A Rare Case of Argatroban-Induced Anaphylaxis in a Patient With Intermediate-High Risk Pulmonary Embolism.

Heparin-induced thrombocytopenia is a rare and potentially devastating complication of heparin therapy. Patients with an absolute indication for anticoagulation, such as those with significant pulmonary embolism, must be switched to a different anticoagulant, such as argatroban, a direct thrombin inhibitor. We report a case of anaphylaxis to argatroban in a patient who was initially on heparin for intermediate-high risk pulmonary embolism but developed suspected type II heparin-induced thrombocytopenia. This case highlights the significance of recognizing and treating anaphylactic reactions and the diagnostic challenges associated with heparin-induced thrombocytopenia.

Baseline neurological deficit and argatroban plus alteplase in acute ischemic stroke: A post hoc analysis of ARAIS trial.

BACKGROUND: The ARAIS trial didn't demonstrate argatroban significantly improve functional outcome at 90 days in acute ischemic stroke. We conducted post hoc analysis of ARAIS to investigate whether baseline neurological deficit was associated with outcomes. METHODS: Patients without endovascular therapy who met screening criteria as protocol and completed argatroban treatment were enrolled and classified into two subgroups according to NIHSS score at admission. Primary outcome was excellent functional outcome at 90 days, defined as mRS score of 0 to 1. Early neurological deterioration (END), defined as an increase of ≥4 in the NIHSS score from baseline within 48 hours, was investigated as secondary outcome. Compared with alteplase alone, we investigated treatment effect of argatroban plus alteplase on outcomes in subgroups and interaction with subgroups. RESULTS: A total of 675 patients from full analysis set were included: 390 were assigned into NIHSS score <10 subgroup and 285 into NIHSS score ≥10 subgroup. For primary outcome, there was similar treatment effect between argatroban plus alteplase and alteplase alone in NIHSS score ≥10 subgroup (adjusted RD, 5.8%; 95% CI, -6.0% to 17.5%; P = 0.33) and in NIHSS score <10 subgroup (adjusted RD, -1.4%; 95% CI, -9.9% to 7.1%; P = 0.75), and no significant interaction (P = 0.43). Occurrence of early neurological deterioration within 48 hours were significantly lower in NIHSS score ≥10 subgroup, compared with NIHSS score <10 subgroup (P = 0.006). CONCLUSION: Among patients with NIHSS score ≥10, argatroban plus alteplase could safely reduce END within 48 hours.

Effects of Argatroban on Hcy, hs-CRP and FIB levels in patients with acute cerebral infarction.

OBJECTIVE: To evaluate the effects of argatroban on the levels of Hcy, hs-CRP and FIB in patients with acute cerebral infarction (ACI). METHODS: A retrospective analysis was performed on 382 patients with ACI who were hospitalized in the Department of Neurology of our hospital from January 2017 to December 2019. Among them, 158 patients received conventional treatment as the control group and 224 patients received combined treatment with argatroban as the study group. NHISS score, mRS score, Hcy, hs-CRP, FIB level, quality of life, adverse reactions were compared between the two groups after treatment. The levels of Hcy and hs-CRP in patients with different mRS scores were compared. RESULTS: A superior clinical efficacy of the study group was observed than the control group (p < 0.05). The study group witnessed a remarkably lower NHISS score, Hcy, hs-CRP and FIB level as compare to the control group (p < 0.05). The ADL and FMA scores in the study group were higher than those in the control group (p < 0.05). The levels of Hcy and hs-CRP in mRS 0-2 patients were lower than those in mRS 3-6 patients (p < 0.05). CONCLUSION: Argatroban in ACI patients can significantly enhance the clinical efficacy and improve the quality of life. It is closely related to the reduction of Hcy and hs-CRP levels, but the mechanism needs to be further studied.

The effect of argatroban on early neurological deterioration and outcomes in minor ischemic stroke: preliminary findings.

Background: Minor ischemic stroke (MIS) is associated with early neurological deterioration (END) and poor prognosis. Here, we investigated whether argatroban administration can mitigate MIS-associated END and improve functional outcomes by monitoring activated partial thrombin time (APTT). Methods: Data were collected for patients with MIS admitted to our hospital from January 2019 to December 2022. Patients were divided into a dual antiplatelet therapy (DAPT) group (aspirin + clopidogrel) and an argatroban group (aspirin + argatroban). Those in the latter group who achieved a target APTT of 1.5-3-fold that of baseline and <100 s at 2 h after argatroban infusion were included in the argatroban subgroup. The primary outcome was the END rate of the DAPT group versus that of the argatroban group or the argatroban subgroup. Secondary outcomes included the proportion of patients with modified Rankin Scale (mRS) 0-2 at 7 and 90 days. In addition, baseline date were compared between patients with and without END in the argatroban group. Results: 363 patients were included in the DAPT group and 270 in the argatroban group. There were no significant differences in any above outcome between them. 207 pairs were included in the DAPT group and the argatroban subgroup after 1:1 propensity score matching (PSM). Significant differences were observed in the proportion of END (OR, 2.337; 95% CI, 1.200-4.550, p = 0.011) and mRS 0-2 at 7 days (OR, 0.624; 95% CI, 0.415-0.939, p = 0.023), but not in mRS 0-2 at 90 days or the hemorrhagic events between the two groups. In the argatroban group, univariate analysis showed that the rate of diabetes (OR, 2.316; 95% CI, 1.107-4.482, p = 0.023), initial random blood glucose (OR, 1.235; 95% CI, 1.070-1.425, p = 0.004), drinking history (OR, 0.445; 95% CI, 0.210-0.940, p = 0.031) or those reaching the target APTT (OR, 0.418; 95% CI, 0.184-0.949, p = 0.033) was significantly different among patients with and without END. However, there were no statistical differences in these parameters between them following multivariate analysis. Conclusion: In patients with MIS, argatroban administration and reaching the target APTT can reduce the incidence of END and improve short-term functional prognosis.

Efficacy and safety of Argatroban in patients with acute ischemic stroke: a systematic review and meta-analysis.

Objective: Argatroban is a highly promising drug for the treatment of acute ischemic stroke (AIS), but there is currently insufficient strong evidence regarding the efficacy and safety of using Argatroban in the treatment of AIS. Therefore, we conducted a systematic review and meta-analysis to evaluate the effectiveness and safety of Argatroban in the treatment of AIS. Methods: Articles on PubMed, Embase and the Cochrane Library databases were searched from these websites' inceptions to 2th February 2023. Randomized controlled trials and observational studies on Argatroban therapy for acute ischemic stroke were included. Meta-analyses were conducted using a random-effects model. Results: Fourteen studies involving 10,315 patients were included in the meta-analysis. The results showed a significant reduction in the rate of early neurological deterioration (END) in the Argatroban group compared with the control group (OR = 0.47, 95% CI: 0.31-0.73, I2 = 15.17%). The rates of adverse events were no significant difference between the two groups (ICH: OR = 1.02, 95% CI: 0.68-1.51, I2 = 0.00%; major extracranial bleeding: OR = 1.22, 95% CI: 1.01-1.48, I2 = 0.00%; mortality: OR = 1.16, 95% CI: 0.84-1.59, I2 = 0.00%). However, the rates of mRS score of 0-1 (OR = 1.38, 95% CI: 0.71-2.67, I2 = 77.56%) and mRS score of 0-2 (OR = 1.18, 95% CI: 0.98-1.42, I2 = 0.00%) during the 90 days did not significantly improved in the Argatroban group. Subgroup analyses showed that the rate of END (OR = 0.41, 95% CI: 0.26-0.65, I2 = 2.77%) and mRS score of 0-2 (OR = 1.38, 95% CI: 1.06-1.81, I2 = 0.00%) had significantly improved when the intervention group adopted Argatroban plus Antiplatelet. Conclusion: Argatroban can improve neurological deterioration, with a low incidence of adverse events such as bleeding and death, and general analysis showed no improvement in mRS. However, subgroup analysis suggests that compared to mono-antiplatelet therapy, combination therapy of Argatroban combined with antiplatelet therapy significantly reduced the incidence of END and improved mRS scores. After using Argatroban, there was no increase in the risk and mortality of intracranial hemorrhage and other bleeding sites.

Heparin-Induced Thrombocytopenia: A Case Report Four Years After the Initiation of Maintenance Hemodialysis.

Heparin-induced thrombocytopenia type II (HIT) is a rare and serious complication of heparin exposure and is always a potential risk in hemodialysis patients who routinely receive heparin. It is particularly likely to occur during the induction phase of dialysis. However, it is known to be less prevalent in long-term maintenance dialysis. In the present study, we experienced a maintenance dialysis patient who developed HIT four years after starting dialysis. After careful diagnosis with antibodies assay and clinical scores, the patient was treated with immediate heparin interruption, argatroban administration followed by nafamostat, and simple plasma exchange, which resulted in remission. Therefore, even in the maintenance phase of hemodialysis, it is important to consider HIT in the differential diagnosis of thrombocytopenia.

Diagnosis and management of heparin-induced thrombocytopenia: third edition

This guideline updates and widens the scope of the previ-ous British Society for Haematology (BSH) Clinical guide-lines for Diagnosis and Management of Heparin-Induced Thrombocytopenia: Second Edition1 to include functional assays in the diagnosis of heparin-induced thrombocytope-nia (HIT), when to use direct-acting oral anti-coagulants, and the role of intravenous (IV) immunoglobulins and plasma exchange in the management of HIT and spontane-ous HIT.HIT is an immune-mediated, highly pro-thrombotic dis-order of platelet activation caused by pathogenic antibodies against a platelet factor 4 (PF4)­heparin complex. It is the most frequent drug-induced immune thrombocytopenia and may lead to life-threatening thrombosis. There are two distinct forms of HIT: type I, also known as heparin-asso-ciated thrombocytopenia, which is a non-immunological response to heparin treatment, mediated by a direct interac-tion between heparin and circulating platelets causing plate-let clumping or sequestration, and type II, which is immune mediated.

Argatroban as an Add-On to rtPA in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

Current treatment options for acute ischemic stroke, including intravenous thrombolysis (IVT) and mechanical thrombectomy, have undoubtedly revolutionized stroke care. The need for additional treatment options has brought into the light direct thrombin inhibitors (DTIs) and, specifically, argatroban as a promising candidate. However, there is uncertainty regarding the safety of adding argatroban to IVT, mainly due to the increased hemorrhagic risk. In this study, we performed a systematic review and meta-analysis examining the safety and efficacy of argatroban as an add-on treatment for IVT. The following databases were searched from inception until the 14th of May 2023: Pubmed/MEDLINE, ClinicalTrials.gov, the EU Clinical Trials Register, EMBASE/Scopus, and the Cochrane Library. Only randomized clinical trials (RCTs) enrolling patients with acute ischemic stroke who underwent IVT evaluating the add-on use of any DTIs were selected for the systematic review and further meta-analysis. The PRISMA guidelines were followed at all stages. Four studies with argatroban were included in the final analysis. Analysis of risk ratio and relative risk shows that the add-on therapy with argatroban seems to be effective and favors a good clinical outcome (mRS 0-2) at 90 days, similar to that of alteplase. All studies showed a low pooled incidence of symptomatic intracerebral hemorrhage (5%), parenchymal hematoma (3%), and other major bleeding (1%). Argatroban as an add-on treatment to IVT seems not to be associated with excessive bleeding risk; however, its efficacy remains unproven. According to this synopsis of the currently available evidence, it is premature to use argatroban as an add-on to IVT treatment outside the current clinical trial setting.

Efficacy of antiplatelet drugs combined with Argatroban in treating acute ischemic stroke and its impact on patients' coagulation function and neurological function: a preliminary trial.

This retrospective study analyzed the efficacy of combined antiplatelet therapy with Argatroban in treating acute ischemic stroke (AIS) and its impact on patients' coagulation and neurological functions. Clinical data of 113 AIS patients admitted between January 2021 and January 2023 were retrospectively analyzed. Patients were divided into control (n = 56) and observation (n = 57) groups based on treatment interventions. The control group patients were treated with antiplatelet drugs, while the observation group patients received combination therapy with apatinib on the basis of the control group treatment. Compared to the control group, the observation group demonstrated higher clinical efficacy, improved coagulation parameters, reduced stroke severity (measured by NIHSS), enhanced daily living abilities (BI scores), and lowered inflammatory and neural injury markers post-treatment. Adverse reaction incidence was similar between groups. Combining Argatroban with antiplatelet drugs in AIS management showed superior efficacy without increasing adverse effects, suggesting its potential for clinical application.

Efficacy and safety of argatroban in the management of acute ischemic stroke: A systematic literature review and meta-analysis.

BACKGROUND: Acute ischemic stroke (AIS) is a leading cause of death and disability. AIS is caused by an embolus or thrombus that restricts blood flow to the brain tissue. Despite intravenous thrombolysis and endovascular thrombectomy, a substantial number of patients do not achieve effective reperfusion. Argatroban, a direct thrombin inhibitor, can potentially improve neurological outcomes in AIS patients. However, there are conflicting results in the medical literature regarding the efficacy and safety of argatroban in this context. OBJECTIVE: This study aims to evaluate the efficacy and safety of argatroban as monotherapy or adjunct therapy for acute ischemic stroke. METHODS: Five major databases (PubMed, Embase, Scopus, Web of Science, and Cochrane Library) were searched for randomized controlled trials (RCTs) that compared the efficacy and safety of using argatroban alone or in combination with recombinant tissue plasminogen activator (r-TPA) in the management protocol of the AIS. We used Review Manager Software (RevMan 5.4.1) for data analysis. RESULTS: We included 1393 patients from eight RCTs (of them, 726 were treated with argatroban alone or combined with r-TPA, while 667 received the placebo, standard therapy (standard treatments based on current guidelines including antihypertensive, antiplatelet agents, and statins) or endovascular r-TPA). Neither argatroban vs control nor argatroban with r-TPA vs r-TPA showed significant difference regarding the activity in daily living; (SMD= 1.69, 95% CI [-0.23, 3.61]; p = 0.09), (SMD= 0.99, 95% CI [-0.88, 2.86]; p = 0.30), respectively. Also, there was no significant difference in the National Institutes of Health Stroke Scale (NIHSS) score at seven days, the number of patients achieving modified Rankin Scale (mRS) of 0-1 or 0-2 at 90 days (p > 0.05). Argatroban did not significantly increase the risk of adverse events or symptomatic intracranial hemorrhage (ICH), or major systemic bleeding compared to control or r-TPA (p > 0.05) CONCLUSIONS: Argatroban does not demonstrate superior efficacy compared to placebo or standard therapy in terms of ADL, NIHSS and mRS outcomes. Importantly, argatroban does not significantly increase the incidence of adverse events, including symptomatic ICH and systemic bleeding.

Association of Argatroban Dose With Coagulation Laboratory Test in Patients on Extracorporeal Membrane Oxygenation: Activated Clotting Time vs Activated Partial Thromboplastin Time.

BACKGROUND: Only some studies have directly compared and analyzed the roles of activated partial thromboplastin time (aPTT) and activated clotting time (ACT) in coagulation monitoring during argatroban administration. OBJECTIVES: This study aims to assess the correlation of argatroban dose with ACT and aPTT values and to identify the optimal coagulation test for argatroban dose adjustment. METHODS: We evaluated 55 patients on extracorporeal membrane oxygenation (ECMO) who received argatroban for more than 72 hours. The correlation between argatroban dose and aPTT and ACT values was evaluated. To compare argatroban dose and bleeding events according to liver dysfunction, the patients were divided into 2 groups based on alanine aminotransferase and total bilirubin. RESULTS: Among the 55 patients, a total of 459 doses and coagulation tests were evaluated. The aPTT and ACT values showed a weak correlation with argatroban dose, with the Pearson correlation coefficients of 0.261 (P < 0.001) and 0.194 (P = 0.001), respectively. The agreement between the target 150 to 180 seconds for ACT and 55 to 75 seconds for aPTT was observed in 140 patients (46.1%). Twenty-four patients (43.6%) had liver dysfunction when they started argatroban. The median argatroban dose was lower in the liver dysfunction group than in the control group (0.094 mcg/kg/min vs 0.169 mcg/kg/min, P = 0.020). Difference was not observed between the 2 groups in the amount of red blood cell (0.47 vs 0.43 pack, P = 0.909) and platelet (0.60 vs 0.08 pack, P = 0.079) transfusion per day. CONCLUSION AND RELEVANCE: A weak correlation was observed between argatroban dose and the aPTT and ACT values. However, the agreement between aPTT and ACT was only 46.1% regarding the scope of target range. Further research is necessary to determine how to assess the optimal argatroban dose for patients administered argatroban while undergoing ECMO at the intensive care unit.

Intraoperative argatroban vessel irrigation during microsurgical anastomosis in heparin-induced thrombocytopenia patients: About two cases.

Patients with heparin-induced thrombocytopenia or confirmed allergies to heparin have a contraindication to heparin therapy, which poses a problem for intraoperative free flap irrigation in reconstruction. The use of argatroban as an alternative to heparin allowed us to perform a free flap for leg salvage and a deep inferior epigastric perforator flap for breast reconstruction without microvascular complication, with a 0.01 mg/mL solution. We reported two cases of using an alternative treatment to heparin in an emergency and planned surgeries for vessel irrigation during microsurgical anastomosis reconstruction without microvascular complications, suggesting the reliability and effectiveness of its use in case of contraindication to heparin.

Veno-venous Extracorporeal Membrane Oxygenation: Anesthetic Considerations in Clinical Practice.

Context: After the COVID-19 pandemic, multiple reviews have documented the success of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Patients who experience hypoxemia but have normal contractility may be switched to veno-venous-ECMO (VV-ECMO). Purpose: In this review, we present three protocols for anesthesiologists. Firstly, transesophageal echocardiography (TEE) aids in cannulation and weaning off inotropes and fluids. Our main objective is to assist in patient selection for the Avalon Elite single catheter, which is inserted into the right internal jugular vein and terminates in the right atrium. Secondly, we propose appropriate anticoagulant doses. We outline day-to-day monitoring protocols to prevent heparin-induced thrombocytopenia (HIT) or resistance. Once the effects of neuromuscular paralysis subside, sedation should be reduced. Therefore, we describe techniques that may prevent delirium from progressing into permanent cognitive decline. Methods: We conducted a PubMed search using the keywords VV-ECMO, TEE, Avalon Elite (Maquet, Germany), and quetiapine. We combined these findings with interviews conducted with nurses and anesthesiologists from two academic ECMO centers, focusing on anticoagulation and sedation. Results: Our qualitative evidence synthesis reveals how TEE confirms cannulation while avoiding right atrial rupture or low flows. Additionally, we discovered that typically, after initial heparinization, activated partial thromboplastin time (PTT) is drawn every 1 to 2 hours or every 6 to 8 hours once stable. Daily thromboelastograms, along with platelet counts and antithrombin III levels, may detect HIT or resistance, respectively. These side effects can be prevented by discontinuing heparin on day two and initiating argatroban at a dose of 1 µg/kg/min while maintaining PTT between 61 - 80 seconds. The argatroban dose is adjusted by 10 - 20% if PTT is between 40 - 60 or 80 - 90 seconds. Perfusionists assist in establishing protocols following manufacturer guidelines. Lastly, we describe the replacement of narcotics and benzodiazepines with dexmedetomidine at a dose of 0.5 to 1 µg/kg/hour, limited by bradycardia, and the use of quetiapine starting at 25 mg per day and gradually increasing up to 200 mg twice a day, limited by prolonged QT interval. Conclusions: The limitation of this review is that it necessarily covers a broad range of ECMO decisions faced by an anesthesiologist. However, its main advantage lies in the identification of straightforward argatroban protocols through interviews, as well as the discovery, via PubMed, of the usefulness of TEE in determining cannula position and contractility estimates for transitioning from VA-ECMO to VV-ECMO. Additionally, we emphasize the benefits in terms of morbidity and mortality of a seldom-discussed sedation supplement, quetiapine, to dexmedetomidine.

Anticoagulation therapy for endocardial/epicardial ablation of infarct-related ventricular tachycardia in a patient with antithrombin deficiency.

In patients with a history of antithrombin deficiency, a direct thrombin inhibitor may be considered as an alternative to intraprocedural anticoagulation. A 55-year-old woman with antithrombin deficiency and prior myocardial infarction suffered from electrical storm and appropriate defibrillator shocks. Substrate mapping guided left ventricular endocardial and epicardial ablations were successfully performed. The direct thrombin inhibitor, argatroban, was safely used as intraprocedural anticoagulation therapy with no complications. Learning objective: Optimal anticoagulation during endocardial and epicardial catheter ablation is essential to prevent thromboembolic and bleeding complications. Although patients with infarct-related electrical storm and antithrombin deficiency require unusual attention to anticoagulation, argatroban, a direct thrombin inhibitor, was safely used as intraprocedural anticoagulation therapy during catheter ablations, with no complications.

Efficacy and safety of Agatroban in improving the prognosis of ischemic stroke patients.

OBJECTIVE: To explore and analyze the efficacy and safety of combined treatment of Agatroban and Aspirin in improving short-term and long-term prognosis of ischemic stroke patients. METHODS: In this retrospective study, the clinical data of patients with ischemic stroke admitted to the Department of Neurology, Songjiang Sijing Hospital from June 2021 to April 2023 were analyzed. A total of 108 patients were selected according to the inclusion and exclusion criteria, including 54 patients treated with Aspirin only, named the control group, and 54 patients treated with Agatroban plus Aspirin, named the study group. RESULTS: Compared with the control group, the study group had a higher effective rate (P=0.047). There was no significant difference in MIESSS and daily living ability scores between the two groups before treatment (P>0.05). After treatment, compared with the control group, the study group had a lower MIESSS score and a higher daily living ability score (P=0.035; P=0.044). There was no significant difference in coagulation indicators between the two groups before treatment (P>0.05). After treatment, compared with the control group, the study group had lower platelet count, fibrinogen, and D-dimer levels (P=0.031; P=0.042; P=0.047). There was no significant difference in inflammatory cytokines between the two groups before treatment (P>0.05). After treatment, compared with the control group, the study group showed significantly decreased tumor necrosis factor (TNF)-α, interleukin-6 (IL-6) and interleukin-8 (IL-8) (P=0.041; P=0.038; P=0.046). Compared with the control group, the incidence of adverse reactions in the study group was lower (P=0.033), while the prognosis was better (P=0.029; P=0.033; P=0.048). CONCLUSION: Compared with Aspirin alone, Argatroban plus Aspirin can optimize coagulation parameters to a greater extent and reduce the level of cellular inflammatory factors, further improve the body's neurological functions, remarkably reduce the occurrence of adverse prognosis, and enhance the patient's ability of daily living, with remarkable therapeutic effect.

Heparin induced thrombocytopenia in pregnancy: A therapeutic challenge case report and literature review.

The anticoagulants of choice for the prevention and treatment of venous thromboembolic disease during pregnancy are unfractionated heparin and low-molecular-weight heparin. Heparin-induced thrombocytopenia (HIT) is introduced as a rare but critical side effect of heparin products raising the thromboembolic event paradoxically. Here, we present a case of HIT in pregnancy with challenging management due to coincidence of lupus anticoagulant (LA) and limited anticoagulant options in the pharmaceutical market of our country of residence. We describe a 6-week pregnant patient with deep venous thrombosis (DVT) and pulmonary thromboembolism (PTE), which developed HIT during antenatal care. Therapeutic anticoagulation was initiated with argatroban, then switched to apixaban due to limited access to argatroban. Another therapeutic challenge was the concurrent incidence of LA. The interdisciplinary care team decided on adding up warfarin and scheduled termination at 12 weeks regarding the hazardous condition of the patient. We also reviewed related case literature to convey a new insight into managing pregnancy-related HIT. HIT is a pro-coagulatory and lethal complication associated with heparin therapy that can be diagnosed by clinical suspicion, the 4T score system, and confirmatory laboratory analyses. Alternative anticoagulation is the cornerstone of the treatment and an interdisciplinary plan will be worthwhile to make the best clinical decision regarding the critical situation and least the thromboembolic events mortality during pregnancy.

Incidence and clinical outcomes of heparin-induced thrombocytopenia: 11 year experience in a tertiary care university hospital.

Heparin-induced thrombocytopenia (HIT) is a rare immuno-mediated adverse reaction with high thrombotic and mortality risk. To evaluate incidence and outcomes of HIT cases diagnosed at a tertiary care hospital from 2007 to 2018. A retrospective study was conducted. Patients with suspected HIT underwent 4Ts score assessment and anti-heparin PF4 IgG antibodies ELISA screening test. If the latter was positive, platelet aggregation test (PAT) was performed. If the latter was positive, any form of heparin was stopped, alternative anticoagulants were started and then overlapped with warfarin. HIT incidence was calculated by dividing HIT cases by the mean yearly number of admitted patients over 11 years. Follow-up was 90 days. Among 2125 screening tests, 96 (4.5%) were positive with confirmatory PAT in 82/90 (3.8% for missing data in 6). Median age was 75; 39 patients were surgical and 51 medical. The median 4Ts score was 5. Unfractionated heparin was employed in 34 (37%). HIT incidence was 0.16/1000/patient/years (95% CI: 0.12-0.23) in surgical and 0.15/1000/patient/years (95%: 0.12-0.20) in medical patients. HIT with thrombosis (HIT-T) was observed in 31 patients (0.05/1000/patient/years 95% CI: 0.04-0.1), with venous thromboses in 25 (80%). HIT without thrombosis was observed in 59 patients (0.1/1000 patient/years; 95% CI: 0.08-0.13, twofold vs HIT-T). All cause mortality was 25.5% (95% CI: 17.6-35.4), major bleeding 7.7% (95% CI:3.2-15.3), and thromboembolic complications 3.3% (95% CI:1.1-9.3). HIT is a rare event with high mortality, despite the use of non heparin anticoagulants.

Bioprosthetic valve thrombosis after transcatheter aortic valve replacement and pulmonary embolism due to heparin-induced thrombocytopenia: a case report.

Background: Bioprosthetic valve thrombosis is a complication of transcatheter aortic valve replacement (TAVR). It is believed to be platelet independent, mainly driven by contact phase activation, and more likely to be targeted by oral anticoagulant (OAC). Case summary: We report case of an 86-year-old man with history of TAVR, who presented an early TAVR aortic valve thrombosis occurring in the context of heparin-induced thrombocytopenia (HIT) and pulmonary embolism. The patient rapidly recovered and was discharged 17 days after readmission. OAC by Coumadin was administered for 3 months. Chest tomography after 3 months showed the disappearance of the hypoattenuated leaflet thickening. Discussion: Although HIT has been fully described and is known for being a prothrombotic disorder, this is the first case report of aortic valve thrombosis after TAVR due to HIT. HIT is rare but possibly lethal. Diagnosis is based on pre-test probability evaluation with the 4T clinical score and confirmation with laboratory evidence of anti-PF4/heparin complexes and positivity of a functional test. Management of HIT is based on heparin discontinuation, and treatment of thrombotic complication with direct anti-IIa inhibitor or anti-Xa inhibitor. According to our knowledge, this case represents the first report of bioprosthetic valve thrombosis after TAVR due to HIT.

Ecarin-Based Methods for Measuring Thrombin Inhibitors.

Ecarin is a venom from the saw-scaled viper, Echis carinatus, which catalyzes prothrombin into meizothrombin. This venom is used in several hemostasis laboratory assays, including ecarin clotting time (ECT) and ecarin chromogenic assays (ECA). The use of these ecarin-based assays was first implemented as a tool for monitoring the infusion of a direct thrombin inhibitor, hirudin. Subsequently, this method has been more recently employed for measuring either the pharmacodynamic or pharmacokinetic properties of the oral direct thrombin inhibitor, dabigatran. In this chapter, the procedure for performing manual ECT and automated and manual ECA for measuring thrombin inhibitors is described.