dalteparin.METHODS: The 162 eligible patients with gynecologic cancers who were treated with either dalteparin (n=60) or rivaroxaban (n=102) were reviewed. The primary outcome was a composite event, which included recurrence or clinically relevant bleeding events during the therapeutic period. Secondary outcomes were recurrence, clinically relevant bleeding events, and mortality.RESULTS: During the therapeutic period, there were no significant differences between the groups in the proportion of composite events, recurrence, or clinically relevant bleeding. Multivariate analysis using the Cox proportional hazards model also showed no significant difference in the number of composite events and clinically relevant bleeding between the groups. In the rivaroxaban group, 44.0% of patients experienced gastrointestinal bleeding and 24.0% experienced urinary tract bleeding. In the dalteparin group, bleeding was most common in the urinary tract (44.4%) and at the injection site (22.2%).CONCLUSION: In this study, although there were no significant differences in effectiveness or safety between the rivaroxaban and dalteparin groups, rivaroxaban use was associated with a higher rate of clinically relevant bleeding than dalteparin. Therefore, caution should be taken when prescribing rivaroxaban for gynecologic cancer-associated VTE and bleeding events should be carefully monitored.]]>
Anticoagulants ; Dalteparin ; Hemorrhage ; Heparin ; Humans ; Mortality ; Multivariate Analysis ; Proportional Hazards Models ; Recurrence ; Rivaroxaban ; Urinary Tract ; Venous Thromboembolism

BACKGROUND/AIMS: Venous thromboembolic events (VTEs) are common events in patients with advanced cancer. We analyzed the clinical characteristics of VTEs in advanced pancreatic and biliary tract cancer to determine the clinical significance, especially in palliative settings. METHODS: Seventy-nine patients with advanced pancreatic cancer or biliary tract cancer who had thromboembolic events were retrospectively reviewed. We investigated the correlation between clinical course and thromboembolic events, and the laboratory risk factors, such as complete blood count profile. RESULTS: The 79 patients consisted of 40 men (50.6%) and 39 women (49.4%) with a median age of 65 years old (range: 41–80). Forty-three patients (54.4%), had thromboembolic events without any symptoms. Pulmonary thromboembolism occurred in only 31 cases (39.2%), and combined thrombosis at more than two sites occurred in 17 cases (21.5%). Of the 51 patients with active chemotherapy, 45 showed progressive disease. The median survival times were 11.9 weeks in all patients, 15.3 weeks in the treatment group, and 3.4 weeks in the palliative group. There was no difference in survival time between patients treated with dalteparin only and those treated with dalteparin combined with thrombolytic intervention. CONCLUSIONS: VTE can be poor prognostic indicator in pancreatic and biliary tract cacner patients, suggestive of progressive disease and a sign of short life expectancy, requiring hospice and terminal care.
Biliary Tract Neoplasms* ; Biliary Tract* ; Biomarkers* ; Blood Cell Count ; Dalteparin ; Drug Therapy ; Female ; Hospices ; Humans ; Life Expectancy ; Male ; Pancreatic Neoplasms ; Pulmonary Embolism ; Retrospective Studies ; Risk Factors ; Terminal Care ; Thrombosis ; Venous Thromboembolism

BACKGROUND: Venous thromboembolism (VTE) is a common and life-threating condition in cancer patients. Low molecular weight heparins (LMWH), such as dalteparin, are recommended in the treatment of VTE. Also, rivaroxaban, an orally administered direct factor Xa inhibitor, was approved for the treatment of VTE. It showed similar efficacy to standard therapy (LMWH or warfarin) and was associated with significantly lower rates of major bleedings. However, in the real world, bleeding has been reported to occur frequently in cancer patient receiving rivaroxaban. The goal of this research was to analyze bleeding risks between rivaroxaban and dalteparin for treatment of VTE in cancer patients. METHODS: Medical records of oncology patients who were treated with rivaroxaban or dalteparin for VTE from July 2012 to June 2014 were retrospectively reviewed. Data collected were as follows: age, sex, weight, height, cancer types and stages, ECOG (eastern cooperative oncology group) PS (performance score), VTE types, concurrently used medications, study drug information (dose and duration of therapy), INR (international normalized ratio), PT (prothrombin time), and platelet counts. Bleeding was classified into major bleedings, clinically relevant non-major bleedings, and minor bleedings. RESULTS: A total of 399 patients were included in the study. Of these patients, 246 were treated with rivaroxaban and 153 with dalteparin. Bleeding rates were significantly higher in the rivaroxaban group than in the dalteparin group (adjusted odds ratio (AOR) 2.09, 95% CI 1.22-3.60) after adjusting for confounders. In addition, rivaroxaban remained independently associated with 1.78-fold (95% CI 1.14-2.76) shorter time to bleeding compared to dalteparin after adjusting other factors known to be associated with poor outcomes. CONCLUSION: This study suggested that rivaroxaban was associated with an increased risk of bleedings in cancer patients.
Dalteparin* ; Factor Xa ; Hemorrhage* ; Heparin, Low-Molecular-Weight ; Humans ; International Normalized Ratio ; Medical Records ; Odds Ratio ; Platelet Count ; Retrospective Studies ; Rivaroxaban* ; Venous Thromboembolism*

Rectus sheath hematoma (RSH) is an uncommon condition caused by hemorrhage into the rectus sheath. RSH is characterized by abdominal pain and an abdominal mass. This condition is associated with old age, childbirth, abdominal surgery, severe coughing, severe sneezing, anticoagulation therapy, and/or coagulation disorders. We report herein a case of RSH and pelvic cavity hematoma that was induced by dalteparin injection in a 77-year-old woman with pulmonary embolism and deep vein thrombosis, and who was successfully treated by conservative management.
Abdominal Pain ; Aged ; Cough ; Dalteparin* ; Female ; General Surgery ; Hematoma* ; Hemorrhage ; Humans ; Parturition ; Pulmonary Embolism ; Sneezing ; Venous Thrombosis

Rectus sheath hematoma (RSH) is an uncommon condition caused by hemorrhage into the rectus sheath. RSH is characterized by abdominal pain and an abdominal mass. This condition is associated with old age, childbirth, abdominal surgery, severe coughing, severe sneezing, anticoagulation therapy, and/or coagulation disorders. We report herein a case of RSH and pelvic cavity hematoma that was induced by dalteparin injection in a 77-year-old woman with pulmonary embolism and deep vein thrombosis, and who was successfully treated by conservative management.
Abdominal Pain ; Aged ; Cough ; Dalteparin* ; Female ; General Surgery ; Hematoma* ; Hemorrhage ; Humans ; Parturition ; Pulmonary Embolism ; Sneezing ; Venous Thrombosis

PURPOSE: To evaluate the effects and problems of venous thromboembolism (VTE) prophylaxis with a reduced dosage and administration period in Korean total knee arthroplasty (TKA) patients. MATERIALS AND METHODS: We analyzed 135 consecutive TKA patients with three different VTE prophylaxis regimens. Group dalteparin-aspirin (DA) injected dalteparin for the first 2 days, followed by taking aspirin for the next 5 days, Group aspirin (A) was on aspirin and Group dalteparin (D) on dalteparin 7 days postoperatively. We evaluated the incidence of VTE and safety among the 3 groups. RESULTS: Symptomatic deep vein thrombosis was detected in 4 cases (Group DA: 2, Group A: 1, Group D: 1). Pulmonary embolism (PE) was found in 1 case in each group with no fatal PE. Although no major bleeding complications were seen, minor bleeding incidents were detected in 14 cases (Group DA: 2, Group A: 1, Group D: 11), which was significant in Group D. No significant differences were observed in perioperative blood loss, effusion in the knee joint, thigh swelling or oozing on the wound area among the groups except thigh bruising, which developed more frequently in group D. CONCLUSION: The reduced dosage and administration period of VTE prophylactic medicine combined with mechanical prophylaxis for Korean TKA patients showed no fatal PE, but some minor bleeding incidents frequently developed with 7 days of dalteparin injections. We need to adjust the dosage and duration of prophylactic medication deliberately for Korean TKA patients, considering prophylaxis effectiveness and bleeding complication risks.
Arthroplasty ; Arthroplasty, Replacement, Knee ; Aspirin ; Dalteparin ; Hemorrhage ; Humans ; Incidence ; Knee ; Knee Joint ; Pulmonary Embolism ; Thigh ; Venous Thromboembolism ; Venous Thrombosis

BACKGROUNDPrimary percutaneous coronary intervention (PCI) is the best treatment of choice for acute ST segment elevation myocardial infarction (STEMI). This study aimed to determine the clinical outcomes of tirofiban combined with the low molecular weight heparin (LMWH), dalteparin, in primary PCI patients with acute STEMI.

METHODSFrom February 2006 to July 2006, a total of 120 patients with STEMI treated with primary PCI were randomised to 2 groups: unfractionated heparin (UFH) with tirofiban (group I: 60 patients, (61.2 ± 9.5) years), and dalteparin with tirofiban (group II: 60 patients, (60.5 ± 10.1) years). Major adverse cardiac events (MACE) during hospitalization and at 4 years after PCI were examined. Bleeding complications during hospitalization were also examined.

RESULTSThere were no significant differences in sex, mean age, risk factors, past history, inflammatory marker, or echocardiography between the 2 groups. In terms of the target vessel and vascular complexity, there were no significant differences between the 2 groups. During the first 7 days, emergent revascularization occurred only in 1 patient (1.7%) in group I. Acute myocardial infarction (AMI) occurred in 1 (1.7%) patient in group I and in 1 (1.7%) in group II. Three (5.0%) patients in group I and 1 (1.7%) in group II died. Total in-hospital MACE during the first 7 days was 4 (6.7%) in group I and 2 (3.3%) in group II. Bleeding complications were observed in 10 patients (16.7%) in group I and in 4 patients (6.7%) in group II, however, the difference was not statistically significant. No significant intracranial bleeding was observed in either group. Four years after PCI, death occurred in 5 (8.3%) patients in group I and in 4 (6.7%) in group II. MACE occurred in 12 (20.0%) patients in group I and in 10 (16.7%) patients in group II.

CONCLUSIONSDalteparin was effective and safe in primary PCI of STEMI patients and combined dalteparin with tirofiban was effective and safe without significant bleeding complications compared with UFH. Although there was no statistically significant difference, LMWH decreased the bleeding complications compared with UFH.

Aged ; Angioplasty, Balloon, Coronary ; Anticoagulants ; therapeutic use ; Dalteparin ; administration & dosage ; therapeutic use ; Female ; Heparin ; administration & dosage ; therapeutic use ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; drug therapy ; therapy ; Treatment Outcome ; Tyrosine ; analogs & derivatives ; therapeutic use

BACKGROUNDPancreatic cancer is one of the most aggressive human malignancies. Lymphangiogenesis plays an important role in lymph node metastasis of many solid tumors. It is well known that low molecular weight heparins (LMWHs) can inhibit cell growth, cell invasion and angiogenesis, which are key processes in tumor progression.

METHODSWe measured the expression of vascular endothelial growth factor C (VEGF-C) in pancreatic cancer cells (PANC-1) using reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. We used an in vitro assay to evaluate the anti-lymphangiogenic effect of an LMWH, Fragmin, on human lymphatic endothelial cell (HLEC) proliferation.

RESULTSFragmin at a low concentration can effectively inhibits HLEC proliferation induced by VEGF-C. VEGF-C secreted by PANC-1 cells stimulated HLEC proliferation. Low concentration LMWH suppressed HLEC proliferation induced by VEGF-C but did not affect proliferation or VEGF-C expression of PANC-1 cells, whereas high concentrations of LMWH inhibited PANC-1 cell proliferation.

CONCLUSIONSThese results suggest that VEGF-C released by cancer cells plays an important role in promoting HLEC proliferation. The LMWH Fragmin has anti-lymphangiogenic effects and may inhibit lymphatic metastasis in pancreatic cancer.

Anticoagulants ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Dalteparin ; pharmacology ; Endothelial Cells ; drug effects ; physiology ; Humans ; Pancreatic Neoplasms ; metabolism ; pathology ; RNA, Messenger ; analysis ; Vascular Endothelial Growth Factor C ; analysis ; genetics ; pharmacology

BACKGROUND AND OBJECTIVES: The therapeutic efficacy of combined platelet glycoprotein IIb/IIIa receptor blocker with low molecular weight heparin (LMWH) is unknown for patients with acute myocardial infarction (AMI) and who underwent percutaneous coronary intervention (PCI). SUBJECTS AND METHODS: A total of 140 patients with AMI and who underwent high-risk PCI was divided into two groups: UFH (group I: 70 patients, 58.7+/-10.5 years of age), and dalteparin (group II: 70 patients, 59.6+/-9.8 years of age). The major adverse cardiac events (MACE) during hospitalization and during the 4 years after PCI were evaluated. RESULTS: The baseline clinical characteristics and angiographic characteristics were not different between the two groups. There were 62.9% totally occluded lesions with thrombus in both groups. Procedural success was achieved for 91.4% of the group I patients and for 90.0% of the group II patients. Any bleeding and hemorrhagic events were not different between the two groups. No significant intracranial bleeding was observed in both groups. The number of in-hospital MACEs was 7 (10.0%) in group I and 4 (5.7%) in group II. Four-year clinical follow-up was performed for 97% of the patients. As a result of the MACEs during the 4 years after PCI, death occurred in 6 (8.6%) patients in group I and in 7 (10.0%) patients in group II. Myocardial infarction occurred in 4 (5.7%) and 4 (5.7%) patients, respectively, target vessel revascularizations were done in 23 (32.9%) and 16 (22.9%) patients, respectively, and coronary artery bypass surgery was done in 3 (4.3%) and 1 (1.4%) patients, respectively. Overall, MACEs occurred in 33 (47.1%) patients of group I and in 26 (35.1%) patients of group II during the 4-year clinical follow-up (p=0.23). CONCLUSION: The long-term clinical outcome of dalteparin combined with abciximab is comparable with that of UFH plus abciximab for the high risk patients with AMI who receive PCI.
Blood Platelets ; Coronary Artery Bypass ; Dalteparin* ; Follow-Up Studies ; Glycoproteins ; Hemorrhage ; Heparin ; Heparin, Low-Molecular-Weight ; Hospitalization ; Humans ; Myocardial Infarction* ; Percutaneous Coronary Intervention* ; Prognosis ; Thrombosis

BACKGROUND AND OBJECTIVES: Heparin is crucial in the treatment of acute coronary syndrome. However, unfractionated heparin has pharmacokinetic, biophysical and biological limitations, but its low molecular weight has been used to overcome these limitations. The aim of this study was to find the optimal dose of dalteparin in Koreans. Instead, significant rises in the levels of aminotransferase were found in the liver during the study. SUBJECTS AND METHODS: A clinical investigation was conducted, at Seoul National University Hospital, between December 2000 and February 2001. The anti-Xa activity was checked just before the first, and 4 hours after, the second and ninth doses of dalteparin. Liver function tests were obtained on the first and follow-up day (day 6 or 7). RESULTS: Of the 17 patients who completed 10 doses of dalteparin, 13 showed significant rises in the levels of liver aminotransferase. In 5 cases, the levels of aminotransferase rose to 3 times, and in one case, to over 10 times the upper normal limit. All of the patients were asymptomatic, and the levels showed a decline one or two days later. The follow-up aminotransferase level was normalized in 8 out of 11 patients whose liver function tests were followed up. CONCLUSION: Previous studies have shown that 120 IU/kg of dalteparin was the optimal dose in Western countries. Whether this is the optimal dose for Koreans has not been proven, and there have been no studies to elucidate its adverse effects (e.g. hepatotoxicity) in Koreans. Therefore, large scale, randomized trials may be warranted to determine the pharmacodynamics and kinetics of dalteparin in Koreans.
Acute Coronary Syndrome* ; Coronary Disease ; Dalteparin* ; Drug-Related Side Effects and Adverse Reactions* ; Follow-Up Studies ; Heparin ; Heparin, Low-Molecular-Weight ; Humans ; Kinetics ; Liver ; Liver Function Tests ; Molecular Weight ; Seoul