title: Traumatic Hemothorax Blood Contains Elevated Levels of Microparticles that are Prothrombotic but Inhibit Platelet Aggregation.
abstract: Autotransfusion of shed blood from traumatic hemothorax is an attractive option for resuscitation of trauma patients in austere environments. However, previous analyses revealed that shed hemothorax (HX) blood is defibrinated, thrombocytopenic, and contains elevated levels of D-dimer. Mixing studies with normal pooled plasma demonstrated hypercoagulability, evoking concern for potentiation of acute traumatic coagulopathy. We hypothesized that induction of coagulopathic changes by shed HX blood may be due to increases in cellular microparticles (MP) and that these may also affect recipient platelet function.
  
  
  
  Shed HX blood was obtained from 17 adult trauma patients under an Institutional Review Board approved prospective observational protocol. Blood samples were collected every hour up to 4 h after thoracostomy tube placement. The corresponding plasma was isolated and frozen for analysis. The effects of shed HX frozen plasma (HFP) and isolated HX microparticles (HMP) on coagulation and platelet function were assessed through mixing studies with platelet-rich plasma at various dilutions followed by analysis with thromboelastometry (ROTEM), platelet aggregometry (Multiplate), enzyme-linked immunosorbent assays, and flow cytometry. Furthermore, HFP was assessed for von Willebrand factor antigen levels and multimer content, and plasma-free hemoglobin.
  
  
  
  ROTEM analysis demonstrated that diluted HFP and isolated HMP samples decreased clotting time, clotting formation time, and increased α angle, irrespective of sample concentrations, when compared with diluted control plasma. Isolated HMP inhibited platelet aggregation in response to adenosine diphosphate, arachidonic acid, and collagen. HFP contained elevated levels of fibrin-degradation products and tissue factor compared with control fresh frozen plasma samples. MP concentrations in HFP were significantly increased and enriched in events positive for phosphatidylserine, tissue factor, CD235, CD45, CD41a, and CD14. von Willebrand factor (vWF) multimer analysis revealed significant loss of high molecular weight multimers in HFP samples. Plasma-free hemoglobin levels were 8-fold higher in HFP compared with fresh frozen plasma.
  
  
  
  HFP induces plasma hypercoagulability that is likely related to increased tissue factor and phosphatidylserine expression originating from cell-derived MP. In contrast, platelet dysfunction is induced by HMP, potentially aggravated by depletion of high molecular weight multimers of vWF. Thus, autologous transfusion of shed traumatic hemothorax blood may induce a range of undesirable effects in patients with acute traumatic coagulopathy.
authors.affiliation: *San Antonio Military Medical Center, Fort Sam Houston, TX †United States Army Institute of Surgical Research, Fort Sam Houston, TX ‡Department of Surgery, The University of Texas Health Science Center at San Antonio, San Antonio, TX §French Armed Forces Biomedical Research Institute, Marseille, France.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Mitchell
authors.forename: Maryanne C
authors.initials: MC
authors.lastname: Herzig
authors.forename: Chriselda G
authors.initials: CG
authors.lastname: Fedyk
authors.forename: Marc A
authors.initials: MA
authors.lastname: Salhanick
authors.forename: Aaron T
authors.initials: AT
authors.lastname: Henderson
authors.forename: Bijaya K
authors.initials: BK
authors.lastname: Parida
authors.forename: Nicolas J
authors.initials: NJ
authors.lastname: Prat
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Dent
authors.forename: Martin G
authors.initials: MG
authors.lastname: Schwacha
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Cap
mesh_terms: D000328:Adult; D001779:Blood Coagulation Factors / Q000378:metabolism; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006491:Hemothorax / Q000378:metabolism*; D006801:Humans; D007118:Immunoassay; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000502:physiology*; D010979:Platelet Function Tests; D011446:Prospective Studies; D013916:Thrombelastography; D014947:Wounds and Injuries / Q000378:metabolism*; D055815:Young Adult
chemical_list: D001779:Blood Coagulation Factors