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PubMed2001

Effect of hydroxyethyl starch on coagulopathy in a swine model of hemorrhagic shock resuscitation.

BACKGROUND: Hydroxyethyl starch (HES) has a known dose-dependant effect on coagulopathy. The purpose of this study was to determine the effect of HES on coagulopathy after a period of hemorrhagic shock. METHODS: Anesthetized swine underwent a 15-minute, 40% blood volume hemorrhage (28 mL/kg) and a 1-hour shock period, followed by resuscitation with sham resuscitation (group I); 6% HES, 15 mL/kg (group II); 5% albumin, 15 mL/kg (group III); lactated Ringer's solution, 39 mL/kg, and 6% HES, 15 mL/kg (group IV); and lactated Ringer's solution, 39 mL/kg, and 5% albumin, 15 mL/kg (group V). Coagulation function was measured by bleeding time, prothrombin time, partial thromboplastin time, fibrinogen, platelet count, and thromboelastography. RESULTS: Platelet counts decreased significantly (p < 0.05) in all resuscitation groups except the sham resuscitation group. A significant decrease in platelets, fibrinogen levels, and maximum amplitude on thromboelastography was related to a dilutional effect of the fluid given and not a result of HES at the dose tested. CONCLUSION: The linear dose-related coagulopathic effects of HES when given at moderate doses does not seem to be worsened by prolonged periods of hemorrhagic shock. The coagulopathy seen during resuscitation from hemorrhagic shock seems to be a dilutional effect.

Analysis of Variance↗
PubMed1977

Thromboelastographic distinction of malignant from benign breast masses: a preliminary report.

Thromboelastography is a newly applied tool for the detection of carcinoma. By comparing the thromboelastograph (TEG) of fresh whole blood (native) to that of blood to which celite has been added (celite activated), enhanced clotting is manifested which allows identification of individuals harboring carcinoma. Twenty women, obtained in a random sampling, entering the North Carolina Baptist Hospital for biopsy of breast masses were studied with routine clotting tests and TEGs preoperatively. TEG prediction of the biopsy result was correct in 16 of 20 patients (P less than 0.05). Thromboelastography may be a useful adjunct in screening for carcinoma in the evaluating persons with masses of unknown histology.

Blood Coagulation Tests↗
PubMed2006

Acidosis impairs the coagulation: A thromboelastographic study.

BACKGROUND: Coagulopathy is a contributor to and predictor of death in bleeding patients. Acidosis is known to be a predictor of worse outcome in trauma patients and to be a coexisting factor in coagulopathic patients, but it has not been studied if it is a causal factor in the development of coagulopathy. METHODS: We have adjusted the pH level in blood samples from healthy volunteers to different levels between 7.4 and 6.8 by the use of hydrochloric acid. Thereafter we have studied the coagulation at the different pH levels by the use of thromboelastography. RESULTS: We found a strong correlation between pH levels and impairment of the coagulation, where the clot strength is increased much slower at pH levels below 7.4 even though the initiation of the clotting seems to be normal. The clot formation time was increased by 168% at pH 6.8 as compared with pH 7.4 (p < 0.00001, r = 0.89) whereas the clotting time was left unaffected. CONCLUSIONS: Acidosis causes a strong impairment of the coagulation as measured with thromboelastography. The impairment found when lowering pH from 7.4 to 7.15 was almost identical to the impairment seen in another study by Kettner et al. when the temperature was lowered from 36 degrees C to 32 degrees C.

Acidosis↗
PubMed2006

Insights into abnormal hemostasis in the Quebec platelet disorder from analyses of clot lysis.

BACKGROUND: The Quebec platelet disorder (QPD) is inherited and characterized by delayed-onset bleeding following hemostatic challenge. Other characteristics include increased expression and storage of active urokinase-type plasminogen activator (u-PA) in platelets in the setting of normal to increased u-PA in plasma. There is also consumption of platelet plasminogen activator inhibitor-1 and increased generation of plasmin in platelets accompanied by proteolysis of stored alpha-granule proteins, including Factor V. AIMS AND METHODS: Although fibrinolysis has been proposed to contribute to QPD bleeding, the effects of QPD blood and platelets on clot lysis have not been evaluated. We used thromboelastography (TEG), biochemical evaluations of whole blood clot lysis, assessments of clot ultrastructure, and perfusion of blood over preformed fibrin to gain insights into the disturbed hemostasis in the QPD. RESULTS: Thromboelastography was not sensitive to the increased u-PA in QPD blood. However, there was abnormal plasmin generation in QPD whole blood clots, generated at low shear, with biochemical evidence of increased fibrinolysis. The incorporation of QPD platelets into a forming clot led to progressive disruption of fibrin and platelet aggregates unless drugs were added to inhibit plasmin. In whole blood perfusion studies, QPD platelets showed normal adherence to fibrin, but their adhesion was followed by accelerated fibrinolysis. CONCLUSIONS: The QPD is associated with "gain-of-function" abnormalities that increase the lysis of forming or preformed clots. These findings suggest accelerated fibrinolysis is an important contributor to QPD bleeding.

Blood Platelet Disorders↗
PubMed2004

Argatroban as an alternative to heparin in extracorporeal membrane oxygenation circuits.

We investigated the anticoagulant effects of argatroban, a direct thrombin inhibitor, versus heparin in extracorporeal membrane oxygenation (ECMO) circuits. Three sham circuits were prepared according to our hospital's standard practice and run for six hours simultaneously. Two circuits were anticoagulated with argatroban (one with heparin in the wet prime and one without). One circuit had heparin in the initial prime and was then anticoagulated with heparin. We measured thrombin generation (prothrombin fragment 1+2, D-dimer and thrombin-antithrombin complexes), activated clotting times (ACTs) and partial thromboplastin times (aPTTs), and monitored thrombus formation using thromboelastography. ACTs were >1000 s in each circuit throughout assessment. No clot initiation was detected by thromboelastography. Thrombin generation was decreased in circuits anticoagulated with argatroban versus heparin, despite aPTTs being less prolonged. These results suggest that argatroban may be more efficacious than heparin for anticoagulation in ECMO. Additional studies are warranted to further evaluate argatroban in this setting.

Arginine↗
PubMed2003

The influence of induced hypothermia for hemostatic function on temperature-adjusted measurements in rabbits.

UNLABELLED: In hypothermic patients, a tendency to bleed may be observed even when hemostatic tests seem to be normal. Coagulation and platelet function tests are usually performed at 37 degrees C. We investigated the influence of induced hypothermia on temperature-adjusted hemostasis function testing using Sonoclot Analyzer (Sonoclot) and Thromboelastography (TEG). Anesthesia was induced and maintained with IV ketamine and fentanyl on 15 male New-Zealand White rabbits. A water blanket was used to induce hypothermia to 30 degrees C and to rewarm to 37 degrees C. Blood samples were obtained at four points: before hypothermia, at 34 degrees C, at 30 degrees C, and after rewarming. Standard coagulation tests were performed at 37 degrees C (C method), and simultaneously, real temperature hemostasis function tests (R method) were run. In Sonoclot(R), activated clotting time and time to peak increased and clot rate decreased significantly at 30 degrees C in the R method compared with those in the C method. In TEG(R), reaction time and clot formation time were prolonged and clot formation rate was diminished at 30 degrees C in the R method compared with those in the C method. Induced hypothermia delayed the coagulation cascade and reduced platelet function. During hypothermia, hemostatic measurements should be performed at real temperature to avoid overestimating patient hemostatic function based on results measured at the standard 37 degrees C. IMPLICATIONS: We investigated the influence of induced hypothermia on temperature-adjusted hemostasis function tests in rabbits using Sonoclot Analyzer and Thromboelastography. Induced hypothermia delayed the coagulation cascade and reduced platelet function. The conventional coagulation tests performed at 37 degrees C failed to detect these hypothermia-induced degradations in hemostasis performance.

Anesthesia↗
PubMed2003

Off-pump coronary artery bypass surgery may produce a hypercoagulable patient.

BACKGROUND: The incidence of thromboembolic events following traditional open heart surgery has not been clinically significant. However, with beating heart surgery, for which cardiopulmonary bypass (CPB) is not required, the incidence of spontaneous intravascular thrombosis may be similar to that encountered after general surgeries. Compounding this risk is that many cases of off-pump coronary artery bypass (OPCAB) surgery are reserved for the elderly patient with multiple comorbidities. The few studies to date that have assessed the coagulation profile in OPCAB patients have been limited to the first 24 hours after surgery. METHODS: We prospectively studied 17 OPCAB and 6 onpump patients over 4 days (hospital course) with daily thromboelastography. A coagulation index (CI) (reflecting R and K times, angle, and maximum amplitude lbrack;MArbrack;) was calculated for the patients, who served as their own controls. RESULTS: The OPCAB patients demonstrated 3 days postoperatively a 17% increase in coagulation compared with the baseline. Specifically, the CI consistently revealed an elevation in the angle and the MA, both of which reflect increased fibrinogen and platelet activity. On the other hand, 3 days following surgery the CI of the CPB group was tightly clustered around their respective baseline CI values, which had recovered from a significant decrease immediately after surgery. CONCLUSION: A state of hypercoagulability, as measured by thromboelastography, exists in the OPCAB patient beyond the first postoperative day, and this finding suggests that prophylactic postoperative anticoagulation therapy targeting fibrinogen and platelet activity may be indicated for these patients.

Adult↗
PubMed2000

Evidence of hypercoagulability in dogs with parvoviral enteritis.

OBJECTIVE: To determine whether dogs with naturally occurring canine parvoviral (CPV) enteritis have laboratory evidence of hypercoagulability. DESIGN: Case-control study. Animals-9 dogs with naturally occurring CPV enteritis and 9 age-matched control dogs. PROCEDURE: Blood was collected from all dogs within 24 hours of admission for thromboelastography (TEG) and determination of activated partial thromboplastin time (aP-TT), prothrombin time (PT), antithrombin III (AT) activity, and fibrinogen concentration. Fibrin-fibrinogen degradation product (FDP) concentration, D-dimer concentration, and platelet count were obtained in dogs with CPV enteritis only. Records were reviewed for evidence of thrombosis or phlebitis. RESULTS: All 9 dogs with CPV enteritis had evidence of hypercoagulability, determined on the basis of significantly increased TEG maximum amplitude and decreased AT activity. Fibrinogen concentration was significantly higher in dogs with CPV enteritis than in control dogs. The aPTT was moderately prolonged in dogs with CPV enteritis, and FDP concentration was < 5 mg/ml in 7 of 9 dogs. No dogs had a measurable D-dimer concentration. Platelet counts were within reference range. Four of 9 dogs had clinical evidence of venous thrombosis or phlebitis associated with catheters. One dog had multifocal splenic thrombosis identified at necropsy. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs with CPV enteritis have a high prevalence of clinical thrombosis or phlebitis and laboratory evidence of hypercoagulability without disseminated intravascular coagulopathy. Thromboelastography may help identify hypercoagulable states in dogs.

Animals↗
PubMed1999

The inhibitory effect of recombinant human soluble thrombomodulin on initiation and extension of coagulation--a comparison with other anticoagulants.

Recombinant human soluble thrombomodulin (rhsTM) was compared with various anticoagulants for in vitro anticoagulant effects on thrombin generation, clotting time, and thromboelastography. rhsTM as well as APC reduced the level of the peak of the thrombin generation curve, but we did not observe any time-delay to reach the peak. This effect of rhsTM was diminished in PC-deficient plasma and was closely associated with the inhibitory effect on prothrombinase and factor Va. On the other hand, hirudin and argatroban delayed the time to reach the level of the peak, without reducing it. rhsTM and other anticoagulants except for activated protein C (APC) were found to have concentration-dependent anticoagulant activity by conventional clotting tests. However, the concentration of rhsTM for clotting time was slightly affected by anti-protein C antibody. Moreover, the concentration of rhsTM required to inhibit thrombin activity directly was 50 times higher than that needed to inhibit thrombin generation. The effect of rhsTM on clot development was compared with that of other anticoagulants by thromboelastography; rhsTM reduced the growth of the clot but had little effect on the time to activate clotting, while the other anticoagulants had the opposite effect. This effect of rhsTM was completely abolished by the addition of anti-protein C or anti-protein S antibody. These findings suggest that rhsTM attenuates blood clotting by reducing the level of generated thrombin through protein C activation and subsequent factor Va inactivation and prothrombinase inhibition.

Anticoagulants↗
PubMed1982

Intraoperative anticoagulation during arterial reconstructive procedures.

The technique of thromboelastography was used to monitor the intraoperative administration of heparin during vascular surgical procedures. Interpatient response to 70 units per kilogram of heparin varied widely. There was no need, in any patient, for the use of protamine to reverse the effect of heparin. This, coupled with the absence of hemorrhagic complications, indicates that thromboelastography is a useful method for monitoring the administration of heparin during vascular surgical procedures.

Aged↗
PubMed1981

[Clinico-biological effectiveness of triflusal during the postoperative period of patients with chronic ischemic syndrome of the extremities].

A group of 15 patients, suffering of chronic ischaemia of the lower limbs, were treated with triflusal, a new antiaggregant and antithrombotic agent, at the dose of 300 mg/day, during the first 90 days after artery by-pass grafting. Clinical exploration of patients included: physical inspection, pulses palpation, intermittent claudication (in metres), arteriography before surgery, and postoperative evolution of oscillometric and Doppler indexes. Determinations of platelet aggregation, induced by ADP, epinephrine and collagen, as well as of prothrombin time, platelet adhesiveness, and of thromboelastography parameters in PRP ane PPP were also carried out. Biochemical and hematological data were determined; gastric tolerance and other side effects were written down. Results show a clear improvement of all patients due to surgery, but with triflusal, it has been possible to maintain a prophylactic effect without thrombosis of the graft or of the distal vessel of patients, during the postoperative period. Actually, lower limbs temperature and pulses were maintained, with a good capillary content and with an improved walking distance. No changes in prothrombin time an platelet adhesiveness, have been observed. Five patients showed a clear hypoaggregant tendency, and thromboelastography in PRP indicates a statistically significant increase of R and K parameters as well as a decrease of am. It must be noticed the absence of gastric, hepatic, renal or metabolic side effects and no haemorrhagic lesions were observed. In conclusion, the treatment of these patients with triflusal prevents the otherwise frequent appearance of postoperative thrombosis in this kind of arterial surgery.

Adult↗
PubMed1998

Effects of wine on plasma fibrinolytic and coagulation systems.

The in-vitro effects of citrus, red and white wines on human plasma fibrinolytic enzymes were compared. When citrus wine was added to plasmin, H-D-Val-Leu-Lys-pNA (S-2251) amidolysis was not changed. Although, it was significantly inhibited when red and white wines were added. The pyro-Glu-Gly-Arg-pNA (S-2444) amidolysis of the plasminogen activator urokinase was inhibited by all types of wine. Since the same amount of Et-OH as the wine's content did not effect on these inhibitions, it can be assumed to be due to other unknown substances in wines besides alcohol. In in-vivo test of 20 normal volunteers (ages 20-52) with various wines equivalent to 30-60 ml of alcohol content, the coagulation parameters of gamma and kappa values on thromboelastography were not so much changed after 1-2 hrs of the application. Also, there was not much difference of the fibrinolytic parameters in terms of the plasma euglobulin clotlysis time, S-2444 amidolysis, and Ma values on thromboelastography. However, the protein concentration and the enzyme activity of the urokinase-like plasminogen activator, which were extracted from the plasma of volunteers who had the citrus wine 1 hr before the test were higher than twice of the before control. The main molecular form of this enzyme was proved to have a molecular weight of about 30,000 by zymography. It is concluded that not only wines induce the endogenous plasminogen activator just like other alcoholic beverages but also wines contain a fibrinolysis inhibitor which works directly to the enzyme dissolubility. This finding warns that extremely complex results can be expected depending on the test method.

Adult↗
PubMed1987

Treatment of acute myocardial infarction with subcutaneous heparin at low doses.

Heparin has been used intensively in the treatment of acute myocardial infarction and preinfarction angina (PA) at full doses as a single drug by us. However, heparin may be used at smaller doses for similar purposes. These doses are not exactly anticoagulant, even though they reduce blood hypercoagulability, and act mainly in an antithrombotic capacity. We studied 529 patients with acute myocardial infarction, of whom 262 were treated with subcutaneous heparin at low doses (5000 IU every 12 h) and 267 received conventional therapy without antithrombotic drugs. Heparin used was Heparina (Abbott) and Liquemine (Roche), in vials with the equivalence 1 cm3 = 50 mg = 5000 IU. Blood rheologic factors (thromboelastography, platelet adhesiveness, total blood viscosity, and number of platelets) were determined in all patients, those treated with heparin at low doses and also the control group, before and after the 30-day treatment period. Diagnosis was based on clinical symptoms, laboratory studies, and electrocardiogram examination. In both the 262 patients treated with heparin at low doses and in the control group of 267 patients, baseline values of rheological factors were high. After 30 days (i.e., after study completion) these high values which are statistically significant compared with normal values, with p less than 0.0001 for both groups, remained constant in the control group who did not receive heparin. On the contrary, in the group treated with heparin at low doses, all these factors changed. Heparin provides protection against thrombosis by increasing the negative charge of the vessel wall and by other reactions at the endothelial surface. Heparin requires a plasmatic component called antithrombine III.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2007

Hemostatic properties of glucosamine-based materials.

Glucosamine- and N-acetyl glucosamine-containing polymers are being used in an increasing number of biomedical applications, including in products for surface (topical) hemostasis. The studies presented here investigate the relationship between the structure (conformation) and function (activation of hemostasis) of glucosamine-based materials. Several polymer systems were studied, including fibers isolated from a microalgal source containing poly-N-acetyl glucosamine polymers that are organized in a parallel, hydrogen-bonded tertiary structure and can be chemically modified to an antiparallel orientation; and gel formulation derivatives of the microalgal fibers consisting of partially deacetylated (F2 gel) and fully deacetylated (F3 gel) polymers. Comparison of the properties of the poly-N-acetyl glucosamine fiber-derived materials with chitin, chitosan, and commercial chitosan-based products are presented. Several studies were performed with the glucosamine-based materials, including (1) an analysis of the ability of materials to activate platelets and turnover of the intrinsic coagulation cascade, (2) an examination of the viscoelastic properties of mixtures of platelet-rich plasma and the glucosamine-based materials via thromboelastography, and (3) scanning electron microscopic studies to examine the morphology of the glucosamine-based materials. The results presented demonstrate that hemostatic responses to the glucosamine-based materials studied are highly dependent on their chemical nature and tertiary/quaternary structure. The unique natural microalgal fibers were found to have strongly prohemostatic activity compared to the other materials studied.

Acetylglucosamine↗
PubMed2006

Ionic liquid-derived blood-compatible composite membranes for kidney dialysis.

A novel heparin- and cellulose-based biocomposite is fabricated by exploiting the enhanced dissolution of polysaccharides in room temperature ionic liquids (RTILs). This represents the first reported example of using a new class of solvents, RTILs, to fabricate blood-compatible biomaterials. Using this approach, it is possible to fabricate the biomaterials in any form, such as films or membranes, fibers (nanometer- or micron-sized), spheres (nanometer- or micron-sized), or any shape using templates. In this work, we have evaluated a membrane film of this composite. Surface morphological studies on this biocomposite film showed the uniformly distributed presence of heparin throughout the cellulose matrix. Activated partial thromboplastin time and thromboelastography demonstrate that this composite is superior to other existing heparinized biomaterials in preventing clot formation in human blood plasma and in human whole blood. Membranes made of these composites allow the passage of urea while retaining albumin, representing a promising blood-compatible biomaterial for renal dialysis, with a possibility of eliminating the systemic administration of heparin to the patients undergoing renal dialysis.

Biocompatible Materials↗
PubMed2005

In vitro biological performances of phosphorylcholine-grafted ePTFE prostheses through RFGD plasma techniques.

Arterial prostheses made of microporous Teflon (ePTFE) are currently used in vascular surgery as bypasses for small and medium vessels. However, several clinical complications, such as thrombosis, frequently occur in these prostheses when implanted in humans. In this work, an original strategy was developed to improve the hemocompatibility of ePTFE prostheses, based on glow-discharge surface modification followed by chemical grafting of phosphorylcholine, known for its hemocompatible properties. This procedure leads to a covalent attachment of the molecules, therefore preventing their removal by shear stress induced by blood flow at the implant wall. The improvement of the blood compatibility properties of the modified ePTFE arterial prostheses have been investigated by in vitro tests such as thromboelastography, neutrophil adsorption, platelet aggregation, and cell cultures. These in vitro tests put in evidence that thrombogenicity index, platelet aggregation, and neutrophil adhesion were decreased by the molecule grafted on the prostheses. Moreover, the cell growth on the surface of the PRC-grafted prostheses was greatly enhanced in comparison to the virgin prosthesis. Based on these results, it could be concluded that PRC grafting on ePTFE prostheses permit to improve in vitro hemocompatibility and biocompatibility in comparison with their virgin counterpart.

Ammonia↗
PubMed1991

The intra-operative use of trasylol (aprotinin) in liver transplantation.

Aprotinin has been reported to reduce blood loss in difficult cases requiring cardiopulmonary bypass surgery and more recently in liver transplantation. Over a 9-month period we compared the effects of an intra-operative infusion of aprotinin on transfusion requirements and coagulation profiles in 12 patients undergoing liver transplantation for end-stage cirrhosis with an equal number of consecutive transplants in patients with similar pathology who did not receive aprotinin. Transfusion of blood and blood products was reduced to one-third in the aprotinin-treated group. Operative time was also significantly reduced, as was ICU stay post-operatively. Aprotinin profoundly inhibits fibrinolysis and this is likely to be the major effect by which blood loss is reduced. Thromboelastography revealed severe fibrinolytic changes in the anhepatic stage in 4 of 6 controlled patients; this accelerated in 3 following reperfusion of the new graft. By contrast, only 1 patient of 12 in the aprotinin-treated group showed fibrinolytic activity in the anhepatic period, and none showed evidence of fibrinolysis following reperfusion of the new graft.

Aprotinin↗
PubMed1975

[Blood coagulation in man during a 3-week daily rg L(+)-ASCORBIC ACID ADMINISTRATION].

A daily dose of 4 g L (+) ascorbic acid administered for 3 weeks showed no significant influence on coagulation of venous blood, as determined by thromboelastography. The investigation was carried out on 11 healthy men aged from 25 to 45 with no history of abnormal blood clotting. The mean values of 7 different coagulation parameters are given, the differences in these parameters in individual subjects (before and after administration of ascorbic acid) being checked for significance by means of the Wilcoxon test for pair differences. The values found are comparable with those in the literature.

Adult↗