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Scientific Calendar November 2018

Which lab parameters could be useful in assessment of disseminated intravascular coagulation (DIC) in septic patients?

Platelet count

vWF Activity

PT/PTT/INR

D-dimer/FDP

Lupus Anticoagulant

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Scientific Background information

Sepsis is a life-threatening organ dysfunction caused by an unregulated host response to infection [1]. White blood cells (WBC) play one of the key roles in immune response to infection. They are the first cells of the immune system to migrate to a site of inflammation, where they play an important role in pathogen elimination. The macrophages, monocytes and neutrophils are known to be a source of tissue factor (TF) and participate in the direct activation of the coagulation cascade in the early phases of sepsis. Due to ongoing activation of the coagulation system and other factors, such as impaired synthesis and increased degradation of coagulation proteins and protease inhibitors, exhaustion of factors and platelets may occur, potentially resulting in profuse bleeding from various sites.  But more common is the occurrence of thrombosis in small and mid-size vessels [5]. In response to pathogen stimuli, activated platelets bind to neutrophils causing the secretion of nuclear content resulting in neutrophil extracellular trap (NET) formation. NETs activate factor XII, inactivate tissue factor pathway inhibitor (TFPI) and provide places for platelet binding and aggregation. NETs have been shown to intercalate within a fibrin clot and form a structural network that is resistant to lysis. TF-mediated and NET-mediated immunothrombosis is a significant factor in early, innate immune response against bacterial spreading, facilitating the recognition and destruction of pathogens, but may lead to disseminated intravascular coagulation (DIC) if uncontrolled [6].

Sepsis is frequently complicated by coagulopathy and in about 35 % of severe cases is complicated by DIC [2]. In the context of severe sepsis and septic shock, DIC is related to increased severity, greater number and seriousness of organ failures, more frequent side-effects from treatment itself, and worse outcomes [3].

Screening assays (global coagulation tests) using scoring parameters, such as prothrombin time, fibrinogen level, platelet count, and levels of fibrin-related markers, provide important information about the degree of coagulation factor activation and consumption. There are at least two separate frameworks of diagnostic criteria for sepsis-induced DIC based on general coagulation tests and clinical symptoms: the International Society of Thrombosis and Haemostasis (ISTH) overt DIC diagnostic criteria and the Japanese Association for Acute Medicine (JAAM) DIC criteria. Recently a new diagnostic criterion was also proposed for sepsis-induced coagulopathy (SIC) exclusively designed for sepsis-associated DIC [7].

The main purpose for such screening tools and diagnostic criteria should be supporting physicians in decision-making for further testing or initiation of treatment to reduce morbidity, mortality, and their associated costs.  Recent studies have shown that prevention of DIC in septic patients by prescribing anticoagulant therapy could potentially reduce mortality from multisystem organ failure [4]. Therefore, the utility and necessity of DIC screening should be determined according to whether it can reduce mortality in patients with sepsis.

References

  1. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).
  2. Kohji Okamoto et al. (2016): Sepsis and disseminated intravascular coagulation. J Intensive Care. 2016; 4: 23.
  3. Jose J Zaragoza et al. (2017): Current approach to disseminated intravascular coagulation related to sepsis - organ failure type. World J Hematol. Feb 6, 2017; 6(1): 11-16.  doi: 10.5315/wjh.v6.i1.11
  4. Yutaka Umemura, et al. (2018): Screening itself for disseminated intravascular coagulation may reduce mortality in sepsis: A nationwide multicenter registry in Japan. Thrombosis Research 161 (2018) 60–66.
  5. Marcel Levi1, MD and Marie Scully, MD et al. (2017): How I treat Disseminated Intravascular Coagulation. Blood First Edition Paper, prepublished online December 18, 2017; DOI 10.1182/blood-2017-10-804096
  6. Małgorzata Lipińska-Gediga et al. (2016): Coagulopathy in sepsis — a new look at an old problem. Anaesthesiology Intensive Therapy 2016, vol. 48, no 5, 352–359. ISSN 1642–5758 10.5603/AIT.a2016.0051
  7. Iba T, Nisio MD, Levy JH, et al. (2017): New criteria for sepsis-induced coagulopathy (SIC) following the revised sepsis definition: a retrospective analysis of a nationwide survey. BMJ Open 2017;7:e017046. doi:10.1136/bmjopen-2017-017046
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