Venous Thromboembolism Incidence In The Cooperative Study Of Sickle Cell Disease: The Untold Story

An increased risk of venous thromboembolism (VTE) among individuals with sickle cell disease (SCD) has only recently been recognized. Unlike arterial thrombosis such as stroke which primarily occurs in children with SCD, VTE risk in SCD appears to increase in young adulthood. To date, no studies have described the incidence of VTE in adolescents and adults with SCD. We performed a secondary analysis of the largest prospective cohort of SCD patients, the Cooperative Study of Sickle Cell Disease (CSSCD), to estimate the incidence rate and age-specific cumulative incidence of first VTE among SS/Sβ⁰ patients aged 15 or older.

We used available data from Phase 1 of the CSSCD,¹ a multi-institution longitudinal prospective study conducted from 1978-1988, to identify cases of first VTE in patients aged 15 or older at enrollment with SS/Sβ⁰ genotype. Individuals with a history of prior VTE were excluded. VTE was defined as any pulmonary embolism (PE) or deep venous thrombosis (DVT) identified by ICD-9 code except in the case of pregnancy where VTE events were explicitly collected. Because the definition of acute chest syndrome (ACS) in the CSSCD also included PE and because the ICD-9 code for PE was also used for pulmonary infarct in cases of potential ACS, PE cases that were identified during an admission for ACS were included only if a negative chest X-ray was recorded. The date of VTE was recorded as being the date of the annual visit for any interim VTE or as the date of discharge for any VTE that occurred during a hospitalization. 95% Confidence intervals (CI) for incidence rates were calculated using a Poisson distribution assumption. Kaplan-Meier failure curves were generated to estimate age-specific cumulative incidence.

A total of 1,133 individuals with SS/Sβ⁰ aged ≥ 15 years with 6,608 years of follow-up were included for analysis. During this study period, 43 incident VTE events were identified. The median age at VTE was 26.3 years (range 17-47 years) and 25 (58%) were female. The overall incidence rate for VTE was 6.5 events/1000 person-years (CI 4.7, 8.8). The Kaplan-Meier failure curve for VTE is shown below. The cumulative incidence of first VTE was estimated as 9.0% (CI 6.4-12.7) by age 30 and 14.1% (CI 10.2-19.2) by age 40.

The incidence rate of first VTE among SS/Sβ⁰ patients aged ≥ 15 years appears to be high, with an estimated cumulative incidence by age 40 that far exceeds that for Factor V Leiden carriers (estimated 6.2% by age 65).² This study underscores the thrombophilic state of SCD and emphasizes the need for further research into the risk factors for VTE in the SCD population.

1. Gaston M, Rosse WF. The cooperative study of sickle cell disease: review of study design and objectives. Am J Pediatr Hematol Oncol 1982; 4: 197-201.

2. Heit JA, Sobell JL, Li H, Sommer S. The incidence of venous thromboembolism among Factor V Leiden carriers: a community-based cohort study. J Throm Haemost 2004; 3: 305-11.

This Abstract was prepared using CSSCD Research Materials obtained from the NHLBI via BioLINCC (https://biolincc.nhlbi.nih.gov/).

Naik:NHLBI: Research Funding. Haywood:NHLBI: Research Funding. Lanzkron:GlycoMimetics, Inc.: Research Funding.