Complications from vascular disrupting agents and angiogenesis inhibitors: aberrant control of hemostasis and thrombosis.
OBJECTIVE
To discuss thrombotic and hemorrhagic complications from angiogenesis inhibitors and vascular disrupting agents, pathogenesis, and recommendations for prophylaxis and management of those complications.


RESULTS
Venous thromboembolism has been a significant complication of the angiogenesis inhibitors thalidomide and lenalidomide. Prophylaxis with aspirin, low-molecular-weight heparin, or warfarin has been shown to decrease rates of venous thromboembolism in patients treated with these agents. Life-threatening hemorrhage and arterial thromboembolism have been observed in patients using treatments that inhibit the vascular endothelial growth factor signaling pathway. Patients should be screened for arterial thromboembolism and hemorrhage risk prior to using vascular endothelial growth factor signal inhibitors. It is not known how angiogenesis inhibitors and vascular disrupting agents upset normal hemostasis. It is likely that disruption of the function and/or integrity of vascular endothelium leads to an increased risk for thrombosis and/or hemorrhage.


CONCLUSIONS
New angiogenesis inhibitors and vascular disrupting agents have been developed that have significant activity against neoplasms. Potentially life-threatening side effects of hemorrhage and thrombosis have been observed with many of these new agents. As new treatments that disrupt angiogenesis or existing tumor vasculature are developed, attention should be given to these toxicities in clinical practice and clinical trials.
van Heeckeren
Willem J
WJ
CASE Comprehensive Cancer Center, CASE School of Medicine, Division of Hematology/Oncology, University Hospitals Case Medical Center, Cleveland, Ohio 44106, USA. wvanheeckeren@yahoo.com
Sanborn
Sharon L
SL
Narayan
Ajita
A
Cooney
Matthew M
MM
McCrae
Keith R
KR
Schmaier
Alvin H
AH
Remick
Scot C
SC
D020533:Angiogenesis Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D000818:Animals; D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005343:Fibrinolytic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D006470:Hemorrhage / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects; D042442:Vascular Endothelial Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D054556:Venous Thromboembolism / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control
D020533:Angiogenesis Inhibitors; D000925:Anticoagulants; D005343:Fibrinolytic Agents; D042442:Vascular Endothelial Growth Factors