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)

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.

Bush SP, Mooy GG, Phan TH. Catastrophic acute ischemic stroke after Crotalidae polyvalent immune Fab (ovine)-treated rattlesnake envenomation. Wilderness Environ Med. 2014 Jun;25(2):198-203. [PMID 24864067]