Category Archives: antivenom

Death by caterpillar or: Consider zebras, but don’t memorize them

I’ve given lectures on lepidoptera before.  There are between 200-3500 envenomations from lonomia spp reported every year in Brazil, but they’ve increased yearly since 2000. This is most likely from increased time in the rain forest by loggers and people recreating, but it was originally described in rubber tree tappers. The giant silkworm moth caterpillar is particularly noted, because they’re the only one reported to cause hemorrhagic syndromes and acute renal insufficiency. The envenomation syndrome is severe enough that fatalities were noted prior to creation of antivenom in Brazil.

Thankfully, this case report doesn’t involve a fatality. What it does involve is the basis of the article, namely delayed presentation. The patient was envenomated, and 24 hours later noticed bleeding from his gums and his other scratches. He waited another 3 days to present for medical treatment. Thankfully, as if it was a snake, the patient brought some caterpillars with him to be identified as Lonomia spp. Initial labs showed “blood incoagulability”, which meant that it was outside the range of normal values of prothrombin activity and clotting times. These values changed ever so slightly by day 6, and on day 8 the patient had a headache, so he was finally treated with antivenom. Thankfully the CT of his head did not show intracranial hemorrhaging. His clotting time returned to normal after antivenom, and he was discharged on day 12.

The venom appears to be a procoagulant that causes thrombin formation, leading to DIC via prothrombin and factor X activators. Due to the moth larval stage living in colonies, often the venom load in the patient is high as the injury is usually from either stepping on or puttting their hand on multiple individual caterpillars.

The antivenom is of equine origin, and is an F(ab)2 product. It’s only recommended for moderate and severe cases, such as the one mentioned in the case report. There’s not a significant amount of evidence for premedication, it is common in Brazil to give antihistamines and steroids.

Of note, while there is danger of misidentification of the condition in Brazil, where it is at least heard of if not common, the risk is even greater in the returning traveler. This is clear in this fatal case report from Canada in 2008. This doesn’t mean that lonomia envenomation should be at the top of your differential for every coagulopathy, but being aware of it may help with those future zebras that come up in travelers. And you should especially be knowledgeable about it if you practice in Brazil.

Severe Hemorrhagic Syndrome After Lonomia Caterpillar Envenomation in the Western Brazilian Amazon: How Many More Cases Are There?
http://www.wemjournal.org/article/S1080-6032(16)30271-X/abstract

No really, snakes can hurt you after they’re dead

Even though we have all (hopefully) been taught that dead snakes can still envenomate people, apparently it hasn’t been reported much in the literature. I say this because this case report is in press as of 18 Nov 2016.
Southern Copperhead
In this instance a young man killed a copperhead by cutting it into three pieces. While holding the piece containing the snake’s head, “his right index finger brushed against the fang and was inadvertently punctured.” I’m sure all of us think that is exactly how this happened. Pain and swelling followed, so the patient went to his local hospital where he received 4 vials of antivenom.
There was further progression of the swelling and ecchymosis, so another 4 vials were administered. The patient was then transferred to a tertiary center “with concern for compartment syndrome of his hand.” Another 2 vials were given and the hand was elevated, and no operative intervention was done. Of note, his labs showed he did not have a bleeding diathesis, but readers of this blog already knew that.
I wish I didn’t have to say it, but sadly some people out there still believe that fasciotomies are required after snake bites. Truthfully, based on the evidence, the best treatment is antivenom and elevation, not surgeries that can cause complications and haven’t been shown to give benefit.
This paper does note that there have been multiple case reports of envenomations by dead rattlesnakes or rattlesnake heads. One even had been freeze-dried, bought at a gift shop, and used as a tie tack. Almost all of those required antivenom. This is an interesting thought, as recently deceased snakes likely retain the ability for the venom gland to contract reflexively. Envenomation from a freeze-dried snake has to be retained protein on the fang itself, as the ducts aren’t functioning anymore. This particular episode is the first documented case involving a copperhead that required antivenom.
So it is more than just an old wives tale. Dead snakes can still evenomate you, even if they’ve been dead for quite a while. So stay away from the pointy ends of snakes, and stop killing them for crying out loud.

Clinically Significant Envenomation From Postmortem Copperhead (Agkistrodon contortrix)
http://www.wemjournal.org/article/S1080-6032(16)30225-3/abstract

Copperheads don’t cause coagulopathy

CopperheadInLeavesCU.JPG
CopperheadInLeavesCU“. Licensed under Public domain via Wikimedia Commons.

Copperheads are common across the southeastern US, and are responsible for a significant number of crotalid envenomations in areas where they are endemic. However, they have the least potent venom of all the pit vipers, and often bites are self-limiting. Prior to development of CroFab, copperhead bites were generally not given antivenom, as the risks of the Wyeth product were felt too high for minimal benefits. Now, CroFab is felt to be safe enough to mitigate even mild symptoms of copperhead envenomations.

However, physicians typically work up copperhead bites the same way they do the other crotalid species. This includes chemistry, complete blood count, and coagulation studies. And often patients are admitted for serial checks of these lab values even if there are no significant physical exam findings.  But are these really necessary when the snake is clearly identified as a copperhead?

These authors suggest that it isn’t. They examined more than 10 years of data from their 2 hospitals in St. Louis and found 106 “probable” or confirmed copperhead bites. Of these, 6 had abnormal coagulation studies, all were minimally outside of normal limits. None had bleeding complications either. Thus, the utility of coagulation studies in copperhead bites is suspect.

So can we stop checking coags on these patients? It’s a decent consideration, in the absence of evidence of coagulopathy. More importantly, patients don’t need to be admitted for serial coagulation studies if the snake in question is definitively a copperhead.  Perhaps checking an initial lab, and if it it’s normal, send them home if no other concerning symptoms. However, if you’re considering giving antivenom, you’re not saving any money by not checking, and you’re probably not sending that patient home.

Lack of Coagulopathy After Copperhead Snakebites
http://www.annemergmed.com/article/S0196-0644(14)01130-5/abstract

Stroke after crotalidae antivenom

When it first came out, crotalidae polyvalent immune Fab (CroFab), was seen as a godsend by many. It didn’t cause anaphylaxis or serum sickness to nearly the same degree as the old product. There was plenty of safety data, so it started to be used in less severe cases that before, antivenom would be withheld because the risks outweigh the benefits. And now there are case reports like this.

Sean Bush, who just happens to have been on the tv show “Venom ER”, collected these two cases of acute ischemic stroke after treatment of snake bites with CroFab. Both were probably Southern Pacific rattlesnakes (one definitively identified, one presumptive).

Crotalus viridis Southern Pacific Rattlesnake Juvenile.jpg
Crotalus viridis Southern Pacific Rattlesnake Juvenile” by Matthew Robinson from Santa Monica, USA – baby rattle. Licensed under CC BY 2.0 via Wikimedia Commons.

The first case was a 50 yr old, bitten on the leg, with pain, swelling, shortness of breath, and parasthesias. He got the initial dose of 6 vials, then had his compartment pressures checked. That got him another 12 vials. Later that evening, he showed classic signs of CVA with slurred speech, right-sided weakness, and right facial droop. Labs remained normal, CT was negative, and tPA was withheld due to risk of hemorrhage. However, he got 6 more vials of antivenom because of neurologic symptoms. MRI showed devastating bilateral lesions, and the patient expired. Autopsy showed emboli in the lungs, heart, and multifocal infarcts of the CNS.

Case 2 was a little different. He was 17, bitten on the finger, and had pain, swelling, and parasthesias of that extremity. He got 6 vials initially, then got 20 more over the next 3 days. On that third day, he showed classic cva symptoms with left-sided facial droop, and total left-sided body weakness. His CT was negative, but again no tPA was given (for good reason). MRI showed multiple infarcts as well, but not as globally as the first.

Both patients were tested for hypercoagulability and were negative. So what gives? Why did two patients in the middle of a classic crotalidae envenomation develop ischemic CVAs after treatment? Fibrinogen and platelet levels were normal in both patients, indicating that they weren’t coagulopathic when given the CroFab. INR isn’t mentioned in the paper, presumably it was normal. The key aspect in this case series is the species of snake itself. One southern pacific rattler (Crotalus oreganus helleri) was discovered to have procoagulant activity in its venom, and among crotalidae, they have some of the most varied venom studied to this point. And it has been demonstrated that CroFab doesn’t have activity against rare, or small proteins that aren’t immunogenic.

Because it is unlikely that CroFab includes fabs specific for this procoagulant protein, in a patient envenomated by a southern pacific that was producing that protein, the net effect would be likely be procoagulation, thus causing the thrombotic phenomena shown. However, we can’t be so sure it is just this snake species, as the references in the paper have numerous other cases of ischemic strokes after multiple other types of snakes.

Yes, these are rare events, but neither of those patients appeared to be so sick that they would have died without antivenom. Perhaps judicious application of antivenom should be considered until the etiology of these events is fully understood.

Catastrophic Acute Ischemic Stroke After Crotalidae Polyvalent Immune Fab(Ovine)-Treated Rattlesnake Envenomation
http://www.ncbi.nlm.nih.gov/pubmed/24864067