A warning for warming catheters: interventional radiology's role.

Concerns have been raised in the literature, regarding the risk of venous thromboembolic events associated with the use of thermoregulatory catheters. Inferior vena cava (IVC) filters are commonly used to prevent venous thromboembolic events. We demonstrate the usefulness of IVC filter placement prior to the removal of thermoregulatory warming catheters. The management of thermoregulatory warming catheter associated venous thromboembolism is outlined through a retrospective case series of three patients. In one case IVC thrombus was incidentally detected at ultrasonography one-week post removal. The second case describes the occurrence of pulseless electrical activity arrest secondary to massive pulmonary embolism immediately post removal of the thermoregulatory catheter, and subsequent interventional radiology management including pulmonary thrombectomy and caval filter placement. The third case is of a patient in whom the removal of the warming catheter was performed in the angiography suite, with placement of IVC filter prior to removal. Venography displayed a large thrombus burden within the IVC filter. There is limited data in the literature regarding the use of IVC filters as prophylaxis in patients with thermoregulatory catheters, particularly warming catheters. We advocate the placement of an IVC filter prior to the removal of warming catheters. We raise awareness regarding the potential risks of venous thromboembolism in this population and the key role interventional radiology has in the management of these patients.

Proactive review by the emergency department before inter-hospital transfer (the PREVENT study).

OBJECTIVES: To determine the population of patients where patient transfer may be prevented by assessment of a senior ED registrar at the referring hospital. METHODS: Patients transferred from Caulfield Hospital, specialising in community services, rehabilitation, aged care and aged mental health to The Alfred Emergency and Trauma Centre, an adult major referral centre within the same clinical network were identified from 1 July 2016 to 31 December 2016. Medical records were reviewed independently by two clinicians to determine preventability of transfer and whether attendance by a senior ED registrar could have prevented the transfer. RESULTS: There were 221 patients included with a mean age of 73.6(15.1) years. The median time spent in the ED was 4 h (interquartile range 2-8) and 197 (89.1%) were admitted. There were 107 (48.6%) transfers deemed preventable or potentially preventable, with 104 preventable by attendance of a senior ED registrar. The most common indication for transfer was acute trauma (n = 55; 24.9%), and the odds of a case being preventable or potentially preventable if transferred for the primary indication of trauma was 3.9 (95% confidence interval 2.1-7.1; P < 0.001). Among the preventable cases, the total cost of transfer was AU$105 984 over 6 months, not accounting for the costs of duplication of care. CONCLUSIONS: This proof-of-concept study suggests that strategies to expand the provision of acute care to outreach within specialist networks and reduce patient transfers should be further explored. An outreach programme for improved acute assessment of patients at the referring hospital particularly after acute trauma may prevent transfers, improving care pathways.

Thrombin based gelatin matrix and fibrin sealant mediated clot formation in the presence of clopidogrel.

BACKGROUND: Platelet inhibitors are commonly used to reduce the risk of atherothrombotic events. The aim of this study was to determine the impact of platelet inhibitors, specifically clopidogrel and aspirin, on clot kinetics, strength, and/or structure during the use of thrombin based gelatin matrices and fibrin sealants. METHODS: Blood was collected and heparinized from donors on clopidogrel (and aspirin) and age matched control donors. Blood component analysis, whole blood platelet aggregometry, and activated clotting time (ACT) were used to monitor compliance to therapy and identify any differences between donor groups. Clot kinetics and strength were analyzed using thrombelastography (TEG). Field Emission Scanning Electron Microscopy (FESEM) was used to analyze clot structure. RESULTS: Blood component profiles were similar for both donor groups. Aggregometry indicated that aggregation response to adenosine diphosphate (ADP) for clopidogrel donors was 12% of that for the controls (p = 0.0021), an expected result of clopidogrel induced platelet inhibition. However, blood from both donor groups had an elevated thrombin induced aggregation response. Heparinization of donor blood resulted in similarly elevated ACTs for both donor groups. TEG results indicated similar clot kinetics and strength between clopidogrel and control donor groups for blood alone and when clotting was induced using thrombin based gelatin matrices and fibrin sealants. FESEM images supported TEG findings in that similar morphologies were observed in ex vivo formed clots from both donor groups when thrombin based gelatin matrices and fibrin sealants were used. CONCLUSION: These results suggest that platelet inhibitors do not negatively impact clot kinetics, strength, and structure when clotting is initiated with thrombin based gelatin matrices and fibrin sealants.

Case study: contamination of heparin with oversulfated chondroitin sulfate.

In late 2007 and early 2008, a cluster of adverse events in patients receiving Heparin Sodium Injection occurred in the United States and in some countries in Europe. The adverse events were reported as being "allergic type" reactions, chiefly characterized by acute hypotension, nausea, and shortness of breath. The root cause of the cluster of adverse events was determined to be a contamination of the heparin by oversulfated chondroitin sulfate. The isolation and structure determination of this contaminant was accomplished by an FDA-led consortium of academic and government laboratories and independently by Baxter Healthcare, whose vial products were first identified in the USA as being associated with the adverse events. Oversulfated chondroitin sulfate was shown to produce acute hypotension in animal models, demonstrating that it was most likely the causative agent responsible for certain of the reported adverse events in patients receiving the contaminated heparin products.

Structure elucidation and biological activity of the oversulfated chondroitin sulfate contaminant in Baxter heparin.

From late December 2007 to February 2008, the number of adverse responses to heparin infusions rose noticeably above baseline levels in North America, ultimately resulting in a widespread recall of all heparin vial products made by Baxter Healthcare. Using various analytical techniques and the de novo synthesis of a fully sulfated chondroitin sulfate (FSCS) derivative, the authors have confirmed the identity of the contaminant as an oversulfated chondroitin sulfate (OSCS) and have also defined the heterogeneity and concentration of this contaminant in various lots of heparin. Using both contaminated heparin products and the synthetically produced derivative, the authors have shown that the OSCS produces a dose-dependent hypotension in both pigs and rats and that the response in rats can be abrogated with bradyzide, a rodent-selective B(2) bradykinin receptor antagonist. The no observed effect level (NOEL) for this contaminant appears to be approximately 1 mg/kg, corresponding to a contamination level in finished lots of heparin of approximately 3%. Using human plasma, the OSCS derivative was shown to activate kallikrein. These data provide insight into the etiology of the adverse events, particularly refractory hypotension, observed in patients who were exposed to heparin contaminated with OSCS.

Hyperactivation of protein kinase B and ERK have discrete effects on survival, proliferation, and cytokine expression in Nf1-deficient myeloid cells.

The Nf1 tumor suppressor encodes a GTPase-activating protein for Ras. Previous work has implicated hyperactive Ras in the aberrant growth of Nf1-deficient cells; however, there are limited data on which effectors modulate specific phenotypes. To address this, we generated myeloid cell lines by infecting fetal liver cells with a retrovirus encoding a truncated allele of c-Myb. Granulocyte-macrophage colony stimulating factor (GM-CSF) promoted the survival of wild-type Myb cells in a dose-dependent manner. By contrast, Nf1-deficient myeloid cells deprived of growth factors, were resistant to apoptosis due to hyperactivation of the phosphoinositide-3-OH kinase/protein kinase B cascade. Nf1(-/-) cells also demonstrated growth factor-independent proliferation and upregulation of GM-CSF mRNA production that were dependent upon Raf/MEK/ERK signaling. These data link specific Ras effectors with discrete cellular phenotypes in Nf1-deficient cells.

MLL5, a homolog of Drosophila trithorax located within a segment of chromosome band 7q22 implicated in myeloid leukemia.

Proteins encoded by Polycomb and Trithorax-group (Pc-G and Trx-G) genes regulate developmental fates by maintaining or repressing HOX gene expression, respectively. In a search for candidate myeloid leukemia tumor suppressor genes from a approximately 2.5 Mb commonly-deleted segment within chromosome band 7q22, we identified a novel human Trithorax (Trx) family member named MLL5. Trx-G genes encode proteins that modulate transcriptional programs through protein-protein interactions that are mediated by PHD and SET domains, and by binding to DNA via A-T hooks and methyltransferase homology motifs. MLL5 is a homolog of the Drosophila gene CG9007; it encodes a 6.5 kb mRNA that is expressed widely. MLL5 includes a SET domain and a single PHD finger, but lacks A-T hooks and methyltransferase homology domains that are found in MLL. The leukemia cell line RCV-ACV-A carries a heterozygous missense mutation within the PHD domain; however, no mutations within the MLL5 coding region were detected in primary leukemias. MLL5 is a novel mammalian Trx-G gene that might modulate transcription by protein association.