Correlations between rotational thromboelastometry (ROTEM) and standard coagulation tests following viper snakebites

BackgroundA high prevalence of venom-induced consumption coagulopathy has been reported in individuals with viper snakebites. Rotational thromboelastometry (ROTEM) is a rapid technique that could be advantageous in assessing and monitoring coagulation disorders.PurposeTo explore correlations between ROTEM and standard coagulation tests.Patients and methodsThis prospective observational study was performed among 41 patients with viper envenomation admitted to the Vietnam Poison Control Center from April 2016 to October 2017. Standard coagulation measurements [platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen level] and ROTEM indicators [clotting time (CT), amplitude (at set time: 5 and 10 minutes), clot information time (CFT) and maximum clot firmness (MCF) for extrinsic (EXTEM), intrinsic (INTEM), and fibrin based (FIBTEM) ROTEM] were obtained.ResultsFor INTEM, EXTEM, the FIBTEM, proportions of patients with prolonged CT were 34.1%, 63.4%, and 61.0% respectively and the proportions of patients with decreased MCF were 62.2%, 62.2%, and 35.5%, respectively. Moderate correlations were observed between PT and EXTEM CT (r = 0.627), aPTT and INTEM CT (r = 0.626), fibrinogen and FIBTEM MCF (r = 0.723), and platelet count and EXTEM MCF (0.60).ConclusionROTEM indicated a hypocoagulation state in patients with viper snakebite and was moderately correlated with standard coagulation parameters.     

Early pathology in venom-induced consumption coagulopathy by Rhabdophis tigrinus (Yamakagashi snake) envenomation

Objective: Rhabdophis tigrinus (Yamakagashi in Japanese) is a venomous non-front-fanged colubroid snake capable of inflicting envenoming with life-threatening defibrinating coagulopathy. However, because of the uncommon incidence of bites and tendency for late development of symptoms/signs, the early effects of the venom on the coagulation system are poorly known.

Case report: We describe a boy bitten by a wild R. tigrinus and report his clinical course starting at 30?min after the bite.

Results: At 30?min after envenomation, only the thrombin-antithrombin complex (TAT) level was elevated. At 90?min after envenomation, laboratory data revealed a prolonged activated partial thromboplastin time (APTT) and increased prothrombin time international normalized ratio (PT-INR) with elevated fibrinogen degeneration product (FDP). At 5.5?h after envenomation, APTT and PT-INR increased beyond a measurable range, and fibrinogen levels dropped below the detection limit. We administered recombinant human soluble thrombomodulin and antivenom prepared against R. tigrinus antivenom. Venom-induced consumption coagulopathy (VICC), which is sometimes reported as disseminated intravascular coagulation (DIC), subsequently improved rapidly.

Discussion: We found that TAT is the earliest marker to detect R. tigrinus envenomation and subsequent VICC occurrence. Although rTM was effective in this case, further studies are necessary to prove its safety and efficacy.     

Acute kidney injury induced by thrombotic microangiopathy in two cases of Bothrops envenomation

Context: Bothrops snakes are the most frequent agents of snakebites in South and Central America. Acute kidney injury (AKI) is one of its complications and has multifactorial origin. Thrombotic microangiopathy (TMA)-induced AKI in snakebites is uncommon and is not described in Bothrops envenomation.

Case details: We report two cases of patients bitten by young Bothrops jararaca who developed AKI induced by TMA. Both patients evolved with mild envenomation and received the specific antivenom within 4?h after the snakebite. None of them had hypotension or shock, bleeding or secondary infection. Patient 1 (P1) was diabetic and using oral hypoglycemic drugs, and patient 2 (P2) was hypertensive without regular use of medication. On admission, both patients had levels of fibrinogen lower than 35?mg/dL, D-dimer higher than 10,000?ng/mL. They evolved with AKI, thrombocytopenia, normal coagulation assays, anemia, lactate dehydrogenase (LDH) elevation, low haptoglobin levels, negative direct antiglobulin test, and presence of schizocytes in peripheral blood. Only P1 required renal replacement therapy, and plasmapheresis was not required. Both patients were discharged and did not require outpatient dialysis, and subsequently had normal creatinine levels.

Discussion: TMA may occur in Bothrops jararaca envenomation, even in mild cases that received early specific antivenom.     

Hump-nosed pit viper (Hypnale hypnale) envenoming causes mild coagulopathy with incomplete clotting factor consumption

Context. Limited information exists on the coagulopathy caused by hump-nosed pit viper (Hypnale hypnale) envenoming. Objectives. This study aimed to characterise the coagulopathy in hump-nosed pit viper bites by measuring laboratory clotting times and factor studies. Materials and methods. Cases of hump-nosed pit viper envenoming were included from a prospective cohort study of Sri Lankan snake-bite patients. Patient age, sex, snake identification, time of bite and clinical effects were recorded. Patients did not receive anti-venom because no specific anti-venom to hump-nosed vipers exists. All patients received supportive care and serial 20-min whole blood clotting tests (WBCT20). The prothrombin time (PT), international normalised ratio (INR), activated partial thromboplastin time (aPTT), coagulation factors I, II, V, VII, VIII, IX and X, von Willebrand factor (vWF) antigen and D-Dimer concentrations were measured. The median of highest or lowest test result for each patient was reported with interquartile range (IQR). Results. There were 80 hump-nosed pit viper bites, median age was 37 years (IQR: 26–51 years) and 48 were male. The WBCT20 was positive in one patient. The median highest INR was 1.9 (1.5–2.2; Range: 1.3 to > 12) and median highest aPTT was 54 s (46–72 s; Range: 35–170 s). There was low fibrinogen [median: 1.3 g/L;1, –1.8 g/L; Range: < 0.2–2.9], low factor VIII levels [median: 23%; 16–37%] and low factor V levels [median: 43%; 23–74%]. D-Dimer concentrations [median: 3.4 mg/L; 2–7.4 mg/L] were slightly elevated. Factors II, VII and X and vWF antigen concentrations were normal. Discussion and Conclusions. Hump-nosed pit viper bites result in a mild coagulopathy which is usually not detected by a WBCT20. It is characterised by mild elevation of INR, low fibrinogen and Factors V and VIII which may be consistent with the venom containing a thrombin-like enzyme.     

Clinical presentation and management of an Aruban rattlesnake bite in the Netherlands

Bites by Aruban Rattlesnake (Crotalus durissus unicolor) are rare and not known to induce severe envenomations. Here, we present a case of a 57 year-old man bitten by his pet Aruban Rattlesnake (Crotalus durissus unicolor). He was admitted to hospital within 15?min. Three and a half hours later his fibrinogen concentration decreased to 0.6?g/L (normal: 2.0–4.0). Nine hours post-bite, he was treated with polyvalent snake antivenom covering Crotalus durissus. Three hours later his fibrinogen became undetectable while at that time clotting times were prolonged (PT 38.7?s (normal: 12.5–14.5) and aPTT 40?s (normal: 25–35)). His platelet count remained within normal limits. Creatine kinase (CK) concentrations reached a maximum of 1868?U/L (normal:?<200) 16?h post-bite. After a second antivenom dose, 10.5?h after the first antivenom administration, clotting times returned to normal. Fibrinogen was restored to normal within three days. He was discharged from hospital on day five. In conclusion, administration of polyvalent snake antivenom covering Crotalus durissus snakebites shows cross-neutralization and is effective in the treatment of patients bitten by Crotalus durissus unicolor.     

Early administration of Fab antivenom resulted in faster limb recovery in copperhead snake envenomation patients

Background: No previous research has studied whether early snake antivenom administration leads to better clinical outcomes than late antivenom administration in North American pit viper envenomation.

Methods: A secondary analysis of data from a clinical trial of Fab antivenom (FabAV) versus placebo for copperhead snake envenomation was conducted. Patients treated before the median time to FabAV administration were classified as receiving early treatment and those treated after the median time were defined as the late treatment group. A Cox proportional hazards model was used to compare time to full recovery on the Patient-Specific Functional Scale (PSFS) instrument between groups. Secondary analyses compared estimated mean PSFS scores using a generalized linear model and the estimated proportion of patients with full recovery at each time point using logistic regression. To evaluate for confounding, the main analysis was repeated using data from placebo-treated subjects.

Results: Forty-five subjects were treated with FabAV at a median of 5.47?h after envenomation. Patients in the early treatment group had a significantly shorter time to full recovery than those treated late (median time: 17 versus 28 days, p?=?.025). Model-estimated PSFS scores were numerically higher at each time point in the early group. No difference was found between patients treated early versus late with placebo.

Conclusions: In this secondary analysis of trial data, recovery of limb function was faster when Fab antivenom was administered soon after envenomation, as opposed to late administration.     

Coagulation parameters in copperhead compared to other Crotalinae envenomation: secondary analysis of the F(ab’)2 versus Fab antivenom trial

Context: Coagulation derangements in copperhead envenomation are considered less severe than other crotaline envenomations, resulting in recommendations to limit both coagulation testing and antivenom treatment. A prospective, blinded, multicenter, randomized clinical trial comparing the effectiveness of F(ab’)₂ versus Fab antivenom in crotaline envenomation patients was completed in 2011. We determined the difference between coagulation parameters in copperhead compared to other crotaline envenomations.

Methods: We performed a post hoc analysis comparing the coagulation parameters (platelets and fibrinogen) prospectively obtained in the aforementioned trial. All the patients received antivenom in one of three treatment arms [F(ab’)₂ with maintenance, F(ab’)₂ with placebo maintenance, or Fab with maintenance]. Coagulation parameters were measured at pretreatment baseline, during acute hospitalization, day 5, day 8, and day 15 post-envenomation. Mean platelet count and fibrinogen levels for the copperhead and other crotaline groups were compared. The platelet and fibrinogen point estimates with distribution are presented graphically over time.

Results: 122 patients were enrolled in the study. There were 22 patients with copperhead envenomation, 93 with other crotaline envenomations, and 7 that could not be definitively determined. The mean age was 42 (SD 20) years. There was a minor pretreatment difference in mean baseline platelet count between the copperhead group (246?×?109/L 95% CI 215, 277) compared to other crotaline envenomation patients (184?×?109/L 95% CI 167, 202). There was a modest pretreatment difference in mean fibrinogen level between copperhead patients (345?mg/dL 95% CI 277, 415) and other crotaline patients (261mg/dL 95% CI 241, 281). Pretreatment coagulation parameter means were normal and converged post treatment.

Conclusion: On average, copperhead envenomations have less severe initial coagulation derangements. However, in mild envenomations, differences in laboratory values are minimal and there is substantial variation in individual patients regardless of species. Species alone should not be used to determine the need for laboratory testing or treatment in crotaline snakebite.     

Use of polyvalent equine anti-viper serum to treat delayed coagulopathy due to suspected Sistrurus miliarius streckeri envenomation in two children

Background: Western Pygmy Rattlesnake (WPR) envenomation reportedly causes refractory and persistent coagulopathy when treated with CroFab^® (Crotalidae Polyvalent Immune Fab). We report two cases where polyvalent equine anti-viper serum (AntivipmynTRI^®) was used to treat recurrent coagulopathy in children.

Case details: The first patient was a 16-month-old male who was bitten by a confirmed WPR. The patient received a total of 18 vials of CroFab^®. His labs normalized, swelling gradually improved, and the child was discharged to home. On day 5, the child returned to the emergency department with a great deal of inguinal tenderness. Labs were obtained and the child’s INR was >13.1, while the fibrinogen was <60?mg/dL and the d-dimer was 11.72?mg/L. A decision was made to administer Antivipmyn TRI^®, and the child received a total of 10 vials. Lab values significantly improved: INR 1.2, fibrinogen 93?mg/dL, and d-dimer 4.21?mg/L. The second patient was a 20-month-old male who presented following snake envenomation. The child was administered a total of 22 vials of CroFab^® over approximately 70?h following envenomation. Physical exam continued to improve, however, lab results showed an increasing INR 1.98, decreasing platelet count 124?×?10³ per μL, fibrinogen <60?mg/dL, and d-dimer?>20 ug/mL. A total of 15 vials of Antivipmyn TRI^® were administered to this patient. Following this administration, labs and clinical exam both significantly improved. Labs revealed INR 1.16, fibrinogen 110?mg/dL, d-dimer 3.2?mg/L and platelet count 215?×?10³/μL.

Discussion: CroFab^® is still the first-line treatment for children bitten by a WPR, but in some cases patients develop a recurrent coagulopathy. The rapid response demonstrated by Antivipmyn TRI^® leads us to conclude that this is a potential therapy for this clinical situation.     

Evaluation of antivenom therapy for Vipera palaestinae bites in children: experience of two large,tertiary care pediatric hospitals

Background: Antivenom has been successfully used to treat systemic and progressive, local manifestations of envenomation inflicted by Vipera (V.) palaestinae, the most common venomous snake in Israel. The objective of this study was to evaluate the fixed dose V. palaestinae monovalent (equine) immunoglobulin G antivenom used in two pediatric emergency departments. In particular, we wanted to assess the need for repeated antivenom administration and the rate of adverse antivenom effects in children.

Methods: A retrospective chart review was performed for all children admitted with definite or probable signs of V. palaestinae envenomation to Chaim Sheba Medical Center and Kaplan Medical Center between 1 March 2008 and 1 March 2014. Extracted data included: age, location of bite, time to hospital arrival, time to antivenom administration if indicated, outcomes, and complications of the envenomation and adverse effects to the antivenom.

Results: 57 patients met inclusion criteria; they ranged from 1 to 17 years in age and median age was 9.5 years. Clinical manifestations were evident in 55 (96.4%) of victims: 18 presented with minimal local signs and 37 showed marked progressive, local features (rapidly progressing edema) and signs of systemic envenomation: tachycardia (20), vomiting (17), abdominal pain (11) and hypotension (6). Two patients developed compartment syndrome and underwent surgical decompression (both received only a loading dose of antivenom with no subsequent maintenance dose). One patient developed thrombocytopenia and three patients presented with mild coagulopathy. Antivenom was administered to 25 (42%) children. Indications for antivenom administration included moderate to severe local signs (19 patients) and systemic signs (6 patients). None of these patients developed adverse reactions, serum sickness, or other side effects to the antivenom. One patient received a single additional 30mL dose of antivenom, due to hypotension and syncope, with good response.

Conclusions: In children, 50?ml dosing of V. palaestinae antivenom is efficacious and safe for the treatment of systemic and progressive local manifestations of envenomation by V. palaestinae.     

Coagulopathy parameters in patients with Crimean‐Congo hemorrhagic fever and its relation with mortality

Background: Crimean‐Congo hemorrhagic fever (CCHF) is an acute illness affecting multiple organ systems and characterized by ecchymosis, visceral bleeding, and hepatic dysfunction. In this study, we aimed to investigate the profile of coagulopathy markers (platelet count, activated partial tromboplastin time (aPTT), prothrombin time (PT), international normalized ratio (INR), fibrinogen, protein C, protein S, antithrombin III, activated protein C resistance (APCR), and D‐dimer) and their clinical significance in 83 CCHF‐infected patients. Subjects and methods: We studied 83 CCHF patients who were admitted to Ankara Numune Education and Research Hospital during the spring and summer of2007. We compared the coagulopathy markers of fatal CCHF patients (n=9) with nonfatal cases (n=74). Results: Platelet count, PT, aPTT, INR, and fibrinogen were prognostic factors associated with mortality for CCHF. Especially, platelet count<20×10⁹ cells/l and aPTT>60 sec were important. Protein C, protein S, APCR, and antithrombin III levels were not associated with mortality. Conclusion: Laboratory tests including classical parameters (platelet count, PT, aPTT, INR, and fibrinogen) of coagulopathy seem to be enough for the followup of CCHF. Protein S, protein C, APCR, and D‐dimer levels were not associated with mortality. J. Clin. Lab. Anal. 24:163–166, 2010. © 2010 Wiley‐Liss, Inc.     

Neurotoxicity in Russell’s viper (Daboia russelii) envenoming in Sri Lanka: a clinical and neurophysiological study

Context: Russell’s viper is more medically important than any other Asian snake, due to number of envenoming’s and fatalities. Russell’s viper populations in South India and Sri Lanka (Daboia russelii) cause unique neuromuscular paralysis not seen in other Russell’s vipers. Objective: To investigate the time course and severity of neuromuscular dysfunction in definite Russell’s viper bites, including antivenom response. Methodology: We prospectively enrolled all patients (>16 years) presenting with Russell’s viper bites over 14 months. Cases were confirmed by snake identification and/or enzyme immunoassay. All patients had serial neurological examinations and in some, single fibre electromyography (sfEMG) of the orbicularis oculi was performed. Results: 245 definite Russell’s viper bite patients (median age: 41 years; 171 males) presented a median 2.5?h (interquartile range: 1.75–4.0?h) post-bite. All but one had local envenoming and 199 (78%) had systemic envenoming: coagulopathy in 166 (68%), neurotoxicity in 130 (53%), and oliguria in 19 (8%). Neurotoxicity was characterised by ptosis (100%), blurred vision (93%), and ophthalmoplegia (90%) with weak extraocular movements, strabismus, and diplopia. Neurotoxicity developed within 8?h post-bite in all patients. No bulbar, respiratory or limb muscle weakness occurred. Neurotoxicity was associated with bites by larger snakes (p?<?0.0001) and higher peak serum venom concentrations (p?=?0.0025). Antivenom immediately decreased unbound venom in blood. Of 52 patients without neurotoxicity when they received antivenom, 31 developed neurotoxicity. sfEMG in 27 patients with neurotoxicity and 23 without had slightly elevated median jitter on day 1 compared to 29 normal subjects but normalised thereafter. Neurological features resolved in 80% of patients by day 3 with ptosis and weak eye movements resolving last. No clinical or neurophysiological abnormality was detected at 6 weeks or 6 months. Conclusion: Sri Lankan Russell’s viper envenoming causes mild neuromuscular dysfunction with no long-term effects. Indian polyvalent antivenom effectively binds free venom in blood but does not reverse neurotoxicity.     

Factor deficiencies in venom‐induced consumption coagulopathy resulting from Australian elapid envenomation: Australian Snakebite Project (ASP‐10)

Summary. Background: Limited information exists on the dynamics of hemostasis in patients with venom‐induced consumption coagulopathy (VICC) from snake envenomation. Objective: The aim of the present study was to investigate specific factor deficiencies and their time course in Australasian elapid envenomation. Methods: We measured coagulation parameters and factor concentrations in patients recruited to the Australian Snakebite Project, an observational cohort study. There were 112 patients with complete VICC, defined as an international normalized ratio (INR) > 3, and 18 with partial VICC. Serial citrated plasma samples were collected from 0.5 to 60 h post‐bite. INR, activated partial thromboplastin time (aPTT), coagulation factors (F)I, II, V, VII, VIII, IX, X, von Willebrand factor antigen (VWF:Ag) and D‐dimer concentrations were measured. Results: Complete VICC was characterized by near/total depletion of fibrinogen, FV and FVIII, with an INR and aPTT that exceeded the upper limits of detection, within 2 h of snakebite. Prothrombin levels never fell below 60% of normal, suggesting that the toxins were rapidly eliminated or inactivated and re‐synthesis of clotting factors occurred irrespective of antivenom. Partial VICC caused limited depletion of fibrinogen and FV, and almost complete consumption of FVIII. Onset of VICC was more rapid with brown snake (Pseudonaja spp.) venom, which contains a group C prothrombin activator toxin, compared with the tiger snake group, which contains a group D prothrombin activator toxin and requires human FVa formation. Resolution of VICC occurred within 24–36 h irrespective of snake type. Conclusions: These results suggest that Australasian elapid prothrombin activators have a potent but short duration of action. Antivenom is unlikely to be administered in time to prevent VICC.     

Lack of significant bleeding despite large acute rivaroxaban overdose confirmed with whole blood concentrations

Background: Since intentional overdose with rivaroxaban is expected to lead to significant coagulopathy and bleeding, prophylactic reversal has been suggested. We report a single massive ingestion confirmed by a blood concentration that was managed with expectant therapy alone.

Case report: A 71-year-old man with atrial fibrillation, aortic valve replacement, and congestive heart failure presented to the emergency department after an intentional ingestion of 97 (1940?mg total) rivaroxaban tablets in a suicide attempt. Initial laboratories revealed: PT, 60.2?s; INR 7.2; aPTT, 55.7?s; BUN 28?mg/dL; and creatinine 1.2?mg/dL. A whole-blood rivaroxaban concentration obtained on hospital-day three was 160?ng/mL. The patient was admitted for continued observation and the coagulation markers trended downward with no major bleeding events. No reversal agents or blood products were given during his hospitalization.

Conclusion: In the setting of a single, acute rivaroxaban overdose, with normal renal function, and no active bleeding, conservative therapy alone may be sufficient.     

Severe Puff Adder (Bitis arietans) Envenomation with Coagulopathy

Background: The puff adder (Bitis arietans) is a highly toxic venomous snake that is responsible for a large proportion of the venomous snakebites in sub-Saharan Africa, where it is indigenous. Puff adder bites in North America result from snakes in captivity. Although thrombolytic enzymes are present in puff adder venom, significant coagulopathy has not been previously reported with a confirmed puff adder envenomation.

Results: We report a serious puff adder envenomation to the finger, characterized by severe swelling, local tissue necrosis, hypotension, thrombocytopenia, severe coagulopathy, and hemorrhage. Fifteen vials of South Africa polyvalent antivenom were administered, beginning 4.5 hours post-envenomation, with step-wise improvement in hematological abnormalities. Other treatments included vasopressors, ventilatory support, leeches, transfusion, and eventual digit amputation. After a prolonged hospital course, the patient had a good outcome.

Conclusions: Puff adder envenomation causes tissue necrosis, hypotension, coagulopathy, thrombocytopenia, and spontaneous bleeding. Severe coagulopathy may occur. Physicians treating severe cases should be prepared to administer at least 15 vials of antivenom if needed.     

A definite bite by the Ornamental Snake (Denisonia maculata) causing mild envenoming

Context: Many bites from mildly venomous elapids occur but identification or presence of systemic envenoming is rarely confirmed. Objective: To confirm systemic envenoming and binding of venom components to a commercial antivenom in a definite bite by the Ornamental Snake (Denisonia maculata) using enzyme immunoassays. Case: A 9-year old boy was bitten by an identified Ornamental Snake. He developed nausea, vomiting, local pain, and swelling. He had a leucocytosis (white cell count, 20.8?×?10⁹/L), an elevated international normalised ratio (INR) of 1.6, but otherwise normal blood tests including D-Dimer and activated partial thromboplastin time. He was treated with Australian Black Snake antivenom because the commercial venom detection kit was positive for Black snake. He was admitted for 36?h with continuing local pain and swelling requiring parenteral analgesia. Materials and methods: Blood samples were collected with informed consent for measurement of venom and antivenom concentrations. Venom-specific enzyme immunoassays were developed using the closely related D. devisi venom with Rabbit anti-Notechis (Tiger Snake) and anti-Tropidechis (Rough-scaled Snake) IgG antibodies to detect venom in serum. Standard curves for measured venom versus actual venom concentrations were made to interpolate Denisonia venom concentrations. In vitro procoagulant and anticoagulant activity of venom was assayed. Results: Denisonia venom was detected in the pre-antivenom sample as 9.6?ng/mL D. devisi venom. No antigenic venom components were detected in post-antivenom samples and there were high antivenom concentrations. D. devisi venom had mild in vitro procoagulant activity with a minimum concentration required to clot after 5?min of 2.5–5?μg/mL and even weaker anticoagulant activity. Conclusions: Denisonia bites appear to cause local effects and possibly mild systemic envenoming (with only non-specific systemic symptoms and leucocytosis), confirmed by detection of antigenic venom components in blood. A significant coagulopathy does not appear to occur.     

Thrombotic microangiopathy following Bothrops jararaca snakebite: case report

Context: Thrombotic microangiopathy (TMA) is an uncommon and severe complication of snakebites, and is similar, in general, to hemolytic-uremic syndrome (HUS). We describe a case of TMA following envenomation by Bothrops jararaca.

Case details: A 56-y-old-woman with controlled hypertension was transferred from a primary hospital to our ER ～7?h after being bitten by B. jararaca in the distal left leg. She developed edema extending from the bite site to the proximal thigh, associated with intense radiating local pain, local paresthesia and ecchymosis at the bite site. Laboratory features upon admission revealed coagulopathy (20?min whole blood clotting time - WBCT20?>?20?min), thrombocytopenia (76,000 platelets/mm³) and slight increase in serum creatinine (1.58?mg/dL; RV Discussion: TMA following snakebite has been reported mainly in India, Sri Lanka and Australia, with several patients needing renal replacement therapy. Although controversial, plasmapheresis has also been used in some cases. Our patient developed microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury, a triad of features compatible with TMA similar to HUS. Despite the severity, the outcome following conservative treatment was good, with complete recovery.     

Recurrent,persistent, or late,new-onset hematologic abnormalities in Crotaline snakebite

Background.?Hematologic effects from rattlesnake envenomation exhibit a phenomenon of recurrent, persistent or late, new onset (late) abnormalities in some Fab antivenom‐treated patients 4 or more days post‐envenomation. Indicators that reliably identify or exclude those patients at risk of late hematologic effects have not been developed.

Methods.?This was a retrospective, observational case series of rattlesnake bite records at two US poison centers. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for D‐dimer, fibrinogen, platelets, platelet count trend, INR and PTT associated with late hematologic abnormalities, were determined.

Results.?Three hundred seventy six cases were reviewed. Sixty cases met inclusion criteria. Overall, 17 of 60 patients (28%) had a hematologic abnormality as a result of envenomation. Eleven of 60 patients (65% of those with a hematologic abnormality; 18% overall) developed late hematologic abnormalities 4 or more days post‐envenomation. Four patients had late, new onset hypofibrinogenemia and/or thrombocytopenia. All were associated with early D‐dimer elevation and/or platelet rise in response to FabAV treatment, respectively. Normal hematologic parameters in the first 48 h post‐envenomation and the lack of a greater than 20% rise in platelets within 4 h post‐antivenom administration had a 100% NPV for late hematologic effects.

Conclusions.?Patients with early onset hypofibrinogenemia, a positive D‐dimer, thrombocytopenia, or a 20% increase in platelet count within 4 h post‐treatment had a significant likelihood of late hematologic effects. Patients in whom fibrinogen, D‐dimer, INR, PTT, and platelet counts remained normal throughout the first 48 h post‐envenomation, and who did not exhibit a >20% increase in platelet count within 4 h post‐antivenom administration, did not develop late hematologic effects.     

Centruroides sculpturatus envenomation in three adult patients requiring treatment with antivenom

Context: Envenomation by Centruroides sculpturatus can manifest with cranial nerve dysfunction and neuromuscular hyperactivity. While these symptoms are most commonly seen in young children, they may also be seen in adults.

Case details: Three cases of adult patients are presented with grades III &; IV scorpion envenomation. They reported symptoms including disconjugate, roving eye movements, and motor involvement. Also reported were hyposmia, difficulty with fine motor movements, and dysgeusia. All were first treated with benzodiazepines with little to no effect. They then received a three vial antivenom bolus with resolution of severe symptoms within 30–60?min.

Discussion: Severe Centruroides envenomation can occur in adults as well as children. These three cases demonstrate the usefulness, safety, and effectiveness of antivenom therapy to quickly relieve symptoms in adult patients with grades III &; IV envenomations.     

Fatal ischemic stroke following Tityus serrulatus scorpion sting in a patient with essential thrombocythemia

Context: Stroke following scorpion stings is rare. We report a fatal envenomation involving multiple, extensive brain infarcts in a patient with a previous diagnosis of essential thrombocythemia (ET) who was stung by Tityus serrulatus (T. serrulatus).

Case details: A 44-year-old woman with a diagnosis of low-risk ET (platelets <1,000,000/mm³, age <60 years and no history of thrombosis; positive JAK2V617F mutation) was admitted to a local ED 1?h after being stung by T. serrulatus on the left foot. She developed signs of severe envenomation, including several episodes of profuse vomiting, pallor and confusion soon after the sting, followed by shock (BP: 90/60 to 60/40?mmHg) and was treated with scorpion antivenom, vasopressors and mechanical ventilation. A brain computed tomography (CT) scan (54-h poststing) revealed diffuse bilateral cerebellar hypodensity, with partial involvement of both occipital lobes and thalamus, obstructive hydrocephaly with signs of cerebrospinal fluid extravasation, and ascending transtentorial herniation, suggestive of bilateral ischemia involving the posterior cerebral circulation. External ventricular drainage resulted in no improvement and brain death was confirmed on day 10.

Discussion: Several mechanisms have been proposed to explain stroke following scorpion stings, such as sympathetic stimulation, myocardial dysfunction, hypotension/shock, arrhythmias and coagulopathy. Ischemic stroke is one of the most serious complications of ET. The risk factors for thrombotic/ischemic events in patients with ET include age (≥60 years) and previous vascular events. Severe scorpion envenomation resulting in myocardial dysfunction and systemic inflammatory response syndrome may increase the overall risk of arterial thrombosis in this patient.