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Biomedical subjects

William E Dager

Publications and source records attributed to William E Dager.

30 records · Page 2Linked to original sources
PubMed2004

Key articles and guidelines relative to treatment of patients with acute coronary syndromes.

Patients with cardiovascular disease who have acute coronary syndromes (ACS) are at risk of significant morbidity and mortality. Also, treatment of these patients in the early-phase setting has a significant financial impact on the health care system. With the existence of numerous pharmacologic agents, abundance of major clinical trials, and several nationally recognized clinical guidelines, compiling the needed reference material to make evidence-based decisions on the care of patients with ACS can be difficult for clinicians. To assist clinicians in this endeavor, we complied pertinent articles and guidelines that have shaped the current treatment of patients with ACS. Owing to the rapidly evolving body of evidence in the management of ACS, this compilation will require periodic updating.

Acute Disease↗
PubMed2004

Special considerations with fondaparinux therapy: heparin-induced thrombocytopenia and wound healing.

Multiple options for anticoagulation therapy are now available, placing an additional responsibility on health care workers for choosing the optimal therapy for each patient. The heparins carry a risk of heparin-induced thrombocytopenia (HIT), an immune-mediated reaction to heparin that may lead to pulmonary embolism and death. Fondaparinux, a new, synthetic pentasaccharide, binds to antithrombin III and potentiates antithrombin III's inhibition of factor Xa. Fondaparinux does not bind to platelet factor 4 and thus is theoretically unable to cause immunoallergic HIT. Unlike low-molecular-weight heparins, fondaparinux does not cross-react in vitro with sera from patients with clinical cases of HIT. These findings suggest that fondaparinux would not lead to formation of HIT antibodies and would not provoke clinical thrombosis in patients who had HIT antibodies because of previous exposure to heparins. To date, no cases of immunoallergic HIT have been associated with fondaparinux use in clinical trials. Anecdotal evidence suggests that fondaparinux eventually may prove to be valuable for preventing and treating thrombosis in patients with HIT. The effect of anticoagulants on wound healing is another consideration when choosing a thromboprophylactic strategy after major surgery. There is evidence that thrombin plays a role in wound healing, but fondaparinux is too small to enable antithrombin III to inhibit thrombin. Thus, fondaparinux may be less likely than a low-molecular-weight heparin to interfere with wound healing.

Anticoagulants↗
PubMed2004

Transitioning from traditional to novel anticoagulants: the impact of oral direct thrombin inhibitors on anticoagulation management.

Limitations of traditional anticoagulants have led to the need for structured services to provide anticoagulation monitoring. Anticoagulation management services have historically filled this role. Novel antithrombotic agents currently in development have the potential to improve on the limitations of vitamin K antagonists and injectable forms of heparin and to change the field of anticoagulation management. Of the emerging agents, oral direct thrombin inhibitors present the most promise and have a more practical clinical profile. The introduction of the oral direct thrombin inhibitors may present both an opportunity and a threat to anticoagulation management services and anticoagulation service providers. Traditional anticoagulation monitoring services will have to retool for the future if they are to remain relevant in the new era of novel antithrombotic.agents.

Administration, Oral↗
PubMed2004

Argatroban therapy for antithrombin deficiency and mesenteric thrombosis: case report and review of the literature.

Antithrombin deficiency is a hypercoagulable state that can increase the risk for thrombosis, especially in the presence of other procoagulant triggers. Unfractionated heparin and low-molecular-weight heparins may not provide effective anticoagulation since they require antithrombin for activity. Direct thrombin inhibitors, however, work independently of antithrombin. A 21-year-old man with a history of heavy alcohol consumption had thrombosis of the superior mesenteric vein. Infusion with unfractionated heparin was started, and despite repeated boluses and increases to 21 U/kg/hour, the maximum activated partial thromboplastin time reached was 39 seconds. The unfractionated heparin was discontinued, and the direct thrombin inhibitor argatroban was infused at rates of 0.4-0.5 microg/kg/minute. Over the course of several weeks, the patient had numerous operations to remove and repair necrotic bowel. When no further surgery was anticipated, warfarin therapy was started; the argatroban infusion was discontinued when the patient reached the therapeutic target international normalized ratio with warfarin. No recurrent thrombosis or major bleeding occurred. Direct thrombin inhibitors, such as argatroban, seem to be suitable alternatives for acute anticoagulation in patients with antithrombin deficiency.

Adult↗
PubMed2003

Warfarin initiation and monitoring with clotting factors II, VII, and X.

OBJECTIVE: To report a case of a patient with antiphospholipid antibody syndrome and multiple thromboses who developed heparin-induced thrombocytopenia (HIT) and subsequent international normalized ratio (INR) prolongation possibly due to antiphospholipid antibodies. CASE SUMMARY: A 56-year-old white woman with a history of antiphospholipid antibody syndrome and thrombosis taking chronic warfarin was admitted for gastrointestinal concerns and found to have an INR >14. Warfarin was discontinued, vitamin K was administered, and a heparin infusion was initiated. Over the next 2 days, thrombocytopenia, hypotension, tachycardia, hyponatremia, and progressive abdominal pain developed. Upon transfer to a tertiary care center, HIT was diagnosed, and a lepirudin infusion was initiated. Subsequently, a sudden elevation of the INR occurred (>14) with low prothrombin (factor II) activity. After INR values declined to 2-3, warfarin was reinitiated with dosing adjusted using factor X and II activity levels. Clotting factors II and X activities were measured to monitor long-term warfarin therapy, with no evidence of complications after 7 months. DISCUSSION: Typically, the INR is used to assess the intensity of anticoagulation. The INR value represents the reduction of clotting factors II, VII, and X. In rare circumstances, an independent inhibitor or interfering substance can interfere with the process of measuring the INR. In such situations, an alternative approach can be direct measurement of clotting factor concentrations. CONCLUSIONS: Factor II and/or factor X activity levels provided an alternative means for measuring the anticoagulant effects of warfarin in the presence of a significant inhibitor (antiphospholipid antibodies) that biased the INR measurements.

Anticoagulants↗
PubMed2003

Low-molecular-weight heparin-induced thrombocytopenia in a child.

OBJECTIVE: To report a case of probable acute venous thrombosis caused by heparin-induced thrombocytopenia (HIT) in a pediatric patient with a normal platelet count after prolonged enoxaparin therapy. CASE SUMMARY: An 11-year-old African American female with Crohn's disease developed extensive vena cava thrombosis. Her deep vein thrombosis (DVT) was treated with intravenous unfractionated heparin followed by extended outpatient warfarin therapy. Four months later, the warfarin was stopped and subcutaneous enoxaparin 1.5 mg/kg once daily was substituted prior to an elective colonoscopy. She was readmitted 6 weeks later with acute DVT with a platelet count of 233 x 10(3)/mm3, significantly lower than the count of 550-700 x 10(3)/mm3 5 months previously and the count of 433 x 10(3)/mm3 3 months earlier. An enzyme-linked immunosorbent assay for heparin-platelet factor 4 antibodies was strongly positive and a d-dimer was elevated at 2.9 mg/L (normal <1.5). She was treated with lepirudin followed by warfarin when repeat d-dimer on day 3 was normal. An ultrasound at that time showed no clot extension, and the platelet count had risen to >300 x 10(3)/mm3. Over the next 4 months, there was no further thrombosis. DISCUSSION: HIT appears to be rare in the pediatric population, and only a few cases treated with a direct thrombin inhibitor have been reported. This is the first case report to our knowledge of a pediatric patient developing HIT secondary to enoxaparin. An interesting feature of this case is the development of HIT in the face of a normal platelet count, which is rare but has been reported in adults. CONCLUSIONS: Pediatric patients receiving low-molecular-weight heparin are still at risk for developing HIT. Treatment of HIT should involve the initial use of a direct thrombin inhibitor to manage thrombosis until the platelet count returns to higher values. Once the platelet count returns, warfarin can be used for long-term thrombosis management.

Anticoagulants↗
PubMed2003

Argatroban for heparin-induced thrombocytopenia in hepato-renal failure and CVVHD.

OBJECTIVE: To report a case of significant hepatic and renal failure with the use of argatroban in a patient with heparin-induced thrombocytopenia (HIT) requiring continuous veno-veno hemodialysis (CVVHD). CASE SUMMARY: A 37-year-old Hispanic man with diabetes mellitus, ethanol abuse, and recent crank use developed a venous thrombosis and possible pulmonary embolism, followed by acute liver and renal failure requiring continuous veno-venous hemofiltration. After several days of heparin therapy, the dialyzer circuit thrombosed and the platelet count decreased to 82 x 10(3)/mm(3). Antibodies for HIT by enzyme-linked immunosorbent assay were positive. Heparin was discontinued, and an argatroban infusion was initiated. After 39 hours on argatroban, the infusion was stopped when minor bleeding was observed with a concurrent activated partial thromboplastin time (aPTT) of 100 seconds. The dialyzer circuit did not clot during the argatroban infusion and did not apparently influence dose-related aPTT measurements. Several days were required for the aPTT to decrease after stopping the argatroban infusion. Fresh frozen plasma had no apparent effect on aPTT values. DISCUSSION: Several different agents are currently available to provide effective anticoagulation in patients who have immune- mediated HIT. Argatroban is hepatically cleared and may be the preferred direct thrombin inhibitor in the presence of significant renal impairment, but conversely has prolonged effects in hepatic failure. Limited data are available regarding use of direct thrombin inhibitors in patients who have severe hepatic impairment with concurrent renal failure requiring CVVHD. Scant data are available regarding the effect of hemodialysis on the elimination of argatroban. CONCLUSIONS: The optimal anticoagulant for use in a patient with HIT and concurrent hepatic and renal failure is unclear. No direct thrombin inhibitor has a proven advantage; therefore, selection may depend on clinical factors. Dosing in these patients requires very careful management.

Acute Disease↗
PubMed2003

Pharmacotherapy of heparin- induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a life-and-limb threatening condition that is associated with the development of antibodies that activate platelets and the coagulation system in the presence of unfractionated heparin or low molecular weight heparin. The binding of antibody to heparin-PF-4 complexes can activate platelets, leading to an acute, often catastrophic, thrombotic diathesis. The most common laboratory finding is the development of thrombocytopenia 5 or more days after beginning heparin treatment, which occur in up to 1 - 5% of patients exposed to heparin, depending on type of heparin and indication for anticoagulation. The onset of thrombocytopenia can be immediate or delayed for several weeks after the exposure to heparin. Approximately 50 - 60% of patients who develop HIT manifest acute venous or arterial thrombosis and a significant percentage of these patients die or develop vascular gangrene of a limb that requires amputation. Given the severe sequelae associated with HIT, recognition and immediate medical management is essential. Treatment of a patient with HIT is complex, as there are several different anticoagulants now available which have been shown to be useful. Optimal management depends on each patient's individual clinical manifestations, as well as the need for ongoing anticoagulation therapy. No single agent or treatment approach can be considered to be 'standard practice' as very few clinical trials have been completed, compare different treatment options. The use of warfarin alone in a patient with HIT, must be avoided in order to avoid the possibility of further activating coagulation, which may hasten the development of venous limb gangrene. There are several different tests available that detect HIT antibodies and each has different sensitivity and specificity for HIT. In this review we discuss the epidemiology and natural history of HIT, risk factors associated with the development of HIT and the clinical and laboratory tests that aid in the diagnosis and treatment. Special emphasis is given to addressing the management of HIT in special populations, particularly patients with renal or liver disease, acute coronary syndromes, pregnancy, paediatrics and patients who require cardiopulmonary bypass surgery.

Administration, Oral↗
PubMed2002

Treatment of heparin-induced thrombocytopenia.

OBJECTIVE: To describe heparin-induced thrombocytopenia (HIT or HIT-2), an immune-mediated adverse reaction to heparin or low-molecular-weight heparin. Available treatment options and considerations in developing a therapy approach are discussed. DATA SOURCES: A search of the National Library of Medicine (1992-June 2001) was done to identify pertinent literature. Additional references were reviewed from selected articles. STUDY SELECTION: Articles related to laboratory recognition and treatment options of HIT, including the use of agents in selected clinical conditions, were reviewed and included. CONCLUSIONS: HIT is a rare but potentially severe adverse reaction to heparin that was, until recently, poorly understood and had limited treatment options. Recent advances describing the recognition and clinical manifestations of immune-mediated HIT, including recently available antithrombotic treatment options, have dramatically changed outcomes for patients having this syndrome.

Animals↗