Tranexamic acid given intraoperatively reduces blood loss after total knee replacement: a randomized, controlled study.

BACKGROUND: Extensive blood loss in total knee replacement (TKR) surgery is well known and is associated with a high transfusion rate of allogenic blood. Tranexamic acid (TXA) has been shown to reduce blood loss by 50% in this patient group, but only in cases with a perioperative loss of 1400-1800 ml. This study was performed to see if TXA offers any advantages in knee replacement surgery with blood loss at 800 ml. METHODS: Thirty consecutive patients scheduled for TKR in spinal anesthesia with the use of a tourniquet, were randomized to TXA or non-TXA. Tranexamic acid 10 mg kg-1 was given at conclusion of surgery and again 3 h later. Blood loss was registered. RESULTS: Total blood loss was at all times significantly lower in the TXA group compared to the non-TXA group (409.7+/-174.9 ml vs. 761.7+/-313.1 ml; P<0.001). There were no differences in coagulation parameters. No patients in the TXA group had a blood transfusion vs. 13% in the non-TXA group (NS). No complications were registered in the two groups. CONCLUSION: We conclude that TXA significantly reduces blood loss after total knee replacement surgery.

Hypotensive epidural anesthesia in total knee replacement without tourniquet: reduced blood loss and transfusion.

BACKGROUND AND OBJECTIVES: [corrected] For decades, hypotensive anesthesia has been used in an attempt to reduce intraoperative blood loss. Hypotensive epidural anesthesia (HEA) is a relatively new technique in hypotensive anesthesia. Use of a tourniquet has been shown to be associated with a higher risk of cardiovascular and thromboembolic complications. The effect of HEA on blood loss and need for transfusion in total knee replacement (TKR) is not known. METHODS: Thirty consecutive patients scheduled for TKR were randomized to HEA without tourniquet or spinal anesthesia with the use of a tourniquet (SPI). HEA was performed as an epidurally induced sympathetic block and there was an infusion of low-dose epinephrine to stabilize the circulation. RESULTS: Intraoperative mean arterial blood pressure was 48 mm Hg (HEA) versus 83 mm Hg (SPI) (P <.001). Intraoperative blood loss was 146 mL (HEA) versus 13 mL (SPI) (P <.001). Postoperative blood loss at any time was significantly reduced in the HEA group, and total loss of blood was 1,056 mL (HEA) versus 1,826 mL (SPI) (P <.001). Half of the bleeding took place during the first 3 postoperative hours and 80% during the first 24 hours. In the HEA group, 57% of the patients went through surgery and the hospital stay without receiving blood transfusion versus 19% in the SPI group (P <.05). There was a significantly reduced amount of blood transfusion in the HEA group (193 mL) versus 775 mL in the SPI group (P <.005). No cardiopulmonary, cerebral, or renal complications were registered. CONCLUSIONS: We conclude that HEA is a safe technique that allows TKR without a tourniquet. Compared with spinal anesthesia, the use of HEA for TKR significantly reduces blood loss and the need for blood transfusion.

Determination of coagulation inhibitor levels and resistance to activated protein C in patients undergoing gastric surgery for benign and malignant disorders.

The aim of the present study was to determine plasma levels of protein C antigen (PC:Ag) and activity (PC:Act), tissue factor pathway inhibitor (TFPI), protein S (PS), antithrombin (AT), heparin cofactor II (HCII), and resistance to activated protein C (APCR) before, during and after elective gastric surgery in order to compare patients with and without gastric malignancy. Blood was collected from a forearm vein of two age-matched patient groups undergoing elective gastric surgery, 9 patients with and 9 patients without gastric malignancy. The plasma levels of the parameters were determined preoperatively, intraoperatively, and on days 1 and 7 postoperatively. On the 1st and 7th postoperative day, plasma levels of HCII were significantly lower in patients operated for gastric malignancy than in those operated for benign disorders, but levels of TFPI, PC:Act, PC:Ag, AT, PS and APCR did not differ in the postoperative period. The day-to-day variation was also rather similar in the two patient groups.

Plasminogen activators and plasminogen activator inhibitor in portal blood from patients with and without gastric malignancy.

BACKGROUND: Plasminogen activators (PA) may be released by the gut and eliminated by the liver. Patients with liver disorders or malignancy often have abnormal plasma levels of PAs. Some tumours may produce PAs. METHODS: In patients undergoing gastric surgery for malignant (n = 18) or benign (n = 21) disorders., blood drawn from the portal vein and a peripheral vein was analysed for tissue-type plasminogen activator antigen and activity (tPA: Ag, tPA: Act), single-chain urokinase-type plasminogen activator activity (scuPA: Act), and plasminogen activator inhibitor antigen and activity (PAI: Ag, PAI: Act). RESULTS AND CONCLUSIONS: In both groups tPA: Act and scuPA: Act levels were significantly higher in portal blood than in peripheral blood, but tPA: Ag and PAI: Act levels did not differ. PAI: Act levels were significantly lower in patients with malignant disease, but levels of the other markers did not differ in the two groups.

Plasminogen activators and plasminogen activator inhibitor before and after surgery in patients with and without gastric malignancy.

Pre- and postoperative plasma levels of tissue-type plasminogen activator (t-PA), single-chain urinary plasminogen activator, and plasminogen activator inhibitor 1 (PAI-1) were measured in 40 patients undergoing gastric surgery in order to compare patients operated for benign (n = 21) and malignant (n = 19) disease. On the 1st postoperative day, the PAI-1 activity was significantly increased and the t-PA activity significantly decreased in the malignant group, whereas only insignificant changes were seen in the benign group. In contrast, the t-PA activity was significantly increased 1 week after surgery in patients without malignancy. In both groups, the single-chain urinary plasminogen activator activity decreased on the 1st postoperative day, but was significantly increased 1 month after operation. Thus, the two groups reacted differently, but it remains to be determined whether this bears any relationship to the well-known high risk of postoperative venous thromboembolism in cancer patients.

Markers of coagulation and fibrinolysis in portal blood from patients with and without gastric malignancy.

BACKGROUND: The origin of coagulation and fibrinolysis abnormalities in cancer patients is unknown. The aim of this study was to measure markers of coagulation and fibrinolysis in portal and peripheral blood from patients with and without gastric malignancy. METHODS: Blood samples were drawn from the portal vein and a peripheral vein in 39 patients undergoing elective gastric surgery, 18 for gastric malignancy and 21 for benign disorders, and analyzed for prothrombin fragment 1 + 2 (F1 + 2), thrombin-anti-thrombin III complex (TAT), fibrinogen and fibrin degradation products (FgDP, FbDP), and fibrinopeptide A (FpA). RESULTS AND CONCLUSIONS: In portal blood, levels of F1 + 2, TAT, FpA, FgDP, and FbDP did not differ in the two groups. In peripheral blood, levels of FpA and FbDP were higher in cancer patients, but in a multiple regression model malignancy did not contribute significantly to variation in peripheral FpA or FbDP levels. In both groups FpA levels were higher in portal blood than in peripheral blood.

Haemostatic activation before and after surgery in patients with and without gastric malignancy.

Pre- and postoperative plasma levels of Prothrombin Fragment 1 + 2 (F1 + 2), Thrombin-antithrombin III complex (TAT), Fibrinopeptide A (FpA), Fibrin and Fibrinogen Degradation Products (FbDP, FgDP) and Soluble Fibrin (SF) were measured in 40 patients undergoing gastric surgery in order to compare patients operated for benign (n = 21) and malignant (n = 19) disease. Plasma levels of F1 + 2, TAT, FbDP and SF on the first postoperative day were significantly higher than before operation. F1 + 2 and FbDP levels were further increased one week after surgery, at which time FgDP levels were also higher than preoperatively. A significant postoperative increase in FpA levels was found only in patients with malignant disease. When age was taken into consideration, significant differences between patients with and without malignancy were found only in the late postoperative period, as cancer patients had higher FpA and FbDP levels one week after surgery and higher FbDP levels one month after discharge from hospital.

Markers of coagulation and fibrinolysis in blood drawn into citrate with and without D-Phe-Pro-Arg-Chloromethylketone (PPACK).

In order to compare levels of Prothrombin Fragment 1 + 2 (F1 + 2), Thrombin-antithrombin III complex (TAT), Fibrinogen Degradation Products (FgDP) and Fibrin Degradation Products (FbDP) in plasma from blood drawn into sodium citrate with and without the protease inhibitor D-Phe-Pro-Arg-Chloromethylketone (PPACK), blood samples were collected from 41 patients on the first day after elective gastric surgery. Levels of F1 + 2, TAT and FbDP were not significantly different in plasma with and without PPACK. FgDP levels were significantly higher in plasma with PPACK. Our results did not support previous suggestions that PPACK should be used as a routine anticoagulant for measurement of haemostatic activation products.

Levels of fibrinolytic activators and inhibitors in plasma after severe trauma.

Levels of tissue plasminogen activator antigen (t-PA:ag), tissue plasminogen activator inhibitor 1 antigen (PAI-1:ag) and tissue plasminogen activator inhibitor activity (PAI activity), and alpha-2-antiplasmin (AAP) were measured in plasma from 19 patients with severe trauma on admission and on days 1, 2, 3 and 7 after the incident. In all patients the Injury Severity Score (ISS) and the number of blood transfusions were recorded. The development of post-traumatic pulmonary dysfunction was observed in four patients. Levels of t-PA:ag, PAI-1:ag and PAI activity were increased, and levels of AAP were low immediately after trauma. Levels of t-PA:ag normalized during the first week, whereas PAI-1:ag levels decreased gradually from day 1 to day 3. Thereafter a secondary increase was observed. A similar trend was observed in levels of PAI activity. Levels of APP increased significantly during the first week. t-PA:ag, PAI-1:ag or PAI activity levels were not correlated with the ISS on any day, but levels of AAP showed a weak correlation with the ISS on day 7. Post-traumatic levels of t-PA:ag and PAI-1:ag were higher in patients who had 6 or more units of blood transfusions for resuscitation. The fibrinolytic markers were not significantly different in patients who had pulmonary dysfunction compared with patients without.

Haemostatic activation in patients with head injury with and without simultaneous multiple trauma.

In a prospective study including 16 patients with multiple trauma and head injury and 14 patients with isolated head injury we measured plasma levels of prothrombin fragment 1 and 2 (F1 + 2) and thrombin/antithrombin III complex (TAT) on admission and on days 1, 2, 3, and 7 after the incident. On admission, all patients had values of F1 + 2 and TAT above the reference range. Admission levels of both F1 + 2 and TAT were significantly higher compared with levels on the following days. Admission levels of F1 + 2 was significantly correlated to the Injury Severity Score. TAT was higher in patients with multiple trauma than in patients with isolated head injury and were significantly correlated to the Injury Severity Score on admission and on day 3. Levels of F1 + 2 were significantly lower on day 1 in four patients with post-traumatic pulmonary dysfunction compared with patients without pulmonary dysfunction. With respect to levels of TAT, no differences were detected between patients with and without pulmonary dysfunction.

[Early osteosynthesis of fractures of the lower extremities in patients with multiple trauma]. / Tidlig osteosyntese af underekstremitetsfrakturer hos multitraumatiserede.

In the early 1970s, some trauma centres began to perform early operative fixation of lower limb fractures in multiple trauma patients. At that time, no clinical studies were available on this topic. At present, several publications have demonstrated lower mortality, reduction of the incidence of Adult Respiratory Distress Syndrome and sepsis, and a shorter stay in hospital after early operative fracture fixation compared with conservative fracture management or late fracture fixation. The incidence of fracture complications appeared not to increase after early operative fracture fixation. The present paper is a review of the most significant reports concerning timing of operative fracture management of patients with multiple trauma. Prospective randomised trials are needed on this subject.

[Low molecular heparin in prevention of thrombosis in orthopedic surgery]. / Tromboseprofylakse med lavmolekylaert heparin i ortopaedkirurgien.

The review encompasses all published clinical studies of prophylactic treatment with low molecular weight (LMW) heparins marketed in Denmark when used to prevent thrombosis in patients undergoing elective or emergency orthopaedic operations. In elective hip surgery, LMW-heparin was more effective than placebo in reducing the incidence of deep vein thrombosis. There was significantly better anti-thrombotic effect of LMW-heparin, given in recommended doses, than of Dextran 70. When compared to low-dose heparin, the incidence of deep vein thrombosis was lowest using LMW-heparin, but only one study found the difference significant. LMW-heparin compared to low-dose heparin in combination with dihydroergotamine showed no significant difference with respect to either effect of safety. The use of LMW-heparin as prophylactic treatment for patients with either trochanteric or femoral neck fractures is as yet not nearly so well-documented. The relatively few studies that have been carried out show large variation between the different LMW-heparins. There is need for a study comparing the effect of LMW-heparin with that of low-dose heparin in these patients, both with respect to thrombosis prevention and influence on total mortality.

Fibrinogen and fibrin derivatives in traumatized patients: relation to injury severity and posttraumatic pulmonary dysfunction.

In a prospective study including 30 traumatized patients, levels of fibrinogen, fibrinopeptide A (FpA), fibrin monomers (FM) and fibrin degradation products (FbDP) were measured on admission and on days 1, 2, 3 and 7 after the incident. High levels of FpA, FM and FbDP were observed immediately after the trauma. Fibrinogen levels increased during the first 7 posttraumatic days whereas FpA and FM decreased. FbDP was significantly higher on day 7 than on day 3. All variables were to some extent correlated to the injury severity score. FbDP were significantly lower on the day after admission in 4 patients who developed pulmonary dysfunction compared with patients without this complication.

Venous thromboembolism and cancer.

The literature was reviewed in an attempt to determine whether patients with cancer have an increased risk of venous thromboembolism, i.e. deep vein thrombosis and pulmonary embolism. From case reports it was apparent that various thromboembolic or thrombophlebitic manifestations may be found in a small number of patients, although it is possible that not all cases belong to the same clinical or pathogenetic entity. In clinical series it was found that the risk of postoperative venous thromboembolism was increased in cancer patients, but the possibility that this was due to associated risk factors, rather than to the mere presence of a tumour, could not be excluded. Little is known about patients not undergoing surgery. Retrospective postmortem studies have found more thrombi in patients with malignancy, but a prospective study failed to demonstrate an association between malignancy and pulmonary embolism. It is possible that different types of cancer show various degrees of association with venous thromboembolism. We conclude that further studies should be performed to provide a firm clinical and pathoanatomical basis for investigations into the pathogenesis of venous thromboembolism.

Markers of coagulation and fibrinolysis after fractures of the lower extremities.

The study was performed to detect activation of coagulation and fibrinolysis in terms of prothrombin fragment 1 and 2 (F1 + 2), thrombin-antithrombin III complex (TAT), fibrin degradation products (FbDP), fibrinogen degradation products (FgDP), and soluble fibrin monomers (FM) in plasma from 39 patients with fractures of the lower extremities. We found substantially elevated levels of the molecular markers at admission and on the day after admission (Day 1) compared with control levels. Admission levels of F1 + 2, TAT, FbDP and FgDP were significantly higher compared with levels on day 1, whereas levels of FM were not significantly different between the two days. Generally there were good correlations between all markers of coagulation and fibrinolysis at admission whereas correlations were weaker or absent on day 1. In conclusion we found substantial haemostatic activation as a immediate response to trauma. Increased levels of F1 + 2, TAT, FM, FbDP and FgDP appear to be a normal physiological reaction after fractures of the lower extremities.

Reduction of plasma levels of prothrombin fragments 1 and 2 during thromboprophylaxis with a low-molecular-weight heparin.

In a randomized double-blind placebo-controlled study, plasma levels of prothrombin fragment 1 and 2 and total fibrin/fibrinogen degradation products were measured preoperatively and on days 1, 3, 5 and 7 postoperatively in 131 patients undergoing total hip replacement. Patients received a subcutaneous injection of either a low molecular weight heparin (Logiparin) or placebo once daily. Postoperative deep vein thrombosis was diagnosed by bilateral phlebography 7 to 10 days after operation. In the placebo group postoperative levels of prothrombin fragments 1 and 2 and total fibrin/fibrinogen degradation products were significantly higher in patients with postoperative thromboembolic complications, whereas in the low-molecular-weight heparin group no statistical differences were observed. Compared with placebo the administration of a low-molecular-weight heparin was associated with a significant reduction in the levels of prothrombin fragments 1 and 2 and total degradation products. Our observations suggest that the postoperative thrombin generation is moderated by thromboprophylaxis with Logiparin.

Biologic tolerance of two different low molecular weight heparins.

Heparin preparations have been used for prophylaxis and treatment of deep vein thrombosis for many years. Several biologic effects of heparin are known. Since 1978, there have been several reports about reversible elevation in serum values of AST and ALT in patients and healthy volunteers given heparin in small and high doses. Few studies report similar events in patients given LMW heparins. Results of two randomized studies (A and B) comprising 456 patients undergoing THR are presented. Two different compounds of LMW heparin (Logiparin or Enoxaparin) were used for thromboprophylaxis. Significant elevation during the postoperative period of AST and AP in study A, and AST, ALT, AP, LDH, and CK in study B were demonstrated in patients given LMW heparins in both studies. In study A the percentages of patients with normal preoperative values who reached pathologic values were 35% for AST and 15% for AP. In study B the percentages of patients with normal preoperative values who reached pathologic values were 36% for AST, 17% of ALT, 14% for AP, and 36% for LDH. The possible biologic mechanisms and the clinical perspectives are discussed. In all cases the changes in the liver enzymes returned to preoperative levels within 14 days.