Surgical patients are primarily at an increased risk of perioperative bleeding; however, after surgery, these patients develop hypercoagulability that favors thrombotic events. Currently, the time course of postoperative coagulation is not well characterized. Thus, the aim of the present study was to provide a detailed description of the changes in procoagulant factors in patients after major surgery and to evaluate coagulation tests based on their ability to detect hypercoagulability. Fifty-one consecutive patients undergoing different types of major surgery were analyzed. Blood samples were taken preoperatively and on postoperative days (PODs) 1, 2, 3, and 6. In addition to prothrombin time (PT) and activated partial thromboplastin time (aPTT), all PT-dependent and aPTT-dependent clotting factors, von Willebrand factor (vWF), and fibrinogen were obtained, and thrombelastometry and multiplate electrode aggregometry (MEA) were performed. On POD 1, the majority of clotting factors, including factors II, VII, X, XI, and XII, showed a significant decrease from baseline. Factors II, X, XI, and XII remained significantly reduced until POD 3. In contrast, starting on POD 2, fibrinogen, factor VIII, and vWF continuously increased. No relevant changes were found for PT or aPTT. Thrombelastometry revealed a continuous increase in clot firmness, and MEA demonstrated an increase in platelet aggregation on POD 6. However, absolute values remained within normal ranges, and only serial measurements showed hypercoagulation. Beginning on POD 2 after major surgery, significant hypercoagulability developed in patients. However, clinically used global coagulation tests and point-of-care devices did not reliably reflect the hypercoagulatory state.
All experiments demonstrate that the Hct is not a constant value but can be considerably changed by physiological measures. Clinical studies show that brain oxygen supply decreases with increasing Hct-values, which are also associated with a higher risk of stroke accidents. We therefore recommend to use a Hct-limit solely under strongly controlled standardized conditions to protect professional cyclists from hazardous manoeuvre until more appropriate methods to detect EPO-doping are developed.
PTI and MCF are useful for monitoring dilution and intervention points. aPTT and CT reflect intervention points when showing pathological values. The type of diluents does not seem to interfere with PTI and aPTT, but HAES impairs haemostasis in ROTEM(®) more profoundly than saline.
In acute hemorrhage, a critical decrease in fibrinogen often induces acquired coagulopathy. Fibrinogen concentrate has been used to supplement fibrinogen during massive hemorrhage. However, there are limited data on the utilization of fibrinogen concentrate in this setting. This prospective, multicenter observational study analyzed clinical treatment with fibrinogen concentrate in acute bleeding. A prospective multicenter web-based register was developed to document closed cases of massive hemorrhage treated with fibrinogen concentrate perioperatively. Anonymized data including the cause and kinetics of the bleeding, coagulation parameters, coagulation therapy, clinical effects and adverse events were recorded. Two hundred and twenty-three cases entered between September 2008 and August 2009 were eligible for analysis. According to patient needs, additional common blood and coagulation products were administered. Fibrinogen substitution by fibrinogen concentrate and fresh frozen plasma (FFP) was initiated at a median blood loss of 2.0 l and plasma fibrinogen of 1.45 g/l. After a median dose of 12.0 g fibrinogen (4 g in fibrinogen concentrate and 8 g in FFP), plasma fibrinogen rose to 2.19 g/l at the end of surgery; corresponding to a median increment of 0.045 g/l per gram of fibrinogen administered. After substitution, 6% of patients had supra-physiological plasma fibrinogen levels. Three percent of patients sustained thromboembolic complications perioperatively. Logistic regression analysis showed positive correlation of postoperative plasma fibrinogen and survival (P < 0.05). Clinical application of fibrinogen concentrate in bleeding patients is included within a multimodal therapeutic concept. High levels of fibrinogen are necessary in order to reach therapeutic goals. In bleeding patients, higher plasma fibrinogen might be associated with higher rates of survival.
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