warfarin and Sepsis

In November 2001, drotrecogin alfa (activated) was approved by the US Food and Drug Administration; in August 2002 it was approved by the European Medicines Agency. Since the approval of drotrecogin alfa (activated), however, critical care physicians have been faced with several challenges, namely its costs, selection of patients who are more likely to benefit from it, and the decision regarding when to start drotrecogin alfa (activated) treatment. There are also operational issues such as how to manage the infusion to deliver an effective treatment while minimizing the risk for bleeding, particularly in patients with deranged clotting, at around the time of surgery or during renal replacement therapy. While addressing these issues, this review remains practical but evidence based as much as possible.

Topics: Adult; Aged; Anti-Infective Agents; APACHE; Aspirin; Child; Clinical Trials as Topic; Cost-Benefit Analysis; Disseminated Intravascular Coagulation; Drug Administration Schedule; Drug Interactions; European Union; Heparin; Humans; IgA Vasculitis; Meningitis; Meningococcal Infections; Multiple Organ Failure; Pancreatitis; Practice Guidelines as Topic; Protein C; Recombinant Proteins; Renal Replacement Therapy; Risk Assessment; Sepsis; Survival Rate; Thrombocytopenia; United States; Warfarin

For many years central venous catheters (CVC) have been utilized to monitor hemodynamics and to deliver parenteral nutrition, blood products, pharmacological therapies or infusion fluids. Recently, CVC use has greatly increased with significant impact on the administration of chemotherapy, stem cell transplantation and other treatments to cancer patients. However, CVC use may be accompanied by a variety of side-effects, which increase with the duration of implantation. The most common catheter-related complications are thrombotic events and blood-stream infections. The true incidence of these complications is still uncertain and has changed over time due to CVC device improvement. More data are available in solid tumor than in oncohematologic patients. Recently, much attention has been paid to the issues of prevention and treatment of these complications. Some strategies have been proposed: fixed dose warfarin or low molecular weight heparins have been evaluated in some clinical trials of thromboprophylaxis in this condition. However, more studies are still needed to address this issue. This review will focus on CVC use and complications in oncohematologic patients.

Topics: Catheterization, Central Venous; Hematologic Neoplasms; Heparin, Low-Molecular-Weight; Humans; Sepsis; Thrombosis; Warfarin

Central venous catheter-associated bacteraemia caused by Nocardia species is very rare; the diagnosis of nocardiosis in patients with cancer is challenging because its clinical presentation is varied, sometimes mimicking metastases, and the high index of clinical suspicion is required for prompt institution of therapy. Herein, we report a case of nocardial sepsis with native aortic valve endocarditis in a patient with breast cancer in whom multidisciplinary team involvement and prompt initiation of therapy have led to successful outcome.

Topics: Amikacin; Anti-Bacterial Agents; Anticoagulants; Aortic Valve; Breast Neoplasms; Central Venous Catheters; Clopidogrel; Cough; Endocarditis, Bacterial; Fatigue; Female; Headache; Heart Valve Prosthesis Implantation; Humans; Meropenem; Middle Aged; Nocardia; Nocardia Infections; Platelet Aggregation Inhibitors; Radiography, Thoracic; Sepsis; Treatment Outcome; Warfarin

Topics: Adult; Cesarean Section; Delivery, Obstetric; Diagnosis, Differential; Female; Follow-Up Studies; Hematoma; Humans; Ovary; Pregnancy; Pregnancy, Multiple; Puerperal Disorders; Pulmonary Embolism; Rectus Abdominis; Risk Factors; Sepsis; Tinzaparin; Tomography, X-Ray Computed; Venous Thrombosis; Warfarin

The development of coagulation abnormalities is common in patients with sepsis. Sepsis-associated coagulopathy (SAC) is typically diagnosed by prothrombin time (PT) prolongation or elevated international normalized ratio (INR) in conjunction with reduced platelet count. INR is also used to monitor warfarin-treated patients. However, due to the different natures of SAC and warfarin anticoagulation, it is likely that the same INR value provides different information in these two patient populations. The purpose of this study was to compare measures of coagulation function and clotting factor levels in patients with SAC to those observed in patients receiving warfarin anticoagulation. Deidentified plasma samples were collected at baseline from patients diagnosed with SAC and from patients receiving warfarin. These plasma samples were evaluated for PT/INR, activated partial thromboplastin time (aPTT), fibrinogen, and functional and immunologic levels of factors VII, IX, and X. Both aPTT and fibrinogen correlated with INR in patients with SAC, but not in patients treated with warfarin. Factors VII, IX, and X showed an inverse relationship with INR in the anticoagulated patients; however, no relationship between factor level and INR was observed in patients with SAC. Distinct patterns of coagulopathy were observed in patients with SAC and patients receiving warfarin anticoagulation, and equivalent INR values were associated with distinct coagulation profiles in the two patient groups. These results suggest that an abnormal INR provides different information about the coagulation status in patients with disseminated intravascular coagulation than in patients receiving warfarin. This may indicate that an equivalently increased INR predicts different bleeding risks in these two patient groups.

Topics: Disseminated Intravascular Coagulation; Female; Humans; International Normalized Ratio; Male; Sepsis; Warfarin

Sepsis is a syndrome of life-threatening organ dysfunction caused by a dysregulated host response to infection. It can have devastating consequences, including bilateral adrenal hemorrhage, particularly in patients at high thrombotic risk, such as those with antiphospholipid syndrome and those on long-term anticoagulation.. A 49-year-old white woman re-presented to hospital with a history suggestive of sepsis. She had a medical background of primary antiphospholipid syndrome on lifelong warfarin. Ten days prior to this presentation, she had been hospitalized following Escherichia coli bacteremia, commenced on intravenous antibiotics, and discharged 2 days later with a prescribed 5-day course of oral amoxicillin. On readmission, she had ongoing fever, myalgia, malaise, and hypotension. Investigations revealed anemia with thrombocytopenia, hyponatremia, and acute-on-chronic kidney injury. Despite treatment for urosepsis, she became tachypneic, clammy, light-headed, drowsy, and hypothermic. Computed tomography revealed bilateral adrenal hemorrhage, and biochemical examination confirmed hypoadrenalism. Following discharge, she had persistent renal and hepatic injury lasting 3 months.. Early identification, intensive monitoring, and aggressive support may reduce the acquired thrombotic risk and avoid potentially life-threatening outcomes of sepsis.

Topics: Abdominal Pain; Adrenal Gland Diseases; Adrenal Glands; Adrenal Insufficiency; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antiphospholipid Syndrome; Diarrhea; Escherichia coli; Female; Hemorrhage; Humans; Hydrocortisone; Middle Aged; Sepsis; Tomography, X-Ray Computed; Treatment Outcome; Vomiting; Warfarin

An increasingly reported entity, Lemierre's syndrome classically presents with a recent oropharyngeal infection, internal jugular vein thrombosis and the presence of anaerobic organisms such as Fusobacterium necrophorum. The authors report a normally fit and well 17-year-old boy who presented with severe sepsis following a 5-day history of a sore throat, myalgia and neck stiffness requiring intensive care admission. Blood cultures grew F. necrophorum and radiological investigations demonstrated left internal jugular vein, cavernous sinus and sigmoid sinus thrombus, left vertebral artery dissection and thrombus within the left internal carotid artery. Imaging also revealed two areas of acute ischaemia in the brain, consistent with septic emboli, skull base (clival) osteomyelitis and an extensive epidural abscess. The patient improved on meropenem and metronidazole and was warfarinised for his cavernous sinus thrombosis. He has an on-going left-sided hypoglossal (XIIth) nerve palsy.

Topics: Adolescent; Anti-Infective Agents; Anticoagulants; Cranial Fossa, Posterior; Fever; Fusobacterium Infections; Fusobacterium necrophorum; Humans; Hypoglossal Nerve Diseases; Jugular Veins; Lemierre Syndrome; Male; Meropenem; Metronidazole; Osteomyelitis; Pharyngitis; Sepsis; Thienamycins; Treatment Outcome; Warfarin

Although numerous studies have shown that anticoagulation of nonvalvular atrial fibrillation (AF) significantly decreases the risk of stroke, anticoagulating critically ill patients in the intensive care unit (ICU) poses many challenges and the benefits have not been determined.. To assess the safety and efficacy of anticoagulation in AF patients with sepsis. Ascertaining the incidence of complications associated with anticoagulation therapy, such as bleeding, can optimize patient care.. This was a retrospective observational study to assess the incidence of stroke and anticoagulation-related complications (eg, bleeding, heparin-induced thrombocytopenia) in AF patients with severe sepsis. This study was undertaken in a surgical/medical ICU of a teaching, community-based hospital. A total of 115 patients with AF who were admitted with a diagnosis of sepsis were included in the study.. Among 115 patients (mean age 81 ± 9.5 years and CHADS2 [congestive heart failure, hypertension, age >75 years, diabetes mellitus, stroke] score 3.17 ± 1.20), 80 (69.6%) did not receive anticoagulation treatment during their hospitalization and none of these patients developed a stroke. Anticoagulation-related complications occurred more often in the group who received anticoagulation (8.6% [3/35] vs 0%, P = .008). In the anticoagulated group, a majority of the patients were within therapeutic range less than 50% of the time during their ICU stay. There was no statistically significant difference in survival rates during their hospitalization (66.2% [53/80] for the non-anticoagulated group vs 74.3% [26/35] in the anticoagulated group, P = .392).. Administration of anticoagulation for elderly patients with a CHADS2 score at 2 or more in the setting of sepsis can be associated with an increased risk of anticoagulation-related complications (eg, bleeding, heparin-induced thrombocytopenia). Managing and targeting a therapeutic goal with warfarin therapy in critically ill patients with sepsis is challenging. Further studies are necessary to provide appropriate recommendations in this setting.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Enoxaparin; Female; Heparin; Humans; Intensive Care Units; Male; Sepsis; Stroke; Warfarin

Coagulopathy occurs frequently in critically ill patients, but its epidemiology, current treatment, and relation to patient outcome are poorly understood. We described the prevalence, risk factors, and treatment of prolongation of the prothrombin time in critically ill patients using the international normalized ratio to standardize data and explored its association with intensive care unit survival.. Prospective multiple center observational cohort study.. Twenty-nine adult intensive care units in the United Kingdom.. All sequentially admitted patients over an 8-wk period.. None.. Prospective daily data were collected concerning prevalence, predefined risk factors, and treatment of coagulopathy throughout intensive care unit admission. Of 1923 intensive care unit admissions, 30% developed abnormal international normalized ratio values (defined as an international normalized ratio > 1.5). Most international normalized ratio abnormalities were minor and short-lived (73% of worst international normalized ratio values 1.6-2.5). Male sex, chronic liver disease, sepsis, warfarin therapy, increments in Acute Physiology and Chronic Health Evaluation II score, severity of renal and hepatic dysfunction, and red cell transfusions were all independent risk factors for international normalized ratio abnormalities (all p < .001). In all regression models, there was a strong independent association between abnormal international normalized ratio values and greater intensive care unit mortality (p < .0001), particularly when international normalized ratio increased after intensive care unit admission. Among patients with abnormal international normalized ratios, 33% received fresh-frozen plasma transfusions during their intensive care unit stay, but the pretransfusion international normalized ratio value varied widely. Fifty-one percent of fresh-frozen plasma treatments were to nonbleeding patients and 40% to nonbleeding patients whose international normalized ratio was normal or only modestly deranged (≤ 2.5). The dose of fresh-frozen plasma administered was highly variable (median dose 10.8 mL/kg (first, third quartile 7.2, 14.4; range, 2.4-41.1 mL/kg).. Prothrombin time prolongation is prevalent in critically ill patients and is independently associated with greater intensive care unit mortality. Wide variation in fresh-frozen plasma treatment exists suggesting clinical uncertainty regarding best practice, particularly as a prophylactic treatment.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Child; Critical Care; Erythrocyte Transfusion; Female; Hospital Mortality; Humans; Intensive Care Units; Liver Diseases; Logistic Models; Male; Middle Aged; Plasma; Prevalence; Prospective Studies; Prothrombin Time; Risk Factors; Sepsis; Severity of Illness Index; Sex Factors; Time Factors; United Kingdom; Warfarin; Young Adult

We describe a severe case of warfarin-induced skin necrosis with extensive full-thickness tissue loss involving approximately 12 per cent of the body surface area. The early management was conservative, with wound observation only, and no aggressive débridement was attempted. Wound and associated systemic sepsis followed, and the patient was transferred to our burn unit. The wounds were then managed with aggressive therapy including surgical excision, temporary coverage with allograft, and final closure with split-thickness autograft. This case illustrates important principles of appropriate surgical management of extensive skin lesions of this type.

Topics: Burn Units; Critical Care; Debridement; Female; Humans; Middle Aged; Necrosis; Sepsis; Skin; Skin Transplantation; Warfarin; Wound Infection

The effect of warfarin treatment on an experimental Staphylococcus epidermidis endocarditis was studied. Warfarin was found to affect both the induction and course of the infection of catheter-induced endocardial vegetations. In warfarin-treated rabbits, larger bacterial inocula were needed to induce an infection, and the degree of infection of the vegetations was also significantly lower, eventually resulting in the total elimination of the bacteria from the vegetations. Thus, warfarin treatment seems to have an inhibitory effect on the induction and development of an S. epidermidis infection of the endocardium. The results differ from previous findings in studies done with Streptococcus anguis, where warfarin was found to have no effect on the induction or course of the infection of endocardial vegetations, which suggests that different mechanisms are involved in the pathogenesis of endocarditis caused by these two species of bacteria.

Topics: Animals; Endocarditis, Bacterial; Male; Rabbits; Sepsis; Staphylococcal Infections; Staphylococcus; Warfarin

The effect of warfarin treatment on an experimental endocarditis was studied in rabbits. Warfarin had no effect on the induction of a Streptococcus sanguis infection in catheter-induced endocardial vegetations, and the course of this infection was also unaltered. However, warfarin treatment resulted in rapidly progressive bacteremia, probably due to impaired circulation in clearing organs such as the lungs, liver, and spleen. Warfarin also reduced the survival time of the infected rabbits, in which pulmonary edema and extensive lung hemorrhages may have been a contributory factor.

Topics: Animals; Endocarditis, Bacterial; Endocardium; Male; Penicillin G; Rabbits; Sepsis; Streptococcus sanguis; Warfarin

Topics: Acute Disease; Adolescent; Adult; Aged; Aneurysm; Child; Chronic Disease; Disseminated Intravascular Coagulation; Embolism, Amniotic Fluid; Female; Fetal Death; Fibrinolysis; Hemangioma; Heparin; Humans; Iliac Artery; Infusions, Parenteral; Lung Neoplasms; Lymphatic Metastasis; Male; Melanoma; Middle Aged; Pregnancy; Sepsis; Streptococcal Infections; Syndrome; Thrombophlebitis; Thumb; Warfarin

Topics: Animals; Endocarditis, Bacterial; Erysipelothrix Infections; Female; Fish Products; Heart Auscultation; Hemoglobins; Humans; Lung; Middle Aged; Occupational Diseases; Penicillins; Radiography; Sepsis; Warfarin