The calcium-clot connection: investigating the association between primary hyperparathyroidism and acute venous thromboembolism

Abstract

Primary hyperthyroidism (PHPT) is a relatively uncommon disease and leads to increased calcium levels. Ionized calcium, known as clotting Factor IV, may lead to overt coagulation cascade activation, increasing the risk of venous thromboembolism (VTE). National Inpatient Sample Database was used to sample individuals with primary hyperparathyroidism, and baseline demographics and comorbidities were collected using ICD-10 codes. Patients with missing data and age less than 18 were excluded. Moreover, patients with other types of hyperparathyroidism and risk factors for VTE, such as malignancy, thrombophilia, chronic kidney and liver disease, fractures, trauma, oral contraceptive/steroid use, and organ transplant, were excluded. Greedy propensity matching using R was performed to match patients with and without primary hyperparathyroidism on age, race, gender, and 10 other comorbidities, including chronic deep venous thromboembolism. Univariate analysis pre- and post-match were performed. Binary logistic regression was performed after matching to assess whether primary hyperparathyroidism was an independent risk factor for acute VTE. A p-value of < 0.05 was considered statistically significant. Out of 460,529 patients included in the study, 1114 (6.5%) had PHPT. Baseline comorbidities were more common in the PHPT group. On univariate analysis, patients with PHPT were more likely to have acute VTE (2.5% vs. 1.4%; p < 0.001). After 1:1 matching, PHPT patients were twice as likely to have Acute VTE. (OR: 2.1 [1.08-4.1]; p < 0.025). These findings suggest an association between PHPT and VTE, which should be further investigated to prevent the increasing incidence of VTE and its recurrence.

Keywords: Hypercalcemia; Hypercoagulable State; Primary hyperparathyroidism; Thrombosis; Venous thromboembolism.