PF431 CLINICAL CHARACTERISTICS, TREATMENT PATTERNS, AND THROMBOEMBOLIC RISK OF PATIENTS WITH COLD AGGLUTININ DISEASE (CAD) IN JAPAN
Authors: Kamesaki T. , Nishimura J.‐I. , Wada H. , Yu E. , Tsao E. , Morales J. , Kanakura Y. 
Published: June 2019

Background:

CAD is a rare form of autoimmune hemolytic anemia with a prevalence in Northern Europe of 16 cases per 1 million inhabitants (Berentsen S. Semin Hematol 2018). Ig M autoantibodies bind to red blood cells and trigger hemolysis via activation of the classical complement pathway. Although clinical and epidemiological studies are limited, recent evidence indicates that CAD patients in Europe and North America have an increased risk of thromboembolic events (TE) (Bylsma LC, et al. EHA 2018; Broome C, et al. Blood 2017). The 1‐year case‐fatality of TE has been reported as 23% (Tagalakis V, et al. Am J Med 2013). There are no studies evaluating the clinical course and risk of TE in CAD patients in Japan or other Asian populations.

Aims:

To describe clinical characteristics, treatment patterns, and risk of TE in CAD patients in Japan.

Methods:

Patients were retrospectively identified from 2008 to 2017 using a hospital‐based administrative claims database (Medical Data Vision), representing approximately 300 hospitals and 20 million patients in Japan. CAD cohort inclusion required age ≥18 years and CAD diagnosis (Japanese Disease Code 2830009) entry on ≥3 separate occasions within the study period. The first CAD diagnostic code entry was used as the index date. Patients in the comparison cohort had no history of CAD and were matched 10:1 to patients in the CAD group by age, sex, year and season of diagnosis, follow‐up time, and comorbidities using the Charlson Comorbidity Index. Conditional logistic regression was used to adjust for these variables when comparing cohorts.

Results:

344 CAD patients were identified with a slight female preponderance (53.2%), mean age of 66.8 years and 18.9‐month mean duration of follow‐up. The most frequently used treatment was steroids (34.2%). Other treatments included cytotoxic chemotherapy (6.9%), rituximab (5.9%), and immunosuppressants (5.9%). A total of 3440 patients with matching characteristics were included in the control group to compare the risk of TE among cohorts. Overall, CAD patients had an increased rate of TE versus patients without CAD (34.8% vs 17.9%, respectively; P < 0.0001) (Figure). The rate of arterial and venous TE was also higher in CAD versus non‐CAD cohorts (25.0% vs 4.6% and 8.4% vs 4.0%, respectively; P < 0.0001 for both analyses). Most cases of arterial TE in CAD patients corresponded to myocardial infarctions (87.2%). There was no difference in cerebral TE among the CAD and non‐CAD groups (10.4% vs 11.9%, respectively). The overall odds ratio (OR [95% confidence interval]) for development of TE in the CAD cohort versus non‐CAD cohort was 2.81 (2.18–3.61). Corresponding ORs for arterial and venous TE were 8.59 (6.16–11.98) and 2.37 (1.56–3.62), respectively.

Summary/Conclusion:

This study is the first to evaluate the clinical characteristics, treatment practices, and TE risk of CAD patients in Japan. Our results indicate that the CAD treatment approach used in Japan (ie, predominantly with steroids) differs from that reported for other countries. However, in accordance with recent reports from non‐Asian populations, this study demonstrates an increased risk of TE in the Japanese population. Interestingly, the rate of arterial TE was higher in Japan, which was mostly attributed to the high prevalence of myocardial infarctions in our CAD cohort. Japanese healthcare providers should be aware of these risks to properly monitor their CAD patients. Prospective studies are needed to further evaluate these findings.

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