Effects of colloid and crystalloid solutions on endogenous activation of fibrinolysis and resistance of polymerized fibrin to recombinant tissue plasminogen activator added ex vivo
ABSTRACT The study was conducted to explore the effects of colloid and crystalloid solutions on activation of fibrinolysis during orthopaedic surgery and to determine whether fluids facilitate clot dissolution at a particular fibrinolytic activity.
Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) were measured in plasma samples of 66 orthopaedic patients randomly receiving gelatin solution, hydroxyethyl starch (HES) (130/0.4), or exclusively Ringer's lactate solution. Plasma obtained before induction of anaesthesia (undiluted) and at the end of surgery (diluted) was exposed to recombinant tissue plasminogen activator (r-tPA) in vitro and analysed by modified thrombelastography (ROTEM).
There were similar changes in t-PA and PAI-1 concentrations in the gelatin, HES, and Ringer's lactate groups. When compared with the effect of r-tPA on undiluted plasma samples, the presence of colloids prompted faster clot dissolution than did Ringer's lactate solution. Lysis index at 30 min decreased significantly [median (min/max); P vs Ringer's lactate solution] to 43 (1/82)% (P=0.007), 14 (3/70)% (P<0.001), and 91 (34/97)%, lysis onset time decreased to 1269 (1054/1743) s (P=0.007), 972 (490/1565) s (P<0.001), and 1970 (1260/2165) s, and lysis time to 2469 (1586/3303) s (P=0.019), 2002 (1569/3600) s (P=0.006), and 3012 (2017/3600) s in the gelatin, HES, and Ringer's lactate groups, respectively.
The type of i.v. fluid used does not influence endogenously occurring fibrinolytic activity in patients undergoing major orthopaedic surgery. However, during hyperfibrinolysis, the presence of HES or gelatin solution facilitates clot disintegration to a greater extent than Ringer's lactate solution, because the weaker clots formed with colloids dissolve faster.
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ABSTRACT: There is continuing concern about the effect of hydroxyethyl starch (HES) solutions on blood coagulation. Rapidly degradable HES solutions with more favorable effects on clot strength have therefore been developed. Because the risk of bleeding is increased after cardiopulmonary bypass, we examined whether these types of HES solutions could be administered after cardiac surgery without an alteration of coagulation. Two new rapidly degradable HES solutions were compared with human albumin in 45 patients scheduled for elective primary cardiac surgery. After admission to the cardiac surgical intensive care unit, the patients were allocated in random order to receive either 15 mL/kg of HES solution with low molecular weight and low molar substitution (either 6% HES200/0.5 or 6% HES130/0.4) or 4% human albumin solution as a short-time (70-240 min) infusion. Clot formation time was prolonged and maximum clot firmness was decreased in thromboelastometry tracings after infusion of both HES solutions. This impairment in thromboelastometry tracings partly recovered (using InTEM and ExTEM coagulation activators) at 2 h after the completion of the study infusion. Platelet contribution to maximum clot firmness remained unaffected in all of the study groups. HES did not induce fibrinolysis. No changes in thromboelastometry tracings were observed after human albumin infusion. Chest tube drainage was comparable in the study groups. We conclude that a short-time infusion of rapidly degradable HES solutions after cardiac surgery produces impairment in fibrin formation and clot strength in thromboelastometry tracings. In this clinical setting, human albumin does not impair hemostasis.Anesthesia and analgesia 02/2009; 108(1):30-6. DOI:10.1213/ane.0b013e31818c1282 · 3.42 Impact Factor
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ABSTRACT: Replacement of fibrinogen is presumably the key step in managing dilutional coagulopathy. We performed an in vitro study hypothesizing that there is a minimal fibrinogen concentration in diluted whole blood above which the rate of clot formation approaches normal. Blood samples from six healthy volunteers were diluted 1:5 v/v with saline keeping haematocrit at 24% using red cell concentrates. We measured coagulation factors and thrombin generation in plasma at baseline and after dilution. Thromboelastometry was used to evaluate (i) speed and quality of clot formation in diluted samples supplemented with fibrinogen 50-300 mg dl(-1) and (ii) clot resistance to fibrinolysis. Diluted and undiluted samples with no added fibrinogen served as controls. Coagulation parameters and platelets were reduced by 74-85% after dilution. Peak thrombin generation was reduced by 56%. Adding fibrinogen led to a concentration-dependent improvement of all thromboelastometric parameters. The half maximal effective concentration (EC50) for fibrinogen replacement in haemodiluted blood was calculated to be 125 mg dl(-1). Adding tissue plasminogen activator, 0.15 microg ml(-1), led to a decrease of clot firmness and lysis time. The target plasma concentration for fibrinogen replacement was predicted by these in vitro results to be greater than 200 mg dl(-1) as only these concentrations optimized the rate of clot formation. This concentration is twice the level suggested by the current transfusion guidelines. Although improved, clots were prone to fibrinolysis indicating that the efficacy of fibrinogen therapy may be influenced by co-existing fibrinolytic tendency occurring during dilutional coagulopathy.BJA British Journal of Anaesthesia 07/2009; 102(6):793-9. DOI:10.1093/bja/aep098 · 4.35 Impact Factor
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ABSTRACT: Haemostatic alterations associated with the use of fluids are related to non-specific dilutional effects and colloid-specific effects, such as acquired von Willebrand syndrome, inhibition of platelet function and fibrin polymerization. Judging by currently available evidence, dextran, hetastarch and pentastarch have a more pronounced impact than tetrastarch, gelatin and albumin. In patients with hypocoagulability, tetrastarch appears to be a suitable volume expander due to its high safety index and volume efficacy. Gelatins have lower inhibitory effects on clot strength compared with tetrastarch, but their volume efficacy is also lower. Dextrans are potent anticoagulants with a high risk for adverse reactions. Albumin has negligible effects on haemostasis, but low volume efficacy and costs limit the use of a blood product as a routine volume replacement fluid. To avoid potential acidosis-induced changes in haemostasis, plasma-adapted carrier solutions may be used instead of saline-based solutions.Baillière' s Best Practice and Research in Clinical Anaesthesiology 07/2009; 23(2):225-36. DOI:10.1016/j.bpa.2008.11.002