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PubMed2006

Activated thrombelastogram in neonates and infants with complex congenital heart disease in comparison with healthy children.

BACKGROUND: The goal of the study was to determine activated thrombelastographic (TEG(R)) parameters with the rotational TEG(R) (ROTEG or ROTEM) device (Pentapharm GmbH, Munich, Germany) in neonates and infants <1 yr with complex congenital heart disease (CCHD) and to compare them with those of healthy children. METHODS: A total of 59 children were included: Group I (Gr I) 24 children, ASA I, scheduled for minor surgery; and Group II (Gr II) 35 children with CCHD, ASA III-IV, scheduled for cardiac surgery. Each group was subdivided into four age groups. Blood samples were obtained before the surgical procedure. RESULTS: Statistically significant differences (two-way anova analysis) between Gr I and Gr II [mean (SD); P-value] were found in INTEG-CT [Gr I 175(19), Gr II 271(162); P=0.049], EXTEG-MCF [Gr I 63(8), Gr II 56(8); P=0.013], EXTEG-MCE [Gr I 186(65), Gr II 137(41); P=0.003], FIBTEG-MCF [Gr I 24(7), Gr II 19(5); P=0.012], FIBTEG-MCE [Gr I 32(13), Gr II 24(8); P=0.012] and EXTEG-MCE-FIBTEG-MCE [Gr I 155(55), Gr II 113(37); P=0.003]. Clotting time via contact activation was prolonged in Gr II and varied widely, mainly in the age group 0-1 month and to a lesser extent in 1-3 months, and maximum clot firmness was reduced in the same age groups. In comparison with Gr II, the healthy children showed relatively homogenous TEG values with a tendency to hypercoagulability; the maximum was found in age group 1-3 months, decreasing towards adult values in the course of the first year of life. CONCLUSIONS: These preliminary TEG results indicate that the coagulation-fibrinolytic system in CCHD patients <1 yr is functionally intact and balanced but at a lower level than in healthy children. This could be interpreted as a reduction in the haemostatic potential with less reserve.

Aging↗
PubMed2003

Thromboelastography, whole-blood haemostasis and recurrent miscarriage.

BACKGROUND: Some cases of recurrent miscarriage have a thrombotic basis. Thromboelastography is a rapid, reproducible test of whole-blood haemostasis. METHODS: Thromboelastography was performed in 494 consecutive, non-pregnant women (median age 35 years; range 21-48) with a history of miscarriages at <12 weeks gestation (median 4; range 3-12) and 55 parous women (median age 33 years; range 20-41) with no history of pregnancy loss. The prospective outcome of untreated pregnancies amongst 108 women with recurrent miscarriage was studied. RESULTS: The maximum clot amplitude (MA) (median 66.0 mm; range 48.0-76.0) was significantly higher and the rate of clot lysis (LY30) (median 2.5%; range 0.5-7.8) significantly lower amongst women with recurrent miscarriage compared with controls (MA 61.5 mm; range 50.0-67.0; P = 0.01; LY30 4.9%; range 2.9-9.7; P = 0.01). The pre-pregnancy MA was significantly higher amongst women who subsequently miscarried (median 66.0 mm; range 54.0-73.0) compared with those whose had a live birth (median 61.7 mm; 48.0-71.5; P < 0.01). A pre-pregnancy MA >or=64 mm has a sensitivity of 68% and specificity of 82% to predict miscarriage. CONCLUSIONS: Thromboelastography identifies a subgroup of women with recurrent miscarriage to be in a prothrombotic state outside of pregnancy. Women in such a state are at increased risk of miscarriage in future untreated pregnancies.

Abortion, Habitual↗
PubMed1995

Heparin neutralization by recombinant platelet factor 4 and protamine.

Protamine is the only available drug to reverse heparin-induced anticoagulation. Platelet factor 4 (PF4) is a basic polypeptide stored in platelets that reverses heparin. To investigate its potential as a reversal drug, we studied recombinant PF4 on anticoagulated blood obtained during cardiac surgery. Blood was obtained from 33 different venous reservoirs, and activated clotting time (ACT), heparin concentrations, and heparinase-ACT were determined. Anticoagulation was reversed by adding incremental PF4:heparin and protamine:heparin ratios to the heparinized blood, and the ACTs were determined (n = 21). Viscoelastic analysis of anticoagulation reversal was performed by adding protamine or PF4 at reversal ratios of 1.3:1 protamine:heparin, and 3.2:1 PF4:heparin using thromboelastography (n = 12). PF4 reversal ratios of 3:1 and 3.5:1 and protamine reversal ratios of 1:1, 1.5:1, 2:1 were not statistically different from heparinase-ACT values. There were no significant differences in viscoelastic measurements of clot formation between protamine and PF4. Recombinant PF4 at a 3.0:1 ratio reverses heparin-induced anticoagulation after cardiopulmonary bypass, and represents a potential alternative, especially for the protamine allergic patient.

Blood Coagulation↗
PubMed1995

The effects of milrinone on platelets in patients undergoing cardiac surgery.

Although amrinone produces thrombocytopenia, no information is available regarding the acute effects of milrinone on platelets. Therefore, we evaluated the effects of milrinone on platelet number and function in cardiac surgical patients. Twenty-seven patients were studied during cardiac surgery requiring cardiopulmonary bypass (CPB). Patients were randomized to receive no milrinone (n = 10), or milrinone (n = 17) at a loading dose of 50-75 micrograms/kg in the CPB circuit followed by 0.5-0.75 micrograms.kg-1.min-1 for 12-24 h. Bleeding times and blood samples for coagulation studies were obtained prior to induction, and at 2 and 24 h after CPB. In both groups, platelet counts decreased significantly from the baseline at 2 and 24 h after CPB, and bleeding time increased significantly from the baseline at 2 and 24 h after CPB. No significant thromboelastoplasty (TEG) changes were observed in either group, and there were no significant differences in platelet aggregation or chest tube drainage between the groups. Acute milrinone administration did not cause significant changes in platelet number or function in patients undergoing cardiac operations requiring CPB, beyond the usual adverse effects of cardiac surgery and CPB.

Adult↗
PubMed1995

Intravenous ketorolac tromethamine does not worsen platelet function during knee arthroscopy under general anesthesia.

Ketorolac (KT) prolongs bleeding time and inhibits platelet aggregation and platelet thromboxane production in healthy, awake volunteers. However, platelet function may be accentuated during the stress of general anesthesia (GA) and surgery. The purpose of this study was to investigate platelet function changes during a standard GA technique and surgery, as well as after a single intraoperative dose of intravenous (i.v.) KT. The study comprised 30 ASA physical status I patients undergoing GA for knee arthroscopy. Subjects were randomized to receive either KT 60 mg IV 15 min after skin incision or placebo i.v. Platelet function testing consisted of an Ivy bleeding time (BT), platelet aggregometry (PA) with adenosine diphosphate (ADP) and collagen, thromboelastography (TEG), and serum thromboxane B2 assays (TxB2). Platelet function testing was performed: 1) 15 min prior to the induction of GA, 2) 10 min after skin incision, and 3) 45 min after administration of study drug. BT decreased significantly in the placebo group from 263 +/- 133 s (mean +/- SD) preoperatively to 207 +/- 89 s postincision. BT did not change in the KT group. PA was unchanged after IV KT. TEG data was unchanged in both groups during anesthesia and surgery. TxB2 levels decreased markedly in the KT group from 106.9 +/- 96.2 ng/mL preoperatively to 0.4 +/- 1.2 ng/mL poststudy drug, P = 0.002. Platelet function appears to be accentuated during GA and surgery as evaluated by BT in the placebo group. Further, platelet function by BT, PA, and TEG was not inhibited after i.v. KT despite near complete abolition of TxB2 production.

Adolescent↗
PubMed1995

Autologous platelet-rich plasmapheresis: risk versus benefit in repeat cardiac operations.

Preoperative platelet-rich plasmapheresis has been suggested as a means of reducing homologous blood transfusions in cardiac surgical patients. The current study evaluated this technique in patients undergoing repeat cardiac operations. Fifty-two patients undergoing repeat myocardial revascularization and/or valve replacement were evaluated in a prospective randomized controlled study design. Autologous platelet-rich plasma (PRP) was harvested after the induction of anesthesia in the experimental group. After reversal of heparin, each patient received his or her autologous plasma. Patients in the control group did not have plasmapheresis and received standard transfusion therapy if coagulation variables were abnormal and a coagulopathy was clinically evident. Routine coagulation tests, thromboelastography (TEG), perioperative bleeding, and transfusion requirements were compared in the two groups. Forty-four patients completed the study. A significantly larger volume of packed red blood cells (PRBCs) was transfused in the PRP group than in the control group (P = 0.03). Platelet and fresh frozen plasma (FFP) transfusions did not differ between the two groups. Mediastinal tube drainage did not differ between the two groups. During PRP infusion, 60% of the patients required treatment for moderate hypotension (mean arterial pressure [MAP] < 60 mm Hg). Only 16% of control patients required treatment for hypotension during the comparable time period (P < 0.05). No patient who completed the study returned to the operating room for postoperative bleeding. These data suggest that PRP did not reduce postbypass bleeding or transfusion requirements in repeat cardiac surgical patients. Moreover, the incidence of hypotension during PRP reinfusion introduces a potential risk to the procedure in the absence of any obvious benefit.

Blood Coagulation Tests↗
PubMed1997

A modified thromboelastographic method for monitoring c7E3 Fab in heparinized patients.

The monoclonal antibody, c7E3 Fab, binds to the platelet surface fibrinogen receptor (GPIIb/IIIa), inhibiting platelet aggregation and clot retraction. We performed an in vitro study to assess the ability of a modification of the thromboelastograph (MTEG) to detect inhibition of clot strength by c7E3 Fab and its reversal with platelet-rich plasma (PRP). In the modified assay (MTEG), thrombin was added to whole blood (WB) and platelet-poor plasma (PPP) and the resultant maximum amplitude (MA) was measured, MAWB and MAPPP, respectively. Anticoagulated blood samples from 17 patients scheduled for cardiac surgery were collected for a dose response (Part I; n = 5) and c7E3 Fab reversal (Part II; n = 12) study. Clot strength was reduced in a dose-dependent manner by c7E3 Fab. Ecteola cellulose effectively reversed the effect of heparin on the thrombin time and the addition of PRP significantly increased the MAWB (P < 0.0001) and MAWP-PPP (P < 0.0001). Subtracting the MAPPP from MAWB significantly magnified the response of MA to the addition of c7E3 Fab (P = 0.002) and its reversal with PRP (P = 0.005). This in vitro study indicates that the MTEG is a responsive assay demonstrating that inhibition by the antiplatelet c7E3 Fab is reversible with PRP.

Abciximab↗
PubMed1997

The effect of anesthetic techniques on blood coagulability in parturients as measured by thromboelastography.

Anesthetic techniques may affect blood coagulability and the subsequent incidence of thromboembolic events. The purpose of this study was to evaluate the effect of spinal and general anesthesia on blood coagulability in normal pregnant women undergoing cesarean section, using thromboelastography. In the spinal anesthesia group (n = 15), thromboelastography was performed after crystalloid preloading and during the immediate postanesthesia course. In the general anesthesia group (n = 15), thromboelastography was performed before induction and during the immediate postanesthesia course. Values for all thromboelastographic variables (reaction time [r], clot formation time [K], coagulation time [rK], maximum amplitude [MA], elastic shear modulus [G], clot formation rate [alpha angle], and coagulation index [CI]) in the preanesthesia period were similar in both the spinal and general anesthesia groups. However, in the postanesthesia period, r and K significantly decreased (P < 0.05), and alpha angle (P < 0.05) and CI significantly increased (P < 0.01) in the general anesthesia group when compared with the spinal anesthesia group. In the postanesthesia period, MA and G were similar in both groups. In the spinal anesthesia group, thromboelastographic variables did not change significantly in the postanesthesia compared with the preanesthesia period. We conclude that the use of general anesthesia for cesarean section is associated with accelerated coagulability when compared with spinal anesthesia.

Adult↗
PubMed1997

Thromboelastographic changes in healthy parturients and postpartum women.

Thromboelastography (TEG) using disposable plastic cups and pins was performed with native whole blood (native group) in 17 nonpregnant volunteers, 134 healthy term pregnant women (>36 wk gestation), and 69 postpartum women. Thromboelastography was also performed with celite-activated whole blood (celite group) in 15 nonpregnant female volunteers, 38 healthy term pregnant women, and 34 postpartum women. The thromboelastographic parameters r and K were significantly decreased in pregnant and postpartum women compared with nonpregnant women in both groups (P < 0.05). The maximum amplitude MA, elastic shear modulus, and alpha angles were significantly increased in pregnant and postpartum women compared with nonpregnant women in both groups (P < 0.05). The TEG coagulation index was significantly greater in pregnant and postpartum women compared with nonpregnant women in both groups. In this study, TEG showed that pregnancy is a hypercoagulable state and that postpartum women remain hypercoagulable through the first 24 h postdelivery. The use of celite in TEG accelerated the speed of TEG analysis.

Blood Coagulation↗
PubMed1997

Does the platelet-activated clotting test (HemoSTATUS) predict blood loss and platelet dysfunction associated with cardiopulmonary bypass?

Platelet dysfunction is a major cause of bleeding after cardiopulmonary bypass (CPB). No timely, simple, point-of-care determinant of platelet function is available for clinical use. Adding platelet-activating factor to conventional activated clotting time methods (platelet-activated clotting test [PACT]) (HemoSTATUS; Medtronic, Inc., Parker, CO) produces rapid results (<3 min) and may yield a measure of platelet responsiveness and whole blood procoagulant activity. Blood samples were drawn for PACT, platelet count, prothrombin time, activated partial thromboplastin time, and thromboelastogram (TEG) from 200 patients undergoing cardiac surgery. The PACT significantly decreased from the baseline to postprotamine time interval (P < 0.001). The PACT correlated with 4-h mediastinal blood loss (r = -0.30, P = 0.014). The TEG maximum amplitude also correlated with 4-h mediastinal blood loss (r = -0.32, P = 0.003). The PACT had a sensitivity and specificity comparable to routine laboratory coagulation tests in predicting blood loss. The TEG maximum amplitude, however, was more predictive than both the PACT and routine coagulation tests in this respect. The PACT may be a useful indicator of platelet responsiveness or whole blood procoagulant activity, but we did not find it superior to other tests of coagulation function for predicting excessive blood loss after CPB.

Adult↗
PubMed1997

Continuous small-dose tranexamic acid reduces fibrinolysis but not transfusion requirements during orthotopic liver transplantation.

Tranexamic acid (TA) is a synthetic drug that inhibits fibrinolysis. It has been administered to decrease the use of blood products during cardiac surgery and orthotopic liver transplantation when infused in larger doses. A small-dose infusion of aprotinin causes a reduction in fibrinolysis and blood product requirement during orthotopic liver transplantation without apparent risk of intravascular thrombosis. This prospective study was designed to investigate whether a small-dose infusion of TA would be equally effective in reducing fibrinolysis and blood product transfusions during orthotopic liver transplantation. A double-blind, controlled study was undertaken to compare the efficacy of a small-dose TA infusion with that of a placebo. Thirty-two consecutive patients were randomized either to the TA group (n = 16), which received an intravenous infusion of 2 mg x kg(-1) x h(-1), or to the control group (n = 16), which received an identical volume of normal saline. Coagulation values were measured, a field rating was made by the surgeon, and a thromboelastogram was produced at four predetermined intervals throughout the case-before TA infusion was started, after portal vein ligation, 10 min after reperfusion, and at the end of surgery. Intraoperative transfusion requirements were recorded during the procedure and for the first 24 h postoperatively. A record was kept of any intraoperative epsilon-aminocaproic acid administered for uncontrolled fibrinolysis. The thromboelastogram clot lysis index was significant for lysis in the control group during both the anhepatic and the neohepatic phases (P < 0.01 and P < 0.05, respectively) when compared with the TA group. Fibrin degradation products were significantly increased (>20 microg/mL) in the control group at reperfusion (P < 0.03) and at the end of surgery (P < 0.01). D-dimers were also significantly increased (>1 mg/L) in the control group at the end of surgery (P < 0.04). Nine of the 16 control patients versus 3 of the 16 TA patients required epsilon-aminocaproic acid rescue for fibrinolysis. There were no other significant differences between groups. Transfusion requirements during surgery and for the first 24 h postoperatively did not differ significantly between the two groups. We conclude that the use of small-dose TA reduces fibrinolysis but not transfusion requirements during orthotopic liver transplantation.

Aminocaproic Acid↗
PubMed1997

Predicting and treating coagulopathies after cardiopulmonary bypass in children.

UNLABELLED: Coagulopathies in children after cardiopulmonary bypass (CPB) are complex. There are very limited data correlating coagulation tests with postoperative bleeding. We evaluated coagulation changes after CPB and after the administration of coagulation products to 75 children. Baseline coagulation tests were obtained and repeated after protamine administration, after transfusion of individual coagulation products, and on arrival in the intensive care unit (ICU). Regression analysis demonstrated no baseline coagulation test to predict postoperative chest tube drainage. Weight and duration of CPB were determined to be the only predictors of bleeding. Further analyses demonstrated that children <8 kg had more bleeding and required more coagulation products than children >8 kg. Postprotamine platelet count and fibrinogen level correlated independently with 24-h chest tube drainage in children <8 kg, whereas postprotamine platelet count and thrombelastographic values did so in patients weighing >8 kg. Platelet administration alone was found to restore effective hemostasis in many patients. With ongoing bleeding, cryoprecipitate improved coagulation parameters and limited blood loss. Fresh-frozen plasma administration after platelets worsened coagulation parameters and was associated with greater chest tube drainage and more coagulation product transfusions in the ICU. Objective data to guide post-CPB component therapy transfusion in children are suggested. IMPLICATIONS: Children <8 kg can be expected to have more severe coagulopathies, require more coagulation product transfusions, and bleed more after cardiopulmonary bypass. Correlations between coagulation tests and postoperative chest tube drainage are defined. Platelets and, if necessary, cryoprecipitate optimally restore hemostasis. Fresh-frozen plasma offers no benefits in correcting postcardiopulmonary bypass coagulopathies in children.

Anticoagulants↗
PubMed1998

Conjugated estrogen reduces transfusion and coagulation factor requirements in orthotopic liver transplantation.

UNLABELLED: We conducted a prospective, randomized study to determine the efficacy of conjugated estrogen in reducing blood product transfusion during orthotopic liver transplantation (OLT). Patients undergoing OLT were included in the study. Only those having a reaction time of more than 30 mm or 15 min (19 -28 mm) on computed thromboelastography (CTEG) at the beginning of surgery were enrolled in the study. Patients were randomized to receive either conjugated estrogen (CE) or placebo. Every patient received a first dose of CE (100 mg i.v.) (20 mL) or placebo (20 mL of isotonic sodium chloride solution) at the beginning of the procedure and a second dose of CE (100 mg i.v.) or 20 mL of placebo (20 mL of isotonic sodium chloride solution) just after reperfusion of the new graft. The two groups were similar in age, weight, requirement for veno-veno bypass, time on veno-veno bypass, CTEG measurement, and preoperative hemoglobin and platelet values. Blood products were given in relation to hematocrit and coagulation (CTEG) variables, which were measured every hour during the surgery. The amount of transfused blood products did not differ in terms of units of cryoprecipitate, but the intraoperative requirements for red blood cells (6 +/- 3 vs 9 +/- 6 U; P = 0.05), platelets (12 +/- 8 U vs 18 +/- 10 U; P = 0.05) and fresh-frozen plasma (3 +/- 3 U vs 6 +/- 4 U; P = 0.001) was significantly less in the estrogen group than in the control group. We conclude that CE is associated with a significant decrease in use of fresh-frozen plasma, platelets, and red blood cells during OLT. IMPLICATIONS: In this study, we prospectively investigated whether i.v. conjugated estrogen could decrease blood product transfusion during orthotopic liver transplantation. Conjugated estrogen-treated patients received less fresh-frozen plasma, red blood cells, and platelets. In this population of patients, conjugated estrogen can be a useful addition in coagulation management during orthotopic liver transplantation.

Blood Coagulation Factors↗