warfarin and Pancreatitis

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

Mesenteric venous thrombosis is a rare, but potentially lethal, complication of pancreatitis. Although management is usually directed toward the underlying pancreatitis, there is no standard defined for treatment of the associated mesenteric venous thrombosis. Anticoagulant therapy was chosen as treatment for the case presented in this report, but other management methods for this entity have been described in the literature. Based on our experience and review of the literature, a management strategy for patients with pancreatitis-associated mesenteric venous thrombosis has been developed.

Topics: Acute Disease; Anticoagulants; Female; Heparin; Humans; Mesenteric Vascular Occlusion; Mesenteric Veins; Middle Aged; Pancreatitis; Thrombosis; Warfarin

Topics: Adult; Alkylation; Biological Transport; Celiac Disease; Cholestasis; Dietary Fats; Feces; Humans; Infant; Intestinal Absorption; Intestines; Lipid Metabolism; Malabsorption Syndromes; Oxides; Pancreatitis; Tritium; Vitamin K; Vitamin K 1; Warfarin

Acute pancreatitis (AP) is a severe disease with high morbidity and mortality in which inflammation and coagulation play crucial roles. The development of inflammation leads to vascular injury, endothelium and leukocytes stimulation, and an increased level of tissue factor, which results in the activation of the coagulation process. For this reason, anticoagulants may be considered as a therapeutic option in AP. Previous studies have shown that pretreatment with heparin, low-molecular-weight heparin (LMWH), or acenocoumarol inhibits the development of AP. The aim of the present study was to check if pretreatment with warfarin affects the development of edematous pancreatitis evoked by cerulein. Warfarin (90, 180, or 270 µg/kg/dose) or saline were administered intragastrically once a day for 7 days consecutively before the induction of AP. AP was evoked by the intraperitoneal administration of cerulein. The pre-administration of warfarin at doses of 90 or 180 µg/kg/dose reduced the histological signs of pancreatic damage in animals with the induction of AP. Additionally, other parameters of AP, such as an increase in the serum activity of lipase and amylase, the plasma concentration of D-dimer, and interleukin-1β, were decreased. In addition, pretreatment with warfarin administered at doses of 90 or 180 µg/kg/dose reversed the limitation of pancreatic blood flow evoked by AP development. Warfarin administered at a dose of 270 µg/kg/dose did not exhibit a preventive effect in cerulein-induced AP. Conclusion: Pretreatment with low doses of warfarin inhibits the development of AP evoked by the intraperitoneal administration of cerulein.

Topics: Acute Disease; Animals; Ceruletide; Heparin, Low-Molecular-Weight; Inflammation; Pancreatitis; Rats; Rats, Wistar; Warfarin

Acute pancreatitis (AP) is the most common gastrointestinal disease leading to hospitalizations and unexpected deaths. The development of AP leads to damage of the pancreatic microcirculation with a cascade of subsequent events resulting, among others, in coagulopathy. Previous research showed that anticoagulants can be important therapeutic agents. Heparin and acenocoumarol can alleviate the course of AP, as well as accelerate healing and post-inflammatory regeneration of the pancreas. The aim of this study was to determine whether warfarin, a drug with more stable effects than acenocoumarol, affects the healing and regeneration of the pancreas in the cerulein-induced AP. AP was evoked in Wistar male rats by intraperitoneal administration of cerulein. The first dose of warfarin (45, 90 or 180 μg/kg) was administered 24 hours after the first dose of cerulein and the doses of warfarin were repeated once a day in subsequent 10 days. The severity of AP was assessed immediately after the last dose of cerulein, as well as at days 1, 2, 3, 5, and 10 after AP induction. Treatment with warfarin dose-dependently increased international normalized ratio (INR) and attenuated the severity of pancreatitis in histological examination and accelerated pancreatic recovery. These effects were accompanied with a faster reduction in the AP-evoked increase in serum activity of amylase and lipase, the serum concentration of pro-inflammatory interleukin-1β, and the plasma level of D-Dimer. In addition, treatment with warfarin decreased pancreatic weight (an index of pancreatic edema) and improved pancreatic blood flow in rats with AP. The therapeutic effect was particularly pronounced after the administration of warfarin at a dose of 90 μg/kg. We conclude that treatment with warfarin accelerated regeneration of the pancreas and recovery in the course of cerulein-induced mild-edematous acute pancreatitis.

Topics: Acenocoumarol; Acute Disease; Animals; Ceruletide; Male; Pancreas; Pancreatitis; Rats; Rats, Wistar; Warfarin

In acute pancreatitis (AP), pancreatic damage leads to local vascular injury, manifesting as endothelial damage and activation, increased vascular permeability, leukocyte rolling, sticking and transmigration to pancreatic tissue as well as activation of coagulation. Previous studies have shown that pretreatment with heparin or acenocoumarol inhibits the development of AP. The aim of the present study was to check the impact of pretreatment with warfarin, an oral vitamin K antagonist, on the development of ischemia/reperfusion-induced AP in rats. AP was induced by pancreatic ischemia followed by reperfusion of the gland. Warfarin (90, 180 or 270 µg/kg/dose) or vehicle were administered intragastrically once a day for 7 days before induction of AP. The effect of warfarin on the severity of AP was assessed 6 h after pancreatic reperfusion. The assessment included histological, functional, and biochemical analyses. Pretreatment with warfarin given at a dose of 90 or 180 µg/kg/dose increased the international normalized ratio and reduced morphological signs of pancreatic damage such as pancreatic edema, vacuolization of acinar cells, necrosis and the number of hemorrhages. These effects were accompanied by an improvement of pancreatic blood flow and a decrease in serum level amylase, lipase, pro-inflammatory interleukin-1β and plasma level of D-dimer. In contrast, pretreatment with warfarin given at a dose of 270 µg/kg/dose led to an increase in severity of pancreatic damage and biochemical indicators of AP. In addition, this dose of warfarin resulted in deaths in some animals. Pretreatment with low doses of warfarin inhibits the development of AP induced by pancreatic ischemia followed by reperfusion.

Topics: Acute Disease; Animals; Anticoagulants; Coumarins; Ischemia; Male; Pancreas; Pancreatitis; Rats; Rats, Wistar; Reperfusion Injury; Warfarin

Acute pancreatitis is associated with activation of coagulation and there is a close relationship between coagulation and the severity of this disease. Administration of anticoagulants such as heparin or acenocoumarol has shown to reduce the severity of acute pancreatitis and accelerate the recovery. The aim of the current study was to determine the impact of warfarin administration on the course of ischemia/reperfusion-induced acute pancreatitis. Acute pancreatitis was induced in rats by pancreatic ischemia followed by reperfusion. Vehicle (1 ml/dose) or warfarin (45, 90 or 180 μg/kg/dose in 1 ml of vehicle) were administered intragastrically once a day. The first dose of warfarin was given 24 h after the start of pancreatic reperfusion. The severity of acute pancreatitis was assessed 2, 5, 9 and 14 days after the beginning of pancreatic reperfusion. Treatment with warfarin reduces pancreatic damage and accelerates recovery in histological examination and this effect is accompanied by a faster reduction in serum activity of pancreatic digestive enzymes, lipase and amylase. In addition, warfarin led to an earlier decrease in serum concentration of pro-inflammatory interleukin-1β and plasma level of D-dimer. These effects were associated with an improvement of pancreatic blood flow. We conclude that warfarin exhibits a therapeutic effect in acute pancreatitis evoked by pancreatic ischemia followed by reperfusion.

Topics: Amylases; Animals; Anticoagulants; Biomarkers; Disease Models, Animal; Fibrin Fibrinogen Degradation Products; Interleukin-1beta; Lipase; Male; Pancreas; Pancreatitis; Rats, Wistar; Reperfusion Injury; Time Factors; Warfarin

Acute pancreatitis is an acute inflammatory process of the pancreas that can trigger a systemic inflammatory response. Pulmonary embolism refers to obstruction of the pulmonary artery or one of its branches by material (usually a thrombus) that originated elsewhere in the body. Extensive lower limb deep vein thrombosis with pulmonary embolism is a rare complication of acute pancreatitis that has been described in a few case reports. Deep vein thrombosis and hypercoagulable states in pancreatitis are thought to be due to release of pancreatic proteolytic enzymes from a cyst that is connected to the pancreatic duct and penetrates into a vessel. Proteolytic damage or inflammation of the vessels may also play a significant part. Acute pancreatitis also causes a systemic inflammatory response that has effects on an endothelium-dependent relaxing response for acetylcholine.. A 38-year-old Sri Lankan man presented with acute pancreatitis and later he developed progressive abdominal distention with bilateral ankle edema. A contrast-enhanced computed tomographic scan showed two pancreatic pseudocysts and deep vein thrombosis in both lower limbs, as well as a pulmonary embolism involving the right lower lobe pulmonary artery and the left segmental pulmonary arteries. One of the pseudocysts in the head of the pancreas was compressing the inferior vena cava without direct communication. The patient's thrombophilia screen result was negative. He was started on subcutaneous enoxaparin 1 mg/kg twice daily and warfarin to achieve a target international normalized ratio of 2-3.. Deep vein thrombosis with pulmonary embolism is a rare but life-threatening complication of acute pancreatitis. Once diagnosed, early treatment with intravenous heparin or thrombolysis is effective. Patients with severe acute pancreatitis may be at risk of deep vein thrombosis due to immobilization and other mechanisms, but anticoagulation as prophylaxis is often not used. However, it may be considered on a case-by-case basis in patients with pancreatitis who are acutely ill and immobilized, need intensive care unit admission, and have multiple risk factors for deep vein thromboembolism. Further studies must be undertaken to determine guidelines for deep vein thromboembolism prophylaxis in these patients.

Topics: Adult; Anticoagulants; Enoxaparin; Humans; Male; Pancreatitis; Pulmonary Embolism; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography, Doppler; Vena Cava Filters; Venous Thrombosis; Warfarin

Practice-based research plays a pivotal role for improving patient care as its primary intent is to solve a clinical dilemma or problem encountered in clinical practice. Its results are immediately applicable to day-to-day clinical practice and essential to the growth of an evidence-based clinical practice. This review emphasizes the importance of this type of research. In addition, it serves to identify common sources for project conception and gives examples based on personal experiences of the author as a clinical practitioner, educator, and researcher. Common barriers to practice-based research are discussed as well as potential solutions offered for consideration.

Topics: Brain Injuries; Calcium; Enteral Nutrition; Evidence-Based Medicine; Food-Drug Interactions; Humans; Hypocalcemia; Insulin; Obesity; Pancreatitis; Phosphorus; Renal Insufficiency, Chronic; Research; Treatment Outcome; Warfarin

The clinical presentation of patients with acute lower-limb ischemia and primary aortic thrombus prompted this review. Following recognition of the first case in early 1994, relevant patients (n = 6) were kept in a database and were reviewed for presentation, treatment, and follow-up. The median age was 41 and five patients were male. Angiography, computed tomography, and/or magnetic resonance angiography demonstrated one or more aortic sessile or pedunculated thrombus(i) without associated atherosclerotic disease. In two cases, a retropancreatic intraaortic mural thrombus was associated with severe pancreatitis. All other cases presented with acute lower-limb emboli requiring limb salvage embolectomy. Because of significant patient illness, systemic anticoagulation was chosen acutely to prevent recurrent emboli. Interestingly, serial studies demonstrated aortic thrombus resolution. Failure to continue warfarin therapy resulted in recurrent problems (n = 1) unless the instigating event had resolved (n = 3). There were no deaths or amputations. We concluded that surgical embolectomy, when required, with subsequent anticoagulation, results in limb salvage and allows for eventual resolution of the primary aortic thrombus. Long-term anticoagulation is required unless the etiologic process resolves. The literature describes patients with atherosclerosis and overlying thrombus but fails to describe the approach to patients with primary thrombus formation.

Topics: Acute Disease; Adult; Aged; Anticoagulants; Aorta, Abdominal; Aortic Diseases; Embolectomy; Embolism; Female; Heparin; Humans; Leg; Male; Pancreatitis; Thrombosis; Warfarin

Topics: Adult; Aged; Androsterone; Anticholesteremic Agents; Cholesterol; Coronary Disease; Drug Synergism; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Pancreatitis; Triglycerides; Warfarin

Topics: Acute Kidney Injury; Arteriosclerosis; Cholesterol; Embolism, Fat; Gangrene; Humans; Hypertension; Male; Middle Aged; Pancreatitis; Toes; Warfarin