Novel targets for anticoagulants lacking bleeding risk
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Novel targets for anticoagulants lacking bleeding risk. / Bickmann, Julia K; Baglin, Trevor; Meijers, Joost C M; Renné, Thomas.
In: CURR OPIN HEMATOL, Vol. 24, No. 5, 09.2017, p. 419-426.Research output: SCORING: Contribution to journal › SCORING: Review article › Research
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TY - JOUR
T1 - Novel targets for anticoagulants lacking bleeding risk
AU - Bickmann, Julia K
AU - Baglin, Trevor
AU - Meijers, Joost C M
AU - Renné, Thomas
PY - 2017/9
Y1 - 2017/9
N2 - PURPOSE OF REVIEW: Arterial and venous thromboembolic diseases are associated with significant morbidity and mortality and present a major medical burden. Currently used anticoagulants for the prevention or treatment of thromboembolic events including heparins, vitamin K-antagonists and inhibitors of thrombin or factor Xa target enzymes of the coagulation cascade that are critical for fibrin formation. However, fibrin is also necessary for hemostatic mechanisms to terminate blood loss at injury sites. As a result currently used anticoagulants substantially raise the risk of bleeding and are associated with an increase in potentially life-threatening hemorrhage, partially offsetting the benefits of reduced thrombosis.RECENT FINDINGS: Within the last decade, experimental and preclinical data have revealed the existence of coagulation mechanisms that principally differ in thrombosis and haemostasis. Some coagulation proteins including, XI and XII have a differential role in haemostasis and thrombosis. Targeting these proteins may provide an opportunity to prevent thromboembolic disease without causing bleeding.SUMMARY: This review summarizes recent studies on selective targeting of coagulation proteins that may allow prevention and treatment of thrombosis without causing bleeding. These novel approaches present a possibility for selective interference with fibrin formation in pathologic thrombosis that may lead to a new generation of safe anticoagulant drugs.
AB - PURPOSE OF REVIEW: Arterial and venous thromboembolic diseases are associated with significant morbidity and mortality and present a major medical burden. Currently used anticoagulants for the prevention or treatment of thromboembolic events including heparins, vitamin K-antagonists and inhibitors of thrombin or factor Xa target enzymes of the coagulation cascade that are critical for fibrin formation. However, fibrin is also necessary for hemostatic mechanisms to terminate blood loss at injury sites. As a result currently used anticoagulants substantially raise the risk of bleeding and are associated with an increase in potentially life-threatening hemorrhage, partially offsetting the benefits of reduced thrombosis.RECENT FINDINGS: Within the last decade, experimental and preclinical data have revealed the existence of coagulation mechanisms that principally differ in thrombosis and haemostasis. Some coagulation proteins including, XI and XII have a differential role in haemostasis and thrombosis. Targeting these proteins may provide an opportunity to prevent thromboembolic disease without causing bleeding.SUMMARY: This review summarizes recent studies on selective targeting of coagulation proteins that may allow prevention and treatment of thrombosis without causing bleeding. These novel approaches present a possibility for selective interference with fibrin formation in pathologic thrombosis that may lead to a new generation of safe anticoagulant drugs.
KW - Journal Article
U2 - 10.1097/MOH.0000000000000367
DO - 10.1097/MOH.0000000000000367
M3 - SCORING: Review article
C2 - 28731874
VL - 24
SP - 419
EP - 426
JO - CURR OPIN HEMATOL
JF - CURR OPIN HEMATOL
SN - 1065-6251
IS - 5
ER -