Efficacy Of Low-dose Heparin Research Articles

Topics in medicine 50 years ago

Topics in medicine 50 years ago

Urokinase can reduce heparin dose in patients with hypercoagulable states during hemodialysis

Heparin is routinely administered at high doses during hemodialysis to patients with hypercoagulable states. This study aimed to evaluate the safety and efficacy of low-dose heparin in combination with urokinase in this patient population. The presence of a hypercoagulable state was confirmed by thromboelastography. Doses of heparin and urokinase were adjusted based on activated partial thromboplastin time (APTT). Clotting in the extracorporeal circuit was evaluated by a semi-quantitative index. Prothrombin time (PT) and APTT were measured before, during and after dialysis. Kt/Vurea was used to assess the efficacy of dialysis. D-dimer levels were measured 2 h after the start of hemodialysis. Hemodialysis data with heparin administered alone prior to dialysis were used as control in the present study. With urokinase treatment, the initial dose of heparin was reduced by 45.0 ± 11.4% during hemodialysis and the maintenance dose by 46.8 ± 12.8% compared with heparin alone. No side effects due to urokinase were observed. Bleeding events were rare. Post-dialysis PT (12.99 ± 1.41 vs. 15.22 ± 3.12 s, p = 0.02) and APTT (97.75 ± 43.62 vs. 140.16 ± 30.12 s, p = 0.002) with urokinase plus heparin were significantly shorter than with heparin alone. Finally, during dialysis, D-dimer levels were significantly higher with heparin alone (0.21 ± 0.11 mg/L) than with heparin and urokinase (0.169 ± 0.122 mg/L, p = 0.017). In conclusion, urokinase significantly reduced the dose of heparin required during hemodialysis without any side effects in patients with hypercoagulable states during hemodialysis.

Low‐Dose Heparin for Elective Percutaneous Coronary Intervention

We evaluated the safety and efficacy of low-dose heparin (40 IU/kg) for elective percutaneous coronary intervention (PCI). Current guidelines recommend a 70-100 IU/kg bolus of heparin for elective PCI, but this dose may be associated with increased bleeding risk. Low-dose heparin may have an advantage in this regard, but has not been well studied. From January 2008 to October 2012, 300 patients underwent elective transfemoral PCI and were treated with an initial bolus of 40 IU/kg of heparin at the UCLA Medical Center. Dual antiplatelet therapy with clopidogrel and aspirin was administered prior to or just after diagnostic coronary angiography. The primary end-point was the composite of cardiac death, myocardial infarction, urgent target vessel revascularization for ischemia, or major bleeding within 30 days after PCI. The mean activating clotting time was 233 ± 28 seconds. The primary end-point occurred in 2.3%. The cardiac death rate was 0.3% but was not related to the PCI. The myocardial infarction rate was 1.3%. Urgent target vessel revascularization occurred in 1 patient (0.3%). The major bleeding rate was 0.3%. No stent thrombosis occurred. Using a lower dose of heparin with dual antiplatelet therapy is safe and is associated with a low bleeding risk after transfemoral PCI while providing suppression of ischemic events. This may also represent a cost savings compared with other antithrombotic strategies. A randomized clinical trial comparing low-dose heparin with bivalirudin in patients is required to determine the optimal anticoagulation strategy.

Complications of subcutaneous low-dose heparin therapy in neurosurgical patients

BACKGROUND Venous thromboembolism is a major cause of postoperative morbidity and mortality in neurosurgery. The use of low-dose unfractionated heparin therapy perioperatively for prophylaxis against deep vein thromboses and pulmonary embolism has been well demonstrated in many other surgical specialties but is less commonly used in neurosurgery because of fears of devastating postoperative hematomas. METHODS The safety of such therapy has been analyzed in 950 patients undergoing an inpatient neurosurgical procedure. 872 patients (152 cranial procedures) completed treatment with 5000 U sodium heparin subcutaneously twice a day, commencing before surgery and continuing till patients were ambulatory. RESULTS There were three minor hemorrhagic complications—two superficial wound hematomas (one requiring treatment) and one gastrointestinal hemorrhage—identified. Three clinically significant major complications developed, two epidural hematomas after spinal surgery requiring evacuation and one intraventricular hemorrhage after brain biopsy. CONCLUSION This report, along with an analysis of previously published reports of low-dose perioperative heparin therapy in neurosurgical patients, suggests that such therapy is unlikely to be associated with increased morbidity. Given the known efficacy of low-dose heparin in reducing venous thromboembolism in other surgical patients, such therapy may reduce mortality and morbidity from thromboembolic complications in neurosurgical patients with minimal risk.

Prevention of Pulmonary Emboli in a Respiratory Intensive Care Unit: Efficacy of Low-dose Heparin

Ninety-eight patients admitted to our respiratory intensive care unit during a one-year period were compared retrospectively with 99 well-matched patients admitted during a second one-year period. The use of prophylactic low-dose heparin in the second year was associated with a significant decrease in pulmonary emboli documented by ventilation-perfusion scan, pulmonary angiography, and autopsy. No specific bleeding complications could be directly attributed to the use of low-dose heparin. The frequency and severity of gastrointestinal hemorrhage as determined by hemoglobin fall and transfusion requirements were not significantly affected by the prophylactic use of low-dose heparin. Low-dose heparin appears to be effective and safe in respiratory intensive care unit patients in the prevention of pulmonary emboli.

The safety of low dose heparin prophylaxis

In a recent survey, eight of ten general surgeons claimed to have a high awareness of the prophylactic use of heparin sodium in subanticoagulant doses, although the use of low dose heparin is considerably lesser. Actual use of this regimen occurs in 4 per cent of surgical patients. Surgeons are reluctant to use anticoagulant therapy in a prophylactic manner due to (1) the fear of bleeding in intra- and postoperative patients and (2) the necessity of regulating the anticoagulant therapy by means of laboratory monitoring. Heparin has recently gained prominence for prophylactic use particularly in older patients undergoing surgery and in those prone to thrombosis for other reasons [16]. The efficacy of low dose heparin in preventing fatal postoperative pulmonary embolism was investigated in the multicenter trial of Kakkar and his associates [3,4,12]. The recommendations for prophylactic use of low dose heparin on a large scale in “high risk” patients undergoing major surgery were further confirmed in our present study of thirty-two surgical patients. We have demonstrated that in a routine surgical environment heparin can be administered according to a prophylactic regimen in a manner easily understood by the staff, without the need of extensive and costly laboratory monitoring, and without bleeding that would have interfered with the surgical procedures.

Efficacy of low-dose heparin : Sagar S., Nairn D., Stomatakis J. D., Maffei F. H., Higgins A. F., Thomas D. P. and Kakkar V. V. (1976) Efficacy of low-dose heparin in prevention of extensive deep-vein thrombosis in patients undergoing total hip replacement. Lancet1, 1151

Efficacy of low-dose heparin : Sagar S., Nairn D., Stomatakis J. D., Maffei F. H., Higgins A. F., Thomas D. P. and Kakkar V. V. (1976) Efficacy of low-dose heparin in prevention of extensive deep-vein thrombosis in patients undergoing total hip replacement. Lancet1, 1151

Heparin Therapy

Heparin remains the most effective antithrombotic drug. It acts by combining with plasma antithrombin, thereby accelerating the neurtalisation of thrombin and other acitvated coagulation factors. Full-dose intravenous heparin is indicated in all cases of pulmonary embolism and established deep venous thrombosis, unless there exist compelling contraindications. Continuous intravenous infusion of heparin appears to be safer than intermittent injection. Low-dose subcutaneous heparin is effective in preventing the initial occurrence of thigh vein thrombi and in reducing the incidence of fatal pulmonary embolism in general surgical patients over the age of 40. The efficacy of low-dose heparin in preventing pulmonary emboli following hip surgery has not been established. The incidence of severe heparin-induced thrombocytopenia appears to be rising. Platelet counts should be performed in all patients receiving heparin by any mode of administration.

PREVENTION OF FATAL POSTOPERATIVE PULMONARY EMBOLISM BY LOW DOSES OF HEPARIN: An International Multicentre Trial

The efficacy of low-dose heparin in preventing fatal postoperative pulmonary embolism has been investigated in a multicentre prospective randomised trial. 4121 patients over the age of forty years undergoing a variety of elective major surgical procedures were included in the trial; 2076 of these were in the control group and 2045 patients received heparin. The two groups were well matched for age, sex, weight, blood-group, and other factors which could predispose to the development of venous thromboembolism. 180 (4·4%) patients died during the postoperative period, 100 in the control and 80 in the heparin group: 72% of deaths in the control and 66% in the heparin group had necropsy examination. 16 patients in the control group and 2 in the heparin group were found at necropsy to have died due to acute massive pulmonary embolism (P<0·005). In addition, emboli found at necropsy in 6 patients in the control group and 3 in the heparin group were considered either contributory to death or an incidental finding since death in these patients was attributed to other causes. Taking all pulmonary emboli together, the findings were again significant (P<0·005). Of 1292 patients in whom the 125I- fibrinogen test was performed to detect deep-vein thrombosis (D.V.T.) 667 were in the control group and 625 in the heparin group. The frequency of isotopic D.V.T. was reduced from 24·6% in the control group to 7·7% in the heparin group (P<0·005). In 30 patients D.V.T. was detected at necropsy; 24 in the control and 6 in the heparin group (P<0·005). 32 patients in the control group and 11 in the heparin group developed clinically diagnosed D.V.T. which was confirmed by venography (P<0·005). In addition, 24 patients in the control and 8 in the heparin group were treated for clinically suspected pulmonary embolism. The difference in the number of patients requiring treatment for D.V.T. and/or pulmonary embolism in the two groups was again significant (P<0·005). 9 patients were found at necropsy to have died from hæmorrhage; 5 were in the control and 4 in the heparin group. A careful objective analysis of operative and postoperative bleeding in 1475 patients showed no statistically significant difference in the blood-transfusion requirements or in the fall in the postoperative hæmoglobin level either in the individual operative groups or in the group as a whole. However, the difference in the number of patients who developed wound hæmatoma in the heparin and control groups was significant (P<0·01). The results of the trial indicate that this form of prophylaxis can now be recommended for use on a large scale in " high-risk " patients undergoing major surgery.