The Thromboembolism Heparinization and AntithrombiN Observational Study (THANOS-1)

Acute pulmonary embolism (PE) affects both hemodynamics and the clotting system, and changes in clotting protein activity may affect the effectiveness of anticoagulation. For example, PE may represent an acute, acquired antithrombin (AT)-deficient state, which may limit heparin effectiveness. However, the incidence and clinical effects of acquired AT deficiency after PE are not known.

Our primary aim was to calculate the proportion of patients with PE and acquired AT deficiency, defined a priori as <80% functional activity. We also analyzed <90%, <100%, and <110% AT activity. Secondary aims were to identify clinical factors and outcomes associated with acquired AT deficiency.

We performed a prospective, observational study of patients diagnosed with acute PE without contraindications to heparin anticoagulation. We obtained blood within 24 hours after positive PE imaging and measured AT activity. Outcomes were culled from the medical record.

We analyzed 200 patients. Mean age was 62 ± 16 years, and 120 (60%) were men. Fifty-four (27%) patients had <80%, 111 (56%) <90%, and 159 (80%) <100% AT activity. Low AT activity (<80%) was associated with longer hospital length of stay (P < .0001), intensive care unit admission (P = .0085), and adverse clinical outcomes (P = .0042), but not subtherapeutic anticoagulation.

Acquired AT deficiency is common after acute PE, occurring in at least one-quarter of all patients. Low AT levels are associated with adverse clinical outcomes, intensive care unit admission, and longer hospital length of stay, but whether this is related to subtherapeutic anticoagulation is not clear.