Antithrombin deficiency is associated with mortality and impaired organ function in septic pediatric patients: a retrospective study

Abstract

BackgroundSepsis remains a major problem in intensive care medicine. It is often accompanied by coagulopathies, leading to thrombotic occlusion of small vessels with subsequent organ damage and even fatal multi-organ failure. Prediction of the clinical course and outcome—especially in the heterogeneous group of pediatric patients—is difficult. Antithrombin, as an endogenous anticoagulant enzyme with anti-inflammatory properties, plays a central role in controling coagulation and infections. We investigated the relationship between antithrombin levels and organ failure as well as mortality in pediatric patients with sepsis.MethodsData from 164 patients under the age of 18, diagnosed with sepsis, were retrospectively reviewed. Antithrombin levels were recorded three days before to three days after peak C-reactive protein to correlate antithrombin levels with inflammatory activity. Using the concept of developmental haemostasis, patients were divided into groups <1 yr and ≥1 yr of age.ResultsIn both age groups, survivors had significantly higher levels of antithrombin than did deceased patients. An optimal threshold level for antithrombin was calculated by ROC analysis for survival: 41.5% (<1 yr) and 67.5% (≥1 yr). The mortality rate above this level was 3.3% (<1 yr) and 9.5% (≥1 yr), and below this level 41.7% (<1 yr) and 32.2% (≥1 yr); OR 18.8 (1.74 to 1005.02), p = 0.0047, and OR 4.46 (1.54 to 14.89), p = 0.003. In children <1 yr with antithrombin levels <41.5% the rate of respiratory failure (66.7%) was significantly higher than in patients with antithrombin levels above this threshold level (23.3%), OR 6.23 (1.23 to 37.81), p = 0.0132. In children ≥1 yr, both liver failure (20.3% vs 1.6%, OR 15.55 (2.16 to 685.01), p = 0.0008) and a dysfunctional intestinal tract (16.9% vs 4.8%, OR 4.04 (0.97 to 24.08), p = 0.0395) occurred more frequently above the antithrombin threshold level of 67.5%.ConclusionIn pediatric septic patients, significantly increased mortality and levels of organ failure were found below an age-dependent antithrombin threshold level. Antithrombin could be useful as a prognostic marker for survival and occurrence of organ failure in pediatric sepsis.

Impact of Antithrombin Supplementation and Concomitant Anticoagulation Therapy in Pediatric Patients With Disseminated Intravascular Coagulation

“…23 A low AT level in septic children is a good prognostic marker for MODS and is associated with higher mortality. 27 In the present study, median AT activity at day 0 was significantly lower for patients <6 months of age, compared to patients >6 months of age (35.5% and 45.5%, P ¼ .005). However, median c-AT activity corrected by an age-equivalent AT activity of <6 months of age was almost equal to that of patients >6 months of age (46.8% and 43.3%, P ¼ .980).…”

Effects of Serum Albumin Levels on Antithrombin Supplementation Outcomes Among Patients With Sepsis-Associated Coagulopathy: A Retrospective Study

“…They demonstrated that antithrombin optimized coagulation and served as a potential regulator of inflammatory processes and subsequent tissue damage. 20 Therefore, antithrombin supplementation may be more effective in patients with hypoalbuminemia, rather than in those with normal albumin levels. Taken together, our findings suggest that antithrombin has a diminished effect in patients with normal albumin levels, which indicates that antithrombin supplementation should be reserved for patients with reduced serum albumin levels.…”

Thrombin Generation Profile in Various Lymphoma Sub-Groups and Its Augmentation by Andexanet Alfa

“… 38 , 39 Increased thrombin generation in antithrombin-deficient patients has also been reported. 40 Another possibility is that andexanet alfa treatment may also inhibit the endogenous heparan sulfate glycosaminoglycan (GAGs) complexes with endothelium bound antithrombin. 41 Taken together, andexanet alfa produces additional effects on endogenous modulators which regulates hemostasis including TFPI, antithrombin, GAGs and may also influence other heparin like mediators.…”