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ABSTRACT: Prophylactic administration of tranexamic acid (TA), an antifibrinolytic agent, decreases bleeding after cardiac surgery with systemic hypothermia (25 degrees C to 29 degrees C). Warmer systemic temperatures during cardiopulmonary bypass (CPB) may reduce bleeding and thus alter the requirement for TA. The effect of three different doses of TA on bleeding after cardiac surgery with mild systemic hypothermia (32 degrees C) is evaluated.
Double-blind, prospective, randomized study.
University hospital.
One hundred fifty adult patients undergoing aortocoronary bypass or valvular cardiac surgery.
Patients received TA, 50 (n = 50), 100 (n = 50), or 150 (n = 50) mg/kg intravenously before CPB with mild systemic hypothermia.
Blood loss through chest drains over 6, 12, and 24 hours after surgery and total hemoglobin loss were measured. Autotransfused blood, transfused banked blood and blood products, and coagulation profiles were measured. Analysis of variance on log-transformed data for blood loss and confidence intervals (CIs) of 0.95 were calculated and transformed to milliliters of blood. No patient was re-explored for bleeding. Blood loss at 6 hours was statistically greater in the 50-mg/kg group compared with the other two groups (p = 0.03; p = 0.02). Total hemoglobin loss was statistically greater in the 50-mg/kg group compared with the 150-mg/kg group (p = 0.04). There was no statistical difference in blood tranfusion rate or coagulation profiles among the three groups. However, preoperative hemoglobin level was statistically lower in the 150-mg/kg group compared with the other two groups (p = 0.01).
Of the three doses of TA studied, the most efficacious and cost-effective dose to reduce bleeding after cardiac surgery with mild hypothermic systemic perfusion is 100 mg/kg.
Journal of Cardiothoracic and Vascular Anesthesia 01/1999; 12(6):642-6. · 1.64 Impact Factor
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ABSTRACT: Patients with end-stage liver disease frequently incur large-volume blood loss during liver transplantation associated with mechanical factors, preexisting coagulopathy, and intraoperative fibrinolysis.
Between April 1992 and May 1994, the authors of this double-blind, randomized, placebo-controlled study examined the effect of high-dose tranexamic acid (maximum of 20 g) on blood loss and blood product requirements in patients undergoing primary isolated orthotopic liver transplantation. Primary outcome measures were volume of blood loss (intraoperative blood loss and postoperative drainage) and erythrocyte, plasma, platelet, and cryoprecipitate use during surgery and the first 24 h of intensive care unit stay.
Patients receiving tranexamic acid (n = 25) had less intraoperative blood loss (median, 4.3 l; interquartile range, 2.5 to 7.9; P = 0.006) compared with the placebo group (n = 20; median, 8 l; interquartile range, 5 to 15.8), and reduced intraoperative plasma, platelet, and cryoprecipitate requirements. Median perioperative erythrocyte use was 9 units (interquantile range, 4 to 14 units) in patients receiving tranexamic acid and 13 units (interquantile range, 7.5 to 31 units) in controls (P = 0.03). Total perioperative donor exposure was 20.5 units (interquantile range, 16 to 41 units) in patients receiving tranexamic acid and 43.5 units (interquantile range, 29.5 to 79 units) in controls (P = 0.003). Results for postoperative wound drainage were similar. Hospital stay and need for retransplantation were comparable in both groups. No patient in either group showed clinical evidence of hepatic artery or portal venous thrombosis within 1 month of transplantation.
High-dose tranexamic acid significantly reduces intraoperative blood loss and perioperative donor exposure in patients with end-stage parenchymal liver disease who are undergoing orthotopic liver transplantation, with marked reductions in platelet and cryoprecipitate requirements.
Anesthesiology 12/1996; 85(5):1043-8; discussion 30A-31A. · 5.36 Impact Factor
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ABSTRACT: This prospective, double-blind, randomized trial assessed the effectiveness of high-dose tranexamic acid given in the preoperative period on blood loss in patients undergoing cardiopulmonary bypass. One hundred fifty patients scheduled to undergo cardiac operations with cardiopulmonary bypass were randomized into three groups of equal size. The first group received 10 gm of tranexamic acid intravenously over 20 minutes before sternotomy and a placebo infusion over 5 hours. The second group received 10 gm of tranexamic acid over 20 minutes and then another 10 gm infused intravenously over 5 hours. The control group received a placebo bolus and a placebo infusion over 5 hours (0.9% normal saline solution). The blood loss after the operation was measured at 6 hours and 24 hours. The homologous blood and blood products given during and up to 48 hours after operation were recorded. Eighteen percent of the control group patients shed more than 750 ml blood in 6 hours compared with only 2% in both tranexamic acid groups. Patients who shed more than 750 ml blood required 93% more red blood cell transfusions than patients without excessive bleeding. Tranexamic acid (10 gm) given intravenously in the period before cardiopulmonary bypass reduced blood loss over 6 hours by 50% and over 24 hours by 35%. Continued tranexamic acid infusion (10 gm over 5 hours) did not reduce bleeding further. There was no difference in the coagulation profile before operation between patients with and without excessive bleeding. However, coagulation tests done in the postoperative period indicated ongoing fibrinolysis and platelet dysfunction in patients with excessive bleeding.
Journal of Thoracic and Cardiovascular Surgery 10/1995; 110(3):835-42. · 3.41 Impact Factor
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ABSTRACT: A 59-year-old male with a mechanical aortic valve taking warfarin presented to hospital with Brown-Séquard syndrome caused by a spontaneous spinal epidural hematoma (SSEH) precipitated by a coughing fit. Guided by a literature review of the risks of administering or withholding anticoagulation in this patient, doctors advised a regimen of warfarin to achieve an international normalized ratio of 1.5 to 2 and dipyridamole (75 mg qid) to protect against thromboembolic complications while minimizing the risk of recurrent SSEH.
The Canadian journal of cardiology 06/1995; 11(5):429-32. · 3.36 Impact Factor
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ABSTRACT: Massive pulmonary embolism is a rare complication in patients undergoing coronary artery bypass grafting. Frequently patients have had exposure to heparin before the operation. In this article we report a patient who 6 days after a cardiac operation suffered a massive pulmonary embolism. The patient was later discovered to have heparin-associated thrombocytopenia with serum heparin antibody. We recommend patients receiving heparin have frequent platelet counts and those with induced thrombocytopenia undergo sensitivity testing.
The Annals of Thoracic Surgery 06/1994; 57(5):1326-8. · 3.74 Impact Factor
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ABSTRACT: In this institution, two antifibrinolytic agents have been in routine use before cardiopulmonary bypass (CPB) to prevent bleeding due to fibrinolysis; epsilon-aminocaproic acid (EACA) or tranexamic acid (TA) are administered as intravenous infusions over 2 hours, from the time of anesthetic induction until the onset of CPB. TA is 10 times more potent and binds more strongly to plasminogen than EACA. Data were collected retrospectively on 411 patients undergoing first-time coronary artery bypass grafting with cardiopulmonary bypass who had received one of four therapy regimens: 10 g of EACA (65 patients), 15 g of EACA (60 patients), 6 g of TA (100 patients), or 10 g of TA (75 patients). Patients who did not receive any drug (91) served as controls. Anesthetic technique and the heparin/protamine protocol did not differ. Blood collected by mediastinal and pleural tubes was autotransfused up to 6 hours postoperatively. Both TA and EACA reduced post-CPB bleeding in the first 24 hours. Ten grams of TA was the most effective, resulting in a 52% and 36% reduction in blood loss over controls at 6 and 24 hours, respectively. Although 10 g of TA was more effective than 6 g of TA in blood loss control for the first 6 hours, the difference was not significant at 24 hours. A significantly lower number of patients in the 10 g TA group received blood products than in control (28% v 49%) patients (P = 0.02). Pretreatment with 10 g of TA prevented excessive (over 750 mL in 6 hours) bleeding after CPB.
Journal of Cardiothoracic and Vascular Anesthesia 09/1993; 7(4):431-5. · 1.64 Impact Factor
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ABSTRACT: The mechanism by which some graft materials are more thrombogenic than others is poorly understood. We hypothesized that differential induction of macrophage procoagulant activity (PCA) by various materials may contribute to variable thrombogenicity.
Thioglycollate-elicited murine peritoneal macrophages were added to disks of Dacron and expanded polytetrafluoroethylene (ePTFE). After adherence, macrophages were incubated with and without endotoxin (lipopolysaccharide) and then recovered by sonication for determination of PCA with a one-step clotting bioassay.
PCA was significantly higher in cells after incubation on Dacron compared with ePTFE both in the absence of lipopolysaccharide (243 +/- 76 vs 68 +/- 39 mU, n = 4) and after stimulation with lipopolysaccharide (491 +/- 137 vs 139 +/- 41 mU, n = 4) (p < 0.01, analysis of variance). Using factor-deficient plasmas, we found that this PCA was consistent with tissue factor. This differential induction of PCA was related to increased macrophage adherence to Dacron compared to that to ePTFE (9374 +/- 1158 vs 2111 +/- 330 cells/mm2; n = 4; p < 0.01, analysis of variance).
The thrombogenic nature of Dacron correlates with its ability to adhere macrophages and induce PCA. Strategies aimed at modulating these effects may reduce the thrombogenicity of vascular grafts and therefore potentially the incidence of graft thrombosis.
Journal of Vascular Surgery 03/1993; 17(3):531-7. · 3.21 Impact Factor
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ABSTRACT: A patient with sickle cell anemia and recurrent ankle ulceration is presented. Multiple previous skin grafts did not resolve the painful ulcers. A radial forearm free flap was attempted. Despite preoperative transfusions to reduce her hemoglobin S levels, postoperative thrombosis occurred. The true risk of free flap failure in sickle cell anemia is unknown and there is still debate about the exact nature of the hypercoagulable state that exists in this disease. We recommend, however, that consideration is given to the use of prophylactic anticoagulation in patients undergoing complex procedures or in whom other risk factors have been identified.
Annals of Plastic Surgery 10/1992; 29(3):278-81. · 1.32 Impact Factor
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ABSTRACT: The effects of normothermic systemic perfusion (35 degrees to 37 degrees C; n = 73) were compared with those of moderately hypothermic systemic perfusion (25 degrees to 29 degrees C; n = 73) with respect to blood loss, transfusion requirements, and platelet levels in 146 patients undergoing isolated, primary coronary artery bypass grafting. In addition, most patients were given an antifibrinolytic medication during operation as follows: tranexamic acid (10 gm intravenously; n = 63), epsilon-aminocaproic acid (15 gm intravenously; n = 63), or no drug as a control. (n = 20). Normothermic patients tended to bleed less at 24 hours (warm, 864 +/- 42 ml and cold, 918 +/- 68 ml), but these differences were not statistically significant. Patients receiving either tranexamic acid or epsilon-aminocaproic acid, regardless of perfusion temperature, bled less after 6, 12, and 24 hours than did cold control patients (p less than 0.05). Warm control patients also bled less than did cold control patients after 6 or 12 hours (p less than 0.05), and neither drug further reduced blood loss in these patients. Circulating platelet levels were better preserved in patients receiving either tranexamic acid or epsilon-aminocaproic acid and in patients with warm perfusion and no drug than in cold control patients. Normothermic systemic perfusion, tranexamic acid, and epsilon-aminocaproic acid each reduced postoperative blood loss and preserved platelets.
Journal of Thoracic and Cardiovascular Surgery 07/1992; 103(6):1155-62; discussion 1162-3. · 3.41 Impact Factor
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ABSTRACT: Deposition of fibrin within the peritoneal cavity is an integral host response to local infection. To directly assess the role of fibrin deposition in the pathogenesis of intraabdominal abscess formation, the ability to induce abscesses in fibrinogen-depleted mice was examined. We hypothesized that systemic defibrinogenation with ancrod would limit the availability of fibrinogen for deposition within the peritoneal cavity and would therefore impair intraabdominal abscess formation. A gelatin capsule containing 50% sterile feces plus Bacteroides fragilis 1 x 10(9) CFU was inserted IP into control or defibrinogenated mice. System defibrinogenation resulted in alteration of the character of abscess formation, as manifested by reduced abscess size and degree of purulence. Abscesses were significantly smaller (0.18 +/- 0.02 gm [n = 29] vs. 0.09 +/- 0.02 gm [n = 11], p less than 0.01) and less purulent (p less than 0.001) in the ancrod-treated mice than in control animals, despite equal numbers of bacteria in the abscesses recovered from both groups. The effect of ancrod was specific for defibrinogenation, because IP repletion with fibrinogen reversed the ancrod effect on abscess size. In addition to its local effects, systemic fibrinogen depletion resulted in a significant elevation in mortality following IP infection (1 of 30 control animals vs. 10 of 23 ancrod-treated animals, p less than 0.01). However, this was not due to an increase in the magnitude of the B. fragilis bacteremia. These studies demonstrate that fibrin deposition contributes to the pathogenesis of purulent abscess formation and that systemic depletion of fibrinogen may alter host susceptibility to the consequences of infection.
Journal of Laboratory and Clinical Medicine 08/1991; 118(1):48-55. · 2.62 Impact Factor
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ABSTRACT: We report a case of acquired von Willebrand's syndrome with severe gastrointestinal bleeding and associated free monoclonal lambda light chains. The patient had a rapid sustained clinical and laboratory response to the administration of prednisone. Of note in this patient was the occurrence of angiodysplasia which has previously been reported in association with acquired von Willebrand's syndrome. No inhibitors of VWF:Ag, VWF:RCoF, or factor VIII:C were detected by mixing studies and the bleeding time was normal. Very few high molecular weight von Willebrand multimers were present prior to prednisone; however, the pattern reverted to a normal distribution following treatment. In appropriate patients with acquired von Willebrand's syndrome and monoclonal para-proteins, a trial of prednisone may be indicated.
Postgraduate Medical Journal 08/1990; 66(777):560-2. · 1.94 Impact Factor
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ABSTRACT: The effect of ancrod, a defibrinating agent, on murine lupus glomerulonephritis in the male BXSB mouse was studied to determine the relationship between macrophage procoagulant activity (PCA), fibrin deposition and glomerulonephritis. Marked renal disease and fibrin deposition were noted by three months of age in control mice, whereas little or no disease was seen in ancrod treated mice until five months of age. Similar high titers of anti-DNA antibodies and renal deposition of IgG were seen in both groups of mice. PCA rose with age in both ancrod treated and untreated mice, although it was significantly higher in control animals than in the ancrod treated group. Furthermore, ancrod therapy resulted in a decrease in plasma PCA inducing activity (PIF) and a decrease in the effectiveness of PIF to induce PCA in peritoneal macrophages in vitro. No mortality was observed in the 20 ancrod treated mice, whereas 10 of 20 control animals died. We conclude that defibrination with ancrod delays the development of renal fibrin deposition and glomerulonephritis and improves survival in BXSB mice. This was associated with a decrease in plasma PCA inducing activity and with an inhibitory effect on PCA induction. These results suggest that PCA contributes to injury in murine lupus glomerulonephritis by promoting fibrin deposition.
Kidney International 02/1990; 37(1):29-35. · 6.61 Impact Factor
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ABSTRACT: Heparin is the anticoagulant used during cardiopulmonary bypass (CPB). Both the use of heparin and the reversal of its effect with protamine have well-documented complications. Ancrod is a defibrinogenating enzyme that has been used as an anticoagulant in humans, but its use as an anticoagulant for CPB has been limited to studies in animals. Twenty patients for elective aortocoronary bypass surgery were anticoagulated by means of an intravenous infusion of ancrod pre-operatively. Target plasma fibrinogen concentrations of 0.40-0.80 g/l were achieved within 13.3 +/- 2.5 h using an average dose of ancrod of 1.65 +/- 0.55 U/g. All perfusions were without incident. Postoperative blood loss (2286 +/- 1311 cc) was compared to that of 20 matched controls (1737 +/- 973 cc), as was blood product use; 4.1 +/- 2.1 U of packed cells versus 2.5 +/- 2.3 U (P less than 0.05) and 5.6 +/- 3.1 U of plasma versus 2.6 +/- 2.9 U (P less than 0.05) in the ancrod and heparin-treated groups, respectively. There were no differences in the postoperative courses or recovery periods of the ancrod-treated and control patients. This study confirms the efficacy and feasibility of ancrod as an alternative form of anticoagulation for CPB.
Anesthesiology 01/1990; 71(6):870-7. · 5.36 Impact Factor
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ABSTRACT: Heparin-induced thrombocytopenia and thrombosis was diagnosed in a 50-year-old man undergoing a repeat heart operation after heparinization led to microemboli and an eventual left transmetatarsal amputation. A third heart operation was aborted when anticoagulation with low molecular weight heparin produced intraoperative thrombi. The patient was referred to Toronto where ancrod (Arvin) was used to lower plasma fibrinogen level, allowing successful repair of a ventricular septal defect using cardiopulmonary bypass support. The patient made an uneventful recovery.
The Annals of Thoracic Surgery 12/1989; 48(5):712-3. · 3.74 Impact Factor
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ABSTRACT: Primary nonfunction following orthotopic liver transplantation is characterized by rapidly rising serum transaminases, minimal bile production, and severe coagulopathy, which can progress to hypoglycemia, hepatic encephalopathy, and acute renal failure. Untreated it has a mortality of over 80% and to date the only treatment has been retransplantation. As a result of the beneficial effect of Prostaglandin E1 infusion in patients with fulminant hepatic failure, this trial was conducted to determine whether PGE1 would be of value in primary nonfunction. We have encountered 16 cases of primary nonfunction in 94 liver transplants, an incidence of 17%. Initially in the program, there were 6 occurrences of nonfunction that did not receive PGE1; 3 underwent retransplantation (2 survivors), 2 died awaiting another liver, and in one recovery of hepatocellular function occurred with supportive care but the patient died of cytomegalovirus infection. Ten patients received PGE1 within 4-34 hr of transplantation. Within 12 hr of treatment, 8 patients responded with a significant fall in the AST (129 U/hr) whereas, in the untreated group, the AST continued to rise (267 +/- 102 U/hr) at the same rate as prediagnosis (337 +/- 95 U/hr). At the conclusion of the infusion (4-7 days) in the 8 responders, there were significant decreases in AST (4386 +/- 546 U/L to 102 +/- 21 U/L), prothrombin time (22 +/- 2 to 12 +/- .4 sec) and partial thromboplastin time (45 +/- 3-29 +/- 4 sec), and significant increases in coagulation factor V (26 +/- 8 to 95 +/- 12%) and factor VII (10 +/- 5 to 61 +/- 4%). No serious side effects occurred, although 2 patients developed diarrhea, and abdominal cramps. Two patients treated with PGE1 were retransplanted at 10-36 hr and were considered nonresponders. Graft survival was 80% in the PGE1-treated group and 17% in the untreated group (P less than 0.05) and patient survival was 90% and 33%, respectively. This study suggests a potential benefit of PGE1 in the treatment of primary nonfunction.
Transplantation 10/1989; 48(3):447-53. · 4.00 Impact Factor
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ABSTRACT: Low-dose catheter-directed fibrinolytic therapy (LDCF) using streptokinase (35) and urokinase (7) was performed on 42 separate occasions in 36 patients for recent lower extremity thromboembolic occlusion. Twenty-seven grafts and 15 native arteries were treated. Causes of occlusion were known in 32 instances: native artery proximal or distal occlusive disease or both (18 vessels); bypass graft stenosis (6); aneurysm (2); embolus (4); and postangiography thrombosis (2). Twenty-nine infusions were technically successful, and patients were clinically improved by 26 of the treatments. Twelve patients had unsuccessful infusions and six underwent subsequent amputation. In all patients, infusions longer than 12 hours resulted in prolonged thrombin times and lowered plasma fibrinogen concentrations; one infusion was discontinued due to a low fibrinogen concentration. Complications occurred on 17 occasions and included hemorrhage (6), distal embolization (3), compartment syndrome (1), retrograde thrombosis during infusion (5), hypotension (1), and systemic fibrinogenolysis (1). The cumulative success rate was 44% +/- 9% at 24 months. Late rethrombosis (five instances) was more common in patients who had inflow or outflow structural lesions not corrected following successful fibrinolysis. LDCF is a useful alternative to other methods of treatment for recent onset lower extremity thromboembolic occlusion. Structural vascular lesions uncovered by successful infusion should be corrected immediately after infusion to ensure long-term patency.
Canadian Association of Radiologists Journal 05/1989; 40(2):98-103. · 0.69 Impact Factor
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Transplantation Proceedings 05/1989; 21(2):3360-1. · 1.00 Impact Factor
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Transplantation Proceedings 05/1989; 21(2):3356-7. · 1.00 Impact Factor
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Transplantation Proceedings 03/1989; 21(1 Pt 2):2385-8. · 1.00 Impact Factor
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Transplantation Proceedings 03/1989; 21(1 Pt 2):2308-10. · 1.00 Impact Factor
