Incidence rates of thrombosis with thrombocytopenia syndrome (TTS) among adults in United States commercial and Medicare claims databases, 2017-2020.

BACKGROUND: Increased risk of thrombosis with thrombocytopenia syndrome (TTS) following adenovirus vector-based COVID-19 vaccinations has been identified in passive surveillance systems. TTS incidence rates (IRs) in the United States (U.S.) are needed to contextualize reports following COVID-19 vaccination. METHODS: We estimated annual and monthly IRs of overall TTS, common site TTS, and unusual site TTS for adults aged 18-64 years in Carelon Research and MarketScan commercial claims (2017-Oct 2020), CVS Health and Optum commercial claims (2019-Oct 2020), and adults aged ≥ 65 years using CMS Medicare claims (2019-Oct 2020); IRs were stratified by age, sex, and race/ethnicity (CMS Medicare). RESULTS: Across data sources, annual IRs for overall TTS were similar between Jan-Dec 2019 and Jan-Oct 2020. Rates were higher in Medicare (IRs: 370.72 and 365.63 per 100,000 person-years for 2019 and 2020, respectively) than commercial data sources (MarketScan IRs: 24.21 and 24.06 per 100,000 person-years; Optum IRs: 32.60 and 31.29 per 100,000 person-years; Carelon Research IRs: 24.46 and 26.16 per 100,000 person-years; CVS Health IRs: 30.31 and 30.25 per 100,000 person-years). Across years and databases, common site TTS IRs increased with age and were higher among males. Among adults aged ≥ 65 years, the common site TTS IR was highest among non-Hispanic black adults. Annual unusual site TTS IRs ranged between 2.02 and 3.04 (commercial) and 12.49 (Medicare) per 100,000 person-years for Jan-Dec 2019; IRs ranged between 1.53 and 2.67 (commercial) and 11.57 (Medicare) per 100,000 person-years for Jan-Oct 2020. Unusual site TTS IRs were higher in males and increased with age in commercial data sources; among adults aged ≥ 65 years, IRs decreased with age and were highest among non-Hispanic American Indian/Alaska native adults. CONCLUSION: TTS IRs were generally similar across years, higher for males, and increased with age. These rates may contribute to surveillance of post-vaccination TTS.

Development and Validation of an Algorithm for Thrombosis with Thrombocytopenia Syndrome (TTS) at Unusual Sites.

Introduction: Thrombosis with thrombocytopenia syndrome (TTS) has been reported following receipt of adenoviral vector-based COVID-19 vaccines. However, no validation studies evaluating the accuracy of International Classification of Diseases-10-Clinical Modification (ICD-10-CM)-based algorithm for unusual site TTS are available in the published literature. Methods: The purpose of this study was to assess the performance of clinical coding to 1) leverage literature review and clinical input to develop an ICD-10-CM-based algorithm to identify unusual site TTS as a composite outcome and 2) validate the algorithm against the Brighton Collaboration's interim case definition using laboratory, pathology, and imaging reports in an academic health network electronic health record (EHR) within the US Food and Drug Administration (FDA) Biologics Effectiveness and Safety (BEST) Initiative. Validation of up to 50 cases per thrombosis site was conducted, with positive predictive values (PPV) and 95% confidence intervals (95% CI) calculated using pathology or imaging results as the gold standard. Results: The algorithm identified 278 unusual site TTS cases, of which 117 (42.1%) were selected for validation. In both the algorithm-identified and validation cohorts, over 60% of patients were 56 years or older. The positive predictive value (PPV) for unusual site TTS was 76.1% (95% CI 67.2-83.2%) and at least 80% for all but one individual thrombosis diagnosis code. PPV for thrombocytopenia was 98.3% (95% CI 92.1-99.5%). Discussion: This study represents the first report of a validated ICD-10-CM-based algorithm for unusual site TTS. A validation effort found that the algorithm performed at an intermediate-to-high PPV, suggesting that the algorithm can be used in observational studies including active surveillance of COVID-19 vaccines and other medical products.

Vaccine exposure during pregnancy among privately and publicly insured women in the United States, 2016-2018.

BACKGROUND: Vaccine use during pregnancy affects maternal and infant health. Many women do not receive vaccines recommended during pregnancy; conversely, inadvertent exposure to vaccines contraindicated or not recommended during pregnancy may occur. We assessed exposure to two recommended vaccines and two vaccines not recommended during pregnancy among privately and Medicaid-insured women in the United States. METHODS: This study includes a retrospective cohort of pregnancies in women aged 12-55 years resulting in live birth, spontaneous abortion, or stillbirth identified in the IBM® MarketScan® Commercial, Blue Health Intelligence® (BHI®) Commercial, and IBM MarketScan Multi-State Medicaid Databases from August 1, 2016, to December 31, 2018. Gestational age at vaccination was determined using a validated algorithm. We examined vaccines (1) recommended by the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices (ACIP) (tetanus, diphtheria, and acellular pertussis [Tdap]; inactivated influenza) and (2) not recommended (human papillomavirus [HPV]) or contraindicated (measles, mumps, and rubella [MMR]). RESULTS: We identified 496,771 (MarketScan Commercial), 858,961 (BHI), and 289,573 (MarketScan Medicaid) pregnancies (approximately 75% aged 20-34 years). Across these three databases, 52.1%, 50.3%, and 31.3% of pregnancies, respectively, received Tdap, most often at a gestational age of 28 weeks, and influenza vaccination occurred in 32.1%, 30.8%, and 18.0% of pregnancies, respectively. HPV vaccination occurred in < 0.2% of pregnancies, mostly in the first trimester among women aged 12-19 years, and MMR was administered in < 0.1% of pregnancies. Use of other contraindicated vaccines per ACIP (e.g., varicella, live attenuated influenza) was rare. CONCLUSION: Maternal vaccination with ACIP-recommended vaccines was suboptimal among privately and Medicaid-insured patients, with lower vaccination coverage among Medicaid-insured pregnancies than their privately insured counterparts. Inadvertent exposure to contraindicated vaccines during pregnancy was rare. This study evaluated only vaccinations reimbursed among insured populations and may have limited generalizability to uninsured populations.