Late, new-onset thrombocytopenia in a rattlesnake envenomation treated with a Fab antivenom

To the Editor:

Recent work on rattlesnake-envenomated patients¹ has suggested that, in patients with normal platelet counts throughout hospitalization, an increase in platelets of greater than 20% within 4 h of the initial dose of antivenom is a highly sensitive indicator of late, new-onset thrombocytopenia. We report a case of late, new-onset thrombocytopenia in a rattlesnake envenomation predicted by this finding.

The patient was a 33-year-old male who was bitten on his ankle by a rattlesnake. Initial control of envenomation effects was achieved following an initial dose of six vials of CroFab^® antivenom, administered at 1.5 h post-envenomation. He then received maintenance antivenom, two vials every 6 h for a total of three doses and was discharged home at 36 h post-envenomation. His laboratory values during hospitalization and at follow-up visits are depicted in Table 1. His platelet nadir occurred on days 8 and 9. By day 10 the platelets were increasing. By day 12 platelets were over 100 × 10³/mm³ and laboratory monitoring was discontinued. The patient did not have any bleeding complications.

Table 1. Management events, platelet counts, fibrinogen concentrations, INR, and aPTT by time post-envenomation.

Management events	Pre-AV	Post-AV	Receiving maintenance AV	Discharge
Hours/days post-envenomation	1.5 h	7 h (˜4 h post AV)	18 h	28 h	44 h	Day 4	Day 8	Day 9	Day 10	Day 12
Platelets × 10^3/mm^3	141	172	166	163	147	143	63	63	72	106
Fibrinogen mg/dL	232	191	234	313	313	320	339	372	341	315
INR	1.49	1.55		1.17	1.13	1.57	1.23	1.15	1.10	1.0
aPTT							37	35	33
D-dimer mcg/mL	< 0.22

AV, antivenom.

Blank cells indicate no specific management or test not performed.

The current consensus recommendation is to follow all patients of North American rattlesnake envenomation post-discharge at 2–4 days and again at 5–7 days for the possibility of either recurrence, or late, new-onset hematologic abnormalities.² Although it was recognized in the CroFab^® clinical trials that the occurrence of thrombocytopenia during the hospitalization phase predicted the possibility of recurrent thrombocytopenia post-discharge,³ findings that would identify those patients at risk of late, new-onset thrombocytopenia were not developed until more recently. In a 2011 study, a platelet increase of greater than 20% following the first dose of antivenom was sensitive in detecting patients at risk of late, new-onset thrombocytopenia.¹ This patient developed significant, late, and new-onset thrombocytopenia despite a normal platelet count on presentation and throughout his hospitalization, as well as at his 4-day follow-up visit. He did, however, exhibit a 22% increase in platelets following his initial dose of antivenom. Thus, the potential for late, new-onset thrombocytopenia was anticipated and the patient was followed for an adequate time period to detect this occurrence. Although he did not develop bleeding and was not felt to require additional antivenom, these might have occurred given the degree of thrombocytopenia and similar cases have required re-hospitalization and/or additional antivenom administration.⁴

We agree with the current recommendation to follow rattlesnake-envenomated patients with laboratory testing at 2–4 days and again at 5–7 days, even when thrombocytopenia (and/or hypofibrinogenemia, which did not occur here) has not occurred up to 4 days post-envenomation.

Despite normal platelet counts early in the course of a rattlesnake envenomation, an increase in the platelet count of greater than 20% within 4 h of the initial dose of antivenom is a sensitive indicator for late, new-onset thrombocytopenia. Rattlesnake-envenomated patients should be followed with laboratory testing post-discharge at 2–4 days and again at 5–7 days.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.