Chang, Simone

Effects of Crotalinae envenomation vary by geographical areas and research into coagulopathy and effects of antivenom are needed to optimize management. This was a single-center retrospective review with testing on presentation and 4 h after; antivenom administration was noted and data analyzed overall and comparing envenomations. One hundred and nineteen snakebites evaluated with 59 identified as Crotalinae and half receiving antivenom. PT/aPTT was elevated in 20% of water moccasin/copperhead and 21% of rattlesnake bites. DIC-like syndrome occurred in 8% water moccasin/copperhead and 6% rattlesnake bites. Antivenom did not seem to correct PT or aPTT at 4 h follow-up in most cases. Thrombotic microangiopathy was not seen. Coagulopathy was prevalent affecting one in five patients in this cohort and does seem to persist at short interval follow-up, even in those receiving antivenom. We support guidelines recommending clinical monitoring and serial coagulation profiles in such cases. Blood Coagul Fibrinolysis 30:000 – 000 Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Congenital factor V deficiency (FVD) is a rare bleeding disorder. In this study, we investigated the genetic basis in an African American patient with factor V activity 3%. Custom sequence capture and targeted next-generation (NGS) sequencing of the F5 gene were undertaken followed by PCR and Sanger sequencing. Two novel variants were identified. In silico analyses correlated clinically with the patient's factor V activity and hemorrhagic tendency. A review of the literature regarding these genomic alterations is presented. We described two novel mutations causing moderate FVD. The first, Chr1:g.169483698C>A with cDNA change (F5):c.6529-1G>T, occurred in a conserved nucleotide at the canonical acceptor splice site of intron 24. The second, Chr1:g.169515775C>T with cDNA change (F5):c.1667G>A, was a missense variant of exon 11, affecting a highly conserved amino acid in the A2 domain. Further research into the mechanisms of F5 mutations leading to FVD and residual factor V expression are needed.

Background: Acute chest syndrome (ACS) frequently complicates sickle cell disease (SCD) and is a leading cause of hospitalization and mortality. Many factors have been implicated in ACS, including infections, thrombosis, fat and pulmonary emboli. However, a clear etiology is not defined in 50% of the cases and ACS is considered a clinical endpoint for different pathogenic processes (Vichinsky et al 2000). The non-specific nature of ACS makes diagnostic tests challenging, and there are no serum tests clinical used to aid diagnosis. Procalcitonin (PCT) is a prohormone of calcitonin and serum PCT rises within hours of an inflammatory stimulus. PCT has clinical utility as a marker of severe systemic inflammation, infection, and sepsis (Becker et al. 2008). Few studies have evaluated PCT as a biomarker for ACS in patients presenting with vaso-occlusive crises (VOC). Two studies have reported no difference in PCT (Biemond et al. 2018 and Stankovic et al 2011), while one study reported higher PCT between ACS and VOC (Patel et al 2014). Methods: We retrospectively reviewed 106 patients with SCD who presented to the emergency department with fever and painful crises during 2015-2019. The patients were divided into two categories based on discharge diagnoses - patients with VOC only (n=88) and patients with ACS (n=18). Inclusion criteria for both groups were patients with SCD, 17 years and older and PCT measurement on presentation. Exclusion criteria were defined as patients who had received empiric antibiotics prior to PCT testing. Data collected on presentation included genotype, age, gender, complete blood count, PCT, creatinine, total bilirubin and hydroxyurea use. Length of stay was recorded. Data was analyzed between the two groups using descriptive statistics and accounting for unequal variances, withp-value set at 0.05 for significance. Results: Demographics and clinical characteristics are summarized in Table 1 (Figure). The sample included primarily adult males (77%), with about two-thirds on hydroxyurea. Genotype HbSS (73.6%) was most prevalent followed by HbSC (22.6%) and HbSβ (3.8%). The ACS group had a higher percentage of HbSS, lower use of hydroxyurea and higher mean bilirubin. Mean PCT for the ACS group was 0.52 ng/mL (range, 0.05-2.04), compared to 0.31 ng/mL (range, 0.02-6.82) in the VOC group; withp=0.084. ROC analysis showed a PCT>0.5ng/mL had 39% sensitivity and 85% specificity for ACS in this sample. Conclusion: In this sample, PCT on presentation was higher in those with ACS compared to VOC, but this difference did not achieve statistical significance. Further study in a larger population would be useful to evaluate this finding. Disclosures No relevant conflicts of interest to declare.

Background: Approximately 5000 snake bites are reported in the United States (US) annually with half of these patients being admitted. Crotalinae species are the most numerous; coral and imported exotic snakes cause a smaller number. Snake venoms are highly stable chemically complex mixtures of proteins. Quantity and composition vary with species and geographic location. Although enzymes contribute to the deleterious effects of the venom, the lethal components may be the smaller low molecular-weight polypeptides. Crotalinae envenomation is known to contain thrombin-like glycoproteins that can induce coagulopathy ranging from asymptomatic lab abnormality to disseminated intravascular coagulopathy (DIC) and life-threatening hemorrhage. In certain geographical areas of the United States thrombocytopenia, hypofibrinogenemia and coagulopathy are common hematological abnormalities, and ones that dictate both a reason for treatment with antivenom as well as an important monitor of therapeutic efficacy. Data on hematological abnormalities following envenomation by crotaline species in Northeast Florida/Southwest Georgia has not been reported before. Methods: We conducted a retrospective review of envenomations that presented to the University of Florida at Jacksonville from April 2013 to October 2018. Patients had to be 16 years or older without any pre-existing hematologic disorder or use of anticoagulant medications. Data including Complete Blood Count, Prothrombin Time (PT), activated Partial Thromboplastin Time (aPTT) and Fibrinogen were measured on presentation, and 4 hours after. Crotaline Fab antivenom (CroFab®) administration was noted if done. Adverse events associated with antivenom therapy, recurrence phenomena, delayed onset of symptoms, and performance of fasciotomy were also recorded. Results: Overall, 119 snakebites were evaluated. The majority were identified as Crotalinae - 25 water moccasin, copperhead or cottonmouth (Agkistrodon piscivorus, Agkistrodon contortrix) bites and 34 rattlesnake (Sistrurus miliarius, Crotalus adamanteus) bites. Male sex dominated the sample with most patients middle-aged (Table 1). More than 80% of patients arrived within 6 hours following the bite. Over 60% of patients received crotaline Fab antivenom. Results are presented in Table 2. Around 12% of patients with water moccasin, copperhead or cottonmouth (Agkistrodon piscivorus, Agkistrodon contortrix) bites had coagulopathy on admission. This compares similarly to data from South Carolina previously showing a 10.89% rate following copperhead bites (Qureshi et al. Blood 2010;116(21):4753). The rate of coagulopathy with rattlesnake bites was however much higher in North Florida at 20.6% - compared to 5.26% in the South Carolina series. Rates of DIC or severe hemorrhage were 8% for water moccasin, copperhead or cottonmouth (Agkistrodon piscivorus, Agkistrodon contortrix) bites and 5.9% for rattlesnake (Sistrurus miliarius, Crotalus adamanteus) bites. When hemostatic defects were looked at separately, the most common abnormality induced was PT/aPTT derangement, followed by hypofibrinogenemia and then thrombocytopenia. This pattern was the same as reported in South Carolina. Recurrence phenomena was observed after 4 hours in a number of patients, however the significance of this remains uncertain as most of these patients remained clinically stable without worsening symptoms. Anaphylactic reaction to the antivenom developed in one patient. Conclusions: In this sample from North Florida, deranged PT/aPTT was the most common hematologic abnormality following envenomation, followed by hypofibrinogenemia and a low rate of thrombocytopenia. Similarities with data from South Carolina were noted, although rattlesnake bites had 4 times higher incidence of coagulopathy in North Florida. DIC or severe hemorrhage was a notable toxicity, affecting 6-8% of Crotalinae cases. Hematologic effects of envenomation do seem to vary by geographic areas in the United States and physicians would benefit from local data to better manage these patients. Disclosures No relevant conflicts of interest to declare.

Background: Patients with sickle cell disease (SCD) are at increased risk of developing bacterial infections as a result of functional asplenia. Fever, a common symptom in SCD often occurs with other sickle cell related conditions and viral infections. This poses a diagnostic challenge and early use of empiric antibiotics is recommended while awaiting cultures. The widespread administration of antibiotics to all patients with SCD with fever can result in problems such as antibiotic resistance and increased medical costs. An early and reliable biomarker is therefore needed to help distinguish between bacterial and non-bacterial causes for fever in SCD. Procalcitonin (PCT) has been shown to be elevated in bacterial but not viral infections. In SCD, few studies have looked at the role of PCT in predicting bacterial infections. Unal et al reported vaso-occlusive crisis (VOC) with or without fever did not increase PCT levels in relation to patients with no crisis and no fever. However, Rincón-López et al reported a PCT < 0.6ng/mL had a negative predictive value of 97.2% and potentially could be used to identify bacterial infection early. Methods: We retrospectively studied 122 patients with SCD who presented to the emergency department with fever from 2015-2019. Inclusion criteria were defined as patients with SCD, 17 years and older and PCT measurement on presentation to the emergency department. Exclusion criteria were defined as patients with SCD and fever who had received empiric antibiotics prior to labs being drawn in the emergency department. The cohort was divided into groups of patients with Confirmed Bacterial Infection (CBI, n=18), Suspected Bacterial Infection (SBI, n=6), Viral Infections (n=10) and Vaso-Occlusive Crises (VOC, n=88) only. CBI was defined as a positive bacterial culture (blood, body fluid, urine, respiratory or cerebrospinal fluid) or C.difficile toxin assay. Viral infections were defined as a negative bacterial culture in the presence of a virus found on PCR obtained with nasopharyngeal swab. Characteristics including genotype, age, gender, complete blood count, PCT, creatinine, total bilirubin, hydroxyurea use and length of stay were examined. Data was analyzed between the groups using descriptive statistics and accounting for unequal variances, with p-value set at 0.05 for significance. Results: Demographics and clinical characteristics are summarized in Table 1 (Figure). The mean age was 34.6 years with predominantly males (64.8%). Almost two-thirds were on hydroxyurea (62.3%). The most common genotype was HbSS (70.5%) followed by HbSC (26.2%) and HbSβ (3.3%). The mean PCT for patients with CBI was 8.99 ng/mL (range, 0.03-78.36) as compared to 0.31 ng/mL (range, 0.02-6.82) in the VOC group. The most common organisms detected were E.coli, C.difficile, Pseudomonas, Staphylococcus and Enterobacter. There was a significant difference between median PCT for patients with CBI and those with VOC (p=0.036) and between patients with CBI and viral infections (p= 0.045). Using a PCT of >0.5ng/mL resulted in 81% Sensitivity and 85% Specificity for CBI. Conclusion: In patients with SCD presenting with fever, PCT on presentation was significantly higher in those with CBI compared to VOC only or Viral Infection. Disclosures No relevant conflicts of interest to declare.