From the Guidelines
Prolonged Activated Partial Thromboplastin Time (APTT) in sepsis patients indicates coagulation dysfunction, specifically a hypocoagulable state that may reflect consumption of clotting factors or development of disseminated intravascular coagulation (DIC), as supported by the most recent study 1.
Clinical Implications
This finding suggests that the intrinsic and common coagulation pathways are impaired, which is common in sepsis due to the systemic inflammatory response triggering widespread activation of coagulation. Clinically, prolonged APTT values (typically above 40 seconds) should prompt immediate evaluation for bleeding risk and consideration of DIC, which requires monitoring of additional parameters including:
- Platelet count
- Fibrinogen levels
- D-dimer
- Prothrombin time Management depends on the severity of coagulation abnormalities and may include:
- Supportive care
- Treatment of the underlying infection with appropriate antibiotics
- In severe cases with active bleeding, replacement of clotting factors with fresh frozen plasma The pathophysiology involves inflammatory cytokines disrupting the balance between procoagulant and anticoagulant mechanisms, leading to both microvascular thrombosis and bleeding tendencies, as discussed in 1 and 1.
Monitoring and Treatment
Serial APTT measurements are valuable for monitoring disease progression and response to treatment in septic patients. The importance of monitoring coagulation status sequentially is highlighted in 1, emphasizing the need for early detection of DIC to potentially improve outcomes. Furthermore, the use of anticoagulant therapies, such as unfractionated heparin, may be beneficial in patients with sepsis-induced coagulopathy, as suggested by 1 and 1, although the effectiveness of these therapies requires further study.
Future Perspectives
The diagnostic criteria and management for sepsis-associated DIC are evolving, with a focus on simple and easy-to-use criteria, such as the SIC scoring system, which can help identify patients who may benefit from targeted therapies, as discussed in 1. The addition of new biomarkers, such as thrombin-related markers, may further improve the diagnostic accuracy and guide treatment decisions. However, the effectiveness of anticoagulant therapies, including antithrombin supplementation, requires high-quality evidence, as noted in 1.
From the Research
Prolonged Activated Partial Thromboplastin Time (APTT) Findings in Sepsis
Prolonged APTT findings in patients with sepsis can indicate a hypocoagulable state, which is associated with greater hospital mortality 2. The following points summarize the key findings:
- Prolonged APTT is a strong predictor of mortality in septic patients, independently of disease severity scores and standard coagulation tests on admission 2.
- Sepsis induces hypercoagulability, hypofibrinolysis, microthrombosis, and endothelial dysfunction, leading to multiple organ failure 2, 3.
- Coagulation system and platelets are fully activated in uncomplicated sepsis, with increased molecular activation markers of coagulation and platelets 3.
- In severe sepsis and septic shock, coagulation factors are depleted, and global coagulation tests are prolonged, indicating exhaustion of hemostasis 3.
Association with Mortality
The association between prolonged APTT and mortality in sepsis is supported by several studies:
- A retrospective single-center study found that APTT prolongation on ICU admission is associated with increased mortality in patients with severe sepsis or septic shock, independent of SAPS 3 score 4.
- Another study found that the TAT/PIC ratio, which includes APTT, is significantly higher in septic patients with organ dysfunction compared to those without organ dysfunction 5.
Clinical Implications
The findings suggest that prolonged APTT in sepsis may be a useful prognostic marker for mortality:
- Monitoring APTT and other coagulation parameters may help identify patients at high risk of mortality and guide therapeutic decisions 2, 4.
- Further research is needed to fully understand the mechanisms underlying the association between prolonged APTT and mortality in sepsis, and to develop effective therapeutic strategies to improve outcomes in these patients 6.