Establishment of a swine model of delayed bleeding after endoscopic procedure.

Objectives: Although delayed bleeding after endoscopic procedures has become a problem, currently, there are no appropriate animal models to validate methods for preventing it. This study aimed to establish an animal model of delayed bleeding after endoscopic procedures of the gastrointestinal tract. Methods: Activated coagulation time (ACT) was measured using blood samples drawn from a catheter inserted into the external jugular vein of swine (n = 7; age, 6 months; mean weight, 13.8 kg) under general anesthesia using the cut-down method. An upper gastrointestinal endoscope was inserted orally, and 12 mucosal defects were created in the stomach by endoscopic mucosal resection using a ligating device. Hemostasis was confirmed at this time point. The heparin group (n = 4) received 50 units/kg of unfractionated heparin via a catheter; after confirming that the ACT was ≥200 s 10 min later, continuous heparin administration (50 units/kg/h) was started. After 24 h, an endoscope was inserted under general anesthesia to evaluate the blood volume in the stomach and the degree of blood adherence at the site of the mucosal defect. Results: Delayed bleeding was observed in three swine (75%) in the heparin-treated group, who had a maximum ACT of >220 s before the start of continuous heparin administration. In the non-treated group (n = 3), no prolonged ACT or delayed bleeding was observed at 24 h. Conclusion: An animal model of delayed bleeding after an endoscopic procedure in the gastrointestinal tract was established using a single dose of heparin and continuous heparin administration after confirming an ACT of 220 s.

Heparin Induced Thrombocytopenia Testing.

This article provides a comprehensive overview of Heparin-Induced Thrombocytopenia (HIT) with an emphasis on laboratory testing and advantages of automation. HIT is a critical condition arising from heparin exposure, leading to a contradictory combination of thrombocytopenia with an increased thrombosis risk. The article discusses HIT's history, clinical presentation, laboratory diagnosis, and management strategies. It highlights the importance of interdisciplinary collaboration for effective diagnosis and treatment, underscoring advancements in technology and targeted therapies that are shaping future approaches to HIT management.

Pre-hospital heparin is not associated with infarct vessel patency and mortality in ST-segment elevation myocardial infarction patients with out-of-hospital cardiac arrest.

BACKGROUND: Pre-hospital heparin administration has been reported to improve prognosis in patients with out-of-hospital cardiac arrest (OHCA). This beneficial effect may be limited to the subgroup of ST-segment elevation myocardial infarction (STEMI) patients. METHODS: To assess the impact of pre-hospital heparin loading on TIMI (Thrombolysis in Myocardial Infarction) flow grade and mortality in STEMI patients with OHCA, we analyzed data from 2,566 consecutive patients from two hospitals participating in the prospective Feedback Intervention and Treatment Times in ST-segment Elevation Myocardial Infarction (FITT-STEMI) trial. RESULTS: In 394 participants with OHCA, 272 (69%) received heparin from the emergency medical service (EMS). Collapse witnessed by EMS (odds ratio (OR) = 3.53, 95%-confidence interval (CI) = 1.54-8.09; p = 0.003) and pre-hospital ECG recording (OR = 3.32, 95% CI = 1.06-10.35; p = 0.039) were identified as parameters significantly associated with pre-hospital heparin use. In univariate analysis, in-hospital mortality was lower in the group receiving heparin in the pre-hospital setting (26.8% vs. 42.6%, p = 0.002). However, in a regression model, pre-hospital heparin use was no longer a significant predictor of mortality (OR = 0.992; p = 0.981). Patency of the infarct artery prior to coronary revascularization, as measured by TIMI flow grade, was not associated with pre-hospital administration of heparin in OHCA patients (OR = 0.840; p = 0.724). CONCLUSIONS: In STEMI patients with OHCA, pre-hospital use of heparin is neither associated with improved early patency of the infarct artery nor with a better prognosis. Our results do not support the assumption of a positive effect of heparin administration in the pre-hospital treatment phase in STEMI patients with OHCA. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00794001.

Intravenous injection of nattokinase-heparin electrostatic complex improves the therapeutic effect of advanced tumors by dissolving cancer-related thrombosis.

AIMS: Cancer-related thrombosis (CAT) is a common complication in cancer patients, significantly impacting their quality of life and survival prospects. Nattokinase (NK) has potent thrombolytic properties, however, its efficacy is limited by low oral bioavailability and the risk of severe allergic reactions with intravenous use. Heparin (HP) is a widely used anticoagulant in clinical settings. This study aimed to overcome the intravenous toxicity of NK and explore its effect on CAT in advanced tumors. MAIN METHODS: In this study, NK-HP electrostatic complexes were constructed, and their safety and thrombolytic efficacy were verified through guinea pig allergy tests, mouse tail vein tests, and both in vivo and in vitro thrombolysis experiments. Additionally, an S180 advanced tumor model was developed and combined with sialic acid-modified doxorubicin liposomes (DOX-SAL) to investigate the impact of NK-HP on CAT and its antitumor effects in advanced tumors. KEY FINDINGS: We observed that NK-HP can eliminate the intravenous injection toxicity of NK, has strong thrombolytic performance, and can prevent thrombosis formation. Intravenous injection of NK-HP can enhance the antitumor effect of DOX-SAL by reducing the fibrin content in advanced tumors and increasing the levels of the cross-linked protein degradation product D-dimer. SIGNIFICANCE: This study developed a method to eliminate the intravenous injection toxicity of NK, proposing a promising therapeutic strategy for CAT treatment, particularly for CAT in advanced tumors, and improving the efficacy of nano-formulations in anti-tumor therapy.

Relation between antithrombin-III activity and activated clotting time for cardiopulmonary bypass.

Heparin resistance (HR) is observed before cardiopulmonary bypass (CPB), despite with normal antithrombin III (AT-III) levels. The relationships between preoperative AT-III activity and activated clotting time (ACT) after the first heparin dose should be clarified. We retrospectively analyzed the data of 818 patients who underwent CPB surgery, with the initial heparin of 300, 400, and 500 IU/kg, between 2017 and 2021. We defined HR as the failure to achieve ACT after the initial heparin dose (Post ACT) of > 480 s.There were no significant correlations between the AT-III activity and Post ACT in all patients, including 143 patients with AT-III activity < 80% and 675 patients with AT-III activity of ≥ 80%. Also, there were no significant correlations between the AT-III activity and Post ACT in 74 patients who received heparin of 300 IU/kg, in 186 patients with 400 IU/kg, and in 339 patients with 500 IU/kg. After identifying smoking, HR, activated partial thromboplastin time, fibrinogen degradation products (FDP), and ACT as influencing factors, multiple comparisons using the Steel-Dwass test showed significant difference in FDP and HR among the patients who received heparin of 300 IU/kg, 400 IU/kg, and 500 IU/kg. There is no association between preoperative AT-III activity and ACT after the first heparin administration for CPB, even in different dose of heparin. Rather, the higher the initial UFH dose is, the higher ACT may be, regardless of the AT-III activity.

Alpha-Gal Syndrome and Cardiac Surgery.

Galactose-alpha-1,3-galactose (alpha-gal) is a carbohydrate expressed by all mammals except for humans and certain old-world primates. It can be found in a plethora of products derived from mammals, including milk, organs, skeletal muscle and gelatin, in addition to products prepared with mammalian cells or constituents. In the late 2000s, an association between tick bites and the development of immunoglobulin E antibodies to the alpha-gal carbohydrate was discovered. The term "alpha-gal syndrome" (AGS) was then coined to describe allergic reactions to mammalian meat or other alpha-gal-containing products derived from mammals. Symptoms are often delayed several hours from consumption and can be urticarial and/or gastrointestinal. Medications and bioprosthetic inserts derived from mammals were also noted to cause allergic reactions in affected patients. Cardiac surgery, in particular, is considered high risk, given that unfractionated heparin has a bovine or porcine origin and is administered in large doses for cardiopulmonary bypass. Bioprosthetic valves have similar origins and risks. Awareness of AGS in cardiac surgery patients can lead to decreased risk preoperatively and inform management perioperatively and postoperatively. In this narrative review, we have reviewed the published literature relevant to AGS in patients undergoing cardiac surgery and shared our treatment approach.

Good outcome with conservative treatment of delayed spinal epidural hematoma following combined spinal-epidural anesthesia: a rare case report.

BACKGROUND: Delayed spinal epidural hematoma (SEH) following central neuraxial block (CNB) is a rare but serious complication. The underlying causes of SEH associated with neuraxial anesthesia are still unclear. Furthermore, the decision between surgical intervention and conservative management for SEH remains a complex and unresolved issue. CASE PRESENTATION: We report a case of delayed SEH in a 73-year-old woman who underwent vaginal hysterectomy under combined spinal-epidural anesthesia, with the administration of postoperative anticoagulants to prevent deep vein thrombosis on the 1st postoperative day (POD). She experienced symptoms 56 h after CNB. Magnetic resonance imaging (MRI) revealed a dorsal SEH at the L1-L4 level with compression of the thecal sac. On conservative treatment, full recovery was achieved after six months. CONCLUSIONS: This case reminds anesthesiologists should be alert to the possible occurrence of a delayed SEH following CNB, particularly with the administration of anticoagulants. Immediate neurological evaluation of neurological deficit and MRI are advised. Conservative treatment combined with close and dynamic neurological function monitoring may be feasible for patients with mild or nonprogressive symptoms even spontaneous recovery.

Heparin-binding protein as a predictor of mortality in patients with diabetes mellitus and community-acquired pneumonia in intensive care unit : a propensity score matched study.

BACKGROUND: Patients with diabetes mellitus (DM) are vulnerable to community-acquired pneumonia (CAP), which have a high mortality rate. We aimed to investigate the value of heparin-binding protein (HBP) as a prognostic marker of mortality in patients with DM and CAP. METHODS: This retrospective study included CAP patients who were tested for HBP at intensive care unit (ICU) admission from January 2019 to April 2020. Patients were allocated to the DM or non-DM group and paired with propensity score matching. Baseline characteristics and clinical outcomes up to 90 days were evaluated. The primary outcome was the 10-day mortality. Receiver operating characteristic (ROC) curves, Kaplan-Meier analysis, and Cox regression were used for statistical analysis. RESULTS: Among 152 enrolled patients, 60 pairs were successfully matched. There was no significant difference in 10-day mortality, while more patients in the DM group died within 28 d (P=0.024) and 90 d (P=0.008). In the DM group, HBP levels at ICU admission were higher in 10-day non-survivors than in 10-day survivors (median 182.21 [IQR: 55.43-300] ng/ml vs. median 66.40 [IQR: 34.13-107.85] ng/mL, P=0.019), and HBP levels could predict the 10-day mortality with an area under the ROC curve of 0.747. The cut-off value, sensitivity, and specificity were 160.6 ng/mL, 66.7%, and 90.2%, respectively. Multivariate Cox regression analysis indicated that HBP was an independent prognostic factor for 10-day (HR 7.196, 95%CI: 1.596-32.455, P=0.01), 28-day (HR 4.381, 95%CI: 1.449-13.245, P=0.009), and 90-day mortality (HR 4.581, 95%CI: 1.637-12.819, P=0.004) in patients with DM. CONCLUSION: Plasma HBP at ICU admission was associated with the 10-day, 28-day, and 90-day mortality, and might be a prognostic factor in patients with DM and CAP.

Perioperative risks associated with administration of andexanet alfa during emergency cardiac surgery with circulatory arrest.

This case report describes the perioperative course of a patient undergoing emergency repair of acute type A thoracic aortic dissection. Andexanet alfa was administered intraoperatively to obtain a dry operative field for right axillary artery exposure and cannulation. Andexanet alfa-induced heparin resistance resulted in cardiopulmonary bypass circuit and pericardial thrombosis requiring more than 400,000 units of unfractionated heparin and antithrombin III to overcome. Postoperatively, excessive chest tube output was observed secondary to protracted heparin rebound requiring continuous dosing of protamine. This case demonstrates the significant challenging perioperative, not just intraoperative, hazards associated with intraoperative andexanet alfa use during emergency cardiac surgery with cardiopulmonary bypass.

Anti-platelet factor 4 immunothrombotic syndromes.

Anti-platelet factor 4 immunothrombotic syndromes comprise a group of disorders that include heparin-induced thrombocytopenia and vaccine-induced immune thrombocytopenia and thrombosis. These are highly prothrombotic, immunological disorders characterised by specific clinical and pathological criteria which include thrombocytopenia and thrombosis. While they are predominantly triggered by heparin and the adenoviral vector vaccines, respectively, other provoking factors have been described, as well as spontaneous forms. The unexplained co-occurrence of thrombocytopenia with thrombosis should raise suspicion and prompt testing. This nutshell review discusses the pathophysiology, presenting features and diagnostic criteria for these conditions.

Post-procedural Anticoagulation With Unfractionated Heparin in Acute Coronary Syndrome: Insight from the STOPDAPT-3 Trial.

The current guidelines for acute coronary syndrome (ACS) discourage the use of anticoagulation after percutaneous coronary intervention (PCI) without specific indications, although the recommendation is not well supported by evidence. In this post hoc analysis of the ShorT and OPtimal Duration of Dual AntiPlatelet Therapy-3 (STOPDAPT-3) trial, 30-day outcomes were compared between the 2 groups with and without post-PCI heparin administration among patients with ACS who did not receive mechanical support devices. The co-primary end points were the bleeding end point, defined as the Bleeding Academic Research Consortium type 3 or 5 bleeding, and the cardiovascular end point, defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke. Among 4,088 patients with ACS, 2,339 patients (57.2%) received post-PCI heparin. The proportion of patients receiving post-PCI heparin was higher among those with ST-elevation myocardial infarction compared with others (72.3% and 38.8%, p <0.001), and among patients with intraprocedural adverse angiographic findings compared with those without (67.6% and 47.5%, p <0.001). Post-PCI heparin compared with no post-PCI heparin was associated with a significantly increased risk of the bleeding end point (4.75% and 2.52%, adjusted hazard ratio 1.69, 95% confidence interval 1.15 to 2.46, p = 0.007) and a numerically increased risk of the cardiovascular end point (3.16% and 1.72%, adjusted hazard ratio 1.56, 95% confidence interval 0.98 to 2.46, p = 0.06). Higher hourly dose or total doses of heparin were also associated with higher incidence of both bleeding and cardiovascular events within 30 days. In conclusion, post-PCI anticoagulation with unfractionated heparin was frequently implemented in patients with ACS. Post-PCI heparin use was associated with harm in terms of increased bleeding without the benefit of reducing cardiovascular events. Trial identifier: STOPDAPT-3 ClinicalTrials.gov number, NCT04609111.

Anticoagulants for the treatment of isolated lower limb superficial vein thrombosis a Bayesian network meta-analysis of randomized controlled trials.

OBJECTIVE: Assess the safety and efficacy of anticoagulants in treating isolated superficial vein thrombosis (iSVT). MATERIALS AND METHODS: A systematic review was conducted according to PRISMA 2020 guidelines, for randomized controlled trials (RCTs) investigating anticoagulants in the treatment of iSVT. The primary endpoint of thrombotic complications encompassed any incident of iSVT progression/recurrence and the development of new-onset (deep vein thrombosis) DVT or (pulmonary embolism) PE. RESULTS: Eight RCT's and 4721 patients treated once daily with either fondaparinux 2.5 mg, rivaroxaban 10 mg, therapeutic, intermediate, and prophylactic low molecular weight heparin (LMW) were included. While all anticoagulants displayed a statistically significant risk reduction compared to placebo in terms of thrombotic complications and iSVT progression/recurrence, only fondaparinux reduced the risk for DVT/PE. Additionally, fondaparinux exhibited enhanced efficacy in decreasing DVT/PE events relative to prophylactic and therapeutic LMWH. Furthermore, rivaroxaban and fondaparinux demonstrated superior outcomes in terms of preventing thrombotic complications compared to all three dosing regimens of LMWH without significant differences between the two, risk ratio RR 1.00(95%CI:0.51-1.92). SUCRA identified fondaparinux as the most effective treatment regarding thrombotic complications, (SUCRA,91.6) and DVT/PE, (SUCRA,96) and rivaroxaban in terms of iSVT progression/recurrence (SUCRA,94.68). Ultimately and despite certain model limitations, meta-regression analysis suggested a possible trend towards improved outcomes with longer treatment durations for thrombotic complications ß = -0.34(95%CI:-16.39to12.23). CONCLUSIONS: Despite inherent limitations such as variations in treatment durations and follow-up periods, this review displayed the efficacy of fondaparinux, rivaroxaban and LMWH in treating iSVT. The improved efficacy of fondaparinux over therapeutic LMWH in terms of DVT/PE outcomes necessitates cautious interpretation underscoring the need for further investigation through adequately powered RCTs.

A study on the prevention of thrombosis after simultaneous pancreas-kidney transplantation.

BACKGROUND: Renal failure is one of the most common chronic complications of diabetes. Simultaneous pancreas-kidney transplantation (SPK) is considered the preferred treatment for individuals with diabetes and chronic renal failure. This procedure has demonstrated efficacy in enhancing the quality of life for patients and minimizing the complications associated with diabetes. OBJECTIVE: In this study, we analyzed the incidence and safety of complications in different thrombosis prevention techniques post simultaneous pancreas-kidney transplantation (SPK). METHODS: Patients who underwent SPK between January 2019 and December 2022 were selectively categorized into two groups: the heparin group and the non-heparin group depending on the utilization of low molecular weight heparin. The occurrence of complications and clinical outcomes were subsequently calculated in each group. RESULTS: In this study, we included a total of 58 recipients who underwent SPK, with 36 in the heparin group and 22 in the non-heparin group. Among the 58 participants, there were 3 cases of pancreatic thrombosis complications, with 2 cases (5.6%) in the heparin group and 1 case (4.6%) in the non-heparin group, and the differences were not statistically significant (P> 0.05). Regarding gastrointestinal bleeding, there were 17 cases out of the total 58 patients, with 14 cases (38.9%) in the heparin group and 3 cases (13.6%) in the non-heparin group, and the difference was statistically significant (P< 0.05). CONCLUSION: After surgery, the use of low molecular weight heparin anticoagulation may increase the likelihood of experiencing gastrointestinal bleeding. Prior to the surgery, a comprehensive evaluation of the coagulation status and medical history of the patient should be performed, enabling stratification of risks involved. Based on this assessment, either low-molecular-weight heparin or aspirin should be selected as a preventive measure against thrombosis.

Flow cytometry vs conventional methods for the evaluation of anti-PF4/heparin antibodies: a single center study.

Aim: Heparin-induced thrombocytopenia (HIT) is a rare, life-threatening, immune-mediated adverse effect of heparin administration. This study compares frequently used laboratory assays in terms of their effectiveness in HIT diagnosis. Materials & methods: Fifty patients with suspected HIT were tested by gel immunoassay and solid phase PF4/heparin antibody ELISA. On positive results, platelet activation markers P-selectin and Annexin V were assayed using flow cytometry. Results: Thirty/50 patients were negative for both immunoassays. Flow cytometry was performed in the 20 immunoassay positive patients. Platelet activation was observed in 7/20 in the presence of low heparin concentration (0.2 IU/ml). Conclusion: The results are in accordance with the currently available literature and flow cytometry seems a promising alternative in HIT laboratory investigation.

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Standardization of Anti-Xa Assay and its Comparison with Activated Partial Thromboplastin Time for Monitoring Unfractionated Heparin Therapy.

Monitoring of anticoagulant activity of unfractionated heparin (UFH) is primarily done with activated partial thromboplastin time (aPTT), which is affected by many factors. Anti-Xa assays are considered to overcome these factors and may provide a better method for monitoring patients on UFH with a narrow therapeutic range. This study aimed to compare the effectiveness of aPTT and anti-Xa assays in UFH monitoring. A prospective non-randomized study was carried out in two stages: first, the anti-Xa assay was standardized using kit instructions; each sample was then analyzed by both tests. The outcomes of the two assays were compared and assessed for agreement of maintaining therapeutic anticoagulant levels. These levels for anti-Xa assay were between 0.3 and 0.7 IU/ml, while it was 1.5-2.5 times the control for aPTT assay. Below this range was regarded as subtherapeutic, and above this as supratherapeutic. A total of 90 samples were tested and analyzed using both assays. Most of them (> 70%) were noted to be in subtherapeutic levels with both tests. The overall concordance was 73.3%, and the estimated kappa value was 0.483 (0.396-0.57). The correlation between aPTT and anti-Xa assay was 0.74 (p < 0.001). With anti-Xa levels in the therapeutic range, aPTT levels were in subtherapeutic in 60% and supratherapeutic in 13.3% cases. Although both the testing strategies had a good agreement and correlation, discordance was observed in interpretative values with anti-Xa levels in therapeutic range and aPTT levels in non-therapeutic range. Its clinical implications need to be evaluated further in future studies.

Long-term outcomes of below-the-knee bypass surgery using heparin-bonded expanded polytetrafluoroethylene grafts.

PURPOSE: To report the outcomes of below-the-knee (BK) bypass surgery using heparin-bonded expanded polytetrafluoroethylene (ePTFE) grafts, performed in two centers since its launch in Japan. METHODS: We conducted a retrospective analysis of databases from two medical centers, evaluating 51 limbs in 42 consecutive patients with peripheral arterial disease (PAD), who underwent BK bypass surgery using heparin-bonded ePTFE grafts between October, 2013 and April, 2023. RESULTS: Thirty-three limbs (64.7%) were classified as Rutherford category 4-6 and 33 limbs (64.7%) had a history of ipsilateral revascularization. Technical success was achieved in 98% of the patients. The 30 day mortality rate was 2.4% (n = 1) and the overall 30 day complication rate was 9.5% (n = 4). The median follow-up period was 38 (interquartile range 13-67) months. Three patients required major amputation and 14 died during follow-up. Primary patency rates at 1, 3, and 5 years were 67.8%, 57.5%, and 46.5%, respectively, while secondary patency rates for these periods were 84.6%, 70.0%, and 66.0%, respectively. Overall survival rates at 1, 3, and 5 years were 90.1%, 74.5%, and 70.9%, respectively. CONCLUSIONS: BK bypass surgery using heparin-bonded ePTFE graft is a viable and durable option for patients with PAD, who are deemed unsuitable for autologous vein bypass surgery.

Comparison of pain after prophylactic anticoagulant injections to prevent venous thromboembolism.

Subcutaneous injection of unfractionated heparin (UH) or low molecular weight heparin (LMWH) is frequently utilized for venous thromboembolism chemoprophylaxis. We previously discovered that nurses believe patients experience more pain with UH compared to the LMWH enoxaparin; however, no published studies that are appropriately powered exist comparing pain associated with subcutaneous chemoprophylaxis. Our objective was to assess if differences exist in pain associated with subcutaneous administration of UH and enoxaparin. We conducted an observational study of patients who underwent major abdominal surgery between 11/2017-4/2019. All patients received one of three prophylactic regimens: (1) UH only, (2) Initial dose of UH followed by enoxaparin, or (3) enoxaparin only. Of the 74 patients observed, 40 patients received UH followed by enoxaparin, 17 received UH only, and 17 received enoxaparin only. There was a significant difference in patients' mean perceived pain between subcutaneous UH and enoxaparin injections (mean post-injection pain after UH 3.3 vs. enoxaparin 1.5; p < 0.001). There was no significant difference in perceived pain for patients who received consecutive UH or enoxaparin injections. Differences in pain associated with different chemoprophylaxis agents may be an unrecognized driver of patient refusals of VTE chemoprophylaxis and may lead to worse VTE outcomes.

Management of Neonatal Aortic Thrombosis: Challenges and Outcomes With Systemic and Intra-arterial Thrombolysis.

Neonatal aortic thrombosis, though rare, is associated with high mortality and is frequently linked to umbilical vessel catheterization, especially in smaller and critically ill infants due to their low levels of natural anticoagulants and increased prothrombotic activity. We report a case of a term neonate with abdominal aortic thrombosis and severe lower limb ischemia, presenting with respiratory distress requiring intubation and subsequent development of thrombosis by day 7. Initial anticoagulation with heparin proved insufficient, necessitating the use of reteplase and intra-arterial thrombolysis, which resulted in clinical improvement despite limited immediate success in Doppler studies. The patient was discharged on low-molecular-weight heparin against medical advice, highlighting the complexities and need for individualized management strategies in neonatal thromboembolism.

Heparin-induced thrombocytopenia after cardiac surgery. A single-center, retrospective cohort study.

Background: Cardiac surgery is a high-risk setting for heparin-induced thrombocytopenia (HIT). However, large differences in its incidence, rate of thrombotic complications, and mortality have been reported in this context. Few studies address the pharmacologic management of HIT specifically in this setting. Objectives: To describe the incidence, outcomes, and management of patients with HIT in our cohort and to compare them with patients presenting platelet factor 4/heparin antibodies but without platelet-activating capacity. Methods: A retrospective observational study was conducted over a period of 10 years and 6 months on 13,178 cardiac operations in a single high-volume cardiac surgery center. Results: HIT was diagnosed in 0.22% of patients. HIT with associated thromboembolic complications occurred in 0.04% of cases. Two deaths at 30 days were registered, both in patients with associated thrombosis. The 4T score showed a 99.9% negative predictive value. The immunoglobulin G-specific chemiluminescence test positivity rate was highly predictive of HIT. Warfarin was often started early after surgery, and although it was rarely stopped when the diagnosis of HIT was made, no new thromboembolic complications subsequently occurred. Thrombocytopenia appeared to be a poor prognostic sign, whatever the cause. Conclusion: Although rare, HIT is characterized by high mortality in this setting, especially if thrombotic complications occur. Large multicentric studies or an international registry should be created to enhance the scientific evidence on HIT diagnosis and management in this context.

A method for rapid and reliable quantification of VEGF-cell binding activity.

Vascular endothelial growth factor (VEGF) is a pleiotropic growth factor that binds a broad spectrum of cell types and regulates diverse cellular processes, including angiogenesis, growth and survival. However, it is technically difficult to quantify VEGF-cell binding activity because of reversible nature of ligand-receptor interactions. Here we used T7 bacteriophage display to quantify and compare binding activity of three human VEGF-A (hVEGF) isoforms, including hVEGF111, 165 and 206. All three isoforms bound equally well to immobilized aflibercept, a decoy VEGF receptor. hVEGF111-Phage exhibited minimal binding to immobilized heparan sulfate, whereas hVEGF206-Phage and hVEGF165-Phage had the highest and intermediate binding to heparan, respectively. In vitro studies revealed that all three isoforms bound to human umbilical vein endothelial cells (HUVECs), HEK293 epithelial and SK-N-AS neuronal cells. hVEGF111-Phage has the lowest binding activity, while hVEGF206-Phage has the highest binding. hVEGF206-Phage was the most sensitive to detect VEGF-cell binding, albeit with the highest background binding to SK-N-AS cells. These results suggest that hVEGF206-Phage is the best-suited isoform to quantify VEGF-cell binding even though VEGF165 is the most biologically active. Furthermore, this study demonstrates the utility of T7 phage display as a platform for rapid and convenient ligand-cell binding quantification with pros and cons discussed.