[A study of human annexin V derivative: its effects of anticoagulation and antithrombosis].
OBJECTIVE
To investigate the effects of a new anticoagulant, annexin V derivative (AND) on anticoagulation and antithrombosis.


METHODS
High and low doses of AND were given to rabbits (groups 1 and 2 respectively) by intravenous (iv) bolus injections followed by half the respective AND doses by iv infusion over 2 hours. Control groups were iv given heparin (group 3) and saline (group 4) of the same volume and procedure as that in group 1 and 2. Blood cell count, activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and fibrinogen level were examined before and 15, 30 and 60 min after iv bolus and 2 hours after the end of iv infusion. A 3.0 mm x 15 mm balloon was put into femoral artery to induce endothelial denudation 15 min after IV bolus and the blood pressure of femoral artery was monitored until the pulse pressure recorded 0 mm Hg when the vessel was occluded completely by a thrombus. The femoral arteries were collected and the thrombi were stripped off for measuring their lengths, wet and dry weights.


RESULTS
Anticoagulation parameters: APTT at 15 min after iv bolus in AND group was significantly longer than that in group 4 (P < 0.05) but shorter than that in group 3 (P < 0.05); APTT and TT in group 3 were significantly longer than those in groups 1, 2 and 4. Fibrinogen: 0.70 mg/kg AND may decrease fibrinogen. Antithrombosis values: the wet and dry weights in AND groups were significantly lighter than those in group 3 and 4 (P < 0.05). The dry weight in high-dose AND group was remarkably lighter than that in low-dose group (P = 0.029). The length of thrombus in low-dose AND group was remarkably shorter than that in group 4 (P = 0.013), but not for group 3 (P > 0.05). It was remarkably shorter in high-dose AND group than in both group 3 (P < 0.001) and 4 (P = 0.015). The time when pulse pressure equaled to 0 was longer in AND group than in group 4 (P < 0.05), but not in 3.


CONCLUSIONS
AND is an effective anticoagulant and antithrombosis agent, the highest anticoagulation effect occurs at 15 min after IV bolus. Its anticoagulation effect is not more potent than that of standard heparin, while antithrombosis capacity is more effective. AND in treating thrombosis clinically might be promising.
Ju
Cheng-wei
CW
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nangjing 210029, China.
Wang
Lian-sheng
LS
Yang
Xiang
X
Ma
Gen-shan
GS
Hua
Zi-chun
ZC
Gao
Xing-ya
XY
D000818:Animals; D017304:Annexin A5 / Q000008:administration & dosage / Q000494:pharmacology*; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D004195:Disease Models, Animal; D005340:Fibrinogen / Q000032:analysis; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D010314:Partial Thromboplastin Time; D011517:Prothrombin Time; D011817:Rabbits; D011897:Random Allocation; D013918:Thrombin Time; D013927:Thrombosis / Q000517:prevention & control*
D017304:Annexin A5; D000925:Anticoagulants; D005340:Fibrinogen