Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149871 (deep vein thrombosis)
 12,364 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 71-year-old woman experienced a pruritic, maculopapular, morbilliform rash on her lower extremities 5 days after starting warfarin for recurrent deep vein thrombosis. The rash extended to her truncal areas and progressively worsened until somewhat painful vesicular lesions developed. Warfarin was discontinued, and subcutaneous injections of enoxaparin were begun; the rash resolved. In addition to a history of deep vein thrombosis, the patient had experienced a hypersensitivity skin reaction to warfarin in the past that necessitated withdrawal of the drug and placement of a vena caval filter. Because no clear consensus exists on whether dyes used in compounding warfarin play a causative role or whether allergic cross-sensitivity occurs among the coumarin derivatives, the patient was rechallenged with a dye-free warfarin 10-mg tablet. The pruritic rash returned along with the vesicular lesions and continued to worsen until the warfarin was discontinued again. The patient subsequently was given oral anticoagulant therapy with anisindione, an indanedione, and her symptoms resolved completely. Health care providers managing patients who are receiving oral anticoagulant therapy should be aware of the maculopapular allergic reactions associated with warfarin and consider alternative treatment options such as anisindione.
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PMID:Anticoagulation with anisindione in a patient with a warfarin-induced skin eruption. 1268 Apr 83

Purple toes syndrome is an extremely uncommon, nonhemorrhagic, cutaneous complication associated with warfarin therapy. It is characterized by the sudden appearance of bilateral, painful, purple lesions on the toes and sides of the feet that blanch with pressure. The syndrome usually develops 3-8 weeks after the start of warfarin therapy. A 47-year-old man with a history of purple toes syndrome that resolved after discontinuing warfarin--prescribed for a deep vein thrombosis (DVT) in his right lower leg--experienced an acute, proximal DVT in his other leg. Warfarin again was prescribed; 1 week later, purple toes syndrome developed in that extremity. Warfarin therapy again was discontinued, and intravenous unfractionated heparin was started; the patient's clinical picture indicated a possible pulmonary embolism, and laboratory analysis suggested antiphospholipid syndrome. The patient's toe pain resolved, but the purple discoloration persisted. Follow-up laboratory analysis confirmed antiphospholipid syndrome, and warfarin was restarted with close monitoring. No further complications occurred with long-term therapy. Although a rare complication of therapy, clinicians should monitor for the development of purple toes syndrome in patients taking warfarin.
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PMID:Purple toes syndrome associated with warfarin therapy in a patient with antiphospholipid syndrome. 1274 43

Deep venous thrombosis (DVT) has potentially debilitating long-term sequelae if left untreated. Conventional treatment (systemic anticoagulation with heparin followed by coumadin or low molecular weight heparin) often does not adequately relieves clot burden or symptoms, and patients may be left with post-thrombotic syndrome. Although the advent of catheter-directed thrombolysis has markedly improved the treatment of DVT and long-term outcomes of patients treated for DVT, it remains only partially effective on subacute or chronic clot. Mechanical thrombolysis may work synergistically with catheter-directed thrombolysis to decrease clot burden, treatment time, and complication rates, thereby improving outcomes.
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PMID:Mechanical thrombectomy for the treatment of lower extremity deep vein thrombosis. 1277 29

The purpose of The Cancer and Leukemia Group B (CALGB) 90203 trial is to determine which of 2 treatment strategies is superior in treating men with high-risk, clinically localized adenocarcinoma of the prostate (stage T1 to T3a NX M0), defined as a predicted probability < or =60% of remaining free from disease recurrence for 5 years after surgery. Patients with a > or =10-year life expectancy will be randomized to either radical prostatectomy (RP) alone versus estramustine and docetaxel before RP. Participants will be excluded if they have received prior therapy for prostate cancer (except transurethral resection of the prostate) or are judged not to be appropriate candidates for RP. Eligible patients will be stratified according to their predicted probability of remaining free from disease recurrence at 5 years after surgery (0% to 20%, 21% to 40%, and 41% to 60%) and randomized. Neoadjuvant chemotherapy will be 6 cycles (1 cycle = 21 days) of estramustine (280 mg tid, days 1 to 5) and docetaxel (70 mg/m2 on day 2). Warfarin (2 mg/day orally) will be given for prophylaxis against deep venous thrombosis. Bilateral pelvic lymph node dissection and RP will be performed within 60 days of registration/randomization for men randomized to the surgery-alone arm. For men randomized to receive preoperative chemotherapy, the surgical procedure will be performed within 60 days of completion of chemotherapy. Patients will be monitored with history review, physical examination, and serum prostate-specific antigen (PSA) levels every 3 months for the first 3 years after surgery, every 6 months for the next 3 years, and annually thereafter. Biochemical disease recurrence will be defined as a serum PSA level >0.4 ng/mL on 2 consecutive occasions > or =3 months apart after RP. The time of biochemical failure is measured from the date of randomization to the time of the first PSA level <0.4 ng/mL that is confirmed on the second serial PSA. The primary study end point is to determine if early systemic treatment with neoadjuvant estramustine and docetaxel before RP in patients with high-risk prostate cancer will decrease 5-year recurrence rates when compared with RP alone. Secondary outcomes will include (1) the safety and tolerability of neoadjuvant estramustine and docetaxel before RP; (2) the impact of this neoadjuvant strategy on pathologic tumor stage, including lymph node and surgical margin status; (3) time to clinically apparent disease recurrence; and (4) overall survival. The impact of RP with and without neoadjuvant estramustine and docetaxel on the patient's quality of life from pretreatment through year 3 will be assessed. Frozen prostate tissue will be obtained from men undergoing prostatectomy who are enrolled in either the treatment or control arms of the trial. These samples will be analyzed for their RNA expression patterns in order to build outcome prediction models. Furthermore, using array-based methods of expression analysis, the sensitivity to chemotherapeutic agents and response to chemotherapy may likewise be predicted. The trial will enroll approximately 700 men during a 48-month period. Patients will be observed for 84 months after study closure. The power to detect a 36% decrease in 5-year recurrence rates is 90%.
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PMID:Cancer and Leukemia Group B (CALGB) 90203: a randomized phase 3 study of radical prostatectomy alone versus estramustine and docetaxel before radical prostatectomy for patients with high-risk localized disease. 1474 42

Venous thromboembolic disease (deep vein thrombosis and pulmonary embolism) are common disorders with serious morbid and mortal complications. Given the varied modes of presentation, a high clinical index of suspicion in patients at risk must exist among physicians. Standard therapy has consisted of intravenous unfractionated heparin and overlapping administration of an oral Vitamin K antagonist, commonly Warfarin. Although an effective strategy, many practical limitations exist, including the need for prolonged hospitalization, frequent laboratory monitoring for anticoagulant effect, and erratic dose-response curves. Recently, subcutaneous low-molecular-weight heparins have emerged as safe and effective alternatives for unfractionated heparin. Appropriate patients may be treated with low-molecular-weight heparins and oral Warfarin entirely as outpatients, with similar efficacy and risk of recurrent thromboembolic events and hemorrhage. Thrombolytic therapy is a reasonable alternative in patients with iliofemoral venous thrombosis and/or pulmonary embolism resulting in hemodynamic compromise or obstructing significant pulmonary vasculature. Risks of serious hemorrhagic side effects including intracranial hemorrhage, along with the added economic burden, have limited widespread acceptance of thrombolytic therapy as primary treatment. Emerging oral direct thrombin inhibitors and other novel agents stand to move the treatment of patients with venous thromboemboli to even greater levels of safety and efficacy.
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PMID:Medical management of venous thromboembolic disease. 1525 62

A group of 256 newly diagnosed myeloma patients were enrolled in a phase III study that included 4 monthly cycles of induction chemotherapy and tandem transplant. All patients were randomized to either receive or not receive thalidomide. A total of 221 patients (86%) received no prophylactic anticoagulation (cohort I); 35 patients received low dose coumadin (cohort II). The incidence of deep vein thrombosis (DVT) was significantly higher in the thalidomide arm hazard ratio: 4.5; P < 0.0001). As low dose coumadin (1 mg/d) failed to decrease thrombotic complications in 35 patients (cohort II), low molecular weight heparin (LMWH, enoxaparin 40 mg s.c. q.d.) was instituted as DVT prophylaxis in the thalidomide-treated patients (n = 68) of the subsequent cohort (n = 130, cohort III). This intervention eliminated the difference in DVT incidence between the two arms (thalidomide and no thalidomide). Within cohorts I and II, 36 patients, in whom thalidomide was discontinued after experiencing a thrombotic episode during chemotherapy, subsequently resumed the drug on full anticoagulation; with a median follow-up of 22 months, DVT recurred in four patients (11%). After completing induction and tandem transplantation, 55 patients were re-exposed to thalidomide and chemotherapy during consolidation treatment. Thrombotic complications were observed in 4%. Our experience, although not based on a randomized study, suggests that the excess frequency of thrombosis in patients treated with chemotherapy and thalidomide can be safely reduced by the prophylactic use of LMWH. The rate of DVT recurrence observed in our study upon thalidomide resumption was sufficiently low to allow its continuation in patients who may benefit from this therapeutic intervention.
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PMID:Deep vein thrombosis in patients with multiple myeloma treated with thalidomide and chemotherapy: effects of prophylactic and therapeutic anticoagulation. 1532 25

Warfarin is the most widely prescribed oral anticoagulant for the management of a wide variety of thromboembolic disorders such as atrial fibrillation and deep vein thrombosis. A panel of warfarin-protein conjugates were produced and characterised and subsequently used for the production of monoclonal antibodies to warfarin. Following characterisation, the monoclonal antibodies were used in the development of a surface plasmon resonance-based inhibition immunoassay for the determination of the physiologically active 'nonprotein'-bound fraction of the drug in plasma ultrafiltrate. The inhibition immunoassay was compared with an existing high-performance liquid chromatography (HPLC) chromatographic technique for the determination of warfarin in plasma ultrafiltrate, and an excellent correlation was achieved between the two independent analytical techniques. The ligand-binding capacity and stability of various immobilised ligands were also compared. The BIACore-based inhibition immunoassay demonstrated an assay precision range of approximately 4-250 ng/ml, which is within the clinical range and demonstrated good reproducibility and robustness.
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PMID:The development and application of a surface plasmon resonance-based inhibition immunoassay for the determination of warfarin in plasma ultrafiltrate. 1534 1

Every year, approximately 2 million people experience a deep venous thrombosis (DVT). Approximately 600,000 of these people are diagnosed with a pulmonary embolism and about 10% of these die. It has been established that surgery, anesthesia, and bed rest increase the risk of DVT, and therefore, patients who undergo a major lower-extremity procedure should receive prophylaxis. During the past 10 years, the choices of pharmacological and mechanical prophylaxis have increased greatly. Warfarin is probably the most widely used prophylactic method in the U.S., but low-molecular-weight heparin (LMWH) use has increased. Also available is a synthetic pentasaccharide that acts as an anti-Xa inhibitor to decrease DVT without increase in bleeding. All but warfarin are given by subcutaneous injection and require no laboratory management to adjust the medication. Another drug in clinical trials is a direct thrombin inhibitor taken orally in a fixed dose that does not require monitoring. Non-pharmacological prophylaxis and/or stacked modalities, although used, have not shown the efficacy of pharmacological prophylaxis. With the incidence of DVT reported in the range of 41% to 85% without prophylaxis in joint replacement and hip-fracture surgery, prophylaxis is warranted in all lower-extremity joint replacement and hip-fracture patients.
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PMID:Advances in DVT prophylaxis and management in major orthopaedic surgery. 1545 36

Patients who undergo orthopaedic surgery are at substantially increased risk for venous thromboembolic events. These include proximal and distal deep vein thrombosis, with the former more likely to lead to pulmonary embolism and fatal complications. Anticoagulants are routinely used for venous thromboembolism prophylaxis in patients undergoing total hip or total knee replacement surgery. Although current treatments offer effective prophylaxis, they have disadvantages. Warfarin is limited by the requirement for coagulation monitoring to ensure effective and safe use. Similarly, low-molecular-weight heparins (LMWHs) have disadvantages, including the need for parenteral administration. This article brings together data from clinical trials of the novel oral direct thrombin inhibitor, ximelagatran, in the prevention of venous thromboembolism in patients undergoing elective total hip or total knee replacement. The ximelagatran clinical trial programme in orthopaedic surgery has focused primarily on five large multicentre studies in Europe (the Melagatran Thromboprophylaxis in Orthopaedic surgery II and III and Expanded Prophylaxis Evaluation Surgery Study studies) and in the United States (the Exanta Used to Lessen Thrombosis A and B studies), which enrolled more than 8000 patients. In addition, the USA clinical trial programme included three other trials that investigated ximelagatran in orthopaedic surgery; two of these studies focused on prevention of venous thromboembolism after total knee replacement, and one study investigated prevention of venous thromboembolism after total hip replacement. These studies compared ximelagatran with the LMWHs dalteparin and enoxaparin and with warfarin, and were designed to reflect regional differences in venous thromboembolism prophylaxis and to build on findings from previous studies. Generally, ximelagatran has been shown to possess comparable or greater efficacy relative to comparators. The timing and dose of ximelagatran have been shown to be important determinants of its efficacy and safety. As ximelagatran can be given in fixed oral dosing without coagulation monitoring, it is an attractive choice for the prevention of venous thromboembolism in major elective orthopaedic surgery.
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PMID:Clinical experience with ximelagatran in orthopaedic surgery. 1558 25

Venous thromboembolism, which is manifested as deep vein thrombosis (DVT) and pulmonary embolism (PE), represents a significant cause of death, disability, and discomfort. Two million people/year are affected by VTE, making it the third most common cardiovascular disease after coronary heart disease and stroke. The rationale for VTE prophylaxis stems from the clinically silent presentation of the disease and its prevalence among hospitalized patients. At greatest risk are patients undergoing major orthopedic surgery and those admitted to the intensive care unit with acute myocardial infarction, heart failure, ischemic stroke, respiratory disease, systemic infection, or other medical conditions that immobilize patients for 5 days or longer. Several anticoagulant regimens have been effective in reducing the risk of VTE after major orthopedic surgery. For patients undergoing total hip or knee replacement, treatment with adjusted-dose warfarin, low-molecular-weight heparins, or fondaparinux may be used. Warfarin, which has been around for more than 50 years, is the only oral anticoagulant available for VTE prophylaxis. Ximelagatran, a new low-molecular-weight oral prodrug of the direct thrombin inhibitor melagatran, has advantages over warfarin that may make it the drug of choice for prevention of VTE.
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PMID:The role of oral direct thrombin inhibitors in the prophylaxis of venous thromboembolism. 1562 37


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