Hemostatic alterations associated with supraceliac aortic cross-clamping.

PURPOSE: The causative role of consumptive coagulopathy in the development of bleeding complications after supraceliac (SC) aortic cross-clamping (AXC) has been challenged by recent reports that ascribe this coagulopathy to primary fibrinolysis. This theory is made on the basis of evidence that tissue plasminogen activator (t-PA) antigen (Ag) levels increase after SC AXC. However, t-PA Ag levels reflect both active and inactive (bound to serum t-PA inhibitors) forms of serum t-PA, and elevations confirm the presence of fibrinolysis only in conjunction with an increase in t-PA activity. METHODS: To investigate the etiology of this coagulopathy, we submitted eight pigs to SC AXC and six pigs to infrarenal (IR) AXC for 30 minutes. Blood was drawn from the portal vein, the hepatic vein, and the carotid artery before AXC, just before unclamping, and 5, 30, and 60 minutes after unclamping. Prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen (FBG), platelets (PLT), thrombin-antithrombin complexes (TAT), t-PA Ag, t-PA activity, plasminogen activator inhibitor-1 (PAI-1), and alpha2-antiplasmin (AP) activities were measured. Statistical analysis was performed by using repeated measures analysis of variance and t tests RESULTS: The PT did not differ between the two groups at any point. After unclamping, in the SC group there was a drop in PLT levels (P =.005), a decrease in FBG levels (P <.001), and a trend toward PTT prolongation (P =.06) compared with baseline. In contrast, there were no changes in PTT, PLT levels, or FBG levels in the IR group. TAT, a serum marker of thrombin generation, increased with SC AXC (P =.04), remained elevated 5 minutes after unclamping (P =.08), and returned to normal 30 minutes after unclamping. In contrast, TAT levels did not change in the IR control group. In the SC AXC group, the TAT levels did not differ between the three test sites at any time. SC AXC was associated with an increase in t-PA Ag just before unclamping (P <.001) and 5 minutes after unclamping (P =.002), but IR AXC was not. t-PA activity levels decreased in both experimental groups 30 and 60 minutes after unclamping. Levels of alpha2-AP activity decreased to a similar degree in both groups after unclamping when compared with baseline CONCLUSION: Thirty minutes of SC AXC results in intravascular thrombosis that cannot be localized to the ischemic visceral circulation. This intravascular thrombosis is associated with consumption of clotting factors. Thirty minutes of SC AXC causes an activation of fibrinolytic pathways that does not result in a hyperfibrinolytic state. An increase in t-PA Ag without a rise in t-PA activity does not represent true fibrinolysis, but rather an increase in the bound, inactive forms of serum t-PA. Both IR and SC AXC result in decreased fibrinolytic activity ("fibrinolytic shutdown") after release of the aortic clamp.     

Activation of fibrinolytic pathways is associated with duration of supraceliac aortic cross-clamping

PURPOSE: The cause of the coagulopathy seen with supraceliac aortic cross-clamping (SC AXC) is unclear. SC AXC for 30 minutes results in both clotting factor consumption and activation of fibrinolytic pathways. This study was undertaken to define the hemostatic alterations that occur with longer intervals of SC AXC. METHODS: Seven pigs underwent SC AXC for 60 minutes. Five pigs that underwent infrarenal aortic cross-clamping (IR AXC) for 60 minutes and 11 pigs that underwent SC AXC for 30 minutes served as controls. No heparin was used. Blood samples were drawn at baseline, 5 minutes before release of the aortic clamp, and 5, 30, and 60 minutes after unclamping. Prothrombin time, partial thromboplastin time, platelet count, and fibrinogen concentration were measured as basic tests of hemostatic function. Thrombin-antithrombin complexes were used to detect the presence of intravascular thrombosis. Fibrinolytic pathway activation was assessed with levels of tissue plasminogen activator antigen and tissue plasminogen activator activity, plasminogen activator inhibitor-1 activity, and alpha2-antiplasmin activity. Statistical analysis was performed with the Student t test and repeated measures of analysis of variance. RESULTS: Prothrombin time, partial thromboplastin time, and platelet count did not differ between groups at any time. Fibrinogen concentration decreased 5 minutes (P =.005) and 30 minutes (P =.006) after unclamping in both SC AXC groups, but did not change in the IR AXC group. Thrombin-antithrombin complexes increased in both SC AXC groups, but were not significantly greater than in the IR AXC group. SC AXC for both 30 and 60 minutes produced a significant increase in tissue plasminogen activator antigen during clamping and 5 minutes after clamping. This increase persisted for 30 and 60 minutes after clamp release in the 60-minute SC AXC group. Tissue plasminogen activator activity, however, increased only in the 60-min SC AXC group during clamping (P =.02), and 5 minutes (P =.05) and 30 minutes (P =.06) after unclamping, compared with both control groups. CONCLUSIONS: Thirty and 60 minutes of SC AXC results in similar degrees of intravascular thrombosis and fibrinogen depletion. Although SC AXC for both 30 and 60 minutes leads to activation of fibrinolytic pathways, only 60 minutes of SC AXC actually induces a fibrinolytic state. Fibrinolysis appears to be an important component of the coagulopathy associated with SC AXC, and is related to the duration of aortic clamping. CLINICAL RELEVANCE: The coagulopathy frequently associated with thoracoabdominal aortic aneurysm repair is thought to revolt visceral ischemia-reperfusion. The nature of this coagulopathy is controversial. The current study demonstrates that the major hemostatic alteration associated with supraceliac aortic cross-clamping is activation of fibrinolytic pathways. The magnitude of this fibrinolytic response is directly related to the duration of supraceliac aortic occlusion. Future efforts to treat this coagulopathy may well include judicious use of autofibrinolytic agents.     

In vitro fertilization-induced alterations in coagulation and fibrinolysis as measured by thromboelastography

Supraphysiologic increases in estrogen produced by in vitro fertilization (IVF) promote the expression of hemostatic markers. Although quantitative studies of individual markers have been performed during IVF, their results are conflicting and do not reveal the qualitative effect of each marker on the overall coagulation and fibrinolytic processes. Thrombelastograph (TEG) coagulation analysis, by contrast, provides a global measure of coagulation and fibrinolysis and can indicate the relative contributions of clotting factors, fibrinogen, and platelets to each process. We studied the serum estrogen concentrations and TEG variables in 24 women at the beginning and conclusion of an IVF stimulation cycle. Serum estradiol (E(2)) concentrations (mean +/- SD) increased from 26.9 +/- 8.6 to 2098 +/- 913 pg/mL (P < 0.005) at baseline and oocyte retrieval, respectively. The measured TEG indices demonstrated alterations in coagulation rather than fibrinolysis. Although significant changes were noted in both the clot formation time and the coagulation index (P < 0.005), all TEG values remained within the normal range. In addition, an increased role of fibrinogen in promoting clot strength was observed. These findings may assist in the treatment of IVF patients who ultimately develop thromboembolic complications as a result of ovarian hyperstimulation. IMPLICATIONS. The dramatic changes in estrogen produced by in vitro fertilization therapies result in hemostatic marker alterations. Thrombelastograph coagulation analysis, which provides a global assessment of these changes, demonstrated significant alterations in two coagulation indices (clot formation time, coagulation index), although all variables remained within normal limits. The relative importance of fibrinogen versus platelets in determining clot strength was observed. No significant alterations in fibrinolysis were detected.     

Surveillance de l'hémostase au cours de la transplantation hépatique : apport du thromboélastogramme

Monitoring of coagulation is mandatory during liver transplantation (LT). Standard coagulation tests may be routinely used. However, they give static information and may be inadequate in case of severe coagulation defect. Interest has been recently focused on thromboelastography (TEG) which could give more suitable and rapid information in these cases. Few studies have evaluated the clinical interest of TEG compared to conventionnal tests. This comparison was the aim of the present study, performed in 89 patients scheduled for LT. The anaesthetic management as well as procedure of transfusion were similar in all patients. Before unclamping, 5000 KUI · kg⁻¹ of aprotinin were injected. Routine tests and TEG were performed at the beginning and end of both preanhepatic and anhepatic phases, and 5, 30, 60, and 120 min after the revascularisation of the new liver. A phase of hypocoagulability was observed after unclamping. Biological signs included an increase in activated thromboplastin time, a reduction of α angle and maximum amplitude on TEG with a lengthening of its r + k component. A strong correlation existed between maximum amplitude and platelets, maximum amplitude and fibrinogen, α and fibrinogen at each time of the surgical procedure. Euglobulin lysis time decreased significantly after clamping, whereas fibrin degradation products increased at the same time. However, typical fibrinolysis with a clot lysis index (CLI) below 55 % was only observed in 15 patients. Twelve of them had a CLI value reaching 0 %, associated with severe generalized oozing. Aprotinin (200 000 to 600 000 KIU) corrected these abnormalities. These results show that TEG may not be very helpful to determine whether platelets or fibrinogen are involved in the phase of hypocoagulability detected after unclamping. However, TEG allows the actual diagnosis of fibrinolysis and guides therapy. Moreover, it may have a predictive value in some limited cases.     

Comparison of viscoelastic measures of coagulation after cardiopulmonary bypass

Postoperative hemorrhage remains a major cause of morbidity after cardiopulmonary bypass (CPB). Treatment remains empiric because of the need for immediate correction and the lack of availability of rapid intraoperative coagulation monitoring (except for ACT) at most institutions. Thrombelastography (TEG) and Sonoclot analysis (SCT) are measures of viscoelastic properties of blood which allow rapid intraoperative evaluation of coagulation factor and platelet activity as well as overall clot integrity from a single blood sample. Routine coagulation tests (RCT) including activated clotting time (ACT), prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen level (FIB), and platelet count (PLT) were determined and compared to TEG and SCT to assess which best predicted clinical hemostasis after CPB. Forty-two patients prospectively felt to be at high risk for excessive post-CPB bleeding had blood obtained for RCT, TEG, and SCT analysis before systemic heparinization and 30 min after protamine administration. Nine of 42 patients had excessive chest tube drainage, but no reoperations were required. After CPB, mean values for RCT were normal, but there were abnormalities in TEG and SCT parameters that reflect platelet-fibrin interaction. Both TEG and SCT were 100% accurate in predicting bleeding in these nine patients and, overall, both tests were significantly better predictors of postoperative hemorrhage than RCT. We conclude that viscoelastic determinants of clot strength may be abnormal after CPB and that SCT and TEG are, therefore, more useful than RCT for the detection and management of coagulation defects associated with CPB.     

Sonoclot凝血和血小板功能分析仪监测肝移植术中凝血功能变化的应用

目的 探讨肝移植术中凝血功能的变化和Sonoclot凝血及血小板功能分析仪(sonoct coagution & piatelet function analgzer,SCA)在肝移植术中的应用.方法 24例择期肝移植手术患者全部采用原位经典非转流手术方法.于麻醉诱导前(TO)、手术开始后60 min(T1),无肝期30 min(T2)、新肝期30 min(T3)、新肝期120 min(T4)和术毕(T5)时分别采集桡动脉血检测,硅燥土激活的全血血栓弹性描记图(thrombelastography,TEG),指标包括R值、K值、Alpha角和MA值;玻璃珠激活的全血SCA,指标包括ACT、CR和PF值;常规凝血指标包括PT、APTT、INR、Fbg和Plt.结果 (1)SCA和TEG诊断凝血因子缺乏、纤维蛋白凝胶形成速度和血小板功能(都正常或者都异常)的Kappa值分别是0.371(P<0.05)、0.363(P<0.05)、0.438(P<0.05).gbACT与R、CR与α角、PF与MA呈正相关(r=0.790,P<0.05;r=0.766,P<0.05;r=0.502,P<0.05),CR与K呈负相关(r=-0.588,P<0.05).(2)与T0时比较,T3～T5时PT、INR、gbACT及R延长和FBG、CR、α及MA降低(P<0.05),T1～T5时APTT、T3时K延长(P<0.05),T2～T4时PF降低.结论SCA能够准确地监测肝移植术中凝血功能的变化.     

Disseminated intravascular coagulation as a result of supraceliac clamping: implications for thoracoabdominal aneurysm repair

Massive coagulopathy and bleeding continues to play a major role in the operative mortality and perioperative multi-system failure of patients requiring elective thoracoabdominal aneurysm repair. It was the purpose of this study to determine the coagulation defect that occurs with supraceliac aortic clamping and the effects of increasing aortic cross-clamp time (AXCT) on the coagulation system and its recovery. Through a standard thoracoabdominal incision, 16 mongrel dogs had their aortas cross-clamped simultaneously just above the diaphragm and at the aortic bifurcation. Animals were divided into four groups of four animals each; sham operation, 30 minute AXCT, 60 minute AXCT, and 90 minute AXCT. Central venous blood was sampled prior to aortic cross clamping (AXC), during AXC and 1 hour, 2 hours, 5 hours, 7 hours, 12 hours, and 24 hours after the clamp was removed. All samples were assayed for platelets, fibrinogen, fibrin split products, prothrombin time (PT) and partial thromboplastin time (PTT). Platelets and fibrinogen decreased as PT and PTT increased with increasing AXCT consistent with disseminated intravascular coagulation (DIC) (P less than .001). Fibrin split products were positive in the 90 minute AXCT group only. The drop in platelets was greater for increasing AXCT and continued to fall in the 30, 60 and 90 minute AXCT groups at 24 hours (p less than .001). Fibrinogen dropped to the lowest levels between two and twelve hours after AXC and returned to normal at twenty-four hours in the 60 and 90 minute AXCT groups (p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Monitoring of blood coagulation in perioperative care

Coagulation disorders often occur perioperatively and monitoring of blood coagulation should be fast and adequate to treat these disorders to protect patients from massive bleeding. Control of hemostasis is one of the main issues in major surgeries. Coagulation test results from a central laboratory may delay making such a perioperative decision. Recently, point-of-care monitoring (POCM), which is able to examine coagulation disorder in an operation theater with short waiting time, has become important. Both prothrombin time (PT) and activated clotting time (ACT) are very useful and popular, but also criticized because they can be monitored only until fibrin formation. On the other hand, viscoelastic monitorings of whole blood, are able to estimate fibrin formation, clot fixation, platelet function and fibrinolysis. In this review article, among variable perioperative POCMs of blood coagulation, three thromboelastographic monitorings, such as TEG ROTEM, and Sonoclot as well as PT and ACT, are described along with their utilities and limits to examine perioperative coagulation.     

Thromboelastography Use in the Acute Young Trauma Patient: Early Experience of Two Level One Trauma Centers

BackgroundThromboelastography (TEG) point-of-care systems allow for analysis of the sum of platelet function, coagulation proteases and inhibitors, and the fibrinolytic system within 30 minutes. This allows a clinician to guide transfusion more precisely with an appropriate type of blood product. Literature has supported that TEG-guided resuscitation had lower mortality compared to standardized 1:1:1 (red blood cells (RBC), fresh-frozen plasma (FFP), and platelets) massive transfusion protocol (MTP) in penetrating trauma patients, but data has been sparse in examining the young trauma patient.MethodsThis was a cross-sectional chart review study performed with patients up to 30 years old seen in two level one trauma centers serving children with active bleeding resulting from trauma from January 1, 2010 to June 26, 2018. TEG use was evaluated in these patients.Results258 patients were included in the analysis. 112 (43%) had penetrating trauma and 225 (87%) had polytrauma. MTP was instituted in 176 (69%) patients and 88 (34%) patients who had TEG measured. There were significant correlations between PTT and alpha (r=-0.46; p<0.001), PTT and Kinetics (r=0.53; p<0.001), PTT and maximum amplitude (r=0.449; p<0.001). There were also significant correlations between PT and alpha (r=-0.29; p=0.008), and PT and maximum amplitude (r= -0.27; p=0.013). There was no significant correlation between TEG measures and INR. There were significant associations with requiring surgery within 24 hours 45% vs 61% (p=0.018), receiving TXA 20% vs 59% (p<0.001), and with receiving MTP 62% vs 83% (p=0.001), respectively.ConclusionsMeasurement of TEG was associated with patients receiving TXA, MTP and larger amounts of blood products. Components of TEG correlated with PT and PTT levels. Although there was no association with survival to hospital discharge, patients having TEG measured were more likely to undergo surgery within the first 24 hours of hospital arrival.     

Does bicarbonate correct coagulation function impaired by acidosis in swine?

BACKGROUND: Coagulopathy is an important contributor to morbidity and mortality in trauma patients. Acidosis contributes to coagulopathy. Acidosis can be neutralized with intravascular bicarbonate, but it is unclear if the coagulation defect is rapidly reversed. The effects of acidosis and bicarbonate neutralization on coagulation function were investigated in vivo. METHODS: Acidosis was induced in 12 pigs by infusing 0.2 mol/L HCl to pH 7.1. Pigs were then infused with either LR to maintain a pH of 7.1 (A-LR, n = 6) or 0.3 mol/L bicarbonate to a pH of 7.4 (A-Bi, n = 6). Blood samples were taken at baseline, 15 minutes after acidosis induction, and 15 minutes after bicarbonate neutralization. Coagulation function was assessed by prothrombin time (PT), partial thromboplastin time (PTT), thrombin generation, initial clot formation time (R), clotting rapidity (alpha), and clot strength (MA). RESULTS: Compared with baseline values, acidosis reduced fibrinogen concentration to 66% +/- 2% in A-LR and to 71% +/- 3% in A-Bi, and decreased platelet counts to 49% +/- 4% in A-LR and to 53% +/- 4% in A-Bi. Thrombin generation decreased to 60% +/- 4% in A-LR and to 53% +/- 7% in A-Bi. Acidosis prolonged PT and PTT about 20% and decreased alpha and MA. After pH neutralization, fibrinogen and platelet levels remained depleted and no reversal of acidosis-induced changes in thrombin generation, PT, PTT, alpha, and MA were observed. CONCLUSION: Acidosis impaired coagulation by depleting fibrinogen and platelets and by inhibiting clotting kinetics. The deficit associated with acidosis was not reversed with bicarbonate pH neutralization.     

Epsilon-aminocaproic acid for treatment of fibrinolysis during liver transplantation

In 97 adult patients receiving liver transplants, the coagulation system was monitored by thrombelastography and by coagulation profile including PT; aPTT; platelet count; level of factors I, II, V, VII, VIII, IX, X, XI, and XII; fibrin degradation products; ethanol gel test; protamine gel test; and euglobulin lysis time. Preoperatively, fibrinolysis defined as a whole blood clot lysis index of less than 80% was present in 29 patients (29.9%), and a euglobulin lysis time of less than 1 h was present in 13 patients. Fibrinolysis increased progressively during surgery in 80 patients (82.5%) and was most severe on reperfusion of the graft liver in 33 patients (34%). When whole blood clot lysis (F less than 180 min) was observed during reperfusion of the graft liver, blood coagulability was tested by thrombelastography using both a blood sample treated in vitro with epsilon-aminocaproic acid (0.09%) and an untreated sample. Blood treated with epsilon-aminocaproic acid showed improved coagulation without fibrinolytic activity in all 74 tests. When whole blood clot lysis time was less than 120 min, generalized oozing occurred, and the effectiveness of epsilon-aminocaproic acid was demonstrated in vitro during the pre-anhepatic and post-anhepatic stages, epsilon-aminocaproic acid (1 g, single intravenous dose) was administered. In all 20 patients treated with epsilon-aminocaproic acid, fibrinolytic activity disappeared; whole blood clot lysis was not seen on thrombelastography during a 5-h observation period, and whole blood clot lysis index improved from 28.5 +/- 29.5% to 94.8 +/- 7.4% (mean +/- SD, P less than 0.001). None of the treated patients had hemorrhagic or thrombotic complications.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thrombelastography. Present and future perspectives in clinical practice

Thrombelastography (TEG) is a method for evaluating the viscoelastic properties of the blood clot, from its formation to its lysis. All major surgeries may be associated with massive blood loss, with blood component transfusion therapy often becoming mandatory. The clinician's goal is thus to optimize and possibly minimize blood components usage. To this end, TEG allows for a qualitative and dynamic analysis of the specific blood clotting process, from clot formation through its lysis, highlighting alterations at every single step in the cascade. With TEG is thus possible to know if bleeding is due to a failure to provide adequate surgical hemostasis, if there is platelet dysfunction, or to detect anomalies in coagulation proteases or their inhibitors, or if the blood loss is associated to early, excessive fibrinolysis. The theoretical advantages of TEG are the ease of performing the test, the fast sample reading times (now 30 minutes) and the informative RESULTS:     

Autotransfusion from experimental hemothorax: levels of coagulation factors

The coagulation system was investigated in five dogs undergoing autotransfusion from experimental hemothorax. One fourth of the blood volume was bled into the pleural space, drained, and autotransfused. The hemothorax blood showed: very prolonged PT and PTT; very low platelets and fibrinogen; midly elevated FDP; very low coagulation factors VIII, and V; reduced XII, prothrombin, X, XI, and VII. Partial clotting, mild fibrinolysis, and fibrin deposition over the pulmonary pleura seemed to cause incoagulability of hemothorax blood. Post autotransfusion arterial blood showed: normal PT and PTT; 25% decrease in platelets, and 31% decrease in fibrinogen from baseline values. There was also an overall 20% reduction of fibrinogen from baseline values. There was also an overall 20% reduction of all clotting factors, but their levels remained above 50% activity. It was concluded that autotransfusion from a hemothorax of 25% the blood volume in dogs causes a mild loss of hemostatic components, but does not significantly compromise the clotting mechanism.     

The effects of platelet count on clot retraction and tissue plasminogen activator-induced fibrinolysis on thrombelastography

Clot retraction and fibrinolysis may present as a decrease in amplitude on thrombelastography (TEG). The former represents normal or hyperactive platelet function, and the latter represents a fibrinolytic state. It is important to distinguish clot retraction from fibrinolysis because the treatment of each condition is different. To distinguish between these phenomena, we performed TEG with platelet-poor plasma (PPP) and platelet-rich plasma (PRP) with an increasing platelet count (range, 50-1200 x 10(9)/L) with or without abciximab. Maximum amplitude (MA) and the percentage decrease of amplitude at 30 and 60 min after MA were examined for each sample. Blood samples to which tissue plasminogen activator (tPA) was added served as positive controls for fibrinolysis. Morphological changes of clots and D-dimer levels were also examined. With higher platelet counts, the percentage decrease of amplitude after MA increased significantly at 30 and 60 min, but not in the abciximab samples. Morphological changes of clots have shown clot retraction in PRP, but not in PPP or PRP pretreated with abciximab. D-dimer levels increased only in samples to which tPA was added, but not in native PPP or PRP samples. In conclusion, we have shown that the decrease in amplitude at 30 and 60 min can be due to platelet-mediated clot retraction and can be attenuated by sample pretreatment with abciximab, which interrupts platelet-fibrin(ogen) binding.     

Perioperative thromboelastography and sonoclot analysis in morbidly obese patients

Purpose

To investigate perioperative coagulation in morbidly obese (MO) patients with the thromboelastograph (TEG) and Sonoclot analyzer.

Methods

Twenty-six consecutive morbidly obese and 26 consecutive lean patients presenting for elective surgery were enrolled in this prospective, observational study. Blood was sampled for TEG and Sonoclot analysis immediately after anaesthetic induction and at the end of surgery in the MO group, and immediately after anaesthetic induction in the lean group. The R and K times, alpha angle, maximum amplitude and percentage fibrinoiysis at 30 and 60 min were recorded from the TEG. The Sonoclot ACT, initial clot rate, peak amplitude and time to peak amplitude were recorded from the Sonoclot.

Results

The TEG in the MO group demonstrated decreased R and K times (8.6 ± 4.8 vs 11.7 ± 3.9 mm, and 2.8 ± 1.2 vs 3.5 ± 0.9 mm respectively (P < 0.05)), and increased alpha angle (73.7 ± 6.0 vs 66.7 ± 6.0°, P < 0.05) and maximum amplitude (72.0 ± 5.4 vs 67.9 ± 4.4 mm, P < 0.05), without change in fibrinolysis. Sonoclot variables in the MO group included increased clot rate (37.5 ± 11.5 vs 23.9 ± 7.7%, P < 0.05) and decreased time to peak impedance (11.7 ± 5.0 vs 17.5 ± 7.2 min, P < 0.05), without change in Sonoclot ACT or peak signature impedance.

Conclusion

The MO group demonstrated accelerated fibrin formation, fibrinogen-platelet interaction, and platelet function compared with lean controls but no difference in fibrinolysis. Viscoelastic measures of coagulation may be useful in MO patients, who are at increased risk of thromboembolic events.     

Hypercoagulable state associated with kidney-pancreas transplantation. Thromboelastogram-directed anti-coagulation and implications for future therapy

BACKGROUND: The clinical consequences of type 1 diabetes mellitus (IDDM) include diabetic triopathy: retinopathy, nephropathy, and neuropathy, as well as microangiopathy, accelerated atherosclerotic disease, and hypercoagulability. The etiology of the hypercoagulability is multifactorial, involving various clotting factors or pathways (for example platelets, fibrinogen, individual components of the clotting system and/or fibrinolysis in different studies). The development of end-stage renal disease (ESRD), with the uremia-related platelet effect has the potential to protect from the existing hypercoagulable state. This has important implications for surgery, particularly simultaneous pancreas-kidney (SPK) transplantation, where the pancreas has historically been prone to thrombosis. This has led us to perform intra-operative thromboelastograms (TEG's) to evaluate the patient's current coagulation status. METHODS: A TEG was performed in 85 SPK recipients along with a control group of 54 non-diabetic kidney transplant (KT) recipients. RESULTS: For each of the 4 TEG coagulation parameters, the SPK recipients were significantly more hypercoagulable than the non-diabetic KT recipients. The use of intra-operative heparin is based on the degree of hypercoagulability by TEG and degree of operative hemostasis. There has been one PT lost to thrombosis (1%) in the first week following transplantation during this time. CONCLUSION: The use of TEG is a helpful adjunct to SPK surgery, demonstrating the patient's current coagulation status. Nearly all SPK recipients (type 1 IDDM with ESRD) have been demonstrated to be hypercoagulable. The TEG allows the judicious use of anti-coagulation at the time of surgery, and beyond.     

Celite-activated thrombelastography in children

STUDY OBJECTIVE: To quantify global coagulation and establish normal ranges for the celite-activated thrombelastograph (TEG) in healthy pediatric patients. DESIGN: Prospective observational study. SETTING: Operating suite of a university-based hospital. PATIENTS: 110 healthy pediatric patients in four age groups and 25 healthy adult patients. INTERVENTIONS: Blood sampling for the celite-activated TEG was carried out after anesthetic induction. MEASUREMENTS: TEG indices: R time (reflecting time to fibrin formation), K time and alpha angle (fibrinogen-platelet interaction), maximum amplitude (reflecting maximal clot strength, platelet and fibrinogen function), TEG index (mathematical incorporation of the prior four measurements), and percent fibrinolysis at 30 minutes, were all recorded. MAIN RESULTS: Statistically significant differences between <12-month group in angle (compared to 25-48 month group) and % fibrinolysis (compared to all other pediatric groups). Significant differences in angle between two pediatric groups and adult group, and in the TEG index between three pediatric groups and adult group (all differences p < 0.05). CONCLUSIONS: These data identify changes of small magnitude in three celite-TEG parameters in healthy children compared to adults, without implication of abnormal coagulation between groups. Changes do not seem to be consistently related to age and will be useful for clinicians using the TEG to monitor (ab) normal coagulation in pediatric patients.     

Effects of hypothermia on thrombelastography in patients undergoing cardiopulmonary bypass

Thrombelastography (TEG) correlates with postoperative chest drain output in patients undergoing cardiopulmonary bypass (CPB). In vitro incubation with heparinase allows TEG monitoring during CPB, despite heparin anticoagulation. Hypothermia impairs coagulation, but these effects cannot be assessed by standard coagulation tests performed at 37 degrees C. The aim of this study was to assess the effects of hypothermia on TEG. Therefore, we have compared normothermic and temperature-adapted TEG in 30 patients undergoing CPB. Our data showed significantly impaired reaction time (r), kinetic time (k), and angle alpha (alpha) in temperature-adapted compared with normothermic TEG. Maximum amplitude (MA), reflecting absolute clot strength, was not affected at temperatures of 33-37 degrees C. These findings indicate a decrease in the speed of clot formation, but not absolute deterioration in clot quality. Furthermore, heparinase-modified TEG indicated that there were nine cases in which heparin effects persisted after heparin reversal with protamine, providing a rational guide to protamine therapy.      

Coagulation status using thromboelastography in patients receiving warfarin prophylaxis and epidural analgesia

To determine the coagulation status of patients receiving postoperative warfarin and epidural analgesia using thromboelastography (TEG(R)).Prospective, observational, clinical study.Orthopedic postoperative division at a university hospital.52 ASA physical status II and III patients undergoing knee arthroplasty and receiving prophylactic warfarin and epidural analgesia.Patients' preoperative and postoperative coagulation status was determined by TEG(R). Daily TEG(R) parameters were obtained until the epidural catheter was removed. TEG(R) parameters include reaction time (R-time or time until the first significant levels of detectable clot formation), K-time (clot firmness), maximum amplitude (MA-clot strength), alpha angle (clot development), and coagulation index (overall coagulation). In addition, daily international normalized ratios (INRs) were obtained as per our routine practice.On the day of catheter removal reaction time was significantly increased compared with preoperative values (p < 0.0001), but it remained within normal ranges. There was no change in the coagulation index. However, INR was abnormal and significantly increased (INR = 1.48+/-0.3; p < 0.0001), compared with preoperative values, on the day when the epidural catheter was removed.When the epidural catheters are removed, overall coagulation status, as measured by TEG(R), and despite an elevated INR (mean INR <1.5), remained within normal limits in patients receiving low-dose warfarin prophylaxis.     

An assessment of the effects on coagulation of midtrimester and final-trimester amniotic fluid on whole blood by Thrombelastograph analysis

The Thrombelastograph((R)) test (TEG; Haemoscope Corporation, Skokie, IL) was used to assess the effects of midtrimester and final-trimester amniotic fluid (AF) on whole blood coagulation. Different volumes of midtrimester and final-trimester AF were added to whole blood from nonpregnant volunteers in a series of TEG tests. The addition of both midtrimester and final-trimester AF resulted in significant decreases in reaction time (P < 0.001) and time from reaction to a fixed level of clot firmness (P < 0.05) and significant increases in angle (P < 0.05) and coagulation index (P < 0.05) values. This reflects accelerated clot initiation and propagation. There was no significant change in the maximal amplitude or % lysis at 30 and 60 min with the addition of either midtrimester or final-trimester AF. There was no significant difference between the effects of midtrimester and final-trimester AF on whole blood TEG. TEG may be an additional useful tool in the treatment of coagulopathy in AF embolism. IMPLICATIONS: We used the Thrombelastograph((R)) test (Haemoscope Corporation, Skokie, IL) to assess the effects of midtrimester and final-trimester amniotic fluid (AF) on whole blood coagulation. Results demonstrate that AF accelerates clot initiation and propagation. The Thrombelastograph((R)) test may be useful in assessing coagulopathy in patients with AF embolism.