Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034065 (pulmonary embolism)
 14,979 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe 2 adult patients with acute lymphoblastic leukaemia (ALL) who died from pulmonary embolism following L-asparaginase treatment. Since this drug is known to cause a decrease in antithrombin III, the most important protein physiologically involved in the neutralization of thrombin, we studied the behaviour of this inhibitor in 14 ALL patients treated with a protocol including a 14-day course of L-asparaginase. A significant but transient fall of biological and immunological antithrombin III and a concomitant reduction of fibrinogen were documented.
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PMID:Fatal pulmonary embolism and antithrombin III deficiency in adult lymphoblastic leukaemia during L-asparaginase therapy. 640 3

Among its multiple toxic effects, L-asparaginase induces allergic reactions that may reduce its biological effect. The impact of hypersensitivity reactions on the duration of leukemia-free survival (LFS) was assessed in adults with newly diagnosed acute lymphoblastic leukemia (ALL) receiving intensive multi-agent chemotherapy. In CALGB study 8811 (Blood 1995; 85: 2025-2037), 197 adults were scheduled to receive 14 doses of Escherichia coil L-asparaginase (6000 U/m2 SC) during 7 of the first 12 weeks of chemotherapy. No further L-asparaginase was given. Chemotherapy was given for 24 months. The median follow-up time has been 5.7 years. Of the 141 patients who remained on study after 12 weeks, 82 (58%) had received all 14 planned doses; 38 (27%) had 12-13 L-asparaginase doses documented in their treatment record; 21 (15%) patients had received < or =11 doses due to a variety of toxic effects. The mean number of doses received prior to experiencing any hypersensitivity reaction was seven (range 1-11). Seven patients had mild hypersensitivity reactions, but all seven eventually received 12-14 doses of E. coil L-asparaginase. Twenty-one other patients had severe hypersensitivity reactions that required discontinuation of E. coil L-asparaginase; 20 of these patients were switched to Erwinia L-asparaginase to complete their treatment. Ultimately, 12 of these 20 patients received 14 doses of L-asparaginase in total, and six received 12-13 doses. Thus, only three of the 21 patients who had severe hypersensitivity reactions received < or =11 total L-asparaginase doses. Other L-asparaginase-related complications included pancreatitis (15 patients), hypofibrinogenemia <100mg/dl (29 patients), and deep venous thrombosis or pulmonary embolism (eight patients); some of these patients had L-asparaginase discontinued after these complications. The estimates for LFS at 3 years were 55% (95% confidence interval, 44-65%) for the patients who received all 14 L-asparaginase doses (median LFS, 5.1 years), 47% (95% CI, 33-62%) for those who received 12-13 doses, and 48% (95% CI, 29-67%) for those who received < or =11 doses. There were no significant differences between these three groups in the length of LFS (P=0.68). LFS did not correlate with a history of severe hypersensitivity reaction (P=0.67). In general, E. coil L-asparaginase was well tolerated in these adult patients, and most patients received all of the planned therapy. Patients who had mild L-asparaginase hypersensitivity reactions and patients who switched to Erwinia L-asparaginase because of more severe allergic reactions did not have significantly shorter LFS than the remaining adults treated on this ALL protocol. The possibility that E. coli L-asparaginase is inactivated or destroyed in those individuals who have become hypersensitive to it becomes less important when allergic patients are secondarily treated with Erwinia L-asparaginase.
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PMID:Hypersensitivity reactions to L-asparaginase do not impact on the remission duration of adults with acute lymphoblastic leukemia. 959 62

Forty-one consecutive children with acute lymphoblastic leukemia (ALL) received prophylaxis therapy with the low molecular weight heparin (LMWH) enoxaparin during L-asparaginase treatment. Enoxaparin was given every 24 h subcutaneously at a median dose of 0.84 mg/kg per day (range, 0.45-1.33 mg/kg per day) starting at the first dose of L-asparaginase until 1 week after the last dose. Molecular analysis for thrombophilic polymorphisms documented prothrombin G20210A mutation in 3/27 (11%), homozygosity for MTHFR C677T mutation in 5/27 (18.5%, and heterozygosity for factor V Leiden mutation in 5/27 (18.5%) children. There were no thrombotic events during 76 courses of L-asparaginase in 41 patients who had received enoxaparin. One patient suffered brain infarct 7 days after enoxaparin was stopped. There were no bleeding episodes. In a historical control group of 50 ALL children who had not received prophylactic enoxaparin during L-asparaginase treatment, two had thromboembolisms (one deep vein thrombosis and one pulmonary embolism). Enoxaparin is safe and seems to be effective in prevention of thromboembolism in ALL patients during L-asparaginase therapy. This study provides pilot data for a future randomized trial of the use of LMWH during ALL therapy for the prevention of asparaginase-associated thrombotic events.
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PMID:Prophylactic therapy with enoxaparin during L-asparaginase treatment in children with acute lymphoblastic leukemia. 1150 79

It is well known that solid cancers are associated with thromboembolic complications, but recent studies have shown that the incidence of thrombosis may be as high (or even higher) in patients with malignant haematological disorders. However, this may be obscured by the significant morbidity and mortality due to other complications of haematological malignancies, such as bleeding and infections. The vast majority of patients with haematological neoplasias also have clinically silent haemostatic abnormalities, but some may show clinical manifestations, including venous thromboembolism, pulmonary embolism, disseminated intravascular coagulation and life-threatening thrombohaemorrhagic syndrome in acute leukaemias. The pathogenesis of thromboembolic disease in haematological malignancies is complex and multifactorial: tumour cell-derived procoagulant, fibrinolytic or proteolytic factors and inflammatory cytokines affect clotting activation, and chemotherapy and anti-angiogenic drugs increase thrombotic risk in patients with lymphoma, acute leukaemia and multiple myeloma. Infectious complications are another important factor: endotoxins from gram-negative bacteria induce the release of tissue factor (TF), Tumor Necrosis Factor (TNF) and interleukin-1b (IL-1b), and gram-positive organisms can release bacterial mucopolysaccharides that directly activate factor XII. Leukaemic patients may be affected by other prothrombotic factors, including hyperleukocytosis, increased TF expression and activation, and the prothrombotic properties of therapeutic agents such as all-trans retinoic acid and L-asparaginase, which can induce thrombosis involving multiple organs. The very high risk of haemorrhaging in these patients warrants prospective randomised trials evaluating optimal anti-thrombotic prophylaxis and treatment.
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PMID:Thromboembolic complications in malignant haematological disorders. 1948