Publications (5) View all
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Article: Association of hemodilution and blood pressure in uncontrolled bleeding.
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ABSTRACT: BACKGROUND: Hemodynamic status and coagulation capacity affect blood loss after injury. The most advantageous fluid and blood pressure to optimize resuscitation and minimize perturbation of coagulation are unclear. We investigated interactions of isovolumic hemodilution on hemodynamics, coagulation, and blood loss after injury. METHODS: Twenty-five male rats were randomized into three groups (Whole Blood Uncontrolled Blood Pressure [WBU], n = 7; Lactated Ringers Uncontrolled Blood Pressure [LRU], n = 10; Whole Blood Controlled Blood Pressure [WBC], n = 8) with isovolumic hemodilution of 50% blood volume, with and without control of pre-injury blood pressure. All rats underwent uniform grade IV liver injury 30 min after serial exchanges. Post-injury blood loss and coagulation function were measured. RESULTS: Dilution occurred, determined by hematocrit, with LRU having a greater reduction. Pre-injury mean arterial pressure (MAP) decreased compared with baseline (98 ± 7 mmHg) with LRU (62 ± 14 mmHg) and WBC (61 ± 10 mmHg), resulting in WBU (101 ± 13 mmHg) being significantly higher and not changed from baseline. Post-injury, MAP decreased from pre-injury, with LRU significantly lower than the other two groups. No differences were observed in prothrombin time/international normalized ratio or thromboelastography. Bleed volume was significantly different between groups: WBU < WBC < LRU and associated with the pre-injury MAP. Controlling baseline MAP, dilution with Lactated Ringers (LR) resulted in greater blood loss than whole blood (3.0 ± 0.4 versus 1.9 ± 0.3 mL). CONCLUSIONS: In this rat model of liver injury, blood loss was associated with baseline MAP and type of fluid used for dilution. Hemodilution with LR did not produce coagulopathy based on laboratory values. When controlling baseline MAP, dilution with LR increased bleeding, confirming a functional coagulopathic state.Journal of Surgical Research 04/2013; · 2.25 Impact Factor -
Article: Influence of resuscitation fluids, fresh frozen plasma and antifibrinolytics on fibrinolysis in a thrombelastography-based, in-vitro, whole-blood model.
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ABSTRACT: Hyperfibrinolysis has been identified as a mechanism of trauma coagulopathy associated with poor outcome. The aim of the study was to create a trauma coagulopathy model (TCM) with a hyperfibrinolysis thrombelastography (TEG) pattern similar to injured patients and test the effects of different resuscitation fluids and antifibrinolytics on fibrinolysis. TCM was established from whole blood by either 15% dilution with isotonic saline, lactated Ringer's, Plasma-Lyte, 5% albumin, Voluven, Hextend, 6% dextran in isotonic saline or 30% dilution with lactated Ringer's plus Voluven and supplementation with tissue factor and tissue plasminogen activator (tPA). These combinations resulted in a TCM that could then be 'treated' with tranexamic acid (TXA) or 6-aminocaproic acid (ACA). Clot formation was evaluated by TEG. Whole-blood dilution by 15% with crystalloids and albumin in the presence of tissue factor plus tPA resulted in an abnormal TEG pattern and increased fibrinolysis, as did dilution with synthetic colloids. TXA 1 μg/ml or ACA 10 μg/ml were sufficient to suppress fibrinolysis when TCM was diluted 15% with lactated Ringer's, but 3 μg/ml of TXA or 30 μg/ml of ACA were needed for fibrinolysis inhibition induced by simultaneous euvolemic dilution with lactated Ringer's plus Voluven by 30%. A total of 15% dilution of whole blood in the presence of tissue factor plus tPA results in a hyperfibrinolysis TEG pattern similar to that observed in severely injured patients. Synthetic colloids worsen TEG variables with a further increase of fibrinolysis. Low concentrations of TXA or ACA reversed hyperfibrinolysis, but the efficient concentrations were dependent on the degree of fibrinolysis and whole-blood dilution.Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis 02/2013; · 1.25 Impact Factor -
Article: Hemostatically distinct FFPs equally improve abnormal TEG variables in an in vitro dilutional coagulopathy model.
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ABSTRACT: To improve fresh frozen plasma (FFP) availability, thawed plasma is stored at 4°C for up to 5 days and considered equivalent to freshly thawed FFP. However, we have shown that hemostatic potential of thawed plasma is highly variable between donors and significantly diminished during storage. We hypothesized that smaller volumes of plasma with higher hemostatic potential (FFP-H) would be needed to restore normal thrombelastogram (TEG) values compared to plasma with lower hemostatic potential (FFP-L). A dilutional coagulopathy model was established from whole blood by diluting plasma with saline to 23%, while cellular components were kept unchanged. Saline was gradually replaced with equal volumes of FFPs with distinctive hemostatic potentials, which was evaluated by the calibrated automated thrombogram. Clot formation in the presence of tissue factor was evaluated by TEG at baseline and after addition of increasing concentrations of FFP-H and FFP-L. Blood dilution with saline in the presence of tissue factor resulted in abnormal TEGs that resemble a pattern observed in severely bleeding trauma patients. All FFPs produced similar improvements in TEG variables despite different hemostatic potentials. TEG changes were solely dependent on FFP volume and reached the normal reference range when plasma concentration increased to 40%. Plasma dilution and tissue factor in whole blood results in an abnormal TEG with a hyperfibrinolytic pattern. A plasma concentration of at least 40% was necessary for TEG normalization after dilution with saline. An effect of FFPs' hemostatic potential on clot formation could not be detected by TEG in this in vitro model.Thrombosis Research 03/2012; 130(3):429-34. · 2.44 Impact Factor -
Article: Decline in platelet microparticles contributes to reduced hemostatic potential of stored plasma.
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ABSTRACT: In an effort to administer life-saving transfusions quickly, some trauma centers maintain thawed plasma (TP). According to AABB, TP is approved for transfusion for up to five days when stored at 1-6° C. However, the alterations in microparticles (MP) contained in the plasma, which are an integral component of plasma's hemostatic capacity, are not well characterized. We report on MP changes in TP between its initial thaw (FFP-0) and five days (FFP-5) of storage. FFP units (n=30) were thawed at 37° C and kept refrigerated for five days. Phenotypes of residual cells, which include platelets, erythrocytes, leukocytes, monocytes, endothelial cells, and MP counterparts of each cell type, were analyzed by flow cytometry. Functional assays were used for MP procoagulant activity, plasma thrombin generation, and clotting properties (thromboelastography). In FFP-0 the majority (94%) of residual cells were platelets, along with significant levels of platelet MPs (4408 × 10(3)/L). FFP-5 showed a decline in MP count by 50% (p<0.0001), and procoagulant activity by 29% (p<0.0001). FFP-5 exhibited only 54% (p<0.0001) of the potential for thrombin generation as FFP-0, while thromboelastography indicated a slower clotting response (p<0.0001) and a longer delay in reaching maximum clot (p<0.01). Removal of MP by filtration resulted in reduced thrombin generation, while the MP replacement restored it. Decline in MP with storage contributes to FFP-5's reduced ability to provide the hemostatic potential exhibited by FFP-0, suggesting the presence of platelet MPs in freshly TP may be beneficial and protective in the initial treatment of hemorrhage.Thrombosis Research 03/2011; 128(1):35-41. · 2.44 Impact Factor -
Article: Multiple levels of degradation diminish hemostatic potential of thawed plasma.
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ABSTRACT: Severe bleeding after injury requires transfusion of blood products, including fresh frozen plasma (FFP). Many centers are keeping thawed plasma (TP) ready for massively transfused patients. According to the American Association of Blood Banks Standards, TP is approved for transfusion up to 5 days after thawing, when stored at 1°C to 6°C. However, there are no clinical data analyzing the effects of the approved 5-day storage on plasma. We hypothesize that the hemostatic potential (HP) of freshly thawed (FFP-0) was superior to plasma stored for 5 days (FFP-5). FFP from 30 single donors were thawed at 37°C and kept at 1°C to 6°C for 5 days. HP was evaluated at day 0 and 5 by measuring kinetics of thrombin generation (TG), kinetics of clot formation by thromboelastography, clotting factors and inhibitors, and cell-derived microparticles (MPs) by flow cytometry. When comparing FFP-5 to FFP-0, FFP-5 exhibited only 40% of the potential of FFP-0 for TG (6.2 nM/min vs. 14.3 nM/min, p<0.0001), a slower clotting response via thromboelastography (reaction time: 4.3 minutes vs. 3.2 minutes, p<0.0001) and a longer delay in reaching maximum thrombus generation (5.7 minutes vs. 4.6 minutes, p<0.01). Diminished HP was accompanied by a significant decline in multiple coagulation proteins, including FV, VII, VIII, von Willebrand factor, and free Protein S, by up to 30%, and a decrease of 50% in MP counts. The HP and clot forming ability of TP significantly declined with storage. Hence, freshly TP may have a greater ability to restore hemostasis and correct coagulopathy compared with FFP-5. The clinical consequences for transfused patients deserve further exploration.The Journal of trauma 01/2011; 70(1):71-9; discussion 79-80. · 2.48 Impact Factor
