Prevalence and significance of coagulation abnormalities in community-acquired pneumonia

Abstract

Coagulation abnormalities are common in severe pneumonia and sepsis, yet little is known about the presence of coagulopathy or its significance in patients with lesser illness severity. We examined coagulation abnormalities in 939 subjects hospitalized with community-acquired pneumonia (CAP) in 28 US hospitals, hypothesizing that abnormalities would increase with illness severity and poor outcomes. We measured plasma coagulation markers (D-dimer, plasminogen activator inhibitor [PAI], antithrombin, factor IX, and thrombin-antithrombin complex [TAT]) at the time of patient presentation to the emergency department and daily during the first wk of hospitalization. Day-1 clinical laboratory test results for international normalized ratio, activated partial thromboplastin time, and platelet count were recorded from the medical record. In our cohort, 32.5% of patients developed severe sepsis and 11.1% died by d 90. Day-1 coagulation abnormalities were common, especially for D-dimer (80.6%) and TAT (36.0%), and increased with illness severity and poor outcomes. However, abnormalities also occurred in those patients who never developed organ dysfunction and differences between groups were modest. The proportion of patients with abnormalities changed over time, yet the magnitude of change was small and not always in the direction of normality. Many patients remaining in the hospital continued to manifest coagulation abnormalities on d 7, especially for D-dimer (86.5%) and TAT (36.9%). In conclusion, coagulation abnormalities were common and persistent in CAP patients, even among the least ill. These findings underscore the complexity of the coagulation response to infection and may offer insights into coagulation-based therapeutics in clinical sepsis trials.

Figure 1

Flow diagram for the entire GenIMS cohort.

Figure 2

Day-1 coagulation abnormalities by initial APACHE III score quartile (top), development of severe sepsis (middle), and 90-d mortality (bottom). The total number of subjects providing at least one day-1 observation was 923 (98.3%), including 734 (78.2%) who had at least one non-clinical marker measured. Number of observations for each marker are listed below the figure. INR, international normalized ratio; PTT, activated partial thromboplastin time; PLT, platelets; AT, antithrombin; PAI, plasminogen activator inhibitor; TAT, thrombin-antithrombin complex. Ever sepsis indicates development of severe sepsis during the hospitalization. See Materials and Methods for cutoffs for abnormality.

Figure 3

Mortality at 90 d by day-1–D-dimer quintiles. Mortality increased progressively with increasing D-dimer levels.

Figure 4

Proportion of hospitalized subjects with abnormal coagulation markers over time. The total number of subjects providing at least one observation was 939. Number of observations for each marker and the number remaining hospitalized each d are listed below the figure. See Materials and Methods for cutoffs for abnormality.

Figure 5

Mean coagulation factor levels over hospital d 1 through 7 in subjects hospitalized with CAP, stratified by initial illness severity (APACHE III quartiles [q]), development of severe sepsis, and 90-d mortality. To accentuate differences between groups, y-axes do not cross zero. Means are geometric means estimated from Tobit models when appropriate. Geometric means roughly approximate medians. Normal values are: D-dimer ≤256 ng/mL, TAT ≤5.0 ng/mL, PAI activity ≤31 IU/mL, factor IX activity ≥60%, and antithrombin activity ≥70%.