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Does coagulation differ between elderly and younger patients undergoing cardiac surgery?

OBJECTIVE: Multiple improvements allow cardiac surgery in an increasingly older population. It is still unclear whether perioperative hemostasis differs between elderly and younger patients. DESIGN: Prospective, observational study. SETTING: Single institutional study at an urban, university-affiliated hospital. PATIENTS: Twenty-one consecutive patients aged over 80 years and 21 consecutive patients aged under 60 years undergoing first-time elective aortocoronary bypass grafting. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Modified thromboelastography (TEG) using different activators [intrinsic TEG (InTEG); extrinsic TEG (ExTEG); fibrinogen TEG (fibTEG)] was carried out to measure coagulation time [CT = reaction time (r)], clot formation time [CFT = coagulation time (k)], and maximum clot firmness [MCF = maximal amplitude (MA)]. Measurements were performed before surgery, at the end and 5 h after surgery on the intensive care unit (ICU), and on the morning of the 1st postoperative day (POD). Blood loss was slightly higher in the elderly than in the younger patients. Most TEG data were already significantly different between elderly and younger patients at baseline, indicating altered coagulation in the elderly prior to surgery (hypocoagulability). After surgery and on the ICU, elderly patients showed similar alterations in TEG to those of the younger patients (e.g. InTEG-CT: from 183+/-21 to 239+/-28 s versus from 146+/-15 to 186+/-26 s). On the 1st POD, most TEG data had returned almost to baseline values, however, they were still different between elderly and younger patients. CONCLUSIONS: Elderly cardiac surgery patients already showed moderately altered coagulation prior to surgery. Thus elderly patients may be at risk of developing postoperative alterations in hemostasis on the ICU. The exact reasons for the impaired coagulation in the elderly remains to be determined.

Age Factors↗

Conventional coagulation and thromboelastograph parameters and longevity of continuous renal replacement circuits.

OBJECTIVE: To determine the relationship between conventional and thromboelastograph (TEG) coagulation parameters and continuous renal replacement therapy (CRRT) circuit longevity. DESIGN: Conventional coagulation and TEG parameters were measured at the commencement of and during CRRT. Time to circuit cessation was measured and only circuits reaching a predetermined rise from baseline in the pressure gradient across the haemofilter were diagnosed as failing due to clotting. All other circuits were excluded from analysis. SETTING: A general critical care unit of a metropolitan tertiary hospital. PATIENTS AND PARTICIPANTS: Fourteen consecutive patients requiring CRRT were studied. The CRRT technique used was continuous veno-venous haemodialysis. INTERVENTIONS: Thromboelastograph measurements were made prior to the commencement of CRRT and daily thereafter for each circuit. The international normalised ratio (INR), activated partial thromboplastin time (APTT) and platelet numbers were measured at commencement and 8 hourly thereafter. Heparin was used for anticoagulation unless considered contraindicated. MEASUREMENTS AND RESULTS: Forty-seven circuits with a mean (SD) circuit life of 33.0 (30.2) h were entered. Twenty-five circuits fulfilled circuit clotting criteria; the mean circuit life was 30.8 (22.1) h. Heparin anticoagulation was found to prolong circuit life significantly despite adequate mean circuit life, 33.2 (35.7) h, in heparin-free circuits. The starting APTT and the TEG variables reaction time (R) and coagulation time (RK) were significantly correlated. The starting APTT, starting RK and mean time taken for the amplitude to increase from 2 to 20 mm (K) were predictive of circuit life. None of these variables predicted which patients would need heparin. CONCLUSION: While TEG variables more closely predicted circuit longevity than conventional coagulation variables, the clinical benefit of TEG monitoring of anticoagulation for CRRT would appear to be minimal.

Acute Kidney Injury↗

Thromboelastographic changes following nonionic contrast medium injection during transfemoral angiography in patients with peripheral arterial occlusive disease.

BACKGROUND/PURPOSE: Patients with peripheral arterial occlusive disease (PAOD) are known to be systemically hypercoagulable and there is concern that exposing them to contrast media during angiography may exacerbate that thrombotic tendency. Many in vitro studies in which blood is exposed to contrast media suggest that nonionic contrast medium (NICM) has a weaker anticoagulant effect than ionic contrast medium (ICM) and some studies suggest that NICM can lead to activation of coagulation thus increasing the risk of thrombotic events where it is employed. We have looked at the changes in coagulation adjacent to the site of contrast injection/potential angioplasty to determine the magnitude of change locally. METHODS: We measured changes in the coagulability of aortic blood samples immediately before and within 2 min after injection of the last bolus of iohexol (NICM) prior to any intervention procedure in 30 patients with PAOD. Samples were analyzed using thromboelastography (TEG) to identify changes in the coagulability of the aortic blood samples. RESULTS: TEG tracings of samples taken from the aorta after injection of NICM showed a significant increase in R time (time to fibrin formation) (p = 0.036) and in k time (dynamics of clot formation) (p = 0.028) and a reduction in Angle (decreased acceleration of fibrin build-up) (p = 0.013), Maximal amplitude (MA) (reduced ultimate clot strength) (p = 0.018) and Coagulation Index (CI) (p = 0.032). CONCLUSION: These changes in TEG parameters show that the local effect of NICM is a reduction in coagulation activity rather than the activation suggested by some previous studies.

Aged↗

Whole blood laboratory model of thrombocytopenia for use in evaluation of hemostatic interventions.

This study describes a laboratory model of whole blood (WB) thrombocytopenia established with blood from healthy volunteers. We obtained a mean platelet count of 16 x 10(9)/l (95% confidence interval, 10-22) in WB by repeatedly replacing the platelet-rich supernatant with autologous platelet-poor plasma from the same individual. Thrombelastographic profiles of WB clot formation and WB clot stability were performed in parallel with measurements of WB platelet aggregation response. Thrombocytopenia reduced the maximum rate of WB clot formation, while ex vivo addition of platelets reversed the coagulopathy of thrombocytopenia. Control experiments revealed minimal changes in coagulation factors, distribution of bloods cells, and platelet activation capabilities. The WB model appears useful in research, development, and evaluation of the effects of hemostatic interventions in thrombocytopenia.

Adult↗

Differences in perioperative coagulation between Japanese and other ethnic groups undergoing laparoscopic cholecystectomy.

BACKGROUND: Japanese patients experience fewer episodes of postoperative thrombosis than those in certain other countries. To investigate this phenomenon, we measured perioperative coagulation activation markers and conducted thromboelastography (TEG) in 27 Japanese patients undergoing laparoscopic cholecystectomy. METHODS: D-dimer, thrombin-antithrombin complex (TAT), and prothrombin fragment 1+2 (F1+2) were measured as coagulation activation markers. TEG was performed to measure reaction time (R), clot formation time (K), maximum amplitude (MA), and maximum elastance (ME). These measurements were performed before and after the operation and the day after the operation. RESULTS: Coagulation activation markers increased significantly postoperatively. With respect to TEG, MA and ME increased postoperatively. R and K did not change. CONCLUSION: Whereas clotting factor activation sthenia is common in Europe and North America, thrombocyte function sthenia occurs in Japanese patients. This difference may account for the differing incidences of phlebothrombosis in Japanese and white populations.

Aged↗

Cellular, hemostatic, and inflammatory parameters of the surgical stress response in pigs undergoing partial pericardectomy via open thoracotomy or thoracoscopy.

BACKGROUND: Thoracoscopy has been shown to reduce the inflammatory and immunologic response to surgical stress, as compared with corresponding open procedures in humans. The influence on the hemostatic system, however, has not been thoroughly evaluated. The current study aimed to compare the perioperative and immediate postoperative changes in cellular, hemostatic, and inflammatory parameters after a partial pericardectomy performed by either thoracoscopy or thoracotomy. METHODS: For this study, 16 pigs were randomly assigned to have a partial pericardectomy performed thoracoscopically or by thoracotomy. Blood was collected intraoperatively, then 10 min, 3 h, and 6 h after surgery. Whole ethylenediaminetetraacetic acid (EDTA)-stabilized blood and plasma were examined for cellular, hemostatic, and inflammatory parameters, respectively, and thromboelastography (TEG) was performed on citrated whole blood. RESULTS: No significant difference in any of the parameters measured was found between the two groups except for the TEG parameter R-time, which was significantly shorter in the thoracoscopic group 3 h postoperatively. In both groups, a significant postoperative state of hypercoagulability and increase in inflammatory parameters was found. Additionally, pig blood showed a high degree of hypercoagulability in preoperative measurements, as compared with other species. CONCLUSIONS: Partial pericardectomy performed by thoracotomy or thoracoscopy in pigs produces a surgical stress response of equal magnitude, as measured by cellular, hemostatic, and inflammatory changes.

Animals↗

Coagulation modifications after laparoscopic and open cholecystectomy in a swine model.

BACKGROUND: The stress response to surgical trauma precipitates a state of transient hypercoagulation. Studies have demonstrated that laparoscopic surgery results in a diminished stress response compared to open surgery. The aim of this study was to determine the extent of postoperative hypercoagulability following laparoscopic cholecystectomy (LC) compared to open cholecystectomy (OC). METHODS: Twenty-one pigs were randomly selected to undergo LC (N = 10) or OC (N = 11). Whole blood was collected preoperatively and on postoperative days (PODs) 1, 2, and 3 for determination of viscoelastic changes using a thromboelastography (TEG) coagulation analyzer. Four parameters were calculated from the TEG: R (reaction time), K (coagulation time), alpha (rate of clot formation), and MA (maximal amplitude). Antithrombin III (AT III) level was measured preoperatively and on POD 1. RESULTS: After OC, three of four TEG parameters changed to reflect a state of hypercoagulation. Only MA values were significantly changed after LC. Comparison between OC and LC showed no difference in the TEG parameter. There was no significant change in AT III levels after LC or OC. CONCLUSIONS: OC results in postoperative hypercoagulation typically encountered in open abdominal surgery. Although there were no differences in TEG or AT III between the two groups, after the laparoscopic approach all but one TEG parameter remained unchanged, suggesting a diminished hypercoagulable state. By reducing postoperative hypercoagulation, laparoscopic surgery may reduce the risk of developing postoperative venous thrombosis.

Animals↗

Host-guest composites for induced hemostasis and therapeutic healing in traumatic injuries.

INTRODUCTION: The United States military currently outfits our soldiers with a zeolite-based hemostatic agent (HA) that is applied directly onto a traumatic wound to induce hemostasis and prevent loss of life from exsanguination. The goals of this work were to identify and implement strategies to attenuate a tissue burning side effect associated with the HA, resulting from a large release of heat upon hydration, without adversely affecting the wound healing properties. Five ion exchanged derivatives of the parent HA were prepared and characterized with regard to their material and thermal properties, in vitro hemostatic efficacy, and antibacterial activity. METHODS: The five host-guest high-surface-area HAs were prepared by ion exchanging the zeolite linde type 5A with aqueous salt solutions under controlled conditions. The modified HAs were characterized by TGA, DSC, Thermal Imaging, SEM, XRD, XPS, BET, and a Thromboelastograph (TEG) was employed to assay the in vitro hemostatic efficacy. Antibacterial activity was assayed by measuring the zone of no growth of Pseudomonas aeruginosa biofilms growing in contact with the ion exchanged HAs. RESULTS: The heat released during application of the HA can be minimized from 680 J/g to 420 J/g by ion exchanging the calcium ions in zeolite linde type 5A with cations of a reduced hydration enthalpy. Zeolite-based HAs that demonstrate in vitro clot induction time of R < or = 1.8 min, and with surfaces areas > or = 634 m2/g, correlate with 75% in vivo swine survivability of a universally lethal groin injury. Silver exchanged HA maintained a zone of no growth of P. aeruginosa with a surface area twice the geometrical surface area of an HA pressed pellet for 24 hours in an LB Agar assay. CONCLUSIONS: Two strategies for reducing the large amount of heat released by a zeolite-based HA during application have been described and quantified: (1) ion exchange and (2) prehydration. Five ion-exchanged derivatives of the original HA have been prepared and assayed for hemostatic efficacy both in vitro, by TEG, and in vivo, by clinical swine trials. Contact activation coagulation rates, alpha, were found to increase with the amount of heat released by the HA. In Vitro clot induction time, R, and HA surface area have been identified as predictors of in vivo hemostatic performance. A proposed rationale for selecting hemostatic materials based on these parameters will likely reduce the quantity of experiments involving animals, and the associated labor and capital costs, necessary to test a new HA. A method for incorporating antibacterial activity against gram negative P. aeruginosa into the Ag-exchanged formulation of zeolite LTA-5A has been described and substantiated.

Animals↗

Deficiency in thrombin-activatable fibrinolysis inhibitor (TAFI) protected mice from ferric chloride-induced vena cava thrombosis.

Thrombin-activatable fibrinolysis inhibitor (TAFI) is a plasma carboxypeptidase that renders a fibrin-containing thrombus less sensitive to lysis. Since the role of TAFI in thrombus formation is still controversial in mice, our present study was designed to evaluate mice deficient in TAFI (TAFI(-/-)) on FeCl(3)-induced vena cava and carotid artery thrombosis. Parallel studies were carried out in wild-type mice using a potato carboxypeptidase inhibitor (PCI), a selective inhibitor of activated TAFI (TAFIa). Significant reduction in thrombus formation was observed in TAFI(-/-) mice (n = 8, P < 0.05 compared to wild-type littermates) but not in heterozygous (TAFI(+/-)) mice in 3.5% FeCl(3)-induced vena cava thrombosis. A similar effect was observed following treatment with 5 mg/kg bolus plus 5 mg/kg/h PCI in the same venous thrombosis model in C57BL/6 mice (n = 8, P < 0.01 compared to vehicle). No compositional difference was observed for the venous thrombi in TAFI(-/-) and wild-type littermates with or without PCI treatment using histological assessment. In contrast, neither TAFI deficiency nor treatment with PCI showed antithrombotic efficacy in the 3.5% FeCl(3)-induced carotid artery thrombosis model. In a tail transection bleeding time model, both TAFI deficiency and PCI treatment increased bleeding time up to 4.5 and 3.5 times, respectively, over controls (P < 0.05, n = 8). Similar ex vivo fibrinolytic activities were demonstrated for both TAFI deficiency and PCI treatment as enhanced lysis of thrombin-induced plasma clots and lysis of whole blood clot in a thrombelastograph. These data provide direct evidence for the role of TAFIa in vena cava thrombosis without the addition of exogenous thrombolytic in mice. The strong ex vivo fibrinolytic activity of TAFI deficiency or TAFIa inhibition by PCI provides a biomarker of TAFIa inhibition that tracks in vivo antithrombotic efficacy.

Animals↗

Conjugated estrogens and hypercoagulability.

A group of 11 menopausal women receiving 1.25 mg. of conjugated estrogens daily had coagulation tests to determine the development of hypercoagulability after taking 5 and 21 tablets. There was no essential change in thrombin generation or fibrinolytic activity as measured by euglobin lysis time. There was a shift toward hypercoagulability in all three parameters of the thrombelastograms. The decrease of the antithrombin III activity was not as pronounced following the administration of conjugated estrogens as had been the change associated with oral contraceptives. Fibrin monomers were observed in some women during the first week of Premarin therapy.

Adult↗

Cord blood coagulation studies in infants of high-risk pregnant women.

A prospective study of cord blood for coagulability, evidence for disseminated intravascular coagulation (DIC), and hematocrit was done in 106 infants who were offspring of mothers with high-risk pregnancies (pre-eclampsia, diabets mellitus, third-trimester bleeders, severe erythroblastosis fetalis, maternal hypertension, fetal distress, and spontaneous premature labor). Significant changes of hypercoagulability (low AT-III and abnormal TEG) were seen in the third-trimester bleeder and premature labor groups which also had the highest incidence of IRDS and necrotizing. Infants undergoing "stress" (pre-eclampsia, fetal distress) had elevated levels of factors V and VIII but were not hypercoagulable or AT-III deficient. Except for mild thrombocytopenia, infants of the diabetic mothers, a group with increased thrombotic complications, did not show any cord blood abnormalities. Offspring of third-trimester bleeders were anemic. The EBF infants were also anemic, severely hypercoagulable, and showed coagulation changes compatible with severe liver disease and/or DIC. Mild changes compatible with intravascular coagulation were seen in six infants and were not related to the the development of IRDS.

Antithrombins↗

Intraoperative physiologic monitoring and management during hepatic lobectomy using the liver isolation-perfusion technic.

The high operative mortality of major hepatic resection for tumor can be improved by a technic of resection using complete vascular isolation and hypothermic perfusion of the liver. Complete clamping of the portal vein, vena cava, and hepatic artery was necessary and well tolerated. Major physiologic, biochemical, and coagulation changes, however, can occur with this technic that requires close monitoring by the anesthesiologist. With astute observation and prompt corrective measures when indicated, these changes can be minimized to enable a safe and smooth resection to be carried out.

Acid-Base Equilibrium↗

Thromboelastogram fails to predict postoperative hemorrhage in cardiac patients.

To determine the clinical usefulness of the thromboelastogram in the prediction of postoperative hemorrhage in cardiac patients, we related the results of routine coagulation tests (RCTs) and thromboelastography with the amount of chest tube drainage postoperatively in 101 patients requiring cardiopulmonary bypass. Our data indicated that there was no correlation between RCT results and thromboelastographic variables. No single variable of RCTs and thromboelastography correlated well with the amount of chest tube drainage postoperatively. Before the onset of cardiopulmonary bypass, the most frequent abnormalities detected by thromboelastograms were fibrinolysis and hypocoagulability resulting from factor deficiency. Hypercoagulability detected by thromboelastograms occurred in 13% of patients after cardiopulmonary bypass and usually was not detected by RCTs. The incidence of false-negative thromboelastograms and RCT results in patients who had excessive hemorrhage of unknown cause was 46% and 52%, respectively. The incidence of fibrinolysis as detected by thromboelastograms was similar before and after bypass, but only 2 of the 18 patients with fibrinolysis had excessive hemorrhage postoperatively. Our results indicate that neither RCTs nor thromboelastography predicts the likelihood of excessive hemorrhage in patients after cardiopulmonary bypass. The thromboelastographic results should be interpreted cautiously because of the high rate of unreliable results.

Blood Coagulation Tests↗