Biology Reference
In-Depth Information
Appendix C
Strategies of Management of
Gram-Negative Septicemia: Are There
Lessons to Be Learned for Managing
Venom-Induced Coagulopathies?
1
Although pathophysiologically distinctive, some general similarities between haz-
ard level 1 colubrid envenoming and gram-negative septicemia can be identified.
Septic patients with endotoxemia-induced consumptive coagulopathy/disseminated
intravascular coagulation (DIC) often are treated with fresh-frozen plasma (FFP),
cryoprecipitate, purified coagulation factors, platelets, protein C, and, occasionally,
drotrecogin-α (Dempfle, 2004). Some investigators have highlighted differences
between coagulopathic envenomations and DIC, questioning the appropriateness of
the term for the venom-induced disease (Isbister, 2010). Isbister (2010) stated that
the lack of evidence of systemic microthrombi, and end-organ failure in venom-
induced coagulopathy, was indicative of an absence of DIC. In addition, he stressed
the differences between the time course of venom-induced coagulopathy and the
mechanism of initiation of coagulation activation, as thrombin generation in DIC
is mediated by the tissue factor/factor VIIa pathway. It can be argued that the renal
injury on hazard level 1 envenomation certainly may constitute end-organ damage
and the pathways (e.g., “intrinsic” and “extrinsic” used as convenient terms of refer-
ence [see Figure 4.1]) can function simultaneously
in vivo
without precise detection.
A current Japanese expert consensus regarding potential pharmacotherapy for
treatment of DIC generally recommends low-molecular weight heparin (LMWH),
unfractionated heparin (UFH), antithrombin, and synthetic protease inhibitor (SPI;
Wada et al., 2010). This consensus also asserted a provisional caution in regard to
treatment of hemorrhagic diathesis in which LMWH, synthetic protease inhibitor
(SPI), and antithrombin were recommended with recognition of a lack of quality
evidence (Wada et al., 2010). However, this panel also declined recommendation of
LMWH, UFH, and danaproid sodium for use in cases with life-threatening bleed-
ing, while SPI is recommended in this scenario as it does not exacerbate bleeding
(Wada et al., 2010). These authors also recognized replacement therapy (blood, FFP,
platelets) as clinically indicated in life-threatening hemorrhagic diathesis. Their
recommendations emphasized concerns regarding the frequent association of DIC
with thrombosis (Wada et al., 2010). This is relevant to some serious hazard level 1
colubrid envenoming, as noted in some of the representative cases analyzed in this
topic (Table 4.1; Section 4.3). The extent of thrombosis in some of these cases can
1
This appendix was solely authored by SAW.
