Pharmacology and Toxicology of a Defibrinating Substance From Malayan Pit Viper Venom

Experimental Defibrination with Bothropase

“…The inhibition of plasminogen activator by EACA did not prevent plasmin formation ( fig. 3), as stated already [5,22,16,3,9]. These results confirm the importance of the fibrinolytic activity during defibrination as reported by K w a a n and Barlow [15], and that the role of the RES in the removal of the fibrinogen related material during defibrination with venom is of only minor importance [16,23,7,8].…”

“…During defibrination therapy with Arvin or Reptilase, there is a decrease of fibrinogen and plasminogen levels and presence of fibrinogen-fibrin de gradation products (FDP), but no increase of plasma fibrinolytic activity [19,9,10], The activation of the endogenous fibrinolytic system as a se condary effect of the intravascular coagulation [24,22,21,25] is not pre vented by EACA [5,22,16,3,9], whereas in Reptilase-treated dogs, Trasylol was able to delay but not to prevent the fibrinolytic response [19,9,10]. On the other hand, the presence of soluble unclottable complexes during defi brination with Ancrod or Defibrase would indicate that FDP is derived from proteolysis of soluble fibrin [2,11,17].…”

The Role of Blood Platelets in Experimental Metastases

“…To study the behaviour of blood platelets in the absence of clottable fibrinogen, the animals were rendered afibrinogenaemic by the injection of ancrod (a fraction of the venom from the Malayan pit viper Akistrodon rhodostoma). Ancrod induces a state of hypofibrinogenaemia in various laboratory animals by formation of intravascular microclots which are rapidly removed from the circulation (Ashford, Ross and Southgate, 1968). The number and function of circulating platelets are not affected by this treatment (Davey and Luischer, 1965).…”

Mechanism of ancrod anticoagulation

“…Both purified coagulants are known to cause a marked lowering of the plasma fibrinogen by converting it to fibrin which in turn, is assumed to be rapidly digested by plasmin before significant vascular occlusion and organ dysfunction occur (3)(4)(5)(6)(7)(8)(9)(10). Of the two preparations, ancrod has been more extensively studied in humans, and to date, there appears to be very few thrombotic, hemorrhagic, or allergic complications associated with its use (5,6,(11)(12)(13)(14)(15)(16)(17).…”

“…As a result of such observations, attention has been focused on these two venom enzymes for their potential usefulness in acute thromboembolic disorders. intravascular fibrin fornmation which in turn evokes an enhanced blood fibrinolytic state (4,6,12,30). Both the increased fibrinolysis and the reticuloendothelial system are thought to be important in the clearance of such intravascular fibrin (31).…”