Markers of coagulation activation after hepatic resection for cancer: evidence of sustained upregulation of coagulation.
Our aim was to further investigate the effects of open liver resection on the coagulation and fibrinolytic pathways in patients with liver cancer. We studied the conventional coagulation tests PT and aPTT as well as specific markers of coagulation turnover and activation. To define ongoing thrombin formation and inhibition and fibrin degradation in vivo more accurately, selective markers of coagulation activation including prothrombin activation fragment 1+2 (PF1+2), thrombinantithrombin complexes (TAT), von Willebrand Factor antigen (vWF-Ag) and fibrinogen were studied. We tested the hypothesis that elevated levels of markers of coagulation activation and prolongation of PT would not result in abnormal coagulation as assessed by thromboelastography (TEG). TEG was used as a global assessment of coagulation.
We performed a prospective observational study from January 2008 to January 2009 after approval from our hospital research ethics committee. We studied American Society of Anesthesiologists physical status I to IV adult patients undergoing open elective hepatic resection for liver cancer. Written informed consent was obtained at the preoperative admission clinic one to two weeks prior to surgery. Exclusion criteria included preexisting liver dysfunction including chronic hepatitis, cirrhotic liver disease, preoperative coagulopathy or distinctive paraneoplastic coagulation disorder (PT >15 seconds or platelet count <100x[10.sup.9]/l), history of thromboembolic disease, preoperative therapy with anticoagulant or antiplatelet medication (e.g. warfarin, heparin, aspirin, clopidogrel) and known allergy to heparin. As part of routine preoperative surgical investigations, all patients underwent abdominal ultrasound and computed tomography of the liver.
Anaesthesia was conducted by a group of specialist anaesthetists and surgeons using a protocol designed to standardise perioperative care. All patients underwent a right subcostal rooftop incision with a midline extension (reverse-L incision). Routine monitoring included continuous electrocardiography, pulse oximetry, capnography, invasive arterial blood pressure, central venous pressure, urine output and core body temperature. In accordance with local protocol at our institution for this operation, all patients received unfractionated heparin (5000 IU) subcutaneously after induction of anaesthesia. Intraoperative normothermia was maintained with warm fluids and a forced-air warming device. During the prehepatic resection phase and for the duration of hepatic parenchymal resection, the administration of fluids was reduced and central venous pressure was maintained at less than 6 mmHg. The use of a haemostat to clamp the hepatoduodenal ligament interrupting the flow of blood through the hepatic artery and the portal vein (Pringle Manoeuvre) was not used. After hepatic resection, an infusion of warm fluids was administered to render patients euvolaemic. Urine output was maintained at greater than 0.5 mg/kg/hour, and systolic blood pressure was maintained within 20% of the preoperative value. No patient received epidural anaesthesia/analgesia. For postoperative analgesia all patients received intravenous morphine delivered via an intravenous morphine patient-controlled analgesia infusion. All patients received postoperative thromboprophylaxis consisting of unfractionated heparin (5000 IU) twice daily for the duration of the hospital stay.
Blood sampling and processing
All blood samples were collected through a 16-gauge central venous catheter or taken by single peripheral aseptic venepuncture from the antecubital fossa using a 21-gauge butterfly needle with a light tourniquet to avoid stasis or platelet activation. Blood samples were drawn before induction of anaesthesia, at the end of surgery and on postoperative days 1, 3 and 5. Twenty millilitres of whole blood was sampled using a two-syringe technique to avoid bias by locally released tissue plasminogen activator. Ten millilitres of blood was aspirated in the first syringe and discarded. For TAT and PF1+2, test tubes were filled to the line. In order to gain plasma, one part of sodium citrate solution (0.11 mol/l) was mixed with nine parts of venous blood, avoiding the formation of foam. The samples were centrifuged within two hours of collection for 10 minutes at 3500 rpm 1500xg and platelet-poor supernatant plasma was withdrawn. The plasma was removed and the sample was stored at -70[degrees]C until ready for assaying. For vWF-Ag blood was collected in citrated tubes. The samples were centrifuged at 3000xg for 10 minutes and platelet-poor plasma was prepared. Again, the plasma was frozen at -70[degrees]C until assaying.
For TEG measurements, within four minutes of collection, 1 ml of native whole blood was added to a vial containing kaolin (TEG[R] Hemostasis System, Haemonetics Corporaton, Illinois, USA). Kaolin is a standardised-reagent consisting of buffered stabilisers and a blend of phospholipids. That serves as a screening test of clotting disorders pertaining to surface activation or the intrinsic pathways of coagulation. According to the manufacturer's protocol (Haemoscope Corporation TEG[R], Illinois, USA), 340 [micro]l of blood was pipetted into a pre-warmed TEG analysis cup. At the same time, a heparinase-modified TEG sample was prepared by adding a further 340 [micro]l of blood to another TEG cup containing 2 IU of lyophilised heparinase enzyme. The heparinase-modified TEG removes the effect of any heparin, allowing the underlying coagulation pattern to be monitored. A Haemoscope TEG[R] 5000 coagulation monitor running two simultaneous channels was used for all TEG measurements. All samples were monitored in the TEG device for a minimum of 60 minutes. The TEG channels were calibrated daily and standardised weekly with biological controls. Thromboelastograph values included reaction time (R-time; time to initial thrombus formation), K time (rate of thrombus formation), maximum amplitude (thrombus strength) and alpha-angle (rate of thrombus formation). Platelet counts were measured with an automatic analyser (blood analyser Sysmex SE 9000; TOA Medical Electronics, Kobe, Japan). PT and aPTT were measured using a fully automated coagulometer (STA; Diagnostica Stago, Asnier sur Seine, France).
A sandwich ELISA Enzygnost[R] (Siemens Healthcare Diagnostics, Melbourne, Victoria) was used for the in vitro determination of human thrombin/antithrombin III complexes. The standards contained in the kit cover the range of 2 to 60 mg/l. (Test kit for 2x96 determinations, Code No. OWMG, containing: Enzygnost, TAT [microtiter plates], [normal reference range 1.0 to 4.1 [micro]g/l, median 1.5 [micro]g/l]). A sandwich ELISA-based assay was used for the in vitro determination of human PF1+2. The standards contained in the kit cover the range of 0.04 to 10 nmol/l. (Test kit for 2x96 determinations, Ref Code No. OPBD 03, containing: Enzygnost, F1+2 [monoclonal] [2x96 microtitre plates], [normal reference interval 69 to 229 pmol/l]. A latex particle enhanced immunoturbidometric assay kit was used to quantify vWF-Ag in plasma. Test kit: HemosIL[TM] vWF-Ag kit (Beckham Coulter, Gladesville, NSW) product number 0020002300, [normal reference range 50 to 200%]). Markers of coagulation activation were tested by the chief laboratory scientist (RD) who was blinded to the results of the TEG and routine coagulation studies. Reagents from a single batch were used to avoid batch-to-batch variability.
All analysis was performed using Stata[TM] version 10 software (StataCorp, College Station, Texas, USA). Continuous data are presented as mean ([+ or -] SD). Categorical variables are reported as percentages. In order to evaluate the statistical significance of the changes to the observed mean values of coagulation markers across the sampling time periods, a repeated measures analysis of variance was performed. If this was found to be significant, paired t-tests comparing the mean value of the marker at each time period with that of the baseline mean only was used in order to limit the number of multiple comparisons. Paired t-tests were also used to compare the mean value of the TEG R and K times at each time period. A P value of <0.05 was considered significant. As this was an observational study, a power calculation was not performed.
Twenty-one patients undergoing open hepatic resection for cancer were enrolled. The mean age of the patients was 58.6 years (range 23 to 78 years). Sixty-seven percent of patients were male. The mean duration of surgery was 229 minutes (SD 104) and the mean hepatic resection weight was 374 g (SD 279.5). The baseline patient demographics and intraoperative fluid intervention are summarised in Table 1. The perioperative conventional coagulation tests are presented in Table 2. Preoperatively the haemoglobin, PT, aPTT, platelet count and liver function tests were normal in all patients. The mean baseline aPTT was 30.2 seconds (SD 2.6) and remained within normal limits throughout the postoperative period. In contrast, the PT value on the first postoperative day was significantly elevated (mean 15.3 seconds, SD 3.32; P <0.001) when compared to the baseline PT value (mean 11.9 seconds, SD 0.65). The changes in PT on the first postoperative day correlated with the volume of liver resected (r=0.5). Immediately postoperatively, the PT was prolonged in three (14%) patients, increasing to eight (38%) patients (range 16 to 25 seconds) on the first postoperative day. By the third postoperative day the PT remained prolonged in four (19%) patients, returning to baseline values in all but one patient by the fifth postoperative day.
Results of the specialised coagulation tests are summarised in Table 3. Preoperatively PF1+2 were elevated in 14 (66%) patients, TAT in 13 (62%) patients and vWF-Ag in 2 (9.5%) patients. Compared to its baseline value (mean 296.3 pmol/l, SD 137.47), PF1+2 increased almost threefold in the immediate postoperative period (mean 720.6 pmol/l, SD 267.65, P <0.001), returned to near baseline values on the first postoperative day (reflecting haemodilution and fluid management) then increased significantly on postoperative day 3 (P=0.019) and was still significantly elevated on the fifth postoperative day (P <0.001). Compared with its baseline value (mean 7.1 [micro]g/l, SD 3.7), TAT complexes peaked immediately postoperatively (mean 18.9 [micro]g/l, SD 11.31, P <0.001) and remained significantly elevated on the first postoperative day. Although TAT remained elevated on postoperative days 3 and 5, compared to its baseline value, this was not statistically significant (P=0.35 and P=0.7 respectively). Plasma vWF-Ag remained significantly elevated above its baseline value on postoperative days 1, 3 and 5 (P <0.001), with the maximum value being recorded on postoperative day 3. Fibrinogen levels peaked on the third postoperative day (mean 6.3 g/l, SD 0.74) and compared to its baseline value, fibrinogen remained elevated until the fifth postoperative day (P <0.001) (Table 3).
Results of the TEG values are summarised in Table 4. There were noticeable differences between the native and heparinase-modified R-time and K-time values preoperatively (P=0.0026, P=0.0592 respectively) and on postoperative day 1 (P=0.0035, P=0.0188), day 3 (P=0.0088, P=0.0363) and day 5 (P=0.0019, P=0.0026). In the native TEG, the R-time decreased on the first postoperative day then increased and peaked on the third postoperative at 9.4 minutes (normal range 4 to 8 minutes). In contrast, the heparinase-modified samples demonstrated a decrease in the R-time, alpha angle and maximum amplitude over the five-day postoperative period reflecting a relative postoperative hypercoagulable state.
We present haematological data obtained from a series of 21 patients undergoing liver resection for cancer. Thromboelastography, conventional (PT, aPTT) and specialised laboratory (PF1+2, TAT, vWF-Ag) measures of thrombin generation were performed in the immediate postoperative period and up to five days postoperatively. We found that some measures such as PT showed reduced clot formation and other direct functional measures remained relatively normal (TEG results), while other more direct measures of thrombin generation (PF1+2, TAT, vWF-Ag) remained significantly increased throughout the postoperative period.
We found evidence of sustained upregulation of haemostasis despite prolongation of the PT in a significant percentage of patients. Even in patients with normal global coagulation testing there was sustained and prolonged coagulation activation of the haemostatic system. We previously reported that after elective liver resection there are significant elevations in the PT on the first postoperative day, even in patients with normal preoperative coagulation and liver function tests (8). Similar to our previous findings, we found that the PT was prolonged in 38% of patients on the first postoperative day. For these patients, the TEG was normal in 75%, PF1+2 was normal in 50%, and TAT and vWF-Ag was elevated in all patients, indicating evidence of sustained haemostatic activity despite isolated prolongation of the PT (Table 5).
A prolonged PT is frequently interpreted as a 'hypocoagulable' state and is thought of as being predictive of clinical bleeding. Post liver resection, a reduction in Factor VII levels from blood loss and/or haemodilution can prolong the PT, however, when performed in isolation the PT may not provide sufficient information to determine if the coagulation balance favours a prothrombotic, antithrombotic or normal coagulation state. Tripodi et al questioned the reliability of abnormal coagulation tests being a consistent predictor of actual bleeding (9,10). After hepatic resection there is destruction of the hepatic parenchymal cells that results in a degree of hepatic insufficiency. The degree of hepatic insufficiency depends in part on the extent of the resection. With destruction of the hepatic parenchymal cells, not only are the procoagulant factors reduced, but also the levels of protease inhibitors, Protein C and S, a situation that is not reflected in the PT or aPTT (2). The conventional coagulation tests, PT and aPTT, measure only the procoagulant side of the haemostatic equation and are not necessarily predictors for acquired coagulopathic states. In other words, the PT and aPTT tell us whether a patient is deficient in one or more clotting factors, but not whether this deficiency is counterbalanced by a parallel deficiency of anticoagulants or an increase in factors, including activated factors resulting in hypercoagulability. Both PT and aPTT can be prolonged by inhibitors such as fibrin degradation products. Caldwell described a patient in liver failure from unrecognised Budd Chiari syndrome whose International Normalised Ratio was prolonged to nine seconds but whose TEG clearly identified a hypercoagulable state (3). The PT and aPTT are therefore responsive to thrombin generated as a function of procoagulants, but much less responsive to thrombin inhibition by the natural anticoagulants, especially Protein C. It is the balance between pro and anticoagulant/antithrombotic activities that ultimately determines whether bleeding, thrombosis or appropriate haemostasis occurs (2,4).
For patients with prolongation of the PT with normal TEG studies we found no clinical evidence of haemostatic failure. Both patients 13 and 21 (Table 5) showed prolongation of PT in the postoperative period. In patient 13, the TEG assay demonstrated normal coagulation parameters, in contrast to the apparent antithrombotic state indicated by the prolonged PT. In contrast, in patient 21, TEG demonstrated a significant increase in the R-time that accurately reflected the prolonged PT. This patient also demonstrated evidence of clinical bleeding. Therefore coagulation factor therapy was instituted to correct the coagulopathy.
We demonstrated that after elective hepatic resection there is significant and prolonged activation of the haemostatic system despite prolongation of the PT. Thrombin-antithrombin levels increased almost three-fold in the immediate postoperative period reflecting significant thrombin generation. Thrombin-antithrombin levels gradually returned to near baseline levels over the subsequent five days. The peak increase in TAT coincided with the peak increase in PF1+2, which also occurred immediately after surgery. Our results suggest that after hepatic resection there is a marked increase in procoagulant factors. However, there may also be reductions in the levels of circulating natural anticoagulants. These findings are not confined to liver resection where decreased coagulation and anticoagulant synthetic function may be affected. Gibbs et al demonstrated similar findings following patients undergoing abdominal aortic surgery and found that patients were "hypercoagulable" in the postoperative period (22). Other researchers have investigated perioperative activation of the coagulation system by assaying PF1+2 and TAT. These specific biochemical markers for the haemostatic processes appear to be most marked in open surgery (23) peaking as early as 24 hours post surgery (24-29). Elevated TAT levels may also relate to the amount of extravasated blood (30). The mechanisms for activation of coagulation are not clear but a common factor appears to be mechanical tissue damage. Similarly acute phase reactants such as fibrinogen and vWF-Ag increase after invasive surgery.
Our study has several limitations. Although all patients were anaesthetised by the same anaesthetic team using a standardised technique, and operated on by the same surgical team, this is a single-centre observational study, which may limit the external validity of our findings. However, our hospital has all the typical characteristics of a tertiary institution in a developed country and a recent comparative study confirmed that its patients and their outcomes were identical to those of other tertiary hospitals in Australia (32). While we were able to examine changes in coagulation activation, the study would not be able to detect the true incidence of complications from a hypocoagulable or hypercoagulable state given the relatively small sample size. Unlike other research groups (22), we did not investigate naturally occurring anticoagulants such as Protein C and antithrombin III. However, we aimed to define ongoing thrombin formation in vivo more accurately and therefore concentrated on the selective markers of coagulation activation, PF1+2, TAT and vWF-Ag.
In conclusion, by identifying the changes in coagulation that occured in this specific group of patients we have shown that it is important to recognise the inherent limitations of the conventional laboratory measurements of coagulation. Following liver resection there is significant and prolonged activation of the haemostatic system despite routine coagulation tests being normal or even prolonged. Basic coagulation assays can be misleading as they do not assess in vivo activation of haemostatic mechanisms. At present there is no gold standard laboratory test that mimics true physiological haemostatic mechanisms. Nevertheless, it is imperative that the clinician not distrust conventional coagulation tests such as the PT or be solely dependent on the TEG. An integrated approach to interpreting haematological data, which includes correlation with the clinical picture before considering therapeutic interventions, seems appropriate.
Austin Hospital, Department of Anaesthesia Research Fund.
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L. WEINBERG *, N. SCURRAH ([dagger]), F. C. PARKER ([double dagger]), R. DAUER ([section]), J. MARSHALL **, P. McCALL ([dagger][dagger]), D. STORY ([double dagger][double dagger]), C. SMITH ([section][section]), L. McNICOL ***
Departments of Anaesthesia and Pathology, Austin Hospital, Heidelberg, Victoria, Australia
* B.Sc., M.B., B.Ch., M.R.C.P., F.A.N.Z.C.A., Dip. Echo. Crit. Care., Anaesthetist, Department of Anaesthesia and Senior Fellow, Department of Surgery, University of Melbourne, Austin Hospital.
([dagger]) M.B., B.S. (Hons), F.A.N.Z.C.A., Dip. Echo. Crit. Care., Anaesthetist, Department of Anaesthesia.
([double dagger]) M.B., B.S., M.Epi., F.A.N.Z.C.A., Anaesthetist, Department of Anaesthesia.
([section]) B.Sc., Chief Scientist, Austin Pathology, Austin Hospital.
** M.B., B.S., F.A.N.Z.C.A., Provisional Fellow, Department of Anaesthesia.
([dagger][dagger]) M.B., B.S. (Hons), F.A.N.Z.C.A., Head of Clinical Operations and Anaesthetist, Department of Anaesthesia, Austin Hospital.
([double dagger][double dagger]) B.Med.Sci. (Hons), M.B., B.S. (Hons), M.D., F.A.N.Z.C.A., Head of Research, Department of Anaesthesia and Associate Professor, Department of Surgery, University of Melbourne, Austin Hospital.
([section][section]) M.B., B.S., M.D., F.R.A.C.P., F.R.C.P.A., Clinical Associate Professor, University of Melbourne and Medical Director, Austin Pathology, Austin Hospital.
*** M.B., B.S. (Hons), F.R.C.A., F.A.N.Z.C.A., Director, Department of Anaesthesia, Medical Director, Anaesthesia, Perioperative and Intensive Care, Clinical Services Unit and Associate Professor, Department of Surgery, University of Melbourne, Austin Hospital.
Address for correspondence: Dr L. Weinberg, Department of Anaesthesia, Austin Hospital, Studley Road, Heidelberg, Vic. 3084. Email: Laurence. Weinberg@austin.org.au
Accepted for publication on April 14, 2011.
TABLE 1 Baseline patient demographics. Values are mean (SD), median (IQR [range]) or number (proportion) No. of patients 21 Gender, M:F 14:7 Age, y 58.6 (15.74, 23-78) Weight, kg 64 (13.69, 42-90) Body mass index, mean, kg/[m.sup.2] 21.7 (3.91, 15.4-31.1) ASA grade ASA I 1 (5%) ASA II 19 (90%) ASA III 1 (5%) Diagnosis Cholangiocarcinoma 1 (4.7%) Metastatic colorectal carcinoma 3 (14.2%) Hepatocellular carcinoma 17 (80.9%) Duration of surgery, min 229.2 (104.04) Resection weight, g 357 (110-660) Intraoperative fluids, ml Total crystalloid 2150 (887.1) Plasmalyte 110 (303.1) Hartmann's 2041 (880.0) Total colloid 662 (674.8) Gelofusine 429 (426.7) 4% Albumex 214 (435.0) Intraoperative blood loss, ml 780 (655.1) Transfusion requirements, no. of patients Red blood cells 2 (10%) Fresh frozen plasma 1 (5%) IQR=interquartile range, M=male, F=female, ASA=American Society of Anesthesiologists. TABLE 2 Conventional laboratory coagulation tests and haemoglobin values. All variables presented as mean, (SD, confidence interval) Preoperative Postoperative Hb 139.6 (16.35, 6.99) 110.3 (15.45, 6.60) PT 11.9 (0.65, 0.28) 13.2 (1.84, 0.78) aPTT 30.2 (6.09, 2.60) 31.4 (6.84, 2.92) Platelets 272.2 (79.83, 34.14) 226.0 (72.53, 31.02) Fibrinogen 4.3 (0.67, 0.29) 3.2 (0.73, 0.31) Day 1 Day 3 Hb 107.5 (14.78, 6.32) 100.7 (14.92, 6.38) PT 15.3 (3.32, 1.41) 13.9 (2.50, 1.07) aPTT 29.9 (3.93, 1.68) 32.8 (6.93, 2.96) Platelets 214.0 (53.48, 22.87) 195.9 (57.20, 24.46) Fibrinogen 4.8 (1.07, 0.45) 6.3 (0.74, 0.31) Day 5 Hb 103.1 (15.91, 6.80) PT 12.9 (2.27, 0.97) aPTT 33.1 (3.06, 1.27) Platelets 262.8 (70.78, 30.27) Fibrinogen 6.0 (0.91, 0.38) PT=prothrombin time (11/15 s), aPTT=activated partial thromboplastin time (25/38 s). Platelets 150-400x[10.sup.9]/l, fibrinogen 2/4 g/l, Hb 120/60 g/l (female), 130 to 170 g/l (male), normal ranges included. TABLE 3 Specialised laboratory coagulation tests. All variables presented as mean, (SD, confidence interval) Preoperative Postoperative vWF-Ag 160.3 (54.86, 23.46) 185.4 (80.98, 34.63) PF1+2 296.3 (135.47, 57.94) 720.6 (267.65, 114.47) TAT 7.1 (3.7, 1.58) 18.9 (11.31, 4.84) Day 1 Day 3 vWF-Ag 296.8 (41.89, 17.91) 320.3 (32.47, 13.9) PF1+2 292.1 (117.94, 50.44) 392.4 (103.28, 44.17) TAT 12.0 (6.10, 2.61) 8.9 (4.11, 1.76) Day 5 vWF-Ag 308.1 (42.90, 18.35) PF1+2 486.65 (133.58, 57.13) TAT 7.2 (2.50, 1.07) vWF/Ag=von Willebrand factor antigen (50/200%), PF1+2=prothrombin fragments 1+2 (69/229 pmol/l), TAT=thrombin/antithrombin complex (1/ 4.1 [micro]g/l), normal ranges included. TABLE 4 Thromboelastograph values. All variables presented as mean, (SD, confidence interval) Preoperative Postoperative Kaolin R-time 9.0 (2.7, 1.16) 8.2 (5.50, 2.35) K-time 2.4 (0.96, 0.41) 3.5 (3.31, 1.41) Alpha angle 57.3 (12.09, 5.17) 53.4 (17.98, 7.69) MA 59.7 (10.49, 4.48) 58.24 (7.68, 3.28) Heparinase R-time 7.2 (1.77, 0.75) 7.3 (3.55, 1.52) K-time 2.0 (0.48, 0.20) 2.9 (2.09, 0.89) Alpha angle 63.8 (6.16, 2.63) 58.6 (11.96, 5.11) MA 61.7 (8.55, 3.66) 55.12 (10.55, 4.51) Day 1 Day 3 Kaolin R-time 7.6 (4.16, 1.78) 9.4 (6.03, 2.58) K-time 2.6 (1.83, 0.78) 3.6 (3.60, 1.53) Alpha angle 57.4 (16.03, 6.85) 54.9 (17.06, 7.29) MA 56.6 (15.28, 6.53) 65.1 (7.94, 3.39) Heparinase R-time 6.0 (2.53, 1.08) 6.3 (1.78, 0.76) K-time 1.8 (0.63, 0.27) 1.7 (0.37, 0.16) Alpha angle 61.7 (13.58, 5.81) 65.0 (10.64, 4.55) MA 58.5 (14.35, 6.13) 60.3 (14.41, 6.16) Day 5 Kaolin R-time 8.3 (3.5, 1.53) K-time 2.1 (1.16, 0.49) Alpha angle 62.7 (12.90, 5.52) MA 63.2 (9.59, 4.10) Heparinase R-time 5.5 (1.57, 0.67) K-time 1.5 (0.32, 0.13) Alpha angle 68.7 (4.68, 2.00) MA 67.9 (8.36, 3.57) R-time=reaction time (4-8 min), K-time=rate of thrombus formation (0- 4 min), alpha angle = 47-74[degrees], MA=maximum amplitude (53-72 mm), normal ranges included. TABLE 5 Patients with day 1 elevations in prothrombin time with corresponding thromboelastography and specialised coagulation tests values PT aPTT R-Time K-Time Alpha Patient 3 17 27 6.7 1.9 64.3 Patient 5 18 40 6.8 2.2 63.7 Patient 6 18 28 3.4 0.6 13.8 Patient 7 16 30 9.8 2.6 55.9 Patient 12 17 28 5.2 2.0 61.9 Patient 13 21 30 4.3 1.3 70.3 Patient 16 17 35 3.1 1.7 71.0 Patient 21 25 36 13 3.7 45.1 MA Platelets vWF-Ag PF1+2 TAT Patient 3 60.3 261 325 167.4 5.8 Patient 5 61.2 181 340 193.1 7.6 Patient 6 44.1 135 335 230.0 11.3 Patient 7 47.2 191 330 412.7 14 Patient 12 55.6 187 348 185.9 17.4 Patient 13 66.9 251 286 397.0 16.3 Patient 16 59.9 211 296 195.6 7.9 Patient 21 52.7 158 295 274.7 18.6 PT=prothrombin time (11/15 s), aPTT=activated partial thromboplastin time (25/38 s), R/time=reaction time (4/8 min), K/time=rate of thrombus formation (0/4 min), Alpha (47/74[degrees]), MA=maximum amplitude (n=53/72 mm), vWF/Ag=von Willebrand factor antigen (50/ 200%), PF1+2=prothrombin fragments 1+2 (69/229 pmol/l), TAT=thrombin/ antithrombin complex (1/4.1 [micro]g/l), platelets 150 to 400x[10.sup.9], normal ranges included.
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|Author:||Weinberg, L.; Scurrah, N.; Parker, F.C.; Dauer, R.; Marshall, J.; McCall, P.; Story, D.; Smith, C.;|
|Publication:||Anaesthesia and Intensive Care|
|Date:||Sep 1, 2011|
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