Influence of High-dose Aprotinin on Anticoagulation, Heparin Requirement, and Celite- and Kaolin-Activated Clotting Time in Heparin-pretreated Patients Undergoing Open-Heart Surgery

1995 ◽  
Vol 83 (4) ◽  
pp. 679-689. ◽  
Author(s):  
W. Dietrich ◽  
G. Dilthey ◽  
M. Spannagl ◽  
M. Jochum ◽  
S. L. Braun ◽  
...  

Background Aprotinin causes a prolongation of the celite-activated clotting time (CACT), but not of the kaolin-activated clotting time (KACT). Therefore, concern has been raised regarding the reliability of CACT to monitor anticoagulation in the presence of aprotinin. The current study was designed to test the efficacy of aprotinin to improve anticoagulation, and to investigate whether the prolongation of CACT reflects true anticoagulation or is an in vitro artifact. To elucidate this antithrombotic effect of aprotinin, this study was done in patients prone to reduced intraoperative heparin sensitivity. Methods In a prospective, randomized, double-blind clinical trial, 30 male patients scheduled for elective primary coronary revascularization and treated with heparin for at least 10 days preoperatively, received either high-dose aprotinin (group A) or placebo (group C). The CACT and KACT were determined, but only CACT was used to control anticoagulation with heparin. Parameters of coagulation that are indicators of thrombin generation and activity (F1+2 prothrombin fragments, thrombin-antithrombin III complex, and fibrin monomers), parameters of fibrinolysis (D-dimers), aprotinin, and heparin plasma concentrations were measured. Postoperative blood loss and allogeneic blood transfused were recorded. Results Total heparin administered was 36,200 units (95% confidence interval: 31,400-41,000; group C) compared with 27,700 (25,500-29,800) units (group A; P < 0.05). Hemostatic activation during cardiopulmonary bypass (CPB) was significantly reduced in group A compared with group C. After 60 min of CPB, all parameters were significantly different (P < 0.05) between the groups (group C vs. group A): F1+2 prothrombin fragments, 9.7 (8.9-11.7) ng/ml versus 7.5 (6.2-8.6) ng/ml; thrombin-anti-thrombin III complex (TAT), 53 (42-68) ng/ml versus 29 (23-38) ng/ml; and fibrin monomers, 23 (12-43) ng/ml versus 8 (3-17) ng/ml. Fibrinolysis was also attenuated; D-dimers at the end of operation were 656 (396-1,089) and 2,710 (1,811-4,055) ng/ml for groups A and C, respectively (P < 0.05). The CACT 5 min after the onset of CPB was 552 (485-627) versus 869 (793-955) s for groups C and A, respectively (P < 0.05), whereas the KACT showed no differences between the groups (569 [481-675] vs. 614 [541-697] s for groups C and A, respectively; P = NS). The 24-h blood loss was 1,496 (1,125-1,995) versus 597 (448-794) ml for groups C and A, respectively (P < 0.05). Conclusions Aprotinin treatment in combination with heparin leads to less thrombin generation during CPB. Aprotinin has anticoagulant properties. Celite-activated ACT is reliable for monitoring anticoagulation in the presence of aprotinin, because the prolonged CACT in the aprotinin group reflects improved anticoagulation. Kaolin-activated ACT does not reflect this effect of aprotinin.

1994 ◽  
Vol 22 (5) ◽  
pp. 529-533 ◽  
Author(s):  
M. J. Swart ◽  
P. C. Gordon ◽  
P. B. Hayse-Gregson ◽  
R. A. Dyer ◽  
A. L. Swanepoel ◽  
...  

Fifty patients undergoing primary coronary artery bypass surgery and 50 patients undergoing valve surgery received either high-dose aprotinin (2 million units loading dose, 2 million units added to the CPB prime, and 500,000 units/hr maintenance infusion) or placebo. Mean postoperative blood loss in the first six hours was reduced from 321 ml in the placebo group to 172 ml in the aprotinin group (95% confidence interval (CI) for difference = 95 to 189 ml). Seven patients in the placebo group and 16 patients in the aprotinin group did not require transfusion with homologous blood. This study adds to the growing body of evidence that the administration of high-dose aprotinin reduces blood loss and blood transfusion requirements associated with primary cardiac surgery.


1996 ◽  
Vol 85 (6) ◽  
pp. 1311-1323. ◽  
Author(s):  
George J. Despotis ◽  
Vladimir Levine ◽  
Kriton S. Filos ◽  
Samuel A. Santoro ◽  
J. Heinrich Joist ◽  
...  

Background This study was designed to evaluate a new point-of-care test (HemoSTATUS) that assesses acceleration of kaolin-activated clotting time (ACT) by platelet activating factor (PAF) in patients undergoing cardiac surgery. Our specific objectives were to determine whether HemoSTATUS-derived measurements correlate with postoperative blood loss and identify patients at risk for excessive blood loss and to characterize the effect of desmopressin acetate (DDAVP) and/or platelet transfusion on these measurements. Methods Demographic, operative, blood loss and hematologic data were recorded in 150 patients. Two Hepcon instruments were used to analyze ACT values in the absence (channels 1 and 2: Ch1 and Ch2) and in the presence of increasing doses of PAF (1.25, 6.25, 12.5, and 150 nM) in channels 3-6 (Ch3-Ch6). Clot ratio (CR) values were calculated with the following formula for each respective PAF concentration: clot ratio = 1-(ACT/control ACT). These values also were expressed as percent of maximal (%M = clot ratio/0.51 x 100) using the mean CRCh6 (0.51) obtained in a reference population. Results When compared with baseline clot ratios before anesthetic induction, a marked reduction in clot ratios was observed in both Ch5 and Ch6 after protamine administration, despite average platelet counts greater than 100 K/microliter. There was a high degree of correlation between clot ratio values and postoperative blood loss (cumulative chest tube drainage in the first 4 postoperative hours) with higher concentrations of PAF: CRCh6 (r = -0.80), %M of CRCh6 (r = -0.82), CRCh5 (r = -0.70), and %M of CRCh5 (r = -0.85). A significant (P < 0.01) improvement in clot ratios was observed with time after arrival in the intensive care unit in both Ch5 and Ch6, particularly in patients receiving DDAVP and/or platelets. Conclusions Activated clotting time-based clot ratio values correlate significantly with postoperative blood loss and detect recovery of PAF-accelerated coagulation after administration of DDAVP or platelet therapy. The HemoSTATUS assay may be useful in the identification of patients at risk for excessive blood loss and who could benefit from administration of DDAVP and/or platelet transfusion.


2017 ◽  
Vol 11 (2) ◽  
pp. 37-41 ◽  
Author(s):  
Sarita Sitaula ◽  
DK Uprety ◽  
A Thakur ◽  
T Pradhan

Aims:The aim of this study was to evaluate the effect of preoperative administration of rectal misoprostol onblood loss during and after elective cesarean delivery.Methods:It was a randomized trial including 200 women, divided into two groups (group A and group B), who were planned for elective cesarean delivery and didn’t have risk of postpartum hemorrhage (PPH). Group A received 400μg misoprostol per-rectal preoperatively and intravenous infusion of oxytocin after delivery as hospital protocol.Group B received only intravenous infusion of oxytocin. Primary outcome measureswere the estimated amount of intraoperative and postoperative (24 hours) blood loss and changes in hemoglobin levels 48 hours after delivery.Results:Intraoperative and postoperative blood loss in rectal misoprostol and oxytocin group were significantly reducedin comparison to oxytocin only group. Mean blood loss in groupA was 326.9±116.2 mlwhereas; in group B was 397.7±110.1 ml with p value of < 0.001 which was significant.The difference between preoperative and postoperative hemoglobin level after 48 hours was also significant (1.10±0.51 vs 1.35± 0.49 g/dl with p value <0.001).Conclusion: Preoperative rectal misoprostol was found to be an effective measure to reduce the intraoperative and postoperative blood loss during elective cesarean delivery.


2017 ◽  
Vol 26 (3) ◽  
pp. 363-367 ◽  
Author(s):  
Junichi Kushioka ◽  
Tomoya Yamashita ◽  
Shinya Okuda ◽  
Takafumi Maeno ◽  
Tomiya Matsumoto ◽  
...  

OBJECTIVE Tranexamic acid (TXA), a synthetic antifibrinolytic drug, has been reported to reduce blood loss in orthopedic surgery, but there have been few reports of its use in spine surgery. Previous studies included limitations in terms of different TXA dose regimens, different levels and numbers of fused segments, and different surgical techniques. Therefore, the authors decided to strictly limit TXA dose regimens, surgical techniques, and fused segments in this study. There have been no reports of using TXA for prevention of intraoperative and postoperative blood loss in posterior lumbar interbody fusion (PLIF). The purpose of the study was to evaluate the efficacy of high-dose TXA in reducing blood loss and its safety during single-level PLIF. METHODS The study was a nonrandomized, case-controlled trial. Sixty consecutive patients underwent single-level PLIF at a single institution. The first 30 patients did not receive TXA. The next 30 patients received 2000 mg of intravenous TXA 15 minutes before the skin incision was performed and received the same dose again 16 hours after the surgery. Intra- and postoperative blood loss was compared between the groups. RESULTS There were no statistically significant differences in preoperative parameters of age, sex, body mass index, preoperative diagnosis, or operating time. The TXA group experienced significantly less intraoperative blood loss (mean 253 ml) compared with the control group (mean 415 ml; p < 0.01). The TXA group also had significantly less postoperative blood loss over 40 hours (mean 321 ml) compared with the control group (mean 668 ml; p < 0.01). Total blood loss in the TXA group (mean 574 ml) was significantly lower than in the control group (mean 1080 ml; p < 0.01). From 2 hours to 40 hours, postoperative blood loss in the TXA group was consistently significantly lower. There were no perioperative complications, including thromboembolic events. CONCLUSIONS High-dose TXA significantly reduced both intra- and postoperative blood loss without causing any complications during or after single-level PLIF.


2005 ◽  
Vol 94 (4) ◽  
pp. 442-444 ◽  
Author(s):  
G. Scha¨lte ◽  
H. Janz ◽  
J. Busse ◽  
V. Jovanovic ◽  
R. Rossaint ◽  
...  

1994 ◽  
Vol 72 (03) ◽  
pp. 438-443 ◽  
Author(s):  
He Lu ◽  
Charles Du Buit ◽  
Jeannette Soria ◽  
Bernard Touchot ◽  
Bernard Chollet ◽  
...  

SummaryIntra- and postoperative blood loss during open heart surgery is reduced by approximately 50% when aprotinin, a potent inhibitor for plasmin and kallikrein, is administered during surgery. But whether aprotinin increases the risk of thrombotic complications remains controversial. The aim of this study was to evaluate the effects of aprotinin administration on coagulation and fibrinolysis during and after cardiopulmonary bypass (CPB). Thirty patients undergoing CPB were randomly assigned to two comparable groups for a double-blind study (16 patients receiving high-dose aprotinin, 14 patients receiving placebo). Patients’ plasma levels of ATM (thrombin-induced modified antithrombin III), FbDP (fibrin degradation products, D-Dimers), t-PA (tissue-type plasminogen activator) and PAI-1 (plasminogen activator inhibitor type 1) were measured at regular intervals. In both groups, ATM level increased during surgery (from less than 30 to 90-110 ng/ml) and returned to normal 24 h after surgery and remained unchanged thereafter. Aprotinin reduced this increase in ATM levels (p = 0.02 at 30 min after the start of CPB). The FbDP generated during surgery was greatly reduced in the aprotinin group (945 ng/ml) in comparison with the placebo group (1889 ng/ml, p = 0.004). After surgery, FbDP levels decreased in both groups with nadirs at 2nd day (placebo group: 940 ng/ml and aprotinin group: 865 ng/ml) indicating a hypo-fibrinolytic period. Then, the FbDP level in both groups started to increase up to the 9th day, in an identical manner. This postoperative hypofibrinolysis is related to the changes of t-PA and PAI-1 levels: immediately after surgery there was a 2’fold increase in t-PA level and a 4-5 fold increase in PAI-1 level in the two groups. During the following 24 h, t-PA levels decreased in both groups. In contrast, PAI-1 levels in the placebo group during the same time increased sharply to a maximum level (175.7 ng/ml). This further increase did not occur in the aprotinin group although it remained at a high level (79.2 ng/ml). The difference in the increase of PAI-1 between the 2 groups (value at 24 h minus preoperative value: Dl-Tl) was significantly different (p = 0.04). Then t-PA continued to decrease and PAI-1 began to decrease steadily. Total blood loss was significantly reduced by aprotinin therapy (3.06 ml/kg versus 5.86 ml/kg). The present study confirms the inhibitory effects of aprotinin on both fibrinolytic activity and blood coagulation activation during CPB, and reveals an hypofibrinolytic period that lasts 48 h after surgery in both aprotinin and placebo groups. This inhibition of fibrinolysis is apparently associated with high PAI-1 level. The data of this study also show that 2 days after aprotinin therapy, there is no prolonged effect of aprotinin on fibrinolysis. In addition, the lower level of PAI-1 in the aprotinin group after surgery might result from a protection of endothelial cells by aprotinin, suggesting an unexpected benefit of aprotinin therapy.


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