[The efficacy and safety of tranexamic acid and epsilon-aminocapronic acid in cardiac surgery under extracorporeal circulation].

Sixty patients who had undergone cardiosurgical operations under extracorporeal circulation (EC) were enrolled in the study. All the patients were divided into 2 groups: (1) 40 patients were injected tranexamic acid (TA) (its loading dose was 15 mg/kg; maintenance infusion 1 mg/kg/h throughout the operation; 500 mg in the primary packing volume for an EC apparatus (EA); (2) 20 patients received epsilon-aminocapronic acid (ACA) (its loading dose was 5 g; 5 g in the primary packing volume for an EA and 10 g for infusion after EC). The effects of TA and ACA on the fibrinolytic system were evaluated from the time of XIIa-kallikrein-dependent fibrinolysis (sec) and the concentration of D-dimer (mg/ml). The hemocoagulation system (activated partial thromboplastin time, thrombin clotting time, prothrombin time with the determination of the international normalized ratio, fibrinogen) was studied. The thromboelastogram (the time R, K, and alpha-angle, MA) was analyzed. The indices were determined at the beginning and end of, and 12 hours after surgery. The analysis of the clinical efficacy and safety of the agents was based on the following perioperative data: the incidence of adverse reactions and complications associated with the administration of the agents, the frequency and amount of transfused donor blood components, the volume of blood loss, and the rate of resternotomies. The laboratory and clinical findings lead to the conclusion that TA (Tranexam, OOO "MIR-PHARM") has a 4-fold antifibrinolytic activity as compared with epsilon-ACA. The more pronounced TA-induced suppression of fibrinolysis affects the clinical course of a perioperative period in this group, which manifests itself as a reduced blood loss volume during and after surgery and a lower frequency of use of donor blood elements. By taking into account these data, TA may be recommended as one of the blood-preserving technology components during cardiosurgical operations under EC.

[Conditions of artificial blood circulation and erythrocytic aggregation in cardiosurgical patients].

Normothermic artificial circulation, irrespective of its duration, enhances erythrocyte aggregation in response to noradrenaline stimulation. Short-term hypothermic perfusion reduces adrenergic aggregation of erythrocytes while in long-term hypothermic artificial circulation changes in erythrocyte adrenergic aggregation are not significant. In the course of cardiosurgical operation in conditions of artificial circulation adrenergic erythrocyte aggregation undergoes changes: a maximal rise before perfusion, linear lowering and rise to the preoperative level. If perfusion lasts longer than 90 min adrenergic aggregation of erythrocytes sharply and significantly falls. This aggregation depends little on hematocrit, but if it falls under 15% aggregation becomes significant which may be of importance in blood loss arrest in massive blood loss, hemodilution, dilution of coagulation factors and marked thrombocytopenia. In such conditions erythrocyte aggregates may seal damaged microvessels acting as hemostatic lock.

[Comparative assessment of criteria for postoperative renal dysfunction in cardiosurgical patients].

The paper presents data on comparison of the detection rate of renal dysfunction after cardiac surgery, by using the criteria developed by Cockroft-Gault, C. M. Mangano, L.-G. Andersson, and G. Zanardo. It is shown that it is expedient to calculate creatinine phosphokinase by the Cochroft-Gault formula that using a patient's individual parameters provides a more objective approach to making the diagnosis of renal dysfunction. The rate of development of renal dysfunctions in patients who have undergone cardiac surgery under extracorporeal circulation (EC) depends on the type of an operation and the duration and temperature of perfusion. By postoperative day 14, renal function became normal in the vast majority of patients. Renal function became chronic in 1% of the patients operated on the heart under EC.

[Comparative assessment of using various glomerular filtration rate calculations in cardiological patients].

The paper gives the data of comparing the use of various formulas to calculate glomerular filtration rate (GFR) for the evaluation of postoperative renal function in cardiosurgical patients. GFR is shown to evaluate renal filterability with a high degree of reliability. Monitoring of GFR changes may characterize the progression of renal diseases. This indicator is an important predictor of the onset of renal insufficiency and the risk of complications due to chronic renal disease. Calculation of GFR in clinical practice enables the agents excreted owing to glomerular filtration to be dosed to prevent their potential toxicity.

[Impact of protamine sulfate on hemostasis system after operations with artificial circulation].

Effects of different doses and lots of protamine sulfate on hemostasis system after cardiac operations with artificial circulation are analyzed. Overall 982 patients underwent cardiac operations with artificial circulation. Quality and purity of protamine may be the causes of side effects. Negative effect of high doses of protamine on hemostasis system is demonstrated. Thrombocyte dysfunction is the main cause of intensive postoperative bleeding after administration of protamine high doses.

[A method for calculating the additional quantity of protamine sulfate during cardiosurgical operations].

The paper describes a method for calculating the additional dose of protamine sulfate solution during incomplete heparin neutralization after cardiac surgery under extracorporeal circulation, by estimating the anti-Xa-activity of venous blood plasma. The method may be an alternative to the use of devices to measure the blood concentration of free heparin, such as a "Hepcon" apparatus.

[The specific features of renal dysfunction in cardiosurgical patients].

Subclinically insignificant glomerular filtration disturbances were found during operations under extracorporeal circulation. After termination of perfusion, dysfunction of the proximal portion of renal tubules was recorded in all patients. This may be associated with that the proximal tubules were more susceptible to ischemia. Further impairments of the distal portions of renal tubules suggest the persistence of ischemic lesions of the tubular apparatus.

[Influence of extracorporeal circuits surface on hemostasis system during off-pump surgeries].

It is demonstrated that special surface of extracorporeal circuit promotes reduction of artificial circulation negative influence on hemostasis system. During artificial circulation coating "duraflo" gradually loses its protective characteristics due to washout of heparin molecules from the surface of extracorporeal circuit, whereas chemical link between heparin and protein in "safe-line" coating is more stable. The results of the study demonstrate no advantages of heparin coating of extracorporeal circuits over protein one. Finally, all the advantages of extracorporeal circuits with "safe-line" coating lead to a decrease of postoperative blood loss.

[Comparison of two schemes of administering the Russian protamine sulfate after extracorporeal circulation in cardiosurgical patients].

The paper presents data of a study comparing two schemes (Scheme 1: a heparin/protamine ratio of 1:2; Scheme 2: a heparin/protamine ratio of 1:3) for administering protamine sulfate to neutralize heparin in patients after extracorporeal circulation. A larger dose of protamine sulfate is shown to induce significant thrombocytic dysfunction, resulting in increased postoperative hemorrhage. To minimize protamine sulfate doses required for neutralization of the anticoagulant effect of heparin is a way of preventing these complications.

[Alterations in certain indices of the haemostasis system following aortic surgery].

MATERIAL AND METHODS: A total of 24 patients were examined after surgery on the thoracic or abdominal aorta. Depending on the level of the aortic clamping at the main stage of the operation, the patients were subdivided into three groups: Group One was composed of 7 patients with aortic coarctation in whom the level of artery clamping was located just below the subclavian artery, Group Two comprised 7 patients with an aneurysm of the infrarenal aortic portion, with the clamp applied immediately underneath the renal arteries, and Group Three consisted of 10 patients with type IV thoracoabdominal aortic aneurysm according to Crawford's classification, with the artery being clamped above the diaphragm. The studies were carried out at the following stages: before and at the end of surgery, then 6 hours thereafter, and at 24 hours postoperatively. RESULTS: The alterations in the indices of plasma-thrombocytic haemostasis at all the stages were insignificant and did not differ reliably between the groups. In Group One patients, the time of XHa-kallikrein-dependent fibrinolysis (XIIaKDF) at the end of the operation was found to be within the range of the normal values(657.5+/-92.3 s) and had no statistically reliable differences from the baseline value (612.0+/-63.7 s). After 6 hours and on day 1 after the operation, we observed inconsiderable inhibition of the fibrinolytic activity (903.0+/-142.3 and 848.9+/-149.5 s, respectively). In Group Two patients at the end of the operation, we registered a statistically reliable, as compared with the baseline value, shortening of the time of XIIaKDF (from 990.0 +/-81.0 to 510.0 +/- 103.6 s, p<0.05). However, the subsequent stages of the follow-up revealed a dramatic decrease in the fibrinolytic activity (to1.388.0+/-183.1 s). Group Three patients demonstrated a considerable activation of fibrinolysis at the end of the operation (348.2 +/-48.5 s), which was noted to remain unchanged during the first 24 postoperative hours, with the alterations in the D-dimer's concentration in patients of all groups at the stages of observation being of a unidirectional pattern, i. e. increasing maximally after 6 hours to be then decreasing on the first 24 hours after the operation. CONCLUSION: To prevent postoperative haemorrhage associated with hyperfibrinolysis in aortic operations, it is necessary to administer antifibrinolytic drugs with due regard for the level of aortic clamping.

The causes of early disorders of cerebral circulation in patients undergoing carotid endarterectomy.

AIM: to examine hemostasis in patients undergoing carotid endarterectomy as dependent on the course of the short-term postoperative period. MATERIALS AND METHODS: altogether 36 patients who had undergone unilateral carotid endarterectomy (CEAE) were examined. Intraoperatively, all the patients received unfractionated heparin (UFH) in a dose of 80 - 100 IU/kg bw. As dependent on the course of the short-term postoperative period the patients were distributed into two groups: group 1 included 12 patients who developed disorders of cerebral circulation (DCC) within the first hours after operation, group 2 included 24 persons with no complications. Plasma-platelet hemostasis, the system of natural anticoagulants and fibrinolysis were examined before, at the end, 6 hours and on the first day after CEAE. RESULTS: prior to operation all the patients had no significant change in the hemostatic system. Toward the end of operation groups 1 and 2 did not differ in the basic parameters of the hemostatic system. Group showed a remarkable platelet hyperaggregation. Six hours after operation group 1 demonstrated significantly lower values of ACT, BCT, MHO, an appreciably higher value of APTT and pronounced inhibition of fibrinolytic activity associated with platelet hyperaggregation. On the first postoperative day group 1 retained a significantly lower value of BCT, showed a significant lowering of APTT as compared to the previous observation stages and comparatively to group 2, demonstrated a significantly lower activity of AT III and fibrinolysis. At this stage ADO-induced platelet aggregation in group 1 was appreciably higher than in group 2. Platelet hyperaggregation in group 1 patients appeared a first manifestation of consumption coagulopathy. The significantly higher value of APTT mirrored a compensatory output of endogenous heparin. On the first postoperative day group 1 demonstrated a remarkable consumption of endogenous heparin, noticeably lower activity of AT III, material XIIaKDF inhibition, and retained pronounced platelet hyperaggregation. CONCLUSION: the intensity and extent of the atherosclerotic process in the cerebral vessels together with platelet hyperaggregation lead to the rise of the thrombogenic potential and increase the risk of thrombogenic complications in the immediate hours following operation. Antiaggregation and anticoagulation therapy should be instituted in such patients in the preoperative period and resumed directly after operation.

[On the mechanism of action of recombinant activated factor VII in massive non-hemophylic bleeding in cardiosurgical patients].

Recombinant activated factor VII was used in a dose of 30 to 140 mcgr/kg in 35 cardiosurgical patients during intra- and postoperative periods complicated by massive uncontrolled (5 to 25 ml/min) bleeding of non-surgical origin. Basing on the analysis of changes in the hemostasis system parameters, the mechanism of action of the preparation may be presented as follows: recombinant fVIIa forms a complex with TF at the site of lesion; the formation of TF-fVIIa complex leads to the appearance of small amount of synthesized thrombin on the membrane of TF-containing cells, which, in turn, activates thrombocytes at the site of lesion; thrombocytes excrete phosphatidylserine, which serves as a matrix for further thrombin formation. FXIII is expressed from a granules ofthrombocytes and gets activated. FXIII binds with a specific receptor on platelets' membrane. It remains active as enzyme and participates in the formation of a firm fibrin plug at the site of lesion. Besides, substances with pro- and antifibrinolytic activity, antiheparin factor 4 and fibronectin are released from alpha granules. Factors IXa, VIIIa, and Va effectively "attach" to the surface of activated thrombocytes, and the forming of IXa-VIIIa complex leads to further activation of factor X, which, together with factor 3 expression, facilitates further local thrombin generation.

[Effects of features of extracorporal circuits on thrombocyte hemostasis, the fibrinolysis system, and development of hemolysis].

The article contains data which demonstrate that use of extracorporal circuits with special coating ("safe-line" and "duraflow") improves preservation of thrombocyte functional activity, and lowers activation of the fibrinolysis system in postoperative period, which results in decrease of postoperative blood loss. Use of heat exchangers with polypropylene coating is less traumatic to blood cells, and thus lowers frequency and degree of hemolysis.

[Effects of aminocapronic acid and small-dose trasilol on blood loss after cardiac surgery with extracorporeal circulation].

The paper presents the results of a retrospective study of small-dose (2,000,000 ECU) trasilol (Group 1) and aminocapronic acid (Group 2) on the size of postoperative blood loss in patients after cardiac surgery under extracorporeal circulation (EC). The mean postoperative blood loss was 4.7 +/- 0.2 and 4.8 +/- 0.4 ml/kg/day in Groups 1 and 2, respectively (p > 0.05). A significantly less blood loss was noted when trasilol was used in patients with normothermal prolonged EC as compared with hypothermal prolonged EC (p < 0.05), which may be associated not only with temperature conditions, but also with the significantly less mean duration of normothermal EC (113.1 +/- 3.4 and 136.9 +/- 6.0 min, respectively (p < 0.05). In Groups 1 and 2, postoperative blood loss after hypothermal prolonged EC did not differ significantly, the duration of EC being significantly higher in Group 1 patients than that in Group 2 (p < 0.02). This is indicative of the advantage of the use of trasilol in cases of prolonged hypothermal perfusion. The use of trasilol is preferable in patients with a large scope of surgical intervention under prolonged hypothermal perfusion. By taking into account the equal efficacy of trasilol and aminocapronic acid in reducing postoperative blood loss, the use of aminocapronic acid is more profitable.

[Changes in hemostasis at aortic surgery under conditions of extracorporeal circulation].

This paper describes hemostatic changes in patients who had undergone aortic surgery under conditions of extracorporeal circulation. The changes in the hemostatic system are marked by the thrombophilic condition made up for activation ox blood fibrinolytic activity in the preoperative period. The basic amount of blood loss falls within the first 6 hours after operation. Prolonged hypothermic extracorporeal circulation and the high intraoperative blood loss (over 35 ml/kg bw) lead to an appreciable decrease in antithrombin III and protein C activity which results in activation of disseminated intravascular blood coagulation in the early postoperative period and ineffectiveness of heparin therapy. Secondary hyperfibrinolysis together with combined thrombocytopenia and platelet dysfunction are the basic causes of higher than usual bleeding in patients after aortic surgery under conditions of extracorporeal circulation.

The platelet componentof hemostasis in aortic surgery.

The lack of significant changes in the count and function of platelets in aortic surgery without use of cardiopulmonary bypass (CPB) confirms that factors of extracorporeal circulation exert a remarkable adverse action on the platelet component of hemostasis. In operations performed under hypothermic perfusion or circulatory arrest, disorders of the platelet component even in case of the use of 2 mln. CIU trasylol (aprotinin) are most pronounced which gives rise to excessive postoperative blood loss in the given patient group. It may be assumed that the increase of the dose of trasylol up to 6 mln. CIU will allow, owing to its cytoprotective action, preserve as well as possible the quantitative and qualitative properties of platelets.