To the Editor:
To contribute to the growing literature on the use of Crotaline Fab antivenom (CroFab™, Protherics, Nashville, TN), we submit what we believe is the first reported successful use of CroFab™ in a third trimester pregnant patient.
A 32-year-old female at 28 5/7 weeks gestation presented to our Emergency Department (ED) having sustained a copperhead (sp. Agkistrodon contortrix) snakebite on her right foot. Within an hour of the bite, she presented with painful swelling to the right foot and ankle. She was awake and alert, with a temperature of 37.4°C, blood pressure 123/61, pulse 88, and respirations of 16/min. Her cardiac, lung, abdominal and neurological exams were normal. Her fundal height was consistent with her gestational age, and the fetal heart rate was 150 beats/minute.
A 10–12 cm area on the dorsal right foot was swollen, ecchymotic and exquisitely tender, with two fang marks on the lateral aspect. Sensation, capillary refill and range of motion were normal distally. There were no other signs of swelling, ecchymoses, petechiae or purpurae elsewhere on the skin.
Laboratory data revealed a normal electrolyte panel, a hemoglobin of 12.9 g/dL and a platelet count of 136,000 cells/mm3. Her prothrombin time (PT) (11.0 seconds) and INR (0.9) were normal, but her partial thromboplastin time (PTT) was elevated at 39.3 secs (range 22.2–32.2 secs).
Serial examinations in the ED revealed a progression of local symptoms, with worsening and ascending swelling of the right ankle. The patient was treated with five vials of CroFab™, and the dose was well tolerated with no adverse reactions noted. A cessation in progression of local effects was noted within 1–2 hours and her coagulation parameters improved (PT 11.2, INR 0.9, and PTT 26.2). Ultrasound revealed a live intrauterine pregnancy with estimated gestational age of 28 weeks; there was no abruption and the biophysical profile was 10/10. She was discharged after 24 hours of observation with no recurrence in symptoms.
The patient went on to deliver a healthy baby girl (birth weight 3.4 kg) at 41 weeks gestation. At 24 months, the child is at, or near, the 50th percentile for all growth parameters, and has met developmental milestones with no signs of adverse sequelae.
Adverse sequelae from crotaline envenomation to both the mother and fetus, including fetal demise, have been described in the medical literature(Citation1, Citation2). A 1992 review, citing 50 cases of snakebites in pregnancy(Citation1), reported a 43% fetal demise rate, and a 10% maternal mortality rate in cases of crotaline envenomation.
A series of 39 pregnant women suffering snake envenomation was published by Senviratne in 2002(Citation3). The abortion rate in this series was 30%, compared to a 7.7% population rate during the same time period, corroborating findings of earlier series. Additionally, their analysis suggested a significantly increased risk of poor fetal outcome earlier in pregnancy (OR 7.3 for 2nd trimester and OR 51.3 for 1st trimester compared with 3rd trimester envenomations).
The exact mechanism of fetal demise is not well understood(Citation2, Citation4). It is likely that the coagulopathic and membrane destabilizing effects of the venom cause microthrombi and hemorrhage at the utero-placental junction(Citation2).
Although crotaline envenomation has been reported to lead to fetal demise in pregnancy, the use of CroFab™ antivenom in pregnancy has not been studied. Pregnant patients were excluded from previous studies, leaving a lack of evidence for any treatment recommendations(Citation7, Citation8).
The newer crotaline Fab antivenom antivenom appears to be safer than its predecessor. Hypersensitivity reactions are less common with CroFab™(Citation7, Citation8); type I hypersensitivity reactions occur with an incidence of 3–6%(Citation7, Citation8). There is up to an 11% rate of serum sickness, and the true incidence is suggested to be even lower(Citation8). To date, there is only one published case report and one retrospective review of 32 patients treated with crotaline Fab antivenom after copperhead envenomation, which concluded that CroFab™ was effective in treating copperhead snakebites(Citation9).
A potential concern with the use of CroFab™ in pregnancy is the thimersol preservative. There is concern regarding potential neurotoxicity from prenatal exposure to thimersol and its metabolite, ethyl mercury(Citation3). These concerns are, however, based on indirect evidence; currently, there is no direct evidence that prenatal exposure causes any neuropathological changes.
This case is, to our knowledge, the first report of the successful use of CroFab™ in a pregnant patient. Although no definitive conclusions can be reached based on this one case, we anticipate further successful reports of its use. Until that time, the decision to use antivenom therapy in pregnant patients should be undertaken on a case by case basis and with consultation with a toxicologist.
REFERENCEs
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