Association of hemodilution and blood pressure in uncontrolled bleeding.

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.

PLASMA RESUSCITATION PROMOTES COAGULATION HOMEOSTASIS FOLLOWING SHOCK-INDUCED HYPERCOAGULABILITY.

BACKGROUND: Increased thrombin generation in injured patients possibly contributes to early consumption of coagulation factors, exacerbating hemorrhage. Identifying optimal resuscitation products for restoring plasma homeostasis following injury is important for improving management of these patients. OBJECTIVES: To determine the effects of crystalloid versus plasma resuscitation on thrombin generation in a rat model of trauma and hemorrhagic shock (HS). PATIENTS/METHODS: Rats were subjected to trauma and HS followed by resuscitation with Lactated Ringer's solution (LR) or fresh frozen plasma (FFP). Blood was collected at baseline, decompensation, and 3-h post-resuscitation. Thrombin generation was measured by calibrated automated thrombogram and antithrombin III (AT) by ELISA. In a prospective observational study, admission blood samples were collected on highest-level activation trauma patients and diluted with LR or FFP for thrombin generation analysis. RESULTS: Resuscitation with LR resulted in persistent hypercoagulability; however, FFP resuscitation reversed this hypercoagulability to baseline thrombin generation or below. Plasma AT levels decreased following HS and remained low in rats receiving LR, but were corrected in rats receiving FFP. Similarly, in trauma patient plasma LR increased thrombin generation while FFP reduced it. However, results with AT-deficient plasma dilution were similar to LR. In patients with admission hypocoagulability, FFP slightly increased thrombin generation. CONCLUSIONS: HS in rats is associated with increased thrombin generation and resuscitation with FFP, not LR, reverses hypercoagulability. Dilution of trauma patient plasma with LR or FFP yielded similar results; however, the modulatory effects of FFP were attenuated when AT was absent. Importantly, FFP reduced thrombin generation in hypercoagulable patient plasma, but slightly increased thrombin generation in hypocoagulable patient plasma. Thus, FFP restores hemostatic balance following trauma and HS which is, in part, by delivering AT.

Establishment of methods for performing thrombelastography and calibrated automated thrombography in rats.

Rodent models of hemorrhagic shock are paramount to our understanding of the pathophysiology of this disease, the effects on coagulation and in exploring the utility of resuscitative methods for managing patients in shock. These models usually require serial blood sampling during experimentation. The lack of standardized practices for these experimental models has resulted in technical variability, discordance in the literature, and incomparable results on blood coagulation analysis between researchers, hindering substantial progress in the field of hemorrhagic shock. The aim of this study was to define the effects of cardiac puncture versus arterial catheterization on coagulation in a rat model to provide data supporting standardization of one practice over another. Blood was collected from anesthetized rats via cardiac puncture or femoral artery catheterization and hemostatic potential analyzed by thrombelastography and calibrated automated thrombography. Our data show that blood collected via cardiac puncture demonstrated hypercoagulability as indicated by faster rates of clot formation and thrombin generation, increased overall clot strength, and a greater thrombin-generating capacity when compared with blood collected via femoral artery catheter. We conclude that blood collection methods have a profound effect on hemostatic potential, and standardization of these practices is necessary to define the effects of shock on coagulation in rodents.