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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.

Adult↗

Thromboelastography: a reliable test?

The thromboelastograph (TEG), a measure of global haemostasis, is routinely used during cardiac and hepatic surgery to optimize blood product selection and usage. It has recently been suggested that it may also be a useful tool to screen patients with hypercoagulable states. Limited published data on performance characteristics has led to speculation regarding its consistency and, therefore, validity of the results. This study was designed to assess the effect of stability of blood samples prior to testing, repeated sampling, intra- and inter-assay variability using the native, celite, tissue factor (TF) and Reopro-modified TEG. Analysis of native and celite samples after storage over 90 min showed a period of instability up to 30 min. Thereafter, all parameters between 30 and 90 min were stable [P = not significant (NS)]. When the same sample was repeatedly assayed, both native and celite TEG parameters showed a significant change towards hypercoagulability (P < 0.01), whereas the TF and Reopro-modified TEG showed no change. Intra- and inter-assay variability on samples tested after 30 min showed excellent reproducibility for all parameters (P = NS). The data suggest that the TEG is a useful tool in haemostasis but requires a formal standard operating procedure to be adopted that takes into account the initial period of sample instability.

Blood Specimen Collection↗

In vitro comparison of the effect of fondaparinux and enoxaparin on whole blood tissue factor-triggered thromboelastography profile.

Fondaparinux and enoxaparin are both effective and safe in preventing post-operative venous thromboembolism. However, neither of them significantly influence the conventional clotting tests. We compared the influence of clinically relevant concentrations of fondaparinux and enoxaparin on normal whole blood (WB) thromboelastographic profiles after triggering TF-pathway with minimal amount of thromboplastin. Diluted thromboplastin was added to WB samples supplemented with buffer (control), fondaparinux (0.25; 0.5; 1 microg/ml), or enoxaparin (0.1; 0.5; 1 anti-Xa IU/ml). Four parameters were analyzed, R: clotting time, K: time required to reach an amplitude of 20 mm, alpha angle: measurement reflecting clot development kinetics and MA: maximal amplitude. At concentrations used in prophylaxis, both enoxaparin (0.1 anti-Xa IU/ml) and fondaparinux (0.25 microg/ml which correspond to 0.27 anti-Xa IU/ml) significantly prolonged the R and K times, but did not significantly modify the alpha angle as compared to the control. At concentrations observed after administration of curative doses for the treatment of DVT (> or = 0.5 anti-Xa IU/ml for enoxaparin and > or = 0.5 microg/ml for fondaparinux) both drugs induced a significant increase of R and K times, and a significant decrease of the alpha angle (p < 0.05). In contrast to fondaparinux, enoxaparin at concentrations equal to or higher than 0.5 anti-Xa IU/ml significantly reduced MA. The present study provides evidence that the whole blood TF-triggered TEG assay is sensitive to the presence of clinically relevant concentrations of enoxaparin or fondaparinux. Moreover, the angle may be used in order to distinguish the effect of prophylactic and therapeutic concentrations, since it was significantly reduced by the later ones. Further studies are needed to evaluate the clinical usefulness of whole blood TF-triggered TEG assay for the monitoring of treatment with enoxaparin or fondaparinux.

Anticoagulants↗

Evidence based coagulation monitors: heparin monitoring, thromboelastography, and platelet function.

The hemostatic management of patients undergoing cardiac surgery is a unique challenge. Since its inception, cardiopulmonary bypass (CPB) has required meticulous attention to maintaining adequate anticoagulation. New anticoagulants and alternative monitoring techniques present an opportunity to investigate potential advances in the area of anticoagulation for CPB. Hemostasis after CPB is still a vexing problem, and the addition of antiplatelet medication to the platelet defect already incurred during CPB has led to hemorrhagic complications in cardiac surgery. The two opposing processes of anticoagulation and hemostasis must be managed carefully and modified with respect to the patient's hematologic status and desired hemostatic outcome. Cardiac surgical patients consume a much larger fraction of perioperative blood transfusions than the percentage of the surgical population they represent. Thus, during CPB, careful attention must be paid to optimal anticoagulation, platelet quiescence, biocompatible circuitry and interventions, and to monitoring hemostasis. The multifactorial etiology of the CPB-induced hemostatic defect requires a multimodal approach to blood conservation and hemostasis monitoring, including heparin maintenance and sophisticated point-of-care hemostasis monitoring. Each technology has its own attributes and each may be suitable for different populations based upon the expected defects being measured. This article reviews the evidence supporting the use of point-of-care monitors in coagulation and hemostasis management in cardiac surgical patients.

Anticoagulants↗

Identification of patients at risk for excessive blood loss during coronary artery bypass surgery: thromboelastography versus coagulation screen.

In light of the potential morbidity associated with transfusion of blood products, a reliable preoperative screening test to identify cardiothoracic surgical patients who are at potential risk for increased intraoperative blood loss would be useful. Accordingly, we examined the efficacy of a variety of coagulation tests to predict intraoperative blood loss in 60 patients presenting for coronary artery bypass surgery (CABG). A complete coagulation screen, activated clotting time (ACT), and thromboelastograph (TEG) were performed before surgery. Intraoperative blood loss was determined by weighing sponges and measuring the quantity of blood in suction canisters. The duration of cardiopulmonary bypass was 100 +/- 4 min, and total surgery time was 5.0 +/- 0.1 h. Total crystalloid and colloid requirements were 5.5 +/- 0.2 and 1.4 +/- 0.1 L. Forty-eight percent of the patients required blood with an average requirement of 2.5 +/- 0.5 units. Total intraoperative blood loss averaged 1590 +/- 95 mL with a range from 640 to 3928 mL. Using multiple linear regression, all coagulation and TEG variables were used to model perioperative blood loss. Results showed that all components of the TEG failed to predict blood loss (r < 0.25, P > 0.78). However, three components of the routine coagulation assay, including bleeding time, prothrombin time, and platelet count could be modeled to predict perioperative blood loss (r = 0.75, P < 0.05). Although TEG has been shown to have potential in identifying postcardiopulmonary bypass coagulopathies, these results suggest that it does not appear to be useful in determining the coagulation status of CABG patients preoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Thromboelastography for the prediction of bleeding after transplant renal biopsy.

The ability of prebiopsy coagulation assays to predict mild postbiopsy bleeding was evaluated in renal transplant patients undergoing renal allograft biopsy (N = 120). The coagulation assays studied included the bleeding time, prothrombin time, partial thromboplastin time, platelet count, and thromboelastograph (TEG). Coagulation results were defined as abnormal if they fell outside the established normal reference range. Bleeding was defined as a drop in the hematocrit equal to or more than 4 points 6 h after the procedure or ultrasound evidence of a new perirenal hematoma. Overall, 21% of patients showed evidence of mild bleeding. Of those who bled, 78% had normal results on all coagulation tests, indicating that most mild bleeding was not associated with coagulation abnormalities. Of the assays tested, only abnormal TEG:angle (P < 0.01) and TEG:k (P < 0.04) values were associated with an increased risk of bleeding. Bleeding times were not predictive of an increased risk of postbiopsy bleeding; five patients had abnormal bleeding times ranging from 10 to 20 min of whom only one bled. All prothrombin time, partial thromboplastin time, and platelet count abnormalities were mild (e.g., no prothrombin times longer than 15 s, no platelet counts below 129,000/microL); none of these assays predicted postbiopsy bleeding. Other clinical characteristics, including patient age, sex, serum creatinine, blood pressure (if less than 160/90 mm Hg), number of biopsy passes, or renal pathology, did not appear to influence bleeding after biopsy. It was concluded that most bleeding after transplant renal biopsy was not associated with coagulation abnormalities and that the TEG was the best assay for detecting mild coagulation abnormalities associated with an increased risk of bleeding.

Biopsy↗