warfarin and Neutropenia

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Antilymphocyte Serum; Cerebrovascular Disorders; Child; Child, Preschool; Cyclosporine; Erythrocyte Transfusion; Female; Hemoglobinuria, Paroxysmal; Hemolysis; Heparin; Humans; Infant; Infant, Newborn; L-Lactate Dehydrogenase; Male; Middle Aged; Myocardial Infarction; Neutropenia; Neutrophils; Registries; Retrospective Studies; Thromboembolism; Warfarin

The role of prophylactic vena cava filters (VCF) in patients with cancer is debated. Although VCF are often placed in patients with cancer after recurrence of venous thromboembolic events (VTE), identification of this subset of patients has not been well-defined. This study was undertaken to assess factors associated with increased risk for recurrent VTE.. All patients with a history of thromboembolism or malignant disease and who required a VCF because of failure of or contraindication to anticoagulation therapy were abstracted from the Michigan Filter Registry. Univariate analysis of potential risk factors for recurrent VTE and logistic regression models were used to identify associations between these variables and recurrent VTE.. Ninety-nine patients (49 men, 50 women) with a mean age of 58 years were included in the study. New metastases occurred in 55% of patients, and 12% of patients had a history of VTE before cancer diagnosis. Corticosteroid agents were used during therapy in 48% of patients. Acute VTE was present in 52% of patients at cancer diagnosis, and in 34% of patients VTE was associated with new metastases. Recurrent VTE occurred in 40% of patients, and significant risk factors included presence of new metastases (odds ratio [OR], 3.3; 95% confidence interval [CI], 1.16-9.09; P =.02) and history of VTE (OR, 10.6; CI, 1.98-57.2; P =.006). Whereas a single episode of neutropenia did not reach significance (OR, 1.1; CI, 0.97-1.35; P =.11), multiple neutropenic episodes were significantly associated with recurrent VTE (P =.04). Smoking, hormone replacement therapy, decreased mobility, post-surgical state, and obesity were not independently associated with increased risk. Mean survival in this series was 30 months, and was significantly worse in patients with VTE at cancer diagnosis and with inability to tolerate anticoagulant therapy in conjunction with VCF.. Patients with malignant disease may be at increased risk for recurrent VTE after development of new metastases or multiple episodes of neutropenia, especially those patients with a history of VTE. VCF may be a reasonable alternative to long-term anticoagulation therapy in this subgroup of patients at high risk patients, provided their quality of life is reasonable.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Blood Vessel Prosthesis Implantation; Cause of Death; Female; Heparin; Humans; Incidence; Male; Michigan; Middle Aged; Neoplasms; Neutropenia; Partial Thromboplastin Time; Recurrence; Risk Factors; Survival Analysis; Thromboembolism; Time Factors; Vena Cava Filters; Venous Thrombosis; Warfarin

Coexposure to a noninjurious dose of bacterial lipopolysaccharide (LPS; 7.4 x 106 EU/kg) and a nontoxic dose of the food-borne toxin monocrotaline (MCT; 100 mg/kg) leads to synergistic hepatotoxicity in Sprague-Dawley rats. Inflammatory factors, such as Kupffer cells (KCs), tumor necrosis factor-alpha (TNF)-alpha, and neutrophils (polymorphonuclear leukocytes; PMNs), are critical to the pathogenesis. Inasmuch as activation of the coagulation system and sinusoidal endothelial cell (SEC) injury precede hepatic parenchymal cell (HPC) injury, and since fibrin deposition occurs within liver lesions, the coagulation system might be a critical component of injury. In this study, this hypothesis is tested, and the interdependence of the coagulation system and inflammatory factors is explored. Administration of the anticoagulants heparin or warfarin to MCT/LPS-cotreated animals attenuated HPC and SEC injury. Morphometric analysis revealed that anticoagulant treatment significantly reduced the area of centrilobular and midzonal lesions. Heparin treatment also reduced fibrin deposition in these regions. Furthermore, anticoagulant treatment decreased hepatic PMN accumulation but did not affect plasma TNF-alpha concentration. Neither KC inactivation nor TNF-alpha depletion prevented activation of the coagulation system. PMN depletion, however, prevented coagulation system activation, suggesting that PMNs are needed for this response. These results provide evidence that the coagulation system and its interplay with PMNs are important in the pathogenesis of MCT/LPS-induced liver injury.

Topics: Animals; Anticoagulants; Blood Coagulation; Chemical and Drug Induced Liver Injury; Drug Antagonism; Drug Synergism; Escherichia coli; Heparin; Lipopolysaccharides; Male; Monocrotaline; Neutropenia; Neutrophils; Rats; Rats, Sprague-Dawley; Warfarin