Is D‐dimer the new test for venom‐induced consumption coagulopathy after snakebite?

Despite its potential value, a number of questions require answers before its role in clinical practice becomes clear

For many clinicians working in rural Australia, people bitten by snakes can present significant diagnostic and logistical challenges. The current advice is that these patients be managed in a hospital with a laboratory, antivenom, and clinicians who can manage the complications of both the envenoming (such as neurotoxicity) and the antivenom (anaphylaxis).1 As many rural hospitals have limited or no immediate access to laboratories, patients (many of whom are not envenomed) must be transported hundreds of kilometres, often after hours. As envenomed patients do better if antivenom is administered early, delaying its provision can increase the risks of complications. Consequently, simple and accurate bedside investigations for diagnosing or excluding envenoming are urgently required, both in Australia and overseas.2

In the study for the Australian Snakebite Project reported in this issue of the MJA, Isbister and colleagues assessed the diagnostic accuracy of laboratory D‐dimer investigations for detecting venom‐induced consumption coagulopathy (VICC) after snakebite.3 They found that D‐dimer assessment two to six hours after a bite, with a cut‐off of 2.5mg/L, provided 97.1% sensitivity and 99.0% specificity for detecting VICC. Further, 95% of people not envenomed had D‐dimer values below 2.5mg/L six hours after the bite.3

Interestingly, D‐dimer values from within 24 hours of a snakebite were high (greater than 4mg/L; median, 20mg/L) for people who developed thrombotic microangiopathy or acute kidney injury.3 Whether this indicates that a greater clot burden plays a role in these complications is unclear, but the finding suggests that a markedly raised D‐dimer value could be used to predict which patients are likely to develop these complications.

Identifying patients with VICC using a D‐dimer strategy could facilitate early treatment with antivenom. Antivenom is of little benefit for treating VICC following envenoming by many Australian snakes,4 but the early identification of patients with VICC who were envenomed by snakes such as tiger snakes and taipans and could develop other complications (rhabdomyolysis, neurotoxicity) would be of great benefit.

While D‐dimer has promise as a marker for VICC, some limitations of the study must temper our enthusiasm. Firstly, as the authors point out, variations between Australian laboratories in D‐dimer testing and reporting are recognised.3 Current snakebite management advice recommends preparing a full coagulation profile.1,5 As coagulation profiles are reported together with D‐dimer results, the latter may be less helpful, as the clinical decision to administer antivenom is based on an abnormal coagulation profile. Further, D‐dimer results in the study by Isbister and colleagues were based on investigations within six hours of snakebite; this speed may be achievable in metropolitan centres, but difficult in many rural areas.

As point‐of‐care testing has become more frequent in rural Australia, could this approach be applied to D‐dimer testing? An Australian case report found that point‐of‐care D‐dimer testing was unreliable for diagnosing VICC,6 so more work is needed before this question can be assessed.

Could we use D‐dimer assessment as a rule‐out test? Isbister and colleagues found that 95% of people who had not been envenomed had D‐dimer values below 2.5mg/L. Could we use clinical findings or other simple investigations (such as the 20‐minute whole blood clotting test, 20WBCT2) to increase the proportion ruled out? Or is it reasonable to treat 5% of non‐envenomed people with antivenom? These questions need to be further investigated and discussed.

And what about snake envenoming outside Australia? The World Health Organization estimates that 2.7 million people are envenomed by snakes each year, although the exact number is unknown.7 In many other countries, vipers are the main cause of snake envenoming. Although people envenomed by vipers may have elevated D‐dimer levels, we cannot directly generalise the findings of Isbister and colleagues to such bites, but they nevertheless provide a direction for further research.

Finally, could other techniques for investigating snakebite coagulopathy be useful? In many major centres in Australia, thromboelastography, thromboelastometry, rotational thromboelastography, and rotational thromboelastometry are used in the management of major haemorrhage after trauma, for example. These techniques have been used as bedside tests to assess coagulopathy in snakebite cases in less well resourced countries,8,9 as well as in a small case series in Australia (taipan bites).10 A major disadvantage is the cost of the required machines (about $US30000 each).10

Isbister and colleagues are to be congratulated for their study, but the question for us all is how we should use D‐dimer assessment in clinical practice for managing people with snakebite in Australia.