Hematology patterns after hemoglobin‐based oxygen carrier resuscitation from severe controlled hemorrhage with prolonged delayed definitive care

Arnaud, Françoise; Fasipe, Daniel; Philbin, Nora; Rice, Jennifer; Flournoy, W. Shannon; Ahlers, Stephen; McCarron, Richard M.; Freilich, Daniel

doi:10.1111/j.1537-2995.2007.01435.x

Cited by 12 publications

(10 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mechanism is unclear and could be completely plasmin independent, or could be through binding of HBOC to plasminogen, thereby directly converting it to plasmin or blocking inhibitor binding sites. These results are consistent with previous reports that recognize coagulopathy in studies of HBOCs (27, 28), and it is important to note that fibrinolysis may be a component of this coagulopathy.…”

Section: Discussionsupporting

confidence: 93%

Hemoglobin-based oxygen carriers promote systemic hyperfibrinolysis that is both dependent and independent of plasmin

Morton

Moore

et al. 2017

Journal of Surgical Research

View full text Add to dashboard Cite

Background Hyperfibrinolysis plays an integral role in the genesis of trauma-induced coagulopathy (TIC). Recent data demonstrates that red blood cell (RBC) lysis promotes fibrinolysis; however, the mechanism is unclear. Hemoglobin-based oxygen carriers (HBOC) have been developed for resuscitation and have been associated with coagulopathy. We hypothesize that replacement of whole blood (WB) using an HBOC results in a coagulopathy due to the presence of free hemoglobin. Materials and Methods Whole blood was sampled from healthy donors (n=6). The clotting profile of each citrated sample was evaluated using native thrombelastography (TEG). Serial titrations were performed using both HBOC (Polyheme) and normal saline (NS) (5%, 25%, and 50%) and evaluated both with and without a 75 ng/microliter tissue-plasminogen activator (tPA) challenge. Tranexamic acid (TXA) was added to inhibit plasmin dependent fibrinolysis. Fibrinolysis was measured and recorded as LY30, the percentage of clot lysis at 30 minutes after maximal clot strength. Dilution of WB with NS or HBOC was correlated using LY30 via Spearman Rho coefficients. Groups were also compared using a Friedman test and post-hoc analysis with a Bonferroni adjustment. Results TPA provoked fibrinolysis was enhanced by both HBOC (median LY30 at 5%, 25%, 50% titrations: 11%, 21%, 44%; Spearman=0.94; p<0.001) and NS (11%, 28%, 58%; Spearman=0.790; p<0.001). However, HBOC also enhanced fibrinolysis without the addition of tPA (1%, 4%, 5%; Spearman=0.735; p=0.001) and NS did not (1%, 2%, 1%; r=0.300; p=0.186.Moreover, addition of TXA did not alter or inhibit this fibrinolysis (WB vs 50% HBOC: 1.8% vs 5.7%, p=0.04). There was no significant difference in fibrinolysis of HBOC with or without TXA (50% HBOC vs 50% HBOC +TXA: 5.6% vs 5.7%, p=0.92). Additionally, the increased fibrinolysis seen with NS was reversed when TXA was present (WB vs 50% NS: 1.8% vs 1.7%, p=1.0). Conclusion HBOCs enhance fibrinolysis both with and without addition of tPA; moreover, this mechanism is independent of plasmin as the phenomenon persists in the presence of TXA. Our findings indicate the hemoglobin molecule or its components stimulate fibrinolysis by both tPA-dependent and innate mechanisms.

show abstract

Section: Discussionsupporting

confidence: 93%

Hemoglobin-based oxygen carriers promote systemic hyperfibrinolysis that is both dependent and independent of plasmin

Morton

Moore

et al. 2017

Journal of Surgical Research

View full text Add to dashboard Cite

show abstract

“…HBOC-201 (HB) or Hextend (HEX) (see Supplementary material for composition) 24 was infused through the femoral vein at 10 ml/kg while SNP or saline was administered concomitantly but separately via right jugular vein. SNP-treated animals received three fixed dose infusions of 0.8 g/kg/min.…”

Section: Treatment Groups and Fluid Infusionmentioning

confidence: 99%

“…This model has been used in our laboratory to screen resuscitation fluids and reliably induced pathophysiologic manifestations of HS in swine that were improved after HBOC-201 resuscitation. 6,17,24 The aim of this study was to assess SNP's effectiveness for neutralizing HBOC-201-induced systemic and pulmonary vasoconstriction in a simple HS swine model.…”

Section: Introductionmentioning

confidence: 99%

Sodium nitroprusside ameliorates systemic but not pulmonary HBOC-201-induced vasoconstriction: An exploratory study in a swine controlled haemorrhage model

et al. 2012

Self Cite

View full text Add to dashboard Cite

“…The exact reason for it was unclear and may be related to protein precipitation, thus methodologies using dual wavelength (Advia device) were considered and readings were possible with wet chemistry without interference up to 6 g/dL [12]. The upper limit of HBOC-201 set in this study corresponded to the maximum plasma hemoglobin concentration reached at 4 hours in the blood samples of hemorrhaged swine ( Figure 4); thereafter the levels decreased due, in part, to HBOC-201 degradation and hemodilution [6,15]./n vivo, secretion of lipase and amylase up to 4 h was low (not different than baseline) but levels rose after 4 h and peaked around 24 h. The fact that plasmatic HBOC was at its highest concentration at 4 h and decreased rapidly thereafter indicated that the presence of HBOC-201 in the present study would minimally affect assay readings as the experiment progresses. The increase of enzyme together with residual HBOC-201 brings the maximum likelihood of interference around 24 h post treatments.…”

Section: Discussionmentioning

confidence: 88%

“…Blood withdrawal was performed via catheter withdrawal on anesthetized Yucatan mini-pigs (-32kg). Surgical procedures and findings from these studies have been extensively reported previously [ 6,14,15]. Briefly, the animals were randomly allocated to different treatments groups: no resuscitation (None) (n = 4), HBOC-201 (n = 14) and…”

Section: Laboratory Animals" Institute Of Laboratory Animalsmentioning

confidence: 99%

Amylase and Lipase Detection in Hemorrhaged Animals Treated with HBOC-201

Arnaud

McCarron

Freilich

2010

Artificial Cells, Blood Substitutes, and Biotechnology

Self Cite

View full text Add to dashboard Cite

HBOC-201 may alter lipase and amylase detection on chemistry analyzers using optical methods and affect pancreatic function after trauma. Amylase and lipase measurements were correlated against HBOC-201 to evaluate interference on samples spiked with 0-6g/dL HBOC-201. The detection threshold was 2.5g/dL or none when measured, respectively, on Vitros 250 or Advia 1650 instruments. Amylase and lipase from blood samples collected from 55% EBV hemorrhaged Yucatan min-pigs showed peaks around 24-48 hours. Amylase increase was not significant between treatments but lipase was higher in HBOC-201-treated animals. Animals particularly affected by the injury had elevated enzymes after hemorrhagic shock, without significant clinical consequences.

show abstract

Hematology patterns after hemoglobin‐based oxygen carrier resuscitation from severe controlled hemorrhage with prolonged delayed definitive care

Cited by 12 publications

References 39 publications

Hemoglobin-based oxygen carriers promote systemic hyperfibrinolysis that is both dependent and independent of plasmin

Hemoglobin-based oxygen carriers promote systemic hyperfibrinolysis that is both dependent and independent of plasmin

Sodium nitroprusside ameliorates systemic but not pulmonary HBOC-201-induced vasoconstriction: An exploratory study in a swine controlled haemorrhage model

Amylase and Lipase Detection in Hemorrhaged Animals Treated with HBOC-201

Contact Info

Product

Resources

About