title: D-dimer elevation and paresis predict thromboembolic events during bevacizumab therapy for recurrent malignant glioma.
abstract: BACKGROUND
  The major side-effects of bevacizumab in glioma treatment are venous thromboembolic events (VTE). We retrospectively evaluated factors potentially predictive of thromboembolic events.
  
  
  METHODS
  Bevacizumab, alone or in combination with chemotherapy was used as salvage therapy for recurrence in malignant glioma every two weeks. None but one patient received anti-coagulants. Before each bevacizumab cycle differential blood cell count, kidney and liver parameters, D-dimers, neurological status, body-mass index, vital signs and signs of venous thrombosis were assessed.
  
  
  RESULTS
  Thirty-eight patients received 428 cycles of bevacizumab. In five patients (13%), six VTE were observed. These complications were preceded four weeks before the onset of symptoms by D-dimer elevation above 0.865 mg/l [p<0.0001; sensitivity=89% (95% confidence interval=83-93%); specificity=89% (95% CI=52-100%)]. An existing hemiparesis constituted a 27-fold risk elevation for thrombotic complication (p<0.0001, χ(2)-test).
  
  
  CONCLUSIONS
  D-Dimer elevation or hemiparesis predict VTE under bevacizumab and chemotherapy, four weeks before the event becomes clinically apparent. Future investigations should determine if prophylactic anti-coagulants for patients at risk may reduce the risk of VTE.
authors: Department of Neurosurgery, University Medicine Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany.
authors: Martin
authors: M
authors: Misch
authors: Marcus
authors: M
authors: Czabanka
authors: Julius
authors: J
authors: Dengler
authors: Mandy
authors: M
authors: Stoffels
authors: Gregor
authors: G
authors: Auf
authors: Peter
authors: P
authors: Vajkoczy
authors: Florian
authors: F
authors: Stockhammer
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D005500:Follow-Up Studies; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009367:Neoplasm Staging; D010291:Paresis / Q000139:chemically induced / Q000175:diagnosis* / Q000378:metabolism; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D013923:Thromboembolism / Q000139:chemically induced / Q000175:diagnosis* / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D000068258:Bevacizumab
keywords: D-dimer; Recurrent malignant glioma; bevacizumab; deep venous thrombosis