevalence of known risk factors for thrombosis (Previtali et al, 2011). Nevertheless, population-based data are few and little is known about how the risk of thrombosis varies according to gender, age and level of comorbidity in cITP patients. We therefore aimed to assess the incidence of thrombotic/thromboembolic events in a Scandinavian population-based cohort of adults with incident cITP, overall and by gender, age, comorbidity burden and splenectomy status. We used data from the National Health Registry Systems (NHRSs) (including diagnostic and vital records) and medical records of Denmark, Norway and Sweden. Through the NHRSs, we identified all adults aged ≥18 years with ≥2 ITP diagnoses made >6 months apart from 1 January 1996 to 31 December 2012 (from 1 January 2008 for Norway). Only patients with an ITP diagnosis confirmed through medical chart review were included. The NHRSs were searched for any diagnosis of AT or VTE, including myocardial infarction, stroke, deep venous thrombosis and pulmonary embolism, occurring between 1 April 2009 and 31 December 2012. Information on comorbidity was also retrieved from the NHRSs. All hospital diagnoses recorded in the 5 years prior to cITP diagnosis or 1 April 2009 (whichever was later) were reviewed to identify the presence of the 19 chronic diseases included in the Charlson Comorbidity Index (CCI) and to calculate a CCI score (Charlson et al, 1987). Comorbidity was classified as low (CCI score=0), moderate (CCI score = 1-2) or high (CCI score≥3). Receipt of prior splenectomy or splenectomy during follow-up was determined through the NHRSs and from medical record review. As comparison cohort we selected, through the Danish Civil Registration system, 10 age- and gender-matched persons per cITP patient from the general Danish population. Incidence rates (IRs) of AT and VTE were calculated as the total number of first events of interest divided by the total person-time at risk, where time at risk was defined as the latest date of cITP diagnosis or 1 April 2009 until the earliest date of the following: first occurrence of the event of interest, death, emigration or 31 December 2012. IRs were calculated for the cohort overall and stratified by gender, age, comorbidity burden and splenectomy status. For the cohort overall, we also calculated IRs among the subset of patients who had no history of the specific event 5 years prior to the cITP date or 1 April 2009 (whichever was later) and classified these events as new. The statistical software package SAS, version 9·2 (SAS Institute Inc., Cary, NC, USA) was used for all statistical analyses. We identified 1,821 adults diagnosed with confirmed primary cITP in the three Scandinavian countries (667 in Denmark, 342 in Norway, and 812 in Sweden) and 18,210 persons from the general Danish population. Median age at time of cITP diagnosis was 58·6 years and 56%, were women. Nearly 70% were considered to have low comorbidity burden. Approximately 6% of the cohort had undergone splenectomy at time of cITP diagnosis. Overall, 68 AT events occurred in the cITP cohort during 4185 person-years of follow-up (IR = 16·3 per 1000 person-years, 95% confidence interval [CI]: 12·8–20·6) and 39 VTE events occurred in the cITP cohort during 4233 person-years of follow-up (IR = 9·2 per 1000 person-years, 95% CI: 6·7–12·6) (Table 1). Among cITP patients with no history of these events, the IR for AT was 11·5 per 1000 person-years (95% CI: 8·6–15·4) and the IR for VTE was 6·7 per 1000 person-years (95% CI: 4·6–9·7). The corresponding IRs for persons in the general population cohort without history of these events were 8·8 (95% CI: 7·9–9·7) per 1000 person-years for AT and 2·8 (95% CI: 2·3 – 3·4) for VTE. The incidence of AT was higher in men than in women (14·8 [95% CI: 9·9-22·0] versus 9·3 [95% CI: 6·1–14·1] per 1000 person-years, respectively), but the incidence of VTE was similar in both genders (Table 2). The occurrence of both AT and VTE increased with increasing age and increasing comorbidity burden (Table 2). The incidence of AT appeared similar between splenectomised and non-splenectomized patients, whereas VTE events seemed to occur more frequently in splenectomized versus non-splenectomized patients (Table 2). This large Scandinavian cohort study including 1821 patients with cITP corroborates findings in previous Danish studies of cITP patients diagnosed between 1996 and 2007 (Severinsen et al, 2011; Nørgaard et al, 2012): that cITP patients have an increased risk of both AT and VTE compared with the general population. Within the cITP population, compared with women, men had a higher incidence of AT while the incidence of VTE was comparable. In both the cITP cohort and comparisons the incidence of both VTE and AT increased with increasing age and with increasing level of comorbidity. The IR of AT in cITP patients and comparisons were similar in patients with moderate and high comorbidity. Despite being the largest study of cITP and risk of thrombosis to date, our study only included around 100 splenectomized patients, making it difficult to compare the IRs by splenectomy status. Nevertheless, the incidence of VTE appeared higher in splenectomized patients, whereas the incidence of AT appeared similar in splenectomized and non-splenectomized patients. We conducted a population-based cohort study with minimal loss to follow-up, which avoided selection bias. Also, the cITP diagnoses were verified through medical record review thereby minimizing misclassification. Importantly, we hereby provide robust and updated estimates of the risk of thrombosis in patients with cITP. These estimates thus supported previous smaller studies suggesting that cITP patients have an elevated risk of AT and VTE despite an increased risk of bleeding. CF Christiansen, S Stryker, K Cetin, and M Nørgaard conceptualized the idea for the study. All authors participated in the study's design and data collestion. NR Kristensen and ML Maegbaek performed the data analyses. M Nørgaard and CF Christiansen directed the statistical analyses. M Nørgaard wrote the first draft of the paper, and all authors participated in writing the final version." @default.
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• W2105320555 date "2015-10-12" @default.
• W2105320555 modified "2023-10-17" @default.
• W2105320555 title "Risk of arterial thrombotic and venous thromboembolic events in patients with primary chronic immune thrombocytopenia: a Scandinavian population-based cohort study" @default.
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• W2105320555 doi "https://doi.org/10.1111/bjh.13787" @default.
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