Effect of Renin-Angiotensin System on Platelet in Patient With Sepsis
Condition: Sepsis
MeSH terms: Sepsis; Toxemia
Study type: Observational

Summary: 
      As a common and serious medical condition , sepsis is a life-threatening organ dysfunction
      caused by a dysregulated host response to infection , which is a major and familiar cause of
      death in intensive care units(ICU). As a frequent laboratory abnormality in patients with
      sepsis , thrombocytopenia on intensive care unit admission is independently associated with
      increased mortality in patients. Furthermore, a low platelet count is a marker with further
      significance , which is always used for evaluating the prognosis of patients. Herein, this
      study aimed to investigate the effect of renin-angiotensin system on thrombocytopenia in
      patient with sepsis and explore the possible underlying molecular mechanisms.
    

Detailed description: 
      Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host
      response to infection. According to the Centers for Disease Control and Prevention, sepsis
      occurs in 1.5 million Americans annually and it causes more than 250,000 deaths annually in
      the United States alone. Thrombocytopenia is a frequent laboratory abnormality in patients
      with sepsis. Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or
      more represents organ dysfunction . As the index of coagulation , platelet count is involved
      in SOFA . The changes of quality and quantity in platelet is closely associated with the
      morbidity and mortality of infectious diseases . Furthermore , thrombocytopenia is
      independently related with increased mortality in severe sepsis patients . Therefore ,
      rectify of thrombocytopenia is of significant role to prevent potentially life-threatening
      complications in patients with sepsis. Currently , donor-derived platelet transfusion is the
      only treatment of severe thrombocytopenia seen in sepsis . However , platelets used in the
      clinic is associated with lots of concerns , for example , sufficient availability , quality
      , and complications due to immunologic and/or infectious issues . So , it is necessary and
      urgent to focus our efforts on the development of therapeutic agents to overcome our
      dependence on donor-derived platelets for transfusion .

      Deriving from megakaryocytes , platelets are anucleate , having only cytoplasmic components
      imparted by megakaryocytes residing in the bone marrow,circulating in the bloodstream and
      having an important role in the body because of their functions in hemostasis , thrombosis ,
      inflammation , and vascular biology . There are numerous reasons why thrombocytopenia often
      accompany patients with sepsis , such as platelet-vessel wall interaction , excessive
      consumption of platelet in DIC and platelet activation . Furthermore, research indicates that
      the intrinsic machinery for programmed cell death (apoptosis) regulates the life span of the
      anucleate platelet. Besides, several mechanisms have been proposed to explain the platelet
      apoptosis ,among which reactive oxygen sepsis(ROS) appears to play critical role.

      More studies have shown that the renin-angiotensin-aldosterone system(RAAS) is activated in
      sepsis,providing an important physiologic mechanism to preserve volume status and vascular
      tone. As the main effect factor of the RAAS, angiotensin II plays a key role in several
      biological processes, including apoptosis,coagulation ,cell growth, and inflammatory response
      in addition to its classical hemodynamic function of regulating arterial blood
      pressure.Numerous researches claimed , angiotensin II (Ang II) has been associated with organ
      failures and mortality by promoting the generation of a large amount of intracellular ROS.
      However, no studies have shown the relation between Ang II-related ROS and thrombocytopenia
      during sepsis.

      Therefore, the investigators hypothesized that Ang II , by promoting the generation of a
      large amount of intracellular ROS , plays a critical role in the development of
      thrombocytopenia during sepsis.In the present study, the investigators will analyze the
      mechanism of platelet apoptosis during sepsis, and explore whether angiotensin II receptor
      blockers could protect ROS induced platelet apoptosis, which is helpful for prevention and
      treatment of thrombocytopenia.
    

Intervention name(s): control; sepsis
Intervention type(s): Other; Other
Other intervention name(s): healthy volunteers; patients with sepsis
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        patients with sepsis
      
Biospecimen description: 
      plasma seperated from venous blood via centrifugation
    
Keywords: thrombocytopenia,Renin-Angiotensin System,platelet