Using Unfractionated Heparin Research Articles

Incidence of Symptomatic Venous Thromboembolisms in Stroke Patients.

Venous thromboembolism (VTE) is a common but preventable complication observed in critically ill patients. Deep vein thrombosis (DVT) is the most common type of VTE, with clinical significance based on location and symptoms. There is an increased incidence of DVT and pulmonary embolism (PE) in ischemic stroke patients using unfractionated heparin (UFH) for VTE prophylaxis compared with those using enoxaparin. However, UFH is still used in some patients due to its perceived safety, despite conflicting literature suggesting that enoxaparin may have a protective effect. The current study aimed to determine the incidence of VTEs in patients with acute ischemic strokes on UFH versus enoxaparin for VTE prophylaxis, subclassifying the VTEs depending on their location and symptoms. It also aimed to examine the safety profile of both drugs. A total of 909 patients admitted to the Neuro-ICU with the diagnosis of acute ischemic stroke were identified, and 634 patients were enrolled in the study-170 in the enoxaparin group and 464 in the UFH group-after applying the exclusion criteria. Nineteen patients in the UFH group (4.1%) and 3 patients in the enoxaparin group (1.8%) had a VTE. The incidence of DVT in the UFH group was 12 (2.6%), all of which were symptomatic, compared with 3 (1.8%) in the enoxaparin group, wherein one case was symptomatic. Nine patients (1.9%) in the UFH group developed a PE during the study period, and all of them were symptomatic. No patients in the enoxaparin group developed PE. No statistically significant difference was found between both groups. However, 18 patients in the UFH group (3.9%) experienced intracranial hemorrhage compared with none in the enoxaparin group, and this difference was statistically significant. Enoxaparin was found to be as effective as and potentially safer than UFH when used for VTE prophylaxis in stroke patients.

Experience in the treatment of patients with pulmonary embolism using apixaban and ultrasound inhalations of unfractionated heparin

Introduction. Pulmonary embolism (PE) is one of the leading causes of death even in hospitalized patients. The standard treatment results are disappointing. Since 2004, we have tested a new method for the treatment of hemodynamically insignificant PE (own patent RU2224525C1) by using unfractionated heparin (UFH) in ultrasound inhalations with a nebulizer, since 2014 – in combination with apixaban. Aim. To improve the treatment of PE. Materials and methods. The hospital mortality rate of 713 patients of the cardiac intensive care unit with hemodynamically insignificant PE (from January 1, 2002 to December 31, 2017) was studied. Since 2004, patients have received ultrasound UFH (5000 units twice a day). Since 2014, nebulased UFH has been supplemented with the use of apixaban (10 mg twice a day for 7 days and 5 mg twice a day thereafter). Results and discussion. There is a distinct tendency to the PE hospital mortality decrease, coinciding with the nebulased UFH use (illustrated by a diagram). Neither the systemic bleeding nor the heparin-induced thrombocytopenia were observed. Clinical cases show first reduction of perfusion disorders are seeing scintigraphicaly in 7 days. Unlike LMWH UFH is recommended in severe kidney damage and obesity, thus ultrasound technique has advantages in such patients. Conclusions. Nebulased UFH is an available, simple, safe and effective in treatmtnt of hemodynamically insignificant PE, especially with the use of apixaban. A real improvement in lung perfusion takes 1 week, as shown scintigraphically.

A novel anticoagulation treatment protocol using unfractionated heparin for coronavirus disease 2019 patients in Japan, 2022.

Hypercoagulability, which can be induced by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays an important role in the pathogenesis of coronavirus disease 2019 (COVID-19). Although anticoagulation therapy is expected to decrease the incidence of thrombosis and mortality in COVID-19 patients, the optimal use of anticoagulation therapy has not been established, especially using unfractionated heparin (UFH). Herein, we suggest a new anticoagulation treatment protocol for the use of UFH in Japanese COVID-19 patients. This protocol considers the safety regarding UFH usage, to lower major bleeding events, and reflects the latest evidence and the current situation regarding anticoagulation therapy in Japan.

Cost-Effective Treatment for Deep-Vein Thrombosis in Rural Tertiary Care Hospital

Objective: The aim was to compare the cost of treating deep-vein thrombosis (DVT) using unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) among patients in rural tertiary care hospitals. Materials and Methods: A retrospective study was conducted at a Rural Tertiary Care Hospital from April 2017 to April 2019. Fifty-four patients who had symptoms of swelling of the unilateral or bilateral lower limb with or without pain were subjected to Padua prediction score and Doppler study of both lower limbs. Confirmed cases of DVT were treated with UFH or LMWH. The cost of these two treatments was compared. Results: The mean cost of heparin was 2493.33 ± 1406.27 Indian rupee (INR) in the study population. The mean cost of LMWH was 13,520 ± 9806.35 (INR) in the study population. There was a statistically significant difference between UFH and LMWH with regard to the cost of drugs (INR) for treatment (P < 0.001), which indicated that UFH was a cost-effective treatment compared to LMWH. Conclusions: The study's findings prove that UFH is a cost-effective treatment compared to LMWH in Rural Tertiary Care Hospitals for DVT. Based on the patient's affordability, the treatment decision can be made.

The Anti-Factor XII Antibody AB052 Is Antithrombotic without Hemostatic Impairment in a Primate Model of Extracorporeal Membrane Oxygenation

In standard clinical practice, accumulation of contact initiated thrombi within extracorporeal membrane oxygenation (ECMO) systems is generally controlled by systemic anticoagulation using unfractionated heparin (UFH). However, the efficacy of UFH is limited by dose-restricting hemorrhagic safety concerns, and thus oxygenator replacement and thrombo-embolic complications are frequent during sustained oxygenation. Since coagulation factor XII (FXII) is essential in contact initiated blood coagulation, but has no known contribution to hemostasis, we sought to further explore the roles of FXII in hemostasis and thrombosis in a baboon ECMO model utilizing the anti-FXII monoclonal antibody AB052. In vitro, using human plasma, AB052 is 30-times more potent at inhibiting FXII activity than corn trypsin inhibitor, as assessed by a doubling of the activated partial thromboplastin time (aPTT). In baboon ECMO experiments, a Terumo CAPIOX RX5 baby oxygenator was inserted into a chronic arteriovenous shunt with blood flow regulated to 100 ml/min. An intravenous bolus of AB052 (5 mg/kg), UFH (20 U/kg), or the combination was given between 15 and 30 min prior to each experiment. ACT times immediately prior to experiments were 382±9 sec (AB052), 271±11 sec (UFH), 473±26 sec (combination), compared to pre-dosing values (207±8 sec). Control experiments without any anticoagulation were also performed, and resulted in high platelet accumulation rates of 1.72x109 min-1 and total deposition of 72±9x109 platelets (n=2), with one device completely occluding during the 60 min study period. Heparinization resulted in a total deposition of 52±11x109 platelets and an accumulation rate of 1.20x109 platelets min-1 over 60 min (n=4). AB052 alone (n=3) or in combination with UFH (n=3) significantly reduced total platelet deposition (28±3x109 and 24±5x109, respectively) as well as the platelet accumulation rates (0.60x109 min-1 and 0.56x109 min-1, respectively) compared to heparinization alone. Fibrin content within the ECMO device was also significantly lower in the AB052 treated groups when compared with either UFH alone or non-anticoagulated controls (45±22 mg (UFH), 15±3 mg (AB052), 15±9 mg (AB052 plus UFH), and 60±11 mg (non-anticoagulated). Furthermore, measurement of systemic thrombin anti-thrombin (TAT) complexes at the end of the experiments showed a marked 63% decrease in TAT levels in the AB052 treatment group and a 67% decrease in the combination treatment group compared to heparinization alone. Importantly, template bleeding time tests (Surgicutt) that were used to assess hemostasis impairment during the experiments showed no prolongation associated with AB052 administration. In summary, our data suggest that selective inhibition of FXII activation may be effective and safe when used alone or in combination with UFH for pharmacological thromboprophylaxis during contact initiated thrombosis. DisclosuresWallisch:Aronora, Inc: Employment, Equity Ownership. Tucker:Aronora, Inc: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Lorentz:Aronora, Inc: Employment, Equity Ownership. Carris:Aronora, Inc: Employment, Equity Ownership. Gruber:Aronora, Inc: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees.

Cardiac Transplantation after Heparin Induced Thrombocytopenia: A Patient-Level Meta-Analysis

Purpose Heparin induced thrombocytopenia (HIT) presents a unique challenge in patients requiring orthotopic heart transplantation (OHT). However, data on management and outcomes are lacking. We sought to pool the existing evidence in a systematic review and meta-analysis. Methods Electronic search was performed to identify all relevant studies published on OHT in patients with HIT. Overall, 20 were selected comprising 30 patients with HIT who required OHT. Patient-level data were extracted for statistical analysis. Results Median patient age was 51 [IQR 41.8, 55.0] years old, with 73.3% (22/30) male. All patients had a clinical diagnosis of HIT, and PF4-Heparin antibodies were positive in 86.7% (26/30). Overall, 67% (20/30) required mechanical circulatory support preoperatively, including temporary support in 53% (16/30), and durable assist devices in 30% (9/30). Durable devices consisted of pulsatile 78% (7/9) and continuous-flow 22% (2/9) LVADs. Median duration from HIT to OHT was 21 [IQR 12, 61] days, and from MCS to OHT 28 [IQR 18, 66] days. Of 30 patients, 17 (56.7%) underwent OHT using unfractionated heparin (UFH), while 13 used other agents. In non-UFH patients, agents included 54% (7/13) Bivalirudin, 15% (2/13) Danaparoid, and 8% (1/13) each of enoxaparin, Argatroban or Lepirudin. Intraoperatively, non-UFH patients required more antifibrinolytics [54% (7/13) vs. 5.9% (5/17), p=0.01] and clotting factors [69.2% (9/13) vs. 11.8% (2/17) p=0.004]. Peri-operative thrombosis occurred in 53.8% (7/13) of non-UFH patients and 0% (0/17) of UFH patients (p=0.002). More non-UFH patients developed serious perioperative bleeding [62% (8/13) vs. 18% (3/17), p=0.04] and required post-operative transfusions [54% (7/13) vs. 0% (0/16), p=0.003]. Postoperative anticoagulation was utilized in 68.8% (11/16) of UFH patients and 7.7% (1/13) of non-UFH patients (p=0.003), with no difference in warfarin use [6.2% (1/16) vs.7.7% (1/13) respectively, p=1.00]. Median follow-up time was 20 [IQR 5, 24] months for UFH patients and 12 [IQR 10, 25] months for non-UFH patients (p=0.46). At the time of last follow-up, 82% (14/17) of UFH and 85% (11/13) of non-UFH patients were alive (p=1). Conclusion Non-UFH anticoagulation during OHT was associated with thrombotic and bleeding complications compared to UFH. However, there was no significant difference in overall survival.

How to Safely Prevent Venous Thromboembolism in Severe Trauma Patients.

Venous thromboembolism (VTE) is a life-threatening complication after trauma. Several studies have reported VTE prophylaxis using low-molecular-weight heparin; however, there is no consensus for prophylaxis after trauma. This study aimed to assess the efficacy and safety of our new anticoagulation therapy protocol using unfractionated heparin (UFH) plus intermittent pneumatic compression (IPC) to prevent post-traumatic VTE in high-risk trauma patients.This study enrolled 70 trauma patients who were admitted to the emergency medical center of Nagasaki University Hospital and had Risk Assessment Profile (RAP) scores ≥ 5. After stopping bleeding at the trauma site, all patients received intravenous UFH (10,000 U/day) plus IPC, which was continued for 14 days or until the patients could walk. On days 7 and 14, all patients underwent lower extremity sonography for deep-vein thrombosis screening. VTE incidences between patients with the above intervention and historical controls with IPC alone were compared.No significant differences in age, sex, and the RAP score were observed between the 105 controls and intervention patients. VTE occurrence was fewer in patients with the intervention (14.3%) than in the controls (28.6%; P = 0.029). No hemorrhagic complications occurred after UFH administration. Multivariable logistic analysis revealed a significant association between the intervention and low incidence of VTE (odds ratio: 0.390; 95% confidence interval: 0.163-0.913; P = 0.030).Routine UFH administration with IPC may prevent post-traumatic VTE without adverse events.

COMPARISON OF BRIDGING ANTICOAGULATION AGENTS IN LEFT VENTRICULAR ASSIST DEVICES

Current guidelines lack comparative evidence and do not distinguish between anticoagulation agents (such as enoxaparin) in left ventricular assist devices (LVADs). Our study sought to evaluate the safety of bridging anticoagulation in LVAD patients using unfractionated heparin (UFH) compared with

Bivalirudin as an adjunctive anticoagulant to heparin in the treatment of heparin resistance during cardiopulmonary bypass-assisted cardiac surgery.

Heparin resistance (unresponsiveness to heparin) is characterized by the inability to reach acceptable activated clotting time values following a calculated dose of heparin. Up to 20% of the patients undergoing cardiothoracic surgery with cardiopulmonary bypass using unfractionated heparin (UFH) for anticoagulation experience heparin resistance. Although UFH has been the "gold standard" for anticoagulation, it is not without its limitations. It is contraindicated in patients with confirmed heparin-induced thrombocytopenia (HIT) and heparin or protamine allergy. The safety and efficacy of the use of the direct thrombin inhibitor bivalirudin for anticoagulation during cardiac surgery has been reported. However, there have been no reports on the treatment of heparin resistance with bivalirudin during CPB. In this review, we report the favorable outcome of our single-center experience with the alternative use of bivalirudin in the management of anticoagulation of heparin unresponsive patients undergoing coronary artery bypass graft surgery.

Effect of Extracorporeal Unfractionated Heparin on Hematological and Electrolyte Markers in Hemodialyzed Patients

End-Stage renal disease is the final stage of chronic kidney disease (CKD), which can be managed by hemodialysis (HD), peritoneal dialysis, or renal transplantation. This study was conducted to investigate the changes in hematological and electrolyte markers that occur pre and post hemodialysis using unfractionated heparin (UFH) to prevent extracorporeal circuit clotting. Fifty patients with end stage renal failure (22 males, 28 females), aged between 15-78 years, maintained on long-term hemodialysis at the hemodialysis center in Sulaimani city during the period between February 20 th 2013 and July 15 th 2013 were enrolled in the present study. All patients provided written informed consent. The results of the hematological and electrolyte parameters measured pre and post hemodialysis were not significantly changed. No significant reduction in Hb level has been reported after dialysis compared to the pre-dialysis level. There were non-significant change in PTT, PT, and platelets count values in post-dialysis, which were not affected by the extracorporeal UFH. Although serum calcium and sodium levels were not significantly affected, serum potassium was significantly decreased in post hemodialysis states compared with pre-dialysis levels. This study revealed that extracorporeal use of UFH did not affect the hematological and electrolyte parameters post-dialysis in chronic renal failure patients maintained on hemodialysis. Only serum potassium was significantly decreased in post hemodialysis states, but still predictable fluctuations may limit the benefits of the procedure.

Abstract 497: Clinical Significance of Heparin Induced Thrombocytopenic Thrombotic Syndrome with Initiation of Anti-heparin Antibodies Negative: A Case Report and Literature Review

Introduction Heparin induced thrombocytopenia thrombosis Syndrome has a high mortality and morbidity in cardiac surgical patients in spite of early diagnosis and management. We present a case with multiple acute deep venous thrombosis (DVT) after using unfractionated heparin (UFH) during coronary artery bypass graft (CABG) with initiation of HIT antibodies negative. Case presentation A 70-year-old male complained of left leg pain 2 days after CABG for an acute ST-elevation myocardial infarction. Patient was treated with UFH intravenous during CABG. Platelet count was 78 x 109/L that was 130 x 109/L before the procedure. Anti-heparin antibodies IgM/IgG were negative. Venous Doppler ultrasound showed an acute deep venous thrombosis (DVT) in the left peroneal vein. However, after the patient was treated with Coumadin anticoagulation for 7 days with INR in therapeutic range (2-3), the patient presented for right low extremity pain. Platelet count was 40 x 109/L. Anti-heparin antibodies IgM and IgG were repeatedly positive. Venous Doppler ultrasound showed multiple bilateral lower extremities acute DVTs. Patient had thrombectomy and continued with coumadin anticoagulation at INR in therapeutic range for 3 months. Discussion HITTS is an immune-mediated drug reaction that occurs more frequently in patients undergoing cardiovascular surgery. Thrombosis caused by the HIT/T syndrome is most commonly venous thromboembolism. Thrombosis is arterial in about 20% of cases, including acute limb ischemia, myocardial infarction, or stroke. Previous clinical data has shown that about 40% of high titer-negative HIT antibodies were associated with a positive result in repeated testing several days later, which is the same as our presentation. The mortality and morbidity rates of HITTS are approximately 30% and 60%, respectively, and an additional ~10% of patients require amputations or suffer other major morbidity. However, with early recognition and intervention, mortality can be reduced from >30 to <10%. Obviously, repeated testing to identify patients who have HIT despite a negative initial HIT test in several days is greatly recommended. Diagnosis is essentially clinical and negative results from laboratory assays do not exclude the diagnosis.

Perioperative Heparin Bridging in Patients Receiving Oral Anticoagulation: Meta-Analysis of Bleeding and Thromboembolic Rates

Abstract 545 Background:Periprocedural bridging using unfractionated heparin (UFH) or low molecular weight heparin (LMWH) in patients receiving chronic oral anticoagulation (OAC) is often utilized with the view to reduce the risk of thromboembolic (TE) events. Optimal perioperative anticoagulant methods have not been established. Methods: Systematic review and meta-analysis of published English-language studies from 2001 to 2010 examining bleeding and TE events in patients receiving bridging therapy during temporary OAC interruption for elective procedures. Results: A search of MEDLINE, EMBASE and Cochrane Collaboration databases yielded 32 studies on 6760 bridged patients. Studies were reviewed by 2 independent data collectors (k=0.869). Study quality was generally poor with risk of bias. Thirty-one studies were observational with 1 randomized controlled trial. Low TE risk and/or non-OAC patient groups were used for comparison in 12 observational studies. Major (22/32, 68.8%) and non-major (27/32, 84.4%) procedures were represented. TE events occurred in 67 of 6760 bridged (0.87%; 95% CI 0.40%–1.35%) and 29 of 4897 non-bridged (0.77%; 95% CI 0.24%–1.30%) patients. Using a random effects model, there was no difference in the risk of TE events in bridged versus non-bridged patients (OR 1.02, 95% CI 0.53–1.95). Bridged patients had a significantly increased risk of overall bleeding (OR 5.47, 95% CI 3.89–7.70) and major bleeding (OR 3.43, 95% CI 1.13–10.4) compared to non-bridged patients. There was no difference in TE events (OR 2.44, 95% CI 0.34–17.4) or overall bleeding (OR 2.40 95% CI 0.72–8.05) in patients receiving full versus intermediate/low dose LMWH. Summary: Patients receiving heparin bridging during OAC interruption appear to be at increased risk of bleeding and similar risk of TE events compared to non-bridged patients. Studies of high methodologic quality are needed to develop an optimal anticoagulation strategy and inform clinical decision-making. Disclosures:Lim:Leo Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Consultancy; Pfizer: Honoraria. Kaatz:Boehringer-Ingelheim: Consultancy, Research Funding, Speakers Bureau; Bristol Myer Squibb: Consultancy, Research Funding; Bayer: Research Funding; National Institute of Health: Research Funding; Canadian Institute of Health Research: Research Funding; Pfizer: Consultancy; Johnson and Johnson: Consultancy; Ortho-McNeil: Consultancy; GlaxoSmithKline: Speakers Bureau; AC Forum: Membership on an entity's Board of Directors or advisory committees; National Certification Board of Anticoagulation Providers: Membership on an entity's Board of Directors or advisory committees; National Blood Clot Alliance: Membership on an entity's Board of Directors or advisory committees.

Does Prophylactic Subcutaneous Heparin Increase the Risk of Wound Infection after Colorectal Surgery?

Chemical prophylaxis using unfractionated heparin (UH) and low-molecular weight heparin is used in surgical patients to prevent venous thromboembolism. There is some evidence that prophylactic doses of heparin may increase the rate of surgical site infection (SSI) after elective orthopedic procedures. Little is known regarding the effect of heparin on SSI after colorectal procedures. We performed this study to study the effect of prophylactic unfractionated heparin on the rate of SSI after colorectal procedures. We did a retrospective analysis of 155 consecutive cases of patients of a single colorectal surgeon who underwent colorectal resection. Subcutaneous unfractionated heparin was given to 52 patients (29%). The rate of SSI in the group that received UH was 33 per cent versus 28 per cent in the group that did not receive UH (P = 0.31). There was also no significant effect of prophylactic heparin on SSI noted among any patient subgroup. The use of prophylactic unfractionated heparin after colorectal procedures does not seem to increase the rate of surgical site infection.

The Effect of Medication on the Risk of Post-ERCP Pancreatitis

Purpose: Pancreatitis remains the most common and significant complication of ERCP. Previous observational studies have suggested a protective effect from various medications. We set out to determine the risk of post-ERCP pancreatitis in patients using unfractionated heparin (UFH), low molecular weight heparin (LMWH), non-steroidal anti-inflammatory drugs (NSAIDs), nitrates and statins. Methods: A database of all inpatient ERCPs performed by one therapeutic endoscopist that has been compiled prospectively was retrospectively reviewed from July 2000 to November 2008. The endoscopic and patient outcomes had been recorded prospectively. Medication exposure was determined by reviewing the electronic file for each patient. Exposure to the medications of interest within one week prior to the procedure was recorded. The rates of pancreatitis were compared between the different groups using chi-squared analysis. Logistic regression analysis was used to identify risk factors for the outcome of pancreatitis. Each medication was considered separately. When a patient was on more than one medication of interest, the interaction of the medications was analysed. We used SPSS (version 17.0) to perform the statistical analysis. A p-value of <0.05 was considered statistically significant. Results: A total of 494 patients were included in this study. The mean age of the patients was 59 +- 19.75. 46.8% were male. The overall rate of pancreatitis was 5.9%; 5.2% in males and 6.5% in females. One hundred and forty four patients received UFH, 13 received LMWH, 24 received NSAIDs, 26 received nitrates and 46 received statins within one week of the procedure. In univariate evidence, pancreatic filling with contrast medium was associated with an increased rate of pancreatitis: 2.4% in patients with no pancreatic filling and 11.2% in patients with any degree of filling, p<0.001. Logistic regression found age and pancreatic filling to be risk factors for the occurrence of pancreatitis (OR=0.98; p=0.041 and OR=5.12; p<0.001, respectively). UHF and NSAIDs usage showed nonsignificant trends towards reduction in the rate of pancreatitis OR=0.685; p=0.38 and OR=0.580; p=0.35, respectively. LMWH, nitrates, statins and the different combinations of the above medications did not show any significant effect. Conclusion: Although there was a non-significant trend toward benefit in patients exposed to unfractionated heparin and NSAIDs, these results suggest that the medications of interest are not effective for prevention of pancreatitis post-ERCP.

Theraputic anticoagulation in the trauma patient: Is it safe?

Trauma patients who require therapeutic anticoagulation pose a difficult treatment problem. The purpose of this study was to determine: (1) the incidence of complications using therapeutic anticoagulation in trauma patients, and (2) if any patient factors are associated with these complications. An 18-month retrospective review was performed on trauma patients >or= 15 years old who received therapeutic anticoagulation using unfractionated heparin (UH) and/or fractionated heparin (FH). Forty different pre-treatment and treatment patient characteristics were recorded. Complications of anticoagulation were documented and defined as any unanticipated discontinuation of the anticoagulant for bleeding or other adverse events. One-hundred-fourteen trauma patients were initiated on therapeutic anticoagulation. The most common indication for anticoagulation was deep venous thrombosis (46%). Twenty-four patients (21%) had at least 1 anticoagulation complication. The most common complication was a sudden drop in hemoglobin concentration requiring blood transfusion (11 patients). Five patients died (4%), 3 of whom had significant hemorrhage attributed to anticoagulation. Bivariate followed by logistic regression analysis identified chronic obstructive pulmonary disease (OR = 9.2, 95%CI = 1.5-54.7), UH use (OR = 3.8, 95%CI = 1.1-13.0), and lower initial platelet count (OR = 1.004, 95%CI = 1.000-1.008) as being associated with complications. Patients receiving UH vs. FH differed in several characteristics including laboratory values and anticoagulation indications. Trauma patients have a significant complication rate related to anticoagulation therapy, and predicting which patients will develop a complication remains unclear. Prospective studies are needed to determine which treatment regimen, if any, is appropriate to safely anticoagulate this high risk population.

Effects of External Electrical Stimulation on Laser-Beam-Induced Experimental Thrombosis

External electrical stimulation (EES) has demonstrated venous antithrombotic properties. The aim of this investigation was to study its antithrombotic properties using unfractionated heparin (UFH) as a reference in arterial and venous mesenteric microvessels. For this purpose a rat model of laser-beam-induced thrombosis was used. Four groups of rats were investigated (n = 7): control, UFH (5 mg /kg), UFH (2.5 mg/kg) and electrical stimulation [e-vascular®, E = 10, alternate polarity, in two protocols: (i) 30 min before and during thrombosis induction and (ii) only 30 min before thrombosis induction as preventive stimulation]. This effect was tested in arterial and venous microvessels in the four groups using the continuous protocol and only in arterial microvessels using the preventive protocol. Three parameters were studied: the number of laser beams needed to induce platelet thrombus formation, the number of emboli and the duration of embolization. Induced hemorrhagic time (IHT), platelet aggregation induced by ADP and coagulation tests (activated partial thromboplastin time, aPTT, prothrombin time, pTT, and fibrinogen level) were also determined. Continuous electrical stimulation decreased the number of emboli and the duration of embolization both in arterioles and in venules. It also significantly reduced the amplitude and velocity of the ex vivo platelet aggregation induced by ADP. Contrary to UFH, neither aPTT nor pTT were affected in platelet-poor plasma collected after the induction of thrombosis by laser beam, nor did it modify IHT. Preventive electrical stimulation produced similar results with fewer effects on induced venous thrombosis. These data suggest that EES has a potent antithrombotic effect on arterial and venous thrombosis without any hemorrhagic adverse effects, making it a very promising tool in the prevention and treatment of venous and arterial thromboembolic complications.

Effect of Low Molecular Weight Heparin on Bone Metabolism and Hyperlipidemia in Patients on Maintenance Hemodialysis

The effect of low molecular weight heparin (LMWH) on serum lipid profile in hemodialysis remains controversial and its effect on bone metabolism has not been studied. A crossover study was conducted in 40 patients on stable hemodialysis using unfractionated heparin (UFH) for more than 24 months. These patients were then treated with a LMWH (nadroparin-Ca) for 8 months during hemodialysis and subsequently switched back to UFH for 12 months. Serum lipid profile, biochemical markers for bone metabolism, and bone densitometry (BMD) were monitored at four-month intervals while all medications remained unchanged. Cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), lipoprotein(a) (Lp(a)), apolipoprotein B (Apo B) were raised in 35%, 29%, 12%, 24% and 24% of patients respectively. High-density lipoprotein-cholesterol (HDL-C) and apolipoprotein A1 (Apo A-1) were reduced in 47% and 9% of patients. Bone-specific alkaline phosphatase (BALP) and intact osteocalcin (OSC), both reflecting osteoblastic activity, were raised in 65% and 94% of patients. Tartrate-resistant acid phosphatase (TRACP) reflecting osteoclastic activity and parathyroid hormone (PTH) were elevated in 35% and 88% of patients. Following LMWH treatment, TC, Tg, Lp(a) and Apo B were reduced by 7%, 30%, 21% and 10% respectively (p<0.05 or <0.01) while Apo A-1 were raised by 7% (p<0.01). Simultaneously, TRACP was reduced by 13% (p<0.05). These biochemical changes were detected soon after 4 months of LMWH administration. Although BMD values in our patients were lower than those of age-matched normal subjects, significant changes were not observed with LMWH treatment. After switching back to UFH for hemodialysis, these biochemical indices reverted to previous values during UFH treatment with a significant higher level in TC and Apo B while serum Apo A-1 remained elevated. Our study suggests LMWH may partially alleviate hyperlipidemia and, perhaps, osteoporosis associated with UFH administration in patients on maintenance hemodialysis.

Low-dose danaparoid sodium catheter flushes in an intensive care infant suffering from heparin-induced thrombocytopenia.

OBJECTIVE: Despite controversy about whether peripheral and central venous catheters should be locked with heparin to prevent catheter-associated clotting, the practice is widespread. We describe a severe side effect of the practice: a case of heparin-induced thrombocytopenia occurring with catheter flushes using unfractionated heparin (UFH) in a 10-month-old boy successfully treated with danaparoid. Patient: A preterm-born patient (33 wks gestational age, birth weight 1200 g) suffering from VACTERL syndrome was repeatedly treated with UFH in the context of several invasive procedures. On day 310 of age, a central venous catheter was inserted to provide total parenteral nutrition. The central catheter was flushed with a continuous infusion of UFH at 100 U/day, and a decrease in platelet counts from 150,000/&mgr;L (on day 310 of age) to 45,000/&mgr;L (on day 319 of age) was observed. Clinically suspected heparin-induced thrombocytopenia (HIT) was serologically confirmed by demonstrating HIT antibodies with platelet factor 4/heparin complex specificity. Main Result: Catheter flushing was switched to low-dose danaparoid sodium as a continuous infusion at 15 anti-factor Xa units per day. Two days later, platelet counts recovered. Neither catheter thrombosis nor systemic thromboembolic complications occurred during the follow up period. CONCLUSIONS: Even continuous infusion of low-dose heparin to provide patency of central venous port catheters may trigger the primary immune response of HIT. Low-dose danaparoid sodium, a heparinoid, can prevent in-catheter thrombus formation and allows normalization of platelet counts in acute HIT.

The Anticoagulant and Hemorrhagic Effects of DHG, a New Depolymerized Holothurian Glycosaminoglycan, on Experimental Hemodialysis in Dogs

We studied the use of depolymerized holothurian glycosaminoglycan (DHG) as an anticoagulant in experimental beagle-dog hemodialysis using a hollow-fiber dialyzer compared to that using unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and nafamostat mesilate (FUT). Effectiveness was based on 5 h hemodialysis and no marked clot deposition in the extracorporeal circuit. At effective doses, UFH and LMWH significantly prolonged template bleeding time, in sharp contrast to FUT and DHG, which scarcely prolonged bleeding time during hemodialysis. DHG prolonged activated partial thromboplastin time (APTT) about 6 times that of normal plasma and prolonged thrombin clotting time (TCT) markedly; FUT showed marked APTT prolongation but hardly prolonged TCT in the hemodialysis circuit at the effective dose. The anticoagulant profile of DHG thus differs completely from that of FUT. These results suggest that DHG may be useful as anticoagulant for hemodialysis with low hemorrhagic risk.