Biology Reference
In-Depth Information
Antifibrinolytics, Vitamin K, and ACTH
Antifibrinolytic therapy, often combined with vitamin K, was used in several cases
of presumed or verified
R. tigrinus
envenomation (Mandell et al., 1980; Mittleman
and Goris, 1974). Mandell et al. (1980) reported clinical improvement in observed
clotting after i.v. administration of aminocaproic acid and hydrocortisone to a pedi-
atric patient envenomed by a presumed
R. tigrinus
. Earlier treatment with vitamin K
was ineffective. Similarly, in one case retrospectively summarized by Mittleman and
Goris (1974), a patient was given i.v. vitamin K
1
,
-aminocaproic acid, and hydro-
cortisone. This treatment reportedly resulted in stable clot formation. Continued
infusion of
-aminocaproic acid for an additional 8 h was said to cause further
improvement in clot formation and cessation of superficial bleeding (Mittleman and
Goris, 1974). A patient with consumptive coagulopathy/DIC and renal failure fol-
lowing
R. tigrinus
envenoming exhibited no clinical benefit from i.v. administration
of transexamic acid (Mittleman and Goris, 1978).
Provision of i.v. vitamin K for
R. subminiatus
venom-induced hemorrhagic dia-
thesis did not produce any clinical benefit (Cable et al., 1984). Administration of i.v.
ACTH to a patient with
R. tigrinus
venom-induced consumptive coagulopathy/DIC
was ineffective, while blood transfusion reportedly corrected aberrant coagulation
(Mittleman and Goris, 1974).
The lysine analogs, transexamic acid and aminocaproic acid, prevent fibrinoly-
sis by inhibiting plasminogen and the binding of plasmin to fibrin (Slaughter and
Greenberg, 1997). Although these have variable utility in controlling perioperative
bleeding and menorrhagia (Schouten et al., 2009; Wellington and Wagstaff, 2003),
their use in management of envenomation is limited to a few isolated cases without
formal clinical evaluation or testing. Therefore, these are contraindicated.
Vitamin K
1
(phytonadione) is used in the prevention and treatment of hypopro-
thrombinemia caused by vitamin K deficiency, oral anticoagulants, or other factors
which impair the absorption or synthesis of vitamin K. Phytonadione is also used in
the prevention and treatment of hemorrhagic disease of newborns. Its mechanism of
action remains unclear, but it is necessary for hepatic synthesis of factor II (prothrom-
bin), factor VII (proconvertin), factor IX (thromboplastin), and factor X (prothrombi-
nase). Aside from a limited retrospective review of seven cases (Dabo et al., 2002), the
use of vitamin K in management of envenoming is without any formal testing or eval-
uation. It has no proven benefit and may carry risk, and is therefore contraindicated.
Similarly, the previously documented use of ACTH or hydrocortisone has no apparent
clinical strategic benefit and is also contraindicated.
4.6.2.10 Prothrombin and Direct Thrombin Inhibitors
There are no data regarding the use of prothrombin inhibitors such as α-drotrecogin,
direct thrombin inhibitors (DTI; e.g., argatroban, bivalirudin, and hirudin), or Factor
Xa inhibitor (fondaparinux) in hemorrhagic-coagulopathic envenoming. Some data
obtained from studies of antithrombotic therapy during percutaneous cardiac interven-
tion (cardiac catheterization) suggest that the DTI, bivalirudin, may offer reduced bleed-
ing risk in comparison with some other assessed antithrombotics (Bonaca et al., 2009).
