title: Effects of bovine polymerized hemoglobin on coagulation in controlled hemorrhagic shock in swine.
abstract: HBOC-201, a bovine polymerized hemoglobin, has been proposed as a novel oxygen-carrying resuscitative fluid for patients with hemorrhagic shock (HS). Herein, we evaluated the hemostatic effects of HBOC-201 in an animal model of HS. A 40% blood loss-controlled hemorrhage and soft tissue injury were performed in 24 invasively monitored Yucatan mini-pigs. Pigs were resuscitated with HBOC-201 (HBOC) or hydroxyethyl starch (HEX), or were not resuscitated (NON) based on cardiac parameters during a 4-h prehospital phase. Afterward, animals received simulated hospital care for 3 days with blood or saline transfusions. Hemostasis measurements included in vivo bleeding time (BT), thromboelastography (TEG), in vitro bleeding time (platelet function; PFA-CT), prothrombin time (PT), and partial thromboplastin time (PTT). Serum lactate was measured and lung sections were evaluated for microthrombi by electron microscopy. During the prehospital phase, BT remained unchanged in the HBOC group. TEG reaction time increased in HBOC pigs during the late prehospital phase and was greater than in NON or HEX pigs at 24 h (P = 0.03). TEG maximum amplitude was similar for the two fluid-resuscitated groups. PFA-CT increased in both resuscitated groups but less with HBOC (P = 0.02) in the prehospital phase; this effect was reversed by 24 h (P = 0.02). In the hospital phase, PT decreased (P < 0.02), whereas PTT increased above baseline (P < 0.01). Lactic acidosis in HBOC and HEX groups was similar. Aspartate aminotransferase was relatively elevated in the HBOC group at 24 h. Electron microscopy showed no evidence of platelet/fibrin clots or microthrombi in any of the animals. Twenty-four-hour group differences mainly reflected the fact that all HEX animals (8/8) received blood transfusions compared with only one HBOC animal (1/8). In swine with HS, HBOC resuscitation induced less thrombopathy than HEX during the prehospital phase. Mild delayed effects on platelet and clot formation during the hospital phase are transient and likely related to fewer blood transfusions. In swine with HS, HBOC resuscitation induced less thrombopathy than HEX during the prehospital phase but more thrombopathy in the hospital phase. The delayed effects on platelet and clot formation during the hospital phase are transient and may be related to the need for fewer blood transfusions.
authors.affiliation: Naval Medical Research Center, RMD Hematomimetics Program, Silver Spring, Maryland 20910-7500, USA. arnaudf@nmrc.navy.mil
authors.forename: Françoise
authors.initials: F
authors.lastname: Arnaud
authors.forename: Mike
authors.initials: M
authors.lastname: Hammett
authors.forename: Ludmila
authors.initials: L
authors.lastname: Asher
authors.forename: Nora
authors.initials: N
authors.lastname: Philbin
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rice
authors.forename: Feng
authors.initials: F
authors.lastname: Dong
authors.forename: Bruce
authors.initials: B
authors.lastname: Pearce
authors.forename: William S
authors.initials: WS
authors.lastname: Flournoy
authors.forename: Carol
authors.initials: C
authors.lastname: Nicholson
authors.forename: Richard
authors.initials: R
authors.lastname: McCarron
authors.forename: Daniel
authors.initials: D
authors.lastname: Freilich
mesh_terms: D000140:Acidosis, Lactic; D000818:Animals; D001760:Bleeding Time; D001777:Blood Coagulation; D001792:Blood Platelets / Q000378:metabolism; D002417:Cattle; D005337:Fibrin / Q000378:metabolism; D006400:Hematocrit; D006454:Hemoglobins / Q000737:chemistry* / Q000494:pharmacology; D006470:Hemorrhage; D006487:Hemostasis; D006863:Hydrogen-Ion Concentration; D006895:Hydroxyethyl Starch Derivatives / Q000737:chemistry; D007773:Lactates / Q000097:blood; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008854:Microscopy, Electron; D009206:Myocardium / Q000378:metabolism; D009336:Necrosis; D010100:Oxygen / Q000378:metabolism; D010314:Partial Thromboplastin Time; D011108:Polymers / Q000737:chemistry; D011517:Prothrombin Time; D012771:Shock, Hemorrhagic / Q000378:metabolism* / Q000628:therapy*; D012965:Sodium Chloride / Q000494:pharmacology; D013552:Swine; D013916:Thrombelastography; D013997:Time Factors
chemical_list: D006454:Hemoglobins; D006895:Hydroxyethyl Starch Derivatives; D007773:Lactates; D011108:Polymers; C096798:HBOC 201; D012965:Sodium Chloride; D005337:Fibrin; D010100:Oxygen