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PubMed1996

Haemodilution induces a hypercoagulable state.

It has been suggested that haemodilution with saline may increase whole blood coagulation. This study was conducted in two parts. First, we investigated the effect of in vitro dilution of blood with saline on whole blood coagulation as measured by the thrombelastogram (TEG). Blood (4 ml) was diluted with 0.9% saline 1 ml and coagulation compared with that of an undiluted control specimen obtained concurrently from the same subject. In the second part, the study was repeated using a modified gelatin colloidal solution (Haemaccel) as the diluent. The r time, k time and r + k time were decreased relative to control in both diluent groups. The alpha angles were increased compared with control in both groups while maximum amplitude was unchanged in the Haemaccel diluted group. We conclude that haemodilution per se increases the coagulability of whole blood in vitro, but that saline haemodilution has a more marked effect on final clot strength.

Blood Coagulation↗
PubMed1998

Surgical/tourniquet pain accelerates blood coagulability but not fibrinolysis.

Tissue damage during surgery induces coagulation factors and activates platelets. Surgical pain may provoke release of catecholamines, leading to hypercoagulability. We have investigated the effect of surgical pain on blood coagulability and fibrinolysis in orthopaedic operations using tourniquets in 22 patients undergoing total knee replacement. Patients were allocated to one of two groups to receive extradural anaesthesia (EA; n = 11) or general anaesthesia (GA; n = 11). The EA group received lumbar extradural block with lidocaine. The GA group received only general anaesthesia, maintained with 1.5-2.5% sevoflurane and 66% nitrous oxide in oxygen. Using a thrombelastogram technique, blood coagulability and fibrinolysis were measured. Mean maximum amplitude (MA), which reflects coagulability, increased after tourniquet inflation (11%) in group GA whereas MA in group EA did not change. After tourniquet deflation, MA values in both GA and EA groups increased significantly (10% and 20%, respectively) (P < 0.05), and there was also a significant difference in MA between groups (P < 0.05). The fibrinolytic rate did not change in either group during tourniquet inflation, but increased significantly (160%) after tourniquet deflation. There was no significant difference in fibrinolytic rate between the groups. We conclude that the hypercoagulability seen in group GA could have been caused by surgical or tourniquet pain, or both, and that extradural anaesthesia is a useful technique to prevent hypercoagulability.

Aged↗
PubMed1999

Effect of 20% in vitro haemodilution with warmed buffered salt solution and cerebrospinal fluid on coagulation.

We have conducted an in vitro coagulation study consisting of two separate groups of 20 subjects using the thrombelastograph. In the first group, haemodilution was performed with a physiological balanced salt solution similar to plasma, with the exception of calcium, and buffered to a normal pH (Plasmalyte B) at 37 degrees C on blood obtained from consenting volunteers. In the second group, a protein-poor body fluid (cerebrospinal fluid (CSF)) obtained from parturient patients undergoing spinal anaesthesia for Caesarean section was used as the diluent. There were statistically significant differences between the warmed Plasmalyte B treated samples and their untreated controls for all variables measured by the thrombelastograph, except for maximum amplitude, and between the CSF treated samples and their untreated controls for all variables. We conclude that electrolyte and acid-base composition of the diluent fluid had no effect on the observation that crystalloid haemodilution produces hypercoagulability. The marked increase in coagulability produced by addition of CSF cannot be explained on a simple haemodilution basis and confirms previous suggestions of the presence of a procoagulant factor in CSF.

Blood Coagulation↗
PubMed1999

Thrombelastogram reveals hypercoagulability after administration of gelatin solution.

We have compared the effects of gelatin, low molecular weight hydroxyethyl starch (HES) or albumin on tests of haemostasis and on the thrombelastogram in 42 ASA I patients undergoing total hip or knee replacement. Patients were allocated randomly to receive one of the three blood substitutes to obtain moderate intraoperative haemodilution. Blood loss and packed red cell infusion was the same in each group. A greater amount of gelatin was given (1.5 times the measured blood loss) because of its shorter half-life. There was a statistically significant but clinically negligible decrease in platelets count, prothrombin time and fibrinogen, and an increase in bleeding time in all groups. Platelets were slightly but significantly lower after HES. Haemodilution was comparable between groups. TEG showed a state of hypercoagulability in the gelatin group with a significant decrease in r, r + k and an increase in alpha angle.

Adult↗
PubMed1999

Pro-coagulant effect of in vitro haemodilution is not inhibited by aspirin.

We have conducted an in vitro coagulation study, using the thrombelastograph (TEG), to determine if the enhanced coagulability of whole blood after haemodilution with normal saline can still be demonstrated after administration of an antiplatelet agent. Aspirin inhibits the platelet-endothelial interaction that is part of the coagulation process. We investigated the role of aspirin in the phenomenon of haemodilution-induced coagulability to identify if the platelet-endothelial system is involved in the process. Previous work showed that the TEG is not altered by oral ingestion of aspirin. Blood from 20 volunteers was divided into two aliquots of 4 ml each. One sample was diluted by 20% by addition of 0.9% saline 1 ml while the other was not diluted and served as a control. Coagulation studies were performed using the TEG and enhanced coagulation was seen in the saline diluted samples. Subjects then received soluble aspirin 375 mg daily for 3 days, after which the tests were repeated. There was no difference in the control TEG values and saline enhancement of coagulation was preserved in all subjects after 3 days of aspirin administration. We conclude that aspirin had no effect on the observation that haemodilution with saline enhances the coagulability of whole blood.

Aspirin↗
PubMed2001

Does prior administration of enoxaparin influence the effects of levobupivacaine on blood clotting? Assessment using the Thrombelastograph.

The low molecular weight heparin, enoxaparin (by inhibition of factors Xa and IIa) and amide local anaesthetics (by altering platelet function) exert anti-clotting effects. Although these agents are often used in combination during the perioperative period, their potential interactive effect on clotting has not been defined. Blood from 10 ASA I-II patients who received enoxaparin 0.5 mg kg(-1) s.c. was studied using a Thrombelastograph (TEG) either alone or in combination with levobupivacaine (2.5 mg ml(-1) or 2.5 microg ml(-1)) or saline (50% dilution). In blood from patients who had received enoxaparin 0.5 mg kg(-1) s.c. 12 h previously, levobupivacaine 2.5 mg ml(-1) (but not 2.5 microg ml(-1)) produced significant changes in TEG clotting parameters (mean (SD) 15.7 (4.8) mm, 29.6 (25.6) mm, 34.4 (14.6) mm, 34.3 (12.2) degrees compared with control values of 6.1 (1.3) mm, 2.5 (0.5) mm, 63.5 (6.4) mm and 74.1 (2.9) degrees for r, K, MA, and alpha angle respectively).

Adult↗
PubMed2001

Isolated reduction of haematocrit does not compromise in vitro blood coagulation.

Low haematocrit values are generally well tolerated in terms of oxygen transport but a low haematocrit might interfere with blood coagulation. We thus sampled 60 ml of blood in 30 healthy volunteers. The blood was centrifuged for 30 min at 2000 g and separated into plasma, which contained the platelet fraction, and packed red blood cells. The blood was subsequently reconstituted by combining the entire plasma fraction with a mixture of packed red blood cells, 0.9% saline, so that the final haematocrit was either 40, 30, 20, or 10%. Blood coagulation was assessed by computerized Thrombelastograph analysis. Data were compared using repeated measures analysis of variance and post-hoc paired t-tests with Bonferroni correction. Decreasing the haematocrit from 40 to 10% resulted in a shortening of reaction time (r) and coagulation time (k), and an increase in angle alpha, maximum amplitude (MA) and clot strength (G) (all P<0.02). This pattern represents acceleration of blood coagulation with low haematocrit values. The isolated reduction in haematocrit, therefore, does not compromise in vitro blood coagulation.

Adult↗
PubMed2002

In vivo effect of haemodilution with saline on coagulation: a randomized controlled trial.

BACKGROUND: Previous studies have shown that 10-30% haemodilution with crystalloid may induce a hypercoagulable state demonstrable by using the Thrombelastograph (TEG). While most are in vitro studies, the few in vivo studies are limited by confounding surgical or 'environmental' factors. We conducted this randomized controlled study to evaluate the coagulation changes associated with in vivo haemodilution. METHODS: Twenty patients undergoing major hepatobiliary surgery were randomly allocated to one of two study groups. Group H (n = 10) had 30% blood volume withdrawn over 30 min and replaced with saline. Group C (n = 10) did not have any blood withdrawn. Blood samples were taken in both groups at 10, 20 and 30 min. Native TEG, complete blood count, coagulation profile, fibrinogen, antithrombin III, protein C and thrombin-antithrombin complex concentrations were measured. RESULTS: Compared with Group C, Group H patients had significantly greater shortening of r-time at 30 min (-30% vs +36%), greater shortening of k-time at all time points (-36% vs +17% at 10 min; -37% vs +44% at 20 min; -45% vs +49% at 30 min), and greater widening of alpha at 30 min (+71% vs +4%). The decrease in antithrombin III and other natural procoagulants and anticoagulants closely followed that of haematocrit, with the exception of thrombin-antithrombin complex. CONCLUSION: In vivo haemodilution of up to 30% with saline can induce a hypercoagulable state. The mechanism remains unclear as disproportionate dilution of natural anticoagulants was not detected. Thrombin-antithrombin complex concentration remained stable despite haemodilution in Group H, which may suggest increased thrombin generation.

Adult↗
PubMed2002

High-dose tinzaparin in pregnancy and the need for urgent delivery.

The prolonged anticoagulant effects of high-dose low molecular weight heparin (LMWH) pose problems in pregnant women when unanticipated delivery is required. We present two pregnant women on therapeutic doses of LMWH whose labour did not progress smoothly. The Thrombelastograph coagulation analyser was used to assess the coagulation status periodically. It influenced surgical and anaesthetic management and there was a safe outcome.

Adult↗
PubMed2004

Comparison of structured use of routine laboratory tests or near-patient assessment with clinical judgement in the management of bleeding after cardiac surgery.

BACKGROUND: Using algorithms based on point of care coagulation tests can decrease blood loss and blood component transfusion after cardiac surgery. We wished to test the hypothesis that a management algorithm based on near-patient tests would reduce blood loss and blood component use after routine coronary artery surgery with cardiopulmonary bypass when compared with an algorithm based on routine laboratory assays or with clinical judgement. METHODS: Patients (n=102) undergoing elective coronary artery surgery with cardiac bypass were randomized into two groups. In the point of care group, the management algorithm was based on information provided by three devices, the Hepcon, thromboelastography and the PFA-100 platelet function analyser. Management in the laboratory test group depended on rapidly available laboratory clotting tests and transfusion of haemostatic blood components only if specific criteria were met. Blood loss and transfusion was compared between these two groups and with a retrospective case-control group (n=108), in which management of bleeding had been according to the clinician's discretion. RESULTS: All three groups had similar median blood losses. The transfusion of packed red blood cells (PRBCs) and blood components was greater in the clinician discretion group (P<0.05) but there was no difference in the transfusion of PRBCs and blood components between the two algorithm-guided groups. CONCLUSION: Following algorithms based on point of care tests or on structured clinical practice with standard laboratory tests does not decrease blood loss, but reduces the transfusion of PRBCs and blood components after routine cardiac surgery, when compared with clinician discretion. Cardiac surgery services should use transfusion guidelines based on laboratory-guided algorithms, and the possible benefits of point of care testing should be tested against this standard.

Aged↗
PubMed2004

In vitro effects of local anaesthetics on the thromboelastographic profile of parturients.

BACKGROUND: Post-dural puncture headache can be an incapacitating complication of obstetric epidural analgesia/anaesthesia and early or prophylactic epidural blood patch (EBP) is one of the treatment options. Although local anaesthetic (LA) agents have been shown to have anticoagulation effects in vitro, peri-partum women are known to be hypercoagulable. We postulated that the presence of residual LA might not result in impaired haemostasis of the EBP in parturients. METHODS: Blood samples from 10 healthy term parturients were subjected to thromboelastography after the addition of four different LA (lidocaine, bupivacaine, levobupivacaine, and ropivacaine) preparations. RESULTS: There was a significant reduction in reaction (R) and coagulation (K) time (P<0.001, P<0.05) and an increase in alpha degrees angle (P<0.01) when comparing undiluted blood with the saline control group. Maximum amplitude (MA) and clot lysis (Ly30) did not change significantly despite the 50% dilution. The thromboelastographic parameters of all four LA-treated groups were no different from their saline controls and from each other. CONCLUSION: At clinical dosages, LA did not cause any hypocoagulable changes on the thromboelastographic profile of healthy parturients.

Amides↗
PubMed2004

Thrombelastographic whole blood clot formation after ex vivo addition of plasma substitutes: improvements of the induced coagulopathy with fibrinogen concentrate.

BACKGROUND: Plasma substitutes such as hydroxyethyl starch (HES) and various dextrans may compromise the haemostatic system, thereby causing potentially dangerous bleeding. Whilst several mechanisms have been advanced to explain the nature of the coagulopathy induced by this colloid, there has been comparably little interest in devising ways to optimize haemostasis after a relative colloid overdose. METHODS: Real-time whole blood (WB) clot formation profiles were recorded using a thrombelastographic method employing activation with tissue factor. The coagulation tracings were transformed into dynamic velocity profiles of WB clot formation. WB from healthy individuals (n=20) was exposed to haemodilution of approximately 55% with isotonic saline, HES 200/0.5, HES 130/0.4, and dextran 70, respectively. Possible modalities for improvement of the induced coagulopathy were explored, in particular ex vivo addition of a fibrinogen concentrate. RESULTS: WB coagulation profiles changed significantly with decreased clot strength, and a compromised propagation phase of clot formation. The duration of the initiation phase of WB coagulation was unchanged. No statistical differences were detected amongst the HES solutions and dextran 70. However, dextran 70 returned a more suppressed clot development and strength compared with the HES solutions. Ex vivo haemostatic addition of washed platelets (75 x 10(9) litre(-1)) and factor VIII (0.6 IU ml(-1)) produced insignificant changes in clot initiation, propagation, and in the clot strength. In contrast, ex vivo addition of a fibrinogen concentrate (1 g litre(-1)) improved the coagulopathy induced by all of the three individual plasma expanders tested. CONCLUSION: Coagulopathy induced by haemodilution with either HES 200/0.5, HES 130/0.4, and dextran 70 may be improved by fibrinogen supplementation.

Adult↗
PubMed2005

Molecular weight of hydroxyethyl starch: is there an effect on blood coagulation and pharmacokinetics?

BACKGROUND: The development of hydroxyethyl starches (HES) with low impact on blood coagulation but higher volume effect compared with the currently used HES solutions is of clinical interest. We hypothesized that high molecular weight, low-substituted HES might possess these properties. METHODS: Thirty pigs were infused with three different HES solutions (20 ml kg(-1)) with the same degree of molar substitution (0.42) but different molecular weights (130, 500 and 900 kDa). Serial blood samples were taken over 24 h and blood coagulation was assessed by Thromboelastograph analysis and analysis of plasma coagulation. In addition, plasma concentration and in vivo molecular weight were determined and pharmacokinetic data were computed based on a two-compartment model. RESULTS: Thromboelastograph analysis and plasma coagulation tests did not reveal a more pronounced alteration of blood coagulation with HES 500 and HES 900 compared with HES 130. In contrast, HES 500 and HES 900 had a greater area under the plasma concentration-time curve [1542 (142) g min litre(-1), P<0.001, 1701 (321) g min litre(-1), P<0.001] than HES 130 [1156 (223) g min litre(-1)] and alpha half life (t(alpha)(1/2)) was longer for HES 500 [53.8 (8.6) min, P<0.01] and HES 900 [57.1 (12.3) min, P<0.01] than for HES 130 [39.9 (10.7) min]. Beta half life (t(beta)(1/2)), however, was similar for all three types of HES [from 332 (100) to 381 (63) min]. CONCLUSIONS: In low-substituted HES, molecular weight is not a key factor in compromising blood coagulation. The longer initial intravascular persistence of high molecular weight low-substituted HES might result in a longer lasting volume effect.

Animals↗
PubMed2005

Activated recombinant factor VII after cardiopulmonary bypass reduces allogeneic transfusion in complex non-coronary cardiac surgery: randomized double-blind placebo-controlled pilot study.

BACKGROUND: Receiving an allogeneic transfusion may be an independent predictor of mortality for patients undergoing cardiac surgery. Furthermore, these patients utilize 15% of all donated blood in the UK. In our unit, 80% of patients undergoing complex non-coronary cardiac surgery requiring cardiopulmonary bypass (CPB) receive an allogeneic transfusion. Activated recombinant FVII (rFVIIa) may be effective in reducing this need for transfusion. METHODS: Twenty patients undergoing complex cardiac surgery were randomized to receive rFVIIa or placebo after CPB and reversal of heparin. RESULTS: Two patients in the rFVIIa group received 13 units of allogeneic red cells and coagulation products compared with eight patients receiving 105 units of allogeneic red cells and coagulation products in the placebo group (relative risk of any transfusion 0.26; confidence interval 0.07-0.9; P=0.037). The groups did not differ for adverse events. CONCLUSION: Despite major limitations (underpowered study and prone to type I error), we have shown that rFVIIa significantly reduces the need for allogeneic transfusion in complex non-coronary cardiac surgery without causing adverse events.

Aged↗
PubMed2006

Molar substitution and C2/C6 ratio of hydroxyethyl starch: influence on blood coagulation.

BACKGROUND: Development of hydroxyethyl starches (HES) with a low impact on blood coagulation but a long intravascular persistence is of clinical interest. A previous in vitro study showed that low substituted high molecular weight HES does not compromise blood coagulation more than medium molecular weight HES. In the present study we assessed the individual effects on blood coagulation of molar substitution and C2/C6 ratio of a high molecular weight HES. METHODS: Blood was obtained from 30 healthy patients undergoing elective surgery and mixed with six high molecular weight (700 kDa) HES solutions differing in their molar substitution (0.42 and 0.51) and C2/C6 ratio (2.7, 7 and 14) to achieve 20, 40 and 60% dilution. Blood coagulation was assessed by Thrombelastograph analysis (TEG) and plasma coagulation tests. Data were compared using a three-way analysis of variance model with repeated measures on the three factors. RESULTS: Higher molar substitution compromised blood coagulation most (for all TEG parameters, P<0.05). The lowest C2/C6 ratio was associated with the lowest effect on blood coagulation; r (P<0.001), angle alpha (P=0.003) and coagulation index (P<0.001). No effect on k and maximum amplitude was observed (P for both >0.50). The higher molar substitution was associated with a lesser increase in PT (P=0.007) and a greater decrease in factor VIII (P=0.010). PTT, functional and antigenic von Willebrand factors were not significantly influenced by molar substitution (P for all >0.20). No significant differences between solutions with the same molar substitution but different C2/C6 ratios were found in plasma coagulation parameters (P for all >0.05). CONCLUSIONS: TEG analysis indicates that high molecular HES with a molar substitution of 0.42 and a C2/C6 ratio of 2.7 has the lowest effect on in vitro human blood coagulation.

Adult↗