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PubMed1995

Heparin neutralization by recombinant platelet factor 4 and protamine.

Protamine is the only available drug to reverse heparin-induced anticoagulation. Platelet factor 4 (PF4) is a basic polypeptide stored in platelets that reverses heparin. To investigate its potential as a reversal drug, we studied recombinant PF4 on anticoagulated blood obtained during cardiac surgery. Blood was obtained from 33 different venous reservoirs, and activated clotting time (ACT), heparin concentrations, and heparinase-ACT were determined. Anticoagulation was reversed by adding incremental PF4:heparin and protamine:heparin ratios to the heparinized blood, and the ACTs were determined (n = 21). Viscoelastic analysis of anticoagulation reversal was performed by adding protamine or PF4 at reversal ratios of 1.3:1 protamine:heparin, and 3.2:1 PF4:heparin using thromboelastography (n = 12). PF4 reversal ratios of 3:1 and 3.5:1 and protamine reversal ratios of 1:1, 1.5:1, 2:1 were not statistically different from heparinase-ACT values. There were no significant differences in viscoelastic measurements of clot formation between protamine and PF4. Recombinant PF4 at a 3.0:1 ratio reverses heparin-induced anticoagulation after cardiopulmonary bypass, and represents a potential alternative, especially for the protamine allergic patient.

Blood Coagulation↗
PubMed1995

Intravenous ketorolac tromethamine does not worsen platelet function during knee arthroscopy under general anesthesia.

Ketorolac (KT) prolongs bleeding time and inhibits platelet aggregation and platelet thromboxane production in healthy, awake volunteers. However, platelet function may be accentuated during the stress of general anesthesia (GA) and surgery. The purpose of this study was to investigate platelet function changes during a standard GA technique and surgery, as well as after a single intraoperative dose of intravenous (i.v.) KT. The study comprised 30 ASA physical status I patients undergoing GA for knee arthroscopy. Subjects were randomized to receive either KT 60 mg IV 15 min after skin incision or placebo i.v. Platelet function testing consisted of an Ivy bleeding time (BT), platelet aggregometry (PA) with adenosine diphosphate (ADP) and collagen, thromboelastography (TEG), and serum thromboxane B2 assays (TxB2). Platelet function testing was performed: 1) 15 min prior to the induction of GA, 2) 10 min after skin incision, and 3) 45 min after administration of study drug. BT decreased significantly in the placebo group from 263 +/- 133 s (mean +/- SD) preoperatively to 207 +/- 89 s postincision. BT did not change in the KT group. PA was unchanged after IV KT. TEG data was unchanged in both groups during anesthesia and surgery. TxB2 levels decreased markedly in the KT group from 106.9 +/- 96.2 ng/mL preoperatively to 0.4 +/- 1.2 ng/mL poststudy drug, P = 0.002. Platelet function appears to be accentuated during GA and surgery as evaluated by BT in the placebo group. Further, platelet function by BT, PA, and TEG was not inhibited after i.v. KT despite near complete abolition of TxB2 production.

Adolescent↗
PubMed1995

Autologous platelet-rich plasmapheresis: risk versus benefit in repeat cardiac operations.

Preoperative platelet-rich plasmapheresis has been suggested as a means of reducing homologous blood transfusions in cardiac surgical patients. The current study evaluated this technique in patients undergoing repeat cardiac operations. Fifty-two patients undergoing repeat myocardial revascularization and/or valve replacement were evaluated in a prospective randomized controlled study design. Autologous platelet-rich plasma (PRP) was harvested after the induction of anesthesia in the experimental group. After reversal of heparin, each patient received his or her autologous plasma. Patients in the control group did not have plasmapheresis and received standard transfusion therapy if coagulation variables were abnormal and a coagulopathy was clinically evident. Routine coagulation tests, thromboelastography (TEG), perioperative bleeding, and transfusion requirements were compared in the two groups. Forty-four patients completed the study. A significantly larger volume of packed red blood cells (PRBCs) was transfused in the PRP group than in the control group (P = 0.03). Platelet and fresh frozen plasma (FFP) transfusions did not differ between the two groups. Mediastinal tube drainage did not differ between the two groups. During PRP infusion, 60% of the patients required treatment for moderate hypotension (mean arterial pressure [MAP] < 60 mm Hg). Only 16% of control patients required treatment for hypotension during the comparable time period (P < 0.05). No patient who completed the study returned to the operating room for postoperative bleeding. These data suggest that PRP did not reduce postbypass bleeding or transfusion requirements in repeat cardiac surgical patients. Moreover, the incidence of hypotension during PRP reinfusion introduces a potential risk to the procedure in the absence of any obvious benefit.

Blood Coagulation Tests↗
PubMed1996

Intravenous ketorolac tromethamine worsens platelet function during knee arthroscopy under spinal anesthesia.

Ketorolac prolongs bleeding time and inhibits platelet aggregation and platelet thromboxane production in healthy, awake volunteers. However, platelet function was recently shown not to worsen after ketorolac was given during general anesthesia. The purpose of this study was to investigate platelet function changes during a standardized spinal anesthetic and surgery, as well as after a single intraoperative dose of intravenous (IV) ketorolac. The study comprised 30 ASA physical status I patients undergoing spinal anesthesia for knee arthroscopy. Subjects were randomized to receive either ketorolac 60 mg IV 15 min after skin incision or placebo IV. Platelet function testing consisted of an Ivy bleeding time, platelet aggregometry with adenosine diphosphate (ADP) and collagen, thromboelastography (TEG), and serum thromboxane B2 (TxB2) assays. Platelet function testing was performed: 1) 15 min prior to the performance of spinal anesthesia; 2) 10 min after surgical skin incision; and 3) 45 min after administration of study drug. The placebo group demonstrated no changes in any platelet function variable during spinal anesthesia and surgery relative to preoperative values. The ketorolac group, however, demonstrated a significant increase in bleeding time from postincision to poststudy drug data points (213 +/- 60s to 275 +/- 85s, mean +/- SD; P < 0.01). Further, platelet aggregometry to collagen was diminished in the ketorolac group from preoperative to poststudy drug data points (90.8% +/- 7.6% to 60.5% +/- 32.5%; P < 0.01). Platelet aggregometry with ADP, however, was unchanged in the ketorolac group. Platelet TxB2 production decreased dramatically in the ketorolac group from preoperative to poststudy drug data points (157.2 +/- 129.4 to 0.3 +/- 0.3 ng/mL; P < 0.01). Platelet function does not appear to be accentuated during spinal anesthesia as it is during general anesthesia. Unlike during general anesthesia, platelet function during spinal anesthesia is impaired, with respect to bleeding time and platelet aggregometry to collagen, by a single intraoperative dose of IV ketorolac.

Adolescent↗
PubMed1998

Conjugated estrogen reduces transfusion and coagulation factor requirements in orthotopic liver transplantation.

UNLABELLED: We conducted a prospective, randomized study to determine the efficacy of conjugated estrogen in reducing blood product transfusion during orthotopic liver transplantation (OLT). Patients undergoing OLT were included in the study. Only those having a reaction time of more than 30 mm or 15 min (19 -28 mm) on computed thromboelastography (CTEG) at the beginning of surgery were enrolled in the study. Patients were randomized to receive either conjugated estrogen (CE) or placebo. Every patient received a first dose of CE (100 mg i.v.) (20 mL) or placebo (20 mL of isotonic sodium chloride solution) at the beginning of the procedure and a second dose of CE (100 mg i.v.) or 20 mL of placebo (20 mL of isotonic sodium chloride solution) just after reperfusion of the new graft. The two groups were similar in age, weight, requirement for veno-veno bypass, time on veno-veno bypass, CTEG measurement, and preoperative hemoglobin and platelet values. Blood products were given in relation to hematocrit and coagulation (CTEG) variables, which were measured every hour during the surgery. The amount of transfused blood products did not differ in terms of units of cryoprecipitate, but the intraoperative requirements for red blood cells (6 +/- 3 vs 9 +/- 6 U; P = 0.05), platelets (12 +/- 8 U vs 18 +/- 10 U; P = 0.05) and fresh-frozen plasma (3 +/- 3 U vs 6 +/- 4 U; P = 0.001) was significantly less in the estrogen group than in the control group. We conclude that CE is associated with a significant decrease in use of fresh-frozen plasma, platelets, and red blood cells during OLT. IMPLICATIONS: In this study, we prospectively investigated whether i.v. conjugated estrogen could decrease blood product transfusion during orthotopic liver transplantation. Conjugated estrogen-treated patients received less fresh-frozen plasma, red blood cells, and platelets. In this population of patients, conjugated estrogen can be a useful addition in coagulation management during orthotopic liver transplantation.

Blood Coagulation Factors↗
PubMed2001

Pentalyte does not decrease heparinoid release but does decrease circulating thrombotic mediator activity associated with aortic occlusion-reperfusion in rabbits.

Hemorrhage and thrombosis are associated with major vascular and trauma surgery. Release of heparinoids and thrombotic mediators may contribute to these complications and have been described in rabbits after aortic occlusion-reperfusion. We hypothesized that the resuscitative fluid used could reduce heparinoid and thrombotic mediator release after aortic occlusion-reperfusion in rabbits as assessed by thromboelastographic variables (R, reaction time; alpha, angle; and G, a measure of clot strength). Anesthetized rabbits were administered lactated Ringer's solution (n = 8) or PentaLyte (n = 8) at reperfusion after 30 min of ischemia. Blood was obtained before ischemia and after 30 min of reperfusion for thromboelastography under four conditions: 1) unmodified sample, 2) platelet inhibition, 3) heparinase, and 4) platelet inhibition and heparinase. During reperfusion, unmodified samples demonstrated a significant increase in R and decrease in alpha and G that was not affected by PentaLyte. In the presence of heparinase, no significant fluid-specific thromboelastographic differences were noted. However, thrombotic mediator release (discerned by a decrease in R and an increase in alpha) during reperfusion in samples with platelet inhibition and heparinase was significantly attenuated by PentaLyte. PentaLyte administration does not decrease heparinoid release but does decrease thrombotic mediator release after aortic occlusion-reperfusion.

Animals↗
PubMed2003

The influence of crystalloid and colloid replacement solutions in acute normovolemic hemodilution: a preliminary survey of hemostatic markers.

Acute normovolemic hemodilution (ANH), in which blood for autologous use is collected immediately before the onset of surgical blood loss, is a recommended autologous blood procurement technique for blood conservation. Both crystalloid and colloid replacement fluids have been used to maintain normovolemia during ANH, but few data are available to justify the use of a particular replacement fluid. Therefore, we designed a prospective, randomized study to determine if the replacement fluid choice affects various coagulation variables and perioperative blood loss. Forty adult patients, ASA physical status 1-3, scheduled for ANH during radical prostatectomy were randomly assigned to one of four replacement fluid groups: (a) Ringer's lactate, (b) 5% albumin, (c) 6% dextran 70 (DEX), or (d) 6% hetastarch (HES). After the induction of a standardized general anesthetic, all patients underwent ANH to a final hemoglobin level of 9 g/dL. Complete blood count, prothrombin time, partial thromboplastin time, fibrinogen, factors V and VIII levels, bleeding time, and thromboelastography (TEG measurements were obtained at similar time points in the procedure. When compared with baseline, activated partial thromboplastin time decreased and factor VIII levels increased in the postanesthesia care unit in both the Ringer's lactate and 5% albumin groups. The DEX and HES groups demonstrated a decrease in TEG maximum amplitude between preoperative and postanesthesia care unit measurements and TEG alpha (angle) was decreased from baseline in the DEX group. The changes in factor VIII, activated partial thromboplastin time, and TEG measurements indicate that HES and DEX may attenuate the hypercoagulability related to surgery.

Aged↗
PubMed1999

The effect of prophylactic epsilon-aminocaproic acid on bleeding, transfusions, platelet function, and fibrinolysis during coronary artery bypass grafting.

BACKGROUND: Antifibrinolytic medications administered before skin incision decrease bleeding after cardiac surgery. Numerous case reports indicate thrombus formation with administration of epsilon-aminocaproic acid (epsilon-ACA). The purpose of this study was to examine the efficacy of epsilon-ACA administered after heparinization but before cardiopulmonary bypass in reducing bleeding and transfusion requirements after primary coronary artery bypass surgery. METHODS: Seventy-four adult patients undergoing primary coronary artery bypass surgery were randomized to receive 125 mg/kg epsilon-ACA followed by an infusion of 12.5 mg x kg(-1) x h(-1) or an equivalent volume of saline. Coagulation studies, thromboelastography, and platelet aggregation tests were performed preoperatively, after bypass, and on the first postoperative day. Mediastinal drainage was recorded during the 24 h after surgery. Homologous blood transfusion triggers were predefined and transfusion amounts were recorded. RESULTS: One patient was excluded for surgical bleeding and five patients were excluded for transfusion against predefined criteria One patient died from a dysrhythmia 2 h postoperatively. Among the remaining 67, the epsilon-ACA group had less mediastinal blood loss during the 24 h after surgery, 529+/-241 ml versus 691+/-286 ml (mean +/- SD), P < 0.05, despite longer cardiopulmonary bypass times and lower platelet counts, P < 0.05. Platelet aggregation was reduced in both groups following cardiopulmonary bypass but did not differ between groups. Homologous blood transfusion was similar between both groups. CONCLUSIONS: Prophylactic administration of epsilon-ACA after heparinization but before cardiopulmonary bypass is of minimal benefit for reducing blood loss postoperatively in patients undergoing primary coronary artery bypass grafting.

Adult↗
PubMed2001

Sevoflurane inhibits unstimulated and agonist-induced platelet antigen expression and platelet function in whole blood in vitro.

BACKGROUND: Previous studies have reported conflicting results about the effect of sevoflurane on platelet aggregation. To clarify this point, we investigated the effects of sevoflurane on platelet antigen expression and function in vitro. METHODS: Human whole blood was incubated for 1 h with 0.5 and 1 minimum alveolar concentration sevoflurane, 21% O(2), and 5% CO(2). A control sample was kept at the same conditions without sevoflurane. After stimulation with adenosine diphosphate or thrombin receptor agonist peptide 6, samples were stained with fluorochrome conjugated antibodies, and the expression of platelet glycoproteins GPIIb/IIIa, GPIb, and P-selectin, as well as activated GPIIb/IIIa, were measured with two-color flow cytometry. In addition, platelet function was assessed by means of thromboelastography and using the platelet function analyzer 100. RESULTS: Already in subanesthetic concentrations, sevoflurane inhibits unstimulated and agonist-induced GPIIb/IIIa surface expression and activated GPIIb/IIIa expression on platelets in whole blood. The agonist-induced redistribution of GPIb into the open canalicular system was also impaired by sevoflurane, whereas no effect on P-selectin expression in activated platelets could be found. Sevoflurane significantly reduced the maximum thromboelastographic amplitude. Furthermore, platelet function analyzer 100 closure times were significantly prolonged. CONCLUSION: The results show that sevoflurane significantly impairs platelet antigen expression in vitro. It is especially the inhibition of GPIIb/IIIa expression and activation that impairs bleeding time as reflected in thromboelastographic measurements and platelet function analyzer 100 closure times. The exact inhibitory mechanism remains unclear.

Anesthetics, Inhalation↗
PubMed1991

Coagulation disorder during liver transplantation.

Detailed haemostatic changes were investigated during eight liver transplantations. The patients were divided into two groups; group 1 had minor operative bleeding (four cases) and group 2 had major bleeding (four cases). Group 2 had lower levels of platelets, fibrinogen, factor V (FV), and alpha 2-antiplasmin than group 1, and the thromboelastography showed fibrinolysis. In both groups, plasma tissue-plasminogen activator levels rose slightly. After revascularization of the graft liver, reductions in the values of PT, fibrinogen, FV and FVII were noted, along with a prolongation of the PTT and an increase in thrombin-antithrombin III complex levels. Plasma levels of protein C, protein S, antithrombin III, and plasminogen remained relatively stable throughout the operation. These results show that the preceding fibrinolysis and subsequent superimposed activation of the clotting system are the main causes of coagulopathy during liver transplantation, which correlate with the amount of operative haemorrhage and the abnormalities found in haemostatic tests.

Adult↗
PubMed2000

Management and monitoring of recombinant activated factor VII.

Recombinant factor VIIa (rFVIIa) has recently been introduced as a new 'bypassing' agent to improve haemostasis in haemophilia patients with inhibitors to factor (F) VIII or FIX. In noninhibitor patients, levels of circulating FVIII or FIX can be used to assess the quality of substitution therapy. In contrast, laboratory monitoring of haemostatic efficacy in patients treated with rFVIIa has proved more complex. Evaluation of patient samples saved during rFVIIa treatment have revealed some correlation between FVII:C levels and improved haemostasis, while whole blood elasticity, as determined by thromboelastography, has been shown to improve following rFVIIa treatment. The investigation aimed to study the efficacy of rFVIIa in activating FX:C and in shortening the whole blood clotting time (WBCT) using the newly-developed roTEG coagulation instrument. Results indicated a substantial and apparently dose-dependent activation of FX:C by rFVIIa. In addition, the presence of FIX appeared to influence FX:C activation. In-vitro and ex-vivo roTEG thromboelastograph measurements showed that FVIIa shortened WBCT, although normalization did not occur. The results presented here are based on a small number of observations in a few patients and further studies should be planned to test the efficacy of these monitoring principles in clinical treatment practice with rFVIIa.

Bleeding Time↗
PubMed2001

Disintegration and reorganization of fibrin networks during tissue-type plasminogen activator-induced clot lysis.

In this study, we investigated tissue-type plasminogen activator (tPA)-induced lysis of glutamic acid (glu)-plasminogen-containing or lysine (lys)-plasminogen-containing thrombin-induced fibrin clots. We measured clot development and plasmin-mediated clot disintegration by thromboelastography, and used scanning electron microscopy (SEM) to document the structural changes taking place during clot formation and lysis. These events occurred in three overlapping stages, which were initiated by the addition of thrombin, resulting first in fibrin polymerization and clot network organization (Stage I). Autolytic plasmin cleavage of glu-plasminogen at lys-77 generates lys-plasminogen, exposing lysine binding sites in its kringle domains. The presence of lys-plasminogen within the thrombin-induced fibrin clot enhanced network reorganization to form thicker fibers as well as globular complexes containing fibrin and lys-plasminogen having a greater level of turbidity and a higher elastic modulus (G) than occurred with thrombin alone. Lys-plasminogen or glu-plasminogen that had been incorporated into the fibrin clot was activated to plasmin by tPA admixed with the thrombin, and led directly to clot disintegration (Stage II) concomitant with fibrin network reorganization. The onset of Stage III (clot dissolution) was signaled by a sustained secondary rise in turbidity that was due to the combined effects of lys-plasminogen presence or its conversion from glu-plasminogen, plus clot network reorganization. SEM images documented dynamic structural changes in the lysing fibrin network and showed that the secondary turbidity rise was due to extensive reorganization of severed fibrils and fibers to form wide, occasionally branched fibers. These degraded structures contributed little, if anything, to the structural integrity of the residual clot, and eventually collapsed completely during the course of progressive clot dissolution. These results provide new perspectives on the major structural events that occur in the fibrin clot matrix during fibrinolysis.

Fibrin↗
PubMed2002

Early intensive care unit intervention for trauma care: what alters the outcome?

This review focuses on early management of multiple trauma patients with traumatic brain injury. Early usage of multislice computed tomography can substantially shorten the time spent on diagnostic workup in the emergency room and, therefore, speeds the initiation of lifesaving interventions for the control of hemorrhage. The important role of hemostatic angiographic embolization and its timing, in addition to surgical control of bleeding in patients suffering from pelvic fracture or organ lesions, is emphasized. The ongoing controversy regarding the strategy of fluid resuscitation is discussed. The concept of permissive hypotension seems to be promising but is absolutely contraindicated in patients with traumatic brain injury. Coagulation management should be guided by coagulation monitoring, including thromboelastography. A novel approach to reduce major bleeding is the application of recombinant factor VIIa. Strong effort should be directed toward the management of traumatic brain injury and the maintenance of cerebral perfusion pressure. The optimization of treatment of patients with multiple trauma, including brain injury, is a multidisciplinary task.

Algorithms↗
PubMedDate not supplied

Subcutaneous low molecular weight heparin for management of anticoagulation in infants on excor ventricular assist device.

Anticoagulation in infants and children on a ventricular assist device presents particular challenges. Unfractionated heparin has poor bioavailability; it can be difficult to achieve a stable anticoagulant effect; and, in the long-term, there is a risk of osteopenia. Long-term warfarin can be difficult to manage in infants on formula milk with vitamin K supplementation. We review our recent experience with subcutaneous low molecular weight heparin. Two patients received a left ventricular assist device (Excor, Berlin Heart AG) as a bridge to transplantation. Initial anticoagulation consisted of unfractionated heparin infusion beginning 6 hours after implantation to maintain an activated partial thromboplastin time of 70 seconds, checked every 4 to 6 hours. Platelet count (aim >80,000/microl) and thromboelastography were assessed daily. Antithrombin required substitution to maintain levels >70 IU/dl. To optimize anticoagulation, both infants were switched to subcutaneous low molecular weight heparin twice daily aiming for an anti-Xa activity between 0.5 and 1.0 IU/ml. Aspirin was added on day 4, checking platelet aggregation every 2 to 4 days, aiming at arachidonic acid stimulated aggregation 10% to 30% of baseline, collagen 100% of baseline. Dipyridamole was added once stability was reached if platelets count exceeded 150,000/microl. There were no clinical thromboembolic or bleeding events. Both patients had successful transplantation.

Anticoagulants↗
PubMed2005

Multi-centre investigation on reference ranges for ROTEM thromboelastometry.

Reagent-supported thromboelastometry (TEM) with the ROTEM Whole Blood Haemostasis Analyser is an enhancement of thromboelastography, a method that is increasingly used for the point of care monitoring of acute perioperative bleeding disorders. We investigated the reference ranges of two activated tests (INTEM and EXTEM) and a test analysing specifically the fibrin component of coagulation (FIBTEM) in a multi-centre approach. The reference ranges obtained for the clotting time (CT), clot formation time (CFT), alpha angle (ALP), maximum clot firmness (MCF) and clot lysis parameters were comparable from centre to centre. INTEM: CT equals; 137-246 s, CFT equals; 40-100 s, MCF equals; 52-72 mm. EXTEM: CT equals; 42-74 s, CFT equals; 46-148 s, MCF equals; 49-71 mm. FIBTEM: MCF equals; 9-25 mm. ROTEM whole blood coagulation correlated weakly with a trend towards enhanced coagulation in females compared with males and in advanced age. The repeatability (within-run imprecision) of the results was dependent on the test with the following coefficients of variation: 1-5% (clot firmness, alpha angle), 3-12% (CT, CFT), 6-13% (FIBTEM clot firmness). Citrated blood samples were stable for ROTEM analysis stored within 6 h from drawing. In summary, the data showed that ROTEM thromboelastometry yields consistent values between centres and that providing general orientating reference ranges seems to be possible.

Age Factors↗
PubMed2006

Resistance of porcine blood clots to lysis relates to poor activation of porcine plasminogen by tissue plasminogen activator.

In-vitro experimentation was performed on porcine and human blood to determine their comparative responsiveness to a novel fibrinolytic inhibitor and thereby assess whether the pig is a suitable animal model for subsequent in-vivo testing of this inhibitor. Thromboelastography showed the clots formed from porcine whole blood to be highly resistant to tissue plasminogen activator (t-PA)-catalyzed lysis, and this communication offers the resistance of porcine plasminogen to activation by t-PA as an explanation. Porcine blood containing 100 and 1500 IU/ml added t-PA lysed very slowly, having LY30 values of 1.9 +/- 1.4 and 2.9 +/- 1.9%, respectively. In contrast, the LY30 values for the human clots containing 100 and 1500 IU/ml t-PA were 77.1 +/- 6.3 and 93.3 +/- 1.3%, respectively. Moreover, purified porcine plasminogen was activated very slowly by added t-PA in the presence of both human and porcine fibrin. Activation of plasminogen by the endogenous activators, as measured by the euglobulin clot lysis time, was greatly prolonged for the pig (22 +/- 3 h) compared with the human (3.5 +/- 1.5 h). These results suggest caution in using the pig as an experimental model when studying the effects of various agents on fibrinolysis.

Animals↗
PubMed2005

Effects of bovine polymerized hemoglobin on coagulation in controlled hemorrhagic shock in swine.

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.

Acidosis, Lactic↗
PubMed2006

Effects of hemorrhage and lactated Ringer's resuscitation on coagulation and fibrinogen metabolism in swine.

Hemorrhagic coagulopathy is a significant complication after traumatic injury, and much of the underlying mechanism remains unclear. We investigated the changes in fibrinogen metabolism and coagulation after a moderate hemorrhage and resuscitation. Pigs of either sex (weight, 40.9+/-0.8 kg) were anesthetized and instrumented with arterial and venous catheters and a thermodilution cardiac output catheter. Pigs were randomized into control (C; n=6), hemorrhage (H; n=6), and hemorrhage and resuscitation (H-LR; n=6) groups. Hemorrhage was induced by bleeding 35% of total blood volume for 30 min in H and H-LR groups. Resuscitation in H-LR group was performed using lactated Ringer's solution (LR) at 3 times the bled volume for 30 min. Fibrinogen metabolism was quantified using a primed constant infusion of 1-13C-phenylalanine (6 h) and d5-phenylalanine (4 h) and subsequent analysis by gas chromatograph-mass spectrometry, together with measurements of hemodynamics (hourly) and coagulation by thromboelastography (at baseline and 4 h after hemorrhage and resuscitation). Hemorrhage caused decreases in arterial pH and base excess, and an increase in arterial lactate content. Fluid resuscitation corrected these changes toward normal levels. Fibrinogen level was unchanged in C and decreased to 76%+/-4% in H and to 73%+/-3% in H-LR (both P<0.05, compared with baseline) after hemorrhage and resuscitation. Fibrinogen breakdown was increased from 3.0+/-0.4 mg kg-1 h-1 in C to 5.4+/-0.6 mg kg-1 h-1 in H and to 5.6+/-0.5 mg kg-1 h-1 in H-LR (both P<0.05, compared with control), but synthesis was unchanged. The clotting reaction time was unchanged in C and shortened to 93%+/-3% in H and to 91%+/-1% in H-LR (both P<0.05, compared with baseline). We conclude that hemorrhagic shock caused accelerated fibrinogen breakdown and coagulation. The LR resuscitation reduced tissue hypoxia indexes but did not affect the changes in fibrinogen metabolism and coagulation from hemorrhage. Thus, effective treatment of hemorrhage should include combining standard-of-care resuscitation with interventions to correct alterations in coagulation.

Animals↗