Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High-dose interleukin-2 (IL-2) immunotherapy can cause hypotension, respiratory distress, interstitial edema, and thrombocytopenia, similar to endotoxic shock. We have observed that IL-2 has no direct effect on coagulation factors in vitro, but it has been observed to alter the coagulant properties of vascular endothelium. Accordingly, we investigated the possibility that IL-2 infusions initiate plasma fibrinolysis and disseminated intravascular coagulation (DIC). We studied the clinical course, platelet count, and coagulation profile in response to IL-2 infusion in seven patients, two with metastatic melanoma and five with metastatic renal cell carcinoma. Every patient experienced hemodynamic instability and thrombocytopenia, and one patient suffered an unusual complication, mesenteric thrombosis. No patient had appreciable changes in the prothrombin time or the partial thromboplastin time, nor did factors V or VIII decline in the two patients observed. In four patients examined, we found decreased titers of Hageman factor (factor XII), high molecular weight kininogen, prekallikrein, and plasma thromboplastin antecedent, as if these had been consumed by reactions of the intrinsic pathway of thrombin formation. Circulating D-dimer fragments were found in the plasma of every patient at some point during each infusion cycle, and we observed decreased titers of plasminogen in the four patients just mentioned, suggesting that IL-2 infusions initiated fibrinolysis. Taken together, the clotting factor derangements and related toxicity phenomena cannot be ascribed firmly to DIC. Activation of the intrinsic (contact) system of coagulation, however, may provide one link between the vascular endothelial surface alterations caused by IL-2 infusions and the development of the systemic toxicity that resembles septic shock.
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PMID:Fibrinolysis, thrombocytopenia, and coagulation abnormalities complicating high-dose interleukin-2 immunotherapy. 198 12

Sunitinib is an increasingly used, orally administered targeted therapy, approved by the European Medicines Agency for the treatment of various types of cancer, including gastrointestinal stromal tumor unresectable or metastatic disease, following disease progression or intolerance to imatinib, and advanced or metastatic renal cell carcinoma, progressive well-differentiated pancreatic neuroendocrine tumors in patients with unresectable, locally advanced or metastatic disease. Sunitinib inhibits several tyrosine kinases, including the vascular endothelial growth factor receptor and the platelet-derived growth factor receptor. Tyrosine kinases inhibitor therapies are generally well-tolerated; nonetheless, they are not void of side effects. The majority of patients reported are grade 1 or 2, and include common and unspecific adverse events, including fatigue, gastrointestinal disorders, skin discoloration, altered taste, cough and dyspnea. Grade 3 or 4 adverse events, including bleeding and hemorrhage, are less frequent. The present study presented the first case of disseminated intravascular coagulation associated with the administration of sunitinib, shortly following the increase of sunitinib dosage.
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PMID:Disseminated intravascular coagulation following administration of sunitinib. 2733 Jul 81

A 64-year-old man was treated with sunitinib as a first-line therapy for metastatic renal cell carcinoma. He was given oral sunitinib in cycles of 50 mg once daily for 2 weeks followed by a week off. During the 5th week of treatment right upper quadrant pain developed, but this resolved spontaneously during the 6th week (off treatment). However, on the 8th week of treatment, he was admitted to hospital because the acute right upper quadrant pain recurred with nausea, vomiting, and fever. Acute acalculous cholecystitis was then diagnosed by ultrasonography and CT. In addition, his laboratory findings indicated disseminated intravascular coagulation. Accordingly, sunitinib therapy was discontinued and broad-spectrum antibiotics initiated. He subsequently recovered after emergent percutaneous cholecystostomy. His Naranjo Adverse Drug Reaction Probability Scale score was 7, indicaing a probable association of the event with sunitinib. Suspicion of sunitinib-related acute cholecystitis is required, because, although uncommon, it can be life-threatening.
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PMID:[Acute Acalculous Cholecystitis Associated with Sunitinib Treatment for Renal Cell Carcinoma]. 3209 65