Prothrombotic state at hospital discharge increases 1-year mortality in pneumonia and sepsis survivors

Introduction

Prothrombotic conditions, like myocardial infarction and pulmonary embolism, are more common after respiratory infections, but underlying mechanisms are unclear. We hypothesized that the imbalance between procoagulant and fibrinolytic response during community-acquired pneumonia (CAP) persists at hospital discharge and increases the risk of 1-year mortality.

Methods

We conducted a 1-year follow-up of 893 hospital survivors of the GenIMS study, an observational cohort of subjects with CAP. We measured coagulation and fibrinolysis markers (antithrombin (AT), thrombin–antithrombin (TAT) complexes, factor IX, D-dimer, and plasminogen activator inhibitor 1 (PAI-1)) at hospital discharge. We used a Gray's model to estimate time-varying hazard ratios of death over 1 year, and the National Death Index to determine all-cause and case-specific mortality.

Results

Geometric means of factor IX and AT activities, TAT, PAI-1, and D-dimer levels were 117.8%, 91.6%, 3.6 ng/ml, 3.7 IU/ml and 605.5 ng/ml, respectively. Although the majority of patients (88.4%) had clinically recovered at hospital discharge, coagulation markers were frequently abnormal. D-dimer, TAT and PAI-1 levels were abnormal in 80%, 40% and 11% of patients. Subjects with higher TAT, D-dimer, and PAI-1 levels were more likely to die over 1 year, even after adjusting for patient demographics, comorbidities, and severity of illness. Risk of death was highest initially and decreased over time (for each log-unit increase the range of adjusted hazard ratios were 1.39 to 1.01 (P = 0.01), 1.48 to 1.03 (P = 0.004), and 1.50 to 0.76 (P = 0.005) for TAT, D-dimer, and PAI-1, respectively). The adjusted hazard ratios remained unchanged when analyses were limited to subjects discharged home, or stratified by severe sepsis occurrence. Most subjects died due to cardiovascular disease (27.8%) and cancer (29.9%). Chronic lower respiratory tract infection (14.6%), infection (10.4%), renal failure (7.6%), and other causes (9.7%) accounted for the remaining deaths.

Conclusion

A prothrombotic state at hospital discharge is associated with increased 1-year mortality in CAP survivors. Pharmacologic interventions targeted to reduce coagulation abnormalities after acute infection should be investigated to improve long-term outcomes.