Received Heparin Infusion Research Articles

Risk-Stratified Anticoagulation Protocol Increases Success of Lower Extremity Free Tissue Transfer in the Setting of Thrombophilia.

Optimal perioperative thromboprophylaxis is crucial to avoid flap thrombosis and achieve high rates of microsurgical success. At the authors' institution, implementation of a risk-stratified anticoagulation (AC) protocol preliminarily showed a reduction in postoperative thrombotic events and flap loss. The authors present an updated analysis of surgical outcomes using risk-stratified AC in thrombophilic patients who underwent free tissue transfer (FTT) reconstruction for nontraumatic lower extremity (LE) wounds. The authors retrospectively reviewed patients who underwent FTT to an LE from 2012 to 2021. Their risk-stratification AC protocol was implemented in July of 2015. Low-risk and moderate-risk patients received subcutaneous heparin. High-risk patients received heparin infusion titrated to a goal partial thromboplastin time of 50 to 70 seconds. Before July of 2015, nonstratified patients were treated with either subcutaneous heparin or low-dose heparin infusion (500 U/hour). Patients were divided into two cohorts (nonstratified and risk-stratified) based on date of FTT reconstruction. Primary outcomes included rates of postoperative complications, flap salvage, and flap success. Two hundred nineteen hypercoagulable patients who underwent FTT to an LE were treated with nonstratified ( n = 26) or risk-stratified ( n = 193) thromboprophylaxis. The overall flap success rate was 96.8% ( n = 212). Flap loss was lower among risk-stratified patients (1.6% versus 15.4%; P = 0.004), which paralleled a significant reduction in postoperative thrombotic events (2.6% versus 15.4%; P = 0.013). Flap salvage was accomplished more often in the risk-stratified cohort (80% versus 0%; P = 0.048). Intraoperative anastomotic revision (OR, 6.10; P = 0.035) and nonrisk stratification (OR, 9.50; P = 0.006) were independently associated with flap failure. Hypercoagulability can significantly affect microsurgical outcomes. Implementation of a risk-stratified AC protocol can significantly improve flap outcomes. Therapeutic, III.

54. Implementation of a Risk-stratified Anticoagulation Protocol Increases Free Flap Success in Thrombophilic Patients With Chronic Lower Extremity Wounds

Purpose: A hypercoagulable state is one of the most challenging preoperative conditions that reconstructive microsurgeons face. Optimal perioperative thromboprophylaxis is crucial to avoid flap thrombosis and to achieve high rates of microsurgical success in patients undergoing lower extremity (LE) free tissue transfer (FTT). At our institution, implementation of a risk-stratified anticoagulation (AC) protocol preliminarily showed a reduction in postoperative thrombotic events and flap loss. After six years of experience with this protocol, we present an updated analysis of surgical outcomes and the utility of risk-stratified AC in thrombophilic patients who underwent FTT reconstruction for chronic LE wounds. Methods: We conducted a retrospective review of patients who underwent FTT to the LE at our institution from January 2012 to August 2021. Patients were preoperatively assessed for hypercoagulability based on history and a screening panel. Our risk-stratification AC protocol was implemented in July 2015. Low-risk (<3 hypercoagulable traits) and moderate-risk (>3 hypercoagulable traits or history of venous thromboembolism) patients were anticoagulated with subcutaneous heparin (SQH). Any intraoperative risk factor (thrombosis, anastomotic revision, presence of calcified vessels) upstaged patients to high microvascular risk. High-risk patients received heparin infusion titrated to a goal PTT of 50-70 seconds. Prior to July 2015, non-stratified patients were treated with SQH for uncomplicated microvascular anastomoses, while patients with microvascular compromise were converted to a low-dose heparin infusion (500 units/hour). Patients were divided into two cohorts (non-stratified and risk-stratified) based on the date of FTT reconstruction. Primary outcomes included rates of postoperative complications, flap salvage, and flap success. Results: A total of 219 hypercoagulable patients who underwent FTT to LE were treated with either non-stratified (n=26) or risk-stratified (n=193) thromboprophylaxis. Overall flap success rate was 96.8% (n=212). Lower rates of flap loss (1.6% vs. 15.4%, p=0.004) were observed among risk-stratified patients, which paralleled a significant reduction in the prevalence of postoperative thrombotic events (2.6% vs. 15.4%, p=0.013). Flap salvage, in the setting of postoperative thrombosis, was accomplished in 80% of cases in the risk-stratified cohort compared to 0% in the non-stratified group (p=0.048). Bleeding complications and transfusion requirements were similar among the two cohorts. On multivariate analysis, intraoperative anastomotic revision (OR: 3.10; p<0.001) and non-risk stratification (OR: 11.2; p=0.001) were independently associated with flap failure. Non-risk stratification for thromboprophylaxis was an independent predictor of perioperative microvascular thrombosis (OR: 3.71; p=0.041). Conclusion: Hypercoagulability can significantly impact microsurgical outcomes. Preoperative identification of hypercoagulable traits and intraoperative risk factors can successfully guide perioperative thromboprophylaxis. Implementation of a risk-stratified AC protocol at our institution has contributed to significant improvements in flap success without creating an increased need for blood transfusion.

Renal vein thrombosis in a recent COVID-19 patient; a case report

We report a 74-year-old male with a recent history of COVID-19 pneumonia who was admitted with acute periumbilical and left lower quadrant pain and respiratory distress. Laboratory data showed pre-renal azotemia and microscopic hematuria. An abdominopelvic computerized tomography (CT) scan with intravenous contrast was conducted, showing signs of right renal vein thrombosis (RVT) with extension to inferior vena cava (IVC), without any evidence of renal ischemia. The patient did not have any risk factors for thrombosis except for probable hypercoagulopathy due to COVID-19 and diabetes mellitus. He was not an appropriate candidate for surgical or radiologic thrombectomy, thus received heparin infusion accordingly. Unfortunately, he died after the cardiopulmonary arrest on the second day of admission. Considering his respiratory distress, we suspect pulmonary embolism as the most probable cause of death.

Management of Moderate Blunt Thoracic Aortic Injuries in Patients with Intracranial Hemorrhage

Blunt thoracic aortic injuries (BTAIs) are the second most common cause of death due to blunt-force trauma in the United States. Patients with minimal injuries do not typically require surgical repair, whereas patients with severe injuries are treated emergently. Moderate aortic injuries are repaired in a semielective fashion, but the optimal management of patients with moderate BTAI with associated intracranial hemorrhage (ICH) is unknown. We sought to analyze the management and outcomes of patients presenting with concomitant moderate BTAI and ICH. Consecutive patients who received a thoracic endovascular aortic repair (TEVAR) at our institution for treatment of moderate BTAI between January 2014 and December 2017 were retrospectively reviewed as part of an institutional review board-approved protocol. Patients were classified by our BTAI classification into "minimal", "moderate", or "severe". ICH was identified on computed tomography scan and its severity determined by the neurosurgical team. Outcome measures included surgical timing and surgical outcomes. Fifty-two patients had a moderate BTAI and underwent TEVAR, 20 (38 %) of whom presented with ICH. Median time from admission to surgery was 58.5hr for patients with ICH and 26.5hr for non-ICH patients. Intraoperative heparin was administered in all patients without ICH and in 19 of 20 (95%) patients with ICH after the ICH met criteria for stability. Protamine reversal was utilized in 80% of patients with ICH and 75% of non-ICH patients. No patient developed ischemic stroke or spinal cord ischemia. Worsening ICH was seen in only one patient, who also received heparin infusion for pulmonary embolus 24hr before TEVAR. There were no aortic-related mortalities in either group. Thirty-day all-cause mortality was 5% for patients with ICH and 3% for non-ICH patients. Patients with moderate BTAI and stable ICH are not at increased risk of TEVAR-related complications. Administration of intraoperative heparin during TEVAR appears to be safe and does not worsen ICH.

The development of an extra-anatomic tissue-engineered artery with collateral arteries for therapeutic angiogenesis in ischemic hind limb

To develop tissue-engineered arteries (TEAs) with collateral arteries(CAs) in ischemic hind limb goat models(IHLMs). The IHLMs created by removing femoral arteries were divided into non-treated control group(NG); non-catheter group (NCG) in which TEA was anastomosed to external iliac artery(EIA), and surrounded with collagen sponge containing autologous MSCs and VEGF-gelatin microspheres, the distal end of TEA was ligated; catheter group(CG) which received the same procedure as NCG, also received heparin infusion through catheter in EIA. TEA patency was assessed weekly by Ultrasound. The TEA and CAs were assessed by angiography, gross examination, histology and electron microscopy. In CG, TEAs remained patent for 1 month, but became partly occluded 1 week after catheter withdrawn. In NCG, TEAs were occluded 1 week after implantation. Angiography demonstrated that communication between CAs arising from the TEAs and the native vessels was established in both groups. NCG had fewer CAs than CG (P < 0.01). At 40 days, TEAs in CG demonstrated of endothelium formation, smooth muscle cells infiltration and collagen regeneration. The CG had more capillaries and mature vessels in adventia of TEAs than NCG (P < 0.01). CG group also had more vessels around TEAs than NCG (P < 0.01) or NG (P < 0.001).

Use of thrombin‐based haemostatic matrix in head and neck reconstructions: a potential risk factor for pulmonary embolism

Haemostatic agents including thrombin-based haemostatic matrix are widely used in patients undergoing cardiac, vascular and spinal surgery. These agents promote local haemostasis through activation of the clotting cascade. To our knowledge, this case series is the first report of pulmonary embolization associated with FloSeal following head and neck oncology resection and free flap reconstruction. We present five patients who were diagnosed with symptomatic pulmonary embolism after oncologic head and neck free flap reconstructions in 2014 and 2015. There were five patients consisting of three males and two females. The mean age was 67 years, ranging from 60 to 74 years. Pulmonary embolism occurred between 3 and 30 days with a mean of 12 days. Four out of the five reported cases showed involvement of more than one lobe, and two cases had bilateral pulmonary involvement. All but one patient underwent infratemporal fossa dissections as part of the cancer resection. Ten millilitres of FloSeal was applied to the pterygoid plexi in the four patients to achieve haemostasis. All patients received heparin infusion followed by warfarin therapy for at least 6 months with no mortality or complications relating to pulmonary embolism to date. Although inconclusive due to study design and small numbers, this series raises the possibility that there may be an association between the use of haemostatic matrix in head and neck oncologic reconstructions and pulmonary embolism. Haemostatic matrix must be used in caution when there is a direct contact with venous endolumens such as the pterygoid plexus and soleus.

Retrospective study of Heparin Administration for Ischemic Stroke when there is an IV-tPA Contraindication.

Background:The majority of patients presenting with an ischemic stroke arrive after the 3-4.5 h time window allowed for intravenous tissue plasminogen activator (IV tPA) administration. Most of the literature on heparin use in acute ischemic stroke does not describe dose-adjusted intravenous unfractionated heparin (IV UFH) without bolus, a common method of administration. This study was designed to test whether an anticoagulation regimen of intravenous dose-adjusted UFH with no bolus, in patients with a contraindication to IV TPA, administered within 24 h of an acute ischemic stroke could be effective and safe.Methods:We conducted a retrospective study of 273 patients over two consecutive years with acute ischemic stroke, who were outside the window for IV tPA. All patients had imaging studies on admission. The primary outcome measure of the study was to evaluate the safety of dose-adjusted IV UFH use in the setting of acute stroke. We looked at duration of heparin infusion, average partial thromboplastin time (PTT) value, and the incidence of new hemorrhagic events.Results:A total of 273 patients met the inclusion criteria. These patients received heparin infusion within 24 h of symptom onset. The duration of intravenous heparin infusion ranged from 1 to 18 days with a mean of 4 days. Mean PTT value was 72.4. Hemorrhagic complications occurred in 26 patients (9.5%), and included 12 asymptomatic petechial or hemorrhagic conversion (4.3%), 2 symptomatic intracranial hemorrhages (0.7%), 5 gastrointestinal bleeds (2 requiring transfusion and interventions), 2 patients experienced benign hematuria, 4 patients with groin hematomas, and one neck hematoma.Conclusion:This study suggests that intravenous dose-adjusted UFH with no bolus can be administered to patients with acute ischemic stroke with relative safety.

Impact of Intelligent Intravenous Infusion Pumps on Directing Care Toward Evidence-Based Standards: A Retrospective Data Analysis

Introduction: Published literature has successfully demonstrated the impact of intravenous (IV) infusion pump safety software on improving the quality of health care delivery. Much of this literature has focused solely on the ability of these devices to prevent potential medication errors, while overlooking the devices' additional valuable advantages. One non-reported benefit is the ability of IV infusion pump safety software to consistently administer doses of IV medication, which are based on evidence. This article describes the process undertaken to implement and evaluate the impact of IV infusion pump safety software on driving care toward evidence-based standards. Methods: An advisory group of expert users was convened for a 2-day session to develop consensus recommendations of best practices for IV infusion pump safety software. Using these recommendations, administrative data were collected from a community hospital to assess the endpoints identified by the advisory panel. Results: Data analysis of rescue agents (ie, flumazenil, glucagon, and protamine sulfate) showed reductions in utilization in the post-implementation period of the safety software. The decreased requirement for blood transfusions in patients receiving heparin infusions suggests that heparin infusions were more safely administered in the post-implementation period. The decreased length of stay and mortality rate observed in patients with complex respiratory infections during the post-implementation period suggests that by correctly infusing antibiotics consistently, patient outcomes may be improved. Additionally, alert and edit data from the pumps demonstrated that the IV infusion pump safety software alerted to and influenced edits on many critical dose rate errors for benzodiazepines, heparin, and several antibiotics. Conclusion: Intravenous infusion pump safety software improves clinical outcomes through consistent application of evidence-based standards of dose rates for IV drugs.

P-27 Comparison of two strategies for early postoperative anticoagulation after valve replacement: a randomized trial

Although the need for anticoagulant therapy in patients with mechanical valves is not in dispute [1Vahania A. Baumgaratner H. Bax J. et al.Guidelines on the management of valvular heart disease The Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology.European Heart Journal. 2007; 28: 230-268PubMed Google Scholar], the optimal early postoperative anticoagulation regimen after valve implantation has been a matter of debate [2Kulik A. Rubens F.D. Wells P.S. et al.Early postoperative anticoagulation after mechanical valve replacement: a systematic review.Ann Thorac Surg. 2006; 81: 770-781Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar]. The objective was to evaluate efficacy and safety of two approaches for early postoperative anticoagulation in patient after valve replacement. Two hundred patients undergoing elective valve replacement surgery were randomly assigned to 2 different treatment options: In Group 1, patients received heparin infusion (12-17 IU kg-1 h-1) started 6-8 hr after ICU admission with a target aPTT of 50-70 sec; In Group 2, patients received enoxaparin s/c (1 mg/kg, twice daily) started 6-8 hr after ICU admission. In both groups, warfarin (2.5 - 5 mg) was started since the 1st postoperative day and heparin/enoxaparin were discontinued when INR reached the target value of 2.0-3.0. The efficacy and safety of the two approaches for early postoperative anticoagulation in patient after valve replacement were estimated, Efficacy by number of thromboembolic events (according to Thromboembolic Level (TEL) [2Kulik A. Rubens F.D. Wells P.S. et al.Early postoperative anticoagulation after mechanical valve replacement: a systematic review.Ann Thorac Surg. 2006; 81: 770-781Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar]) and Safety by number of bleeding complications (according to Bleeding Level (BL) [2Kulik A. Rubens F.D. Wells P.S. et al.Early postoperative anticoagulation after mechanical valve replacement: a systematic review.Ann Thorac Surg. 2006; 81: 770-781Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar]). The coagulation state (aPTT, PT, INR, Plts, fibrinogen, RBC) was evaluated twice daily in both groups and the major complications (thromboembolic or bleeding) were noted. The study is in progress until March 2011. There is a trend towards the more efficacious and safe approach by the administration of LMWH (enoxaparin).

Effect of continuous veno-venous hemodiafiltration on endotoxin-induced acute lung injury of the piglets

To evaluate the effect of continuous veno-venous hemodialysis filtration (CVVHDF) on cardiopulmonary function and clearance of inflammatory mediators in piglets with endotoxin-induced acute lung injury. A randomized controlled trial. An animal laboratory in a tertiary care pediatric center. : Eighteen piglets, weighing 6-8 kg. The piglets were anesthetized, ventilated, and received an intravenous infusion of 150 μg/kg of endotoxin. They were then randomly divided into three groups: control group (n = 6) received Ringer's lactate solution; the heparin group (n = 6) received heparin infusion plus Ringer's lactate solution; and the CVVHDF group (n = 6) received CVVHDF plus heparin infusion and Ringer's lactate solution. Parameters measured simultaneously were: heart rate, mean arterial blood pressure, central venous pressure, pulse contour cardiac index, cardiac function index, left ventricular contractile index, and systemic vascular resistance index; extra vascular lung water index, respiratory rate, dynamic pulmonary compliance, airway resistance, Pao2/Fio2 ratio, serum tumor necrosis factor-α, and soluble tumor necrosis factor receptor. Lung tissue was obtained for pathologic lung injury scoring and wet/dry weight ratio. Endotoxin challenge decreased oxygenation and pulmonary mechanics, suppressed cardiac function, increased extravascular lung water, and elevated serum inflammatory mediators (tumor necrosis factor-α and soluble tumor necrosis factor receptor). After CVVHDF, pulmonary function and oxygenation improved (Pao2/Fio2, 291.5 ± 75.9 vs. 217.2 ± 45.4, respectively, p < .05); arterial blood pressure and cardiac function were restored (pulse contour cardiac index, 3.95 ± 0.52 L/min/m(2) vs. 2.69 ± 0.49 L/min/m(2), respectively, p < .05); extravascular lung water decreased, and serum inflammatory markers also decreased. Lung injury score improved and wet/dry weight ratio decreased. Early CVVHDF has a beneficial effect on acute lung injury in piglets and is associated with a reduction in inflammatory cytokines, improving pulmonary function and hemodynamics and decreasing extravascular lung water and lung damage.

The Right Atrial Thrombus: The Sword of Damocles With Real Risk of Massive Pulmonary Embolism

Cases of 6 patients admitted at the intensive care unit for massive pulmonary embolism are reported. All patients presented with dyspnea, tachypnea, and tachycardia, and 4 were hypotensive and had syncope. Lung ventilation/ perfusion scans revealed perfusion defects in 4 patients. Transthoracic echocardiography (TTE) demonstrated acute cor pulmonale. It also revealed mobile right atrial thrombi in 5 patients, adherent thrombus in the right atrium in 1 patient and patent foramen ovale in 4 patients. Thrombolytic therapy was initiated in 4 patients, and 2 patients received heparin infusion only. Effects of thrombolysis were monitored using bedside TTE during the first 24 hours and in follow-up. The outcome of 4 patients who received thrombolytic therapy was good whereas other 2 patients, who received only heparin, died. Thrombotic mass disappeared 8 to 12 hours after initiation of therapy, and 10 weeks after discharge TTE showed normalized right ventricle dimensions and function in all 4 patients.

Developing a model to determine the effects of adverse drug events in hospital inpatients

A study was conducted to develop a model to identify adverse drug events (ADEs) and quantify their effect on quality and cost in a large tertiary care hospital. The drug-ADE relationship between unfractionated heparin and heparin-induced bleeding was studied for all inpatients receiving heparin infusions at the hospital between January 1 and December 31, 2004. Activated partial thromboplastin time (aPTT) values were used to help determine if the patients received blood products in response to excessive anticoagulation with heparin. The number of aPTT values of > or =150 seconds and the last aPTT value before discharge were evaluated. The key outcome measures were length of stay, cost per admission, and mortality. Of the 1455 admissions to the hospital, 122 patients received blood products before receiving heparin infusion only, 264 received blood products after receiving the drug only, 221 received blood products both before and after, and 848 who received the drug never received blood products. Differences in full cost and length of stay between the group receiving heparin infusion only and the groups receiving both blood products were significant. Differences in mortality between the group only receiving heparin infusion and the groups receiving both heparin infusion and blood products were also significant. Using the model developed to study the effect of heparin-induced bleeding, we found that the cost per patient day was highest for patients receiving blood products after heparin infusion treatment. There was a positive correlation between one or more aPTT values of > or =150 seconds and undesirable patient outcomes.

Use of heparin to lower the incidence of phlebitis induced by anti‐neoplastic agents used in ovarian cancer

To investigate whether heparin infusion with the administration of anti-neoplastic agents in ovarian cancer can reduce the occurrence of phlebitis as a complication of chemotherapy. The subjects were 20 patients with ovarian cancer who developed phlebitis following their first course of anti-cancer chemotherapy. In the subsequent chemotherapy course, 10 patients received heparin infusion of 5000 U, starting 3 h before the administration of anti-neoplastic agents and continuing concomitantly with the agents for 12 h. The other 10 patients (control) were treated with anti-neoplastic agents alone. Only one (10%) of 10 patients who had received heparin developed phlebitis, while eight patients (80%) in the control group did (P=0.005). In the heparin group, there were no toxic effects of heparin observed. The prothrombin time, activated partial thromboplastin time, fibrinogen, and platelet count did not differ before and after the completion of chemotherapy. Concurrent infusion of heparin and anti-neoplastic agents in ovarian cancer is a safe and effective method of preventing phlebitis induced by chemotherapy.

Catheter-Directed Thrombolysis for the Treatment of Acute Iliofemoral Deep Venous Thombosis

Objective: Acute iliofemoral deep venous thrombosis (DVT) is a serious venous thrombotic disorder with potentially morbid post-thrombotic sequelae. The purpose of this report is to present our single-centre evolution of technique and the results of catheter-directed thrombolysis for the treatment of acute iliofemoral DVT, and put it into perspective with current literature. Patients and methods: Between May 1988 and April 2000, 54 patients were treated with catheter-directed thrombolysis for occlusive iliofemoral and vena caval thrombosis. Average age was 45 years (range 17-68 years) and the duration of leg symptoms was 5.2 days (range 2-30 days). Routine vena caval filters were not used, although caval filters were inserted in patients with irregular and non-occlusive vena caval thrombus. Initially, urokinase infusion via a right jugular vein and/or contralateral femoral vein approach was used, delivering a 250000-500000 U bolus followed by continuous infusion of 250000-300000 LVh. Catheter delivery has evolved to an ultrasound-guided popliteal or posterior tibial vein puncture and the use of recombinant tissue plasminogen activator at a bolus dose of 4–8 mg followed by 2–4 mg/h. All patients received heparin infusion at 500-1000 U/h. Results: Fifty-one of the 54 patients had successful catheter positioning. Forty-five (83%) had a successful outcome. Of those that failed, 2 were treated with a known chronic occlusion and in 2 patients plasminogen deficiency was suspected. Two patients had persistent iliac vein lesions which led to early re-thrombosis. Overall, 14 (26%) were asymptomatic, 28 (52%) demonstrated moderate improvement, 6 (11%) showed mild improvement and 6 (11%) had no clinical improvement. Serious complications occurred in 5 patients (9%). Four (7%) required blood transfusion and 1 (2%) required operative evacuation of an inguinal haematoma with repair of the common femoral vein. Eight patients (15%) developed a puncture site haematoma and 1 patient (2%) had a guidewire perforation of the common femoral vein. Conclusions: Catheter-directed thrombolysis is the preferred treatment for symptomatic iliofemoral DVT. Following successful lysis, residual iliac vein lesions should be corrected with balloon angioplasty and stenting if necessary. Considering the current results and those of contemporary series, a successful outcome can be anticipated in 80-85% of patients, with a significant improvement in quality of life when compared with standard anticoagulation.

Anticoagulation for Cardiac Surgery in Patients Receiving Preoperative Heparin: Use of the High-Dose Thrombin Time

Patients receiving heparin infusions have an attenuated activated clotting time (ACT) response to heparin given for cardiopulmonary bypass (CPB). We compared patients receiving preoperative heparin (Group H) to those not receiving heparin (REF group) with respect to ACT, high-dose thrombin time (HiTT), and markers of thrombin generation during CPB. Sixty-five consecutive patients (33 Group H, 32 REF group) undergoing elective CPB were evaluated. ACT and HiTT were measured at multiple time points. Plasma levels of thrombin-antithrombin III complex and fibrin monomer were determined at baseline, during CPB, and after protamine administration. Transfusion requirements and postoperative blood loss were measured and compared. ACT values after heparinization increased less in Group H and were significantly lower than those in the REF group (P < 0.01). HiTT values did not differ significantly between the two groups. Blood loss and transfusion requirements were not significantly different between the two groups. Plasma levels of thrombin-antithrombin III complexes and fibrin monomer also did not differ between groups at any time, despite a lower ACT in Group H after heparinization and during CPB. Our data suggest that thrombin formation and activity are not enhanced in patients receiving heparin therapy, despite a diminished ACT response to heparin. The utility of ACT and the threshold values indicative of adequate anticoagulation for CPB are relatively undefined in patients receiving preoperative heparin. HiTT should be investigated as a safe and accurate monitor of anticoagulation for CPB in patients receiving preoperative heparin therapy. Implications: The diminished activated clotting time response to heparin, in patients receiving preoperative heparin therapy, poses difficulties when attempting to provide adequate anticoagulation for cardiopulmonary bypass. Current data suggest that heparin resistance is not observed when high-dose thrombin time is used to monitor anticoagulation and that a lower activated clotting time value in these patients may be safe.

Anticoagulation for cardiac surgery in patients receiving preoperative heparin: use of the high-dose thrombin time.

Patients receiving heparin infusions have an attenuated activated clotting time (ACT) response to heparin given for cardiopulmonary bypass (CPB). We compared patients receiving preoperative heparin (Group H) to those not receiving heparin (REF group) with respect to ACT, high-dose thrombin time (HiTT), and markers of thrombin generation during CPB. Sixty-five consecutive patients (33 Group H, 32 REF group) undergoing elective CPB were evaluated. ACT and HiTT were measured at multiple time points. Plasma levels of thrombin-antithrombin III complex and fibrin monomer were determined at baseline, during CPB, and after protamine administration. Transfusion requirements and postoperative blood loss were measured and compared. ACT values after heparinization increased less in Group H and were significantly lower than those in the REF group (P < 0.01). HiTT values did not differ significantly between the two groups. Blood loss and transfusion requirements were not significantly different between the two groups. Plasma levels of thrombin-antithrombin III complexes and fibrin monomer also did not differ between groups at any time, despite a lower ACT in Group H after heparinization and during CPB. Our data suggest that thrombin formation and activity are not enhanced in patients receiving heparin therapy, despite a diminished ACT response to heparin. The utility of ACT and the threshold values indicative of adequate anticoagulation for CPB are relatively undefined in patients receiving preoperative heparin. HiTT should be investigated as a safe and accurate monitor of anticoagulation for CPB in patients receiving preoperative heparin therapy. The diminished activated clotting time response to heparin, in patients receiving preoperative heparin therapy, poses difficulties when attempting to provide adequate anticoagulation for cardiopulmonary bypass. Current data suggest that heparin resistance is not observed when high-dose thrombin time is used to monitor anticoagulation and that a lower activated clotting time value in these patients may be safe.

Endemic nosocomial Gram-negative bacteraemias resulting from contamination of intravenous heparin infusions

Following several cases of Gram-negative bacteraemia secondary to intravenous heparin infusion contamination, we retrospectively reviewed nosocomial bacteraemias associated with heparin infusions at our institution. Thirty-one episodes of heparin-infusion related bacteraemia occurred in 30 patients over a 23-month period affecting 2% patients receiving heparin infusions for more than 48 h. Gram-negative bacteria were responsible for all bacteraemias. The care of infusions during clinical use was prospectively surveyed, revealing that approximately 20% of lines and cannulae were left for more than 72 h before replacement, and significant discordance occurred between line replacement and syringe and cannula exchange. We concluded that contamination of the infusions was probably extrinsic and secondary to manipulations of the system during use. Prolonged usage and discordant exchange of infusion components were likely important factors in initial contamination and subsequent bacterial proliferation. The problem resolved following the introduction of a policy for routine and simultaneous replacement of lines and syringes at 24-h intervals and upon cannula exchange.

Changes in plasma antithrombin (heparin cofactor activity) during intravenous heparin therapy: observations in 198 patients with deep venous thrombosis.

Plasma antithrombin (AT) measured as heparin cofactor activity decreased 0.16 +/- 0.13 U/ml (mean +/- SD) in 198 patients who received heparin infusion during 1 wk for deep venous thrombosis (DVT). The decrease was weakly, but significantly correlated to heparin dose (r = 0.15, p = 0.02) and to heparin plasma concentration (r = 0.12, p = 0.05). In patients with subnormal AT at start of heparin treatment, AT decreased less and tended to normalize at the end of heparin infusion, suggesting increased synthetic rate. The decrease in AT was apparently unrelated to the extension or the fate of the thrombus, and also unrelated to other patient and disease characteristics apart from a significantly higher decrease in diabetics. 5 out of 9 patients with AT values below 0.60 U/ml had serious disease, and 1 died from pulmonary embolism (PE) shortly after cessation of heparin (AT 0.22 U/ml). We conclude that the main decrease in AT occurs during the initial 3 d of heparin treatment. If AT stays above 0.70 U/ml after 3 d of treatment, further AT monitoring is hardly indicated.