Differential Use of Glycoprotein IIb/IIIa Inhibitors with Bivalirudin in Patients with STEMI Undergoing PCI: A Systematic Review and Meta-Analysis.

AIM: The efficacy and safety of bivalirudin when used concurrently with glycoprotein IIb/IIIa inhibitors (GPI) is uncertain. In this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of bivalirudin versus heparin in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) and to explore the impact of differential use (greater and balanced) of GPI. METHODS: Online databases were queried from inception to March 2023 to identify eight randomized controlled trials (n = 22,483) for inclusion. The primary outcomes included all-cause mortality, major bleeding, major adverse cardiovascular events (MACE), and net adverse clinical events (NACE). Secondary efficacy endpoints included cardiac death, reinfarction, stent thrombosis (ST), and stroke. Data were pooled using a random-effects model to derive risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: When compared to heparin, bivalirudin was associated with a significant reduction in all-cause mortality (RR 0.83; 95% CI 0.72-0.97; P = 0.02), major bleeding (RR 0.73; 95% CI 0.57-0.93; P = 0.01), cardiac death (RR 0.79; 95% CI 0.66-0.94; P = 0.01), and NACE (RR 0.80; 95% CI 0.72-0.89; P < 0.0001). However, while the bivalirudin arm showed an increased likelihood of ST in the greater GPI subgroup (RR 1.70; 95% CI 1.13-2.56; P = 0.01), it was associated with a decreased likelihood of ST in the balanced GPI subgroup (RR 0.40; 95% CI 0.24-0.65; P = 0.0003). CONCLUSION: Overall, our findings suggest that bivalirudin may be a more efficacious intervention than heparin for reducing certain adverse events in patients with STEMI undergoing primary PCI.

Acute pulmonary embolism in cancer patients admitted to intensive care unit: Impact of anticoagulant treatment on 90-day mortality and risk factors, results of a multicentre retrospective study.

BACKGROUND: Acute pulmonary embolism (PE) is a life-threatening situation in cancer patients. In this situation, anticoagulant therapy is complex to administer due to the risk of bleeding. Only few studies have been conducted when these patients are admitted to the intensive care unit (ICU). The aim of this study was to assess the association between anticoagulation strategies as well as other factors with 90-day mortality in patients with cancer and PE admitted to ICU. Major bleeding was also evaluated according to the type of anticoagulation. METHODS: Retrospective study carried out in 4 ICUs in France over a 12-year period (2009-2021). All patients with cancer and PE were included. An overlap propensity score weighting analysis was performed in the subgroup of patients treated with either unfractionated heparins (UFH) alone or low-molecular-weight heparins (LMWH) alone on 90-day mortality and major bleeding. RESULTS: A total of 218 consecutive cancer patients admitted to ICU and presenting PE were included. The 90-day mortality rate was 42 % for the global cohort. After propensity score analysis in the subgroup of patients treated with either "UFH alone" (n = 80) or "LMWH alone" (n = 71), the 90-day mortality was similar in patients treated with UFH alone (42.6 %) vs LMWH alone (39.9 %): OR = 1.124, CI 95 % [0.571-2.214], p = 0.750. There was a significant increased toward major bleeding rates in the "UFH alone" group (25.5 %) as compared to "LMWH alone" group (11.5 %), p = 0.04. CONCLUSION: In 218 patients admitted to ICU and presenting PE, the 90-day mortality rate was 42 %. Treatment with UFH alone was associated with a mortality comparable to treatment with LMWH alone but it appeared to be more prone to major bleeding.

Effectiveness and safety of rivaroxaban for anticoagulation therapy in COVID-19: A meta-analysis of randomized controlled trials.

OBJECTIVES: To evaluate the effectiveness and safety of rivaroxaban anticoagulation in COVID-19 patients. METHODS: PubMed, Embase, Cochrane Library electronic databases, and ClinicalTrials.gov were searched to identify all relevant randomized controlled trial studies from December 2019 to July 2023. RESULTS: A total of 6 randomized controlled trials, which included a total of 3323 patients, were considered for evaluation. Overall, short-term all-cause mortality and hospitalization rates were not significantly different between the rivaroxaban and control groups. Thrombotic events were significantly reduced in the rivaroxaban prophylaxis group compared to the placebo control group. However, the reduction in thrombotic events was not significantly different between rivaroxaban therapy and heparin or low-molecular-weight heparin (LMWH). Rivaroxaban prophylaxis and the therapeutic dose may be associated with a higher rate of overall bleeding rate, but major bleeding rates did not differ substantially. CONCLUSION: Rivaroxaban may reduce thrombotic events in COVID-19 patients, but it does not appear to have an advantage over heparin or LMWH, and it may increase the risk of bleeding.INPLASY Reg. No.: INPLASY 202370097.

Intestinal obstruction as a result of intra-abdominal hematoma: a complication of low molecular weight heparin in pediatric patients. / Obstrucción intestinal por hematoma intraabdominal: una complicación de la heparina de bajo peso molecular en el paciente pediátrico.

INTRODUCTION: Hematomas are a rare cause of intestinal obstruction. Subcutaneous heparin can bring about direct punctures on small bowel loops, potentially leading to traumatic hematoma and intestinal obstruction. CASE REPORTS: We present three cases of pediatric patients with clinical signs of intestinal obstruction treated with subcutaneous heparin. Two cases had increased acute-phase reactants and radiological signs of intestinal suffering, so surgical treatment was decided upon, with intramural hematoma emerging as an intraoperative finding. The third case was conservatively managed with anticoagulant discontinuation and gut rest, since the patient had an adequate general condition and no findings compatible with ischemia or necrosis were noted in the complementary tests. DISCUSSION: The administration of subcutaneous heparin may cause intestinal wall hematomas due to its anticoagulating effect and to the risk of inadvertent punctures on small bowel loops.

INTRODUCCION: Los hematomas son una causa poco frecuente de obstrucción intestinal. La heparina subcutánea tiene riesgo de producir la punción directa de un asa intestinal, provocando un hematoma traumático que genere una obstrucción intestinal. CASOS CLINICOS: Se describen tres casos de pacientes pediátricos con clínica de obstrucción intestinal en tratamiento con heparina subcutánea. Dos casos presentaron elevación de reactantes de fase aguda y signos radiológicos de sufrimiento intestinal por lo que se optó por tratamiento quirúrgico, con el hallazgo intraoperatorio de hematoma intramural. El tercer caso fue manejado de manera conservadora con supresión de la anticoagulación y reposo intestinal, dado el adecuado estado general y ausencia de hallazgos compatibles con isquemia o necrosis en las pruebas complementarias. COMENTARIOS: La administración de heparina subcutánea puede provocar la aparición de hematomas de pared intestinal, tanto por su efecto anticoagulante, como por el riesgo de punción inadvertida de un asa intestinal.

A Case Report of Pulmonary Embolectomy Under Cardiopulmonary Bypass in a Patient with Intracranial Hemorrhage and History of Heparin-Induced Thrombocytopenia.

Pulmonary embolism is a common complication after intracranial hemorrhage. As thrombolysis is contraindicated in this situation, surgical pulmonary embolectomy may be indicated in case of high-risk pulmonary embolism but requires transient anticoagulation with heparin during cardiopulmonary bypass. We report the case of a patient with a history of heparin-induced thrombocytopenia who presented with a high-risk pulmonary embolism 10 days after the spontaneous onset of a voluminous intracerebral hematoma. Despite high doses of heparin required to run the cardiopulmonary bypass and subsequent anticoagulation by danaparoid sodium, the brain hematoma remained stable and the patient was discharged without complications 30 days after surgery.

Bivalirudin as a substitute for heparin in neurointervention for patients with heparin-induced thrombocytopenia.

OBJECTIVES: Heparin-induced thrombocytopenia is a known complication of heparin exposure with potentially life-threatening sequelae. Direct thrombin inhibitors can be substituted for heparin in patients with heparin-induced thrombocytopenia that require anticoagulation. However, the use of direct thrombin inhibitors as a substitute for heparin has not been widely reported in the neuroendovascular literature. MATERIALS AND METHODS: Here we report the first use of the direct thrombin inhibitor bivalirudin in a neuroendovascular procedure as a substitute for heparin in a patient with a ruptured pseudoaneurysm and heparin-induced thrombocytopenia, and review the literature on the use of bivalirudin and argatroban for such patients. RESULTS: Bivalirudin was safely and effectively used in the case reported, with no thrombotic or hemorrhagic complications. Our literature review revealed a paucity of studies on the use of heparin alternatives, including bivalirudin, in neuroendovascular procedures in patients with heparin-induced thrombocytopenia. CONCLUSIONS: Heparin-induced thrombocytopenia is an important iatrogenic disease process in patients undergoing neuroendovascular procedures, and developing protocols to diagnose and manage heparin-induced thrombocytopenia is important for healthcare systems. While further research needs to be done to establish the full range of anticoagulation options to substitute for heparin, our case indicates bivalirudin as a potential candidate.

Comparison of Outcomes in Patients Requiring Mechanical Circulatory Support Who Received Cangrelor in Addition to Anticoagulation Versus Anticoagulation Alone.

OBJECTIVES: To evaluate the safety of cangrelor administered concurrently with heparin or bivalirudin in patients on mechanical circulatory support. DESIGN: A single-center, retrospective cohort study of adult patients consecutively admitted between January 2016 and October 2020. SETTING: A tertiary medical center. PARTICIPANTS: Adult patients admitted to the cardiovascular intensive care unit put on mechanical circulatory support for acute myocardial infarction (AMI) or non-AMI indications. Patients who received cangrelor underwent percutaneous coronary intervention with stenting during the index event or within the last year. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the incidence of major bleeding, defined by the Extracorporeal Life Support Organization criteria, in patients with mechanical circulatory support receiving cangrelor plus anticoagulation with heparin or bivalirudin with or without aspirin versus patients who did not receive cangrelor. Sixty-eight patients were included in the study. Twenty-nine patients received cangrelor, and 39 did not. Cangrelor was not associated with an increase in major bleeding; however, the CI was wide (adjusted hazard ratio 1.93, 95% CI 0.61-6.11; p = 0.262). CONCLUSIONS: Patients receiving cangrelor did not appear to be at higher risk of major bleeding compared to patients not receiving cangrelor. Larger trials should be conducted to better evaluate the safety of cangrelor in patients with mechanical circulatory support.

Accuracy of Diagnosing Heparin-Induced Thrombocytopenia.

Importance: Heparin-induced thrombocytopenia (HIT) is a life-threatening condition that requires urgent diagnostic clarification. However, knowledge of the diagnostic utility of the recommended diagnostic tests is limited in clinical practice. Objective: To evaluate the current diagnostic practice for managing the suspicion of HIT. Design, Setting, and Participants: This prospective diagnostic study was conducted from January 2018 to May 2021 among consecutive patients with suspected HIT from 11 study centers in Switzerland, Germany, and the United States. Detailed clinical data and laboratory information were recorded. Platelet factor 4/heparin antibodies were quantified using an automated chemiluminescent immunoassay (CLIA). A washed-platelet heparin-induced platelet activation (HIPA) test was used as a reference standard to define HIT. Exposures: Suspicion of HIT. Main Outcomes and Measures: The primary outcome was the diagnostic accuracy of the 4Ts score, the CLIA, and the recommended algorithm serially combining both tests. Results: Of 1448 patients included between 2018 and 2021, 1318 were available for the current analysis (median [IQR] age, 67 [57-75] years; 849 [64.6%] male). HIPA was positive in 111 patients (prevalence, 8.4%). The most frequent setting was intensive care unit (487 [37.0%]) or cardiovascular surgery (434 [33.0%]). The 4Ts score was low risk in 625 patients (46.8%). By 2 × 2 table, the numbers of patients with false-negative results were 10 (9.0%; 4Ts score), 5 (4.5%; CLIA), and 15 (13.5%; recommended diagnostic algorithm). The numbers of patients with false-positive results were 592 (49.0%; 4Ts score), 73 (6.0%; CLIA), and 50 (4.1%; recommended diagnostic algorithm), respectively. Conclusions and Relevance: In this diagnostic study of patients suspected of having HIT, when the recommended diagnostic algorithm was used in clinical practice, antibody testing was required in half the patients. A substantial number of patients were, however, still misclassified, which could lead to delayed diagnosis or overtreatment. Development of improved diagnostic algorithms for HIT diagnosis should be pursued.

Antiplatelets versus anticoagulants in the treatment of blunt cerebrovascular injury (BCVI) - A systematic review and meta-analysis.

INTRODUCTION: Blunt cerebrovascular injury (BCVI) occurs in 1-3% of blunt traumas and is associated with stroke, disability, and mortality if unrecognized and untreated. Early detection and treatment are imperative to reduce the risk of stroke, however, there is significant variation amongst centers and trauma care providers in the specific medical management strategy used. This study compares antiplatelets vs. anticoagulants to determine BCVI-related stroke risk and bleeding complications to better understand the efficacy and safety of various treatment strategies. METHODS: A systematic review of MEDLINE, Embase, and Cochrane CENTRAL databases was conducted with the assistance of a medical librarian. The search was supplemented with manual review of the literature. Included studies reported treatment-stratified risk of stroke following BCVI. All studies were screened independently by two reviewers, and data was extracted in duplicate. Meta-analysis was conducted using pooled estimates of odds ratios (OR) with a random-effects model using Mantel-Haenszel methods. RESULTS: A total of 3315 studies screened yielded 39 studies for inclusion, evaluating 6552 patients (range 8 - 920 per study) with a total of 7643 BCVI. Stroke rates ranged from 0% to 32.8%. Amongst studies included in the meta-analysis, there were a total of 405 strokes, with 144 (35.5%) occurring on therapy, for a total stroke rate of 4.5 %. Meta-analysis showed that stroke rate after BCVI was lower for patients treated with antiplatelets vs. anticoagulants (OR 0.57; 95% CI 0.33-0.96, p = 0.04); when evaluating only the 9 studies specifically comparing ASA to heparin, the stroke rate was similar between groups (OR 0.43; 95% CI 0.15-1.20, p = 0.11). Eleven studies evaluated bleeding complications and demonstrated lower risk of bleeding with antiplatelets vs. anticoagulants (OR 0.29; 95% CI 0.13-0.63, p = 0.002); 5 studies evaluating risk of bleeding complications with ASA vs. heparin showed lower rates of bleeding complications with ASA (OR 0.16; 95% CI 0.04-0.58, p = 0.005). CONCLUSIONS: Treatment of patients with BCVI with antiplatelets is associated with lower risks of stroke and bleeding complications compared to treatment with anticoagulants. Use of ASA vs. heparin specifically was not associated with differences in stroke risk, however, patients treated with ASA had fewer bleeding complications. Based on this evidence, antiplatelets should be the preferred treatment strategy for patients with BCVI.

Therapeutic strategies in FcγIIA receptor-dependent thrombosis and thromboinflammation as seen in heparin-induced thrombocytopenia (HIT) and vaccine-induced immune thrombocytopenia and thrombosis (VITT).

INTRODUCTION: Fcγ-receptors (FcγR) are membrane receptors expressed on a variety of immune cells, specialized in recognition of the Fc part of immunoglobulin G (IgG) antibodies. FcγRIIA-dependent platelet activation in platelet factor 4 (PF4) antibody-related disorders have gained major attention, when these antibodies were identified as the cause of the adverse vaccination event termed vaccine-induced immune thrombocytopenia and thrombosis (VITT) during the COVID-19 vaccination campaign. With the recognition of anti-PF4 antibodies as cause for severe spontaneous and sometimes recurrent thromboses independent of vaccination, their clinical relevance extended far beyond heparin-induced thrombocytopenia (HIT) and VITT. AREAS COVERED: Patients developing these disorders show life-threatening thromboses, and the outcome is highly dependent on effective treatment. This narrative literature review summarizes treatment options for HIT and VITT that are currently available for clinical application and provides the perspective toward new developments. EXPERT OPINION: Nearly all these novel approaches are based on in vitro, preclinical observations, or case reports with only limited implementation in clinical practice. The therapeutic potential of these approaches still needs to be proven in larger cohort studies to ensure treatment efficacy and long-term patient safety.

Molecular architecture and platelet-activating properties of small immune complexes assembled on heparin and platelet factor 4.

Heparin-induced thrombocytopenia (HIT) is an adverse reaction to heparin leading to a reduction in circulating platelets with an increased risk of thrombosis. It is precipitated by polymerized immune complexes consisting of pathogenic antibodies that recognize a small chemokine platelet factor 4 (PF4) bound to heparin. Characterization of these immune complexes is extremely challenging due to the enormous structural heterogeneity of such macromolecular assemblies and their constituents. Native mass spectrometry demonstrates that up to three PF4 tetramers can be assembled on a heparin chain, consistent with the molecular modeling studies showing facile polyanion wrapping along the polycationic belt on the PF4 surface. Although these assemblies can accommodate a maximum of only two antibodies, the resulting immune complexes are capable of platelet activation despite their modest size. Taken together, these studies provide further insight into molecular mechanisms of HIT and other immune disorders where anti-PF4 antibodies play a central role.

Unfractionated heparin: optimizing laboratory monitoring and reducing unwanted interference in everyday hemostasis test practice.

Unfractionated heparin (UFH) serves as a commonly used anticoagulant. It is widely utilized for a variety of reasons, including to 1) anticoagulate patients and help treat and / or prevent thrombosis, 2) maintain patency in artificial blood flow circuits, and 3) anticoagulate blood samples collected for laboratory testing (typically for biochemical assays or blood gas analysis). As such, the presence of UFH is nearly ubiquitous in a hospital setting. Therefore, in laboratory practice, UFH may be present in samples intended for monitoring patients on UFH therapy or intended for biochemical tests, or it may interfere with other (hemostasis) laboratory tests. The aim of this manuscript is to review the role of UFH from the perspective of optimizing laboratory testing to monitor UFH therapy and to avoid or overcome unwanted interference with other laboratory tests.

[Unfractionned heparin wastage at a French university hospital]. / Gaspillage d'héparine sodique dans un centre hospitalo-universitaire français.

OBJECTIVES: In a context of heparin shortage, we studied the wasted quantities in three intensive care units (ICU) of a university hospital where two electric syringe pump (ESP) heparin protocols coexist (20,000UI/48mL used in the cardiology ICU and 25,000UI/50mL use in the medical and surgical ICUs). METHOD: We performed a prospective observational study of patients treated with heparin ESP. We collected the information recorded in the prescription software connected to the ESP (dosage, start time, infusion rate, interruption times, date and time of end of treatment). We observed the ESPs, noted the time of start written on the label and the quantity remaining, and questioned nurses about the constraints that lead for changing the ESPs. RESULTS: Between 23/03/23 and 19/05/23, 164 vials of 25,000UI/5mL were used. The wasted quantity was equivalent 42 vials: 18 vials (43%) of treatment stopped, nurses practices such as changing the ESP in advance 6 vials (14%), application of the rule "discard the ESP 24hours after preparation" 9 vials (21.5%) and 9 vials (21.5%) corresponding to the 45mL discarded for the 45 ESP prepared in the cardiology ICU. CONCLUSION: More than a quarter of the heparin purchased is wasted. The results should lead to policy decisions concerning the medications supply chain, i.e. abandoning the 20,000UI/48mL protocol, supply of ready to use heparin syringes by industry or by the pharmacy. It is essential that these data be fed back to nurses' teams, in order to gather their suggestions before considering any changes of their practices.

Use of bivalirudin after initial heparin management among adult patients on long-term venovenous extracorporeal support as a bridge to lung transplant: A case series.

A growing body of evidence supports the use of bivalirudin as an alternative to unfractionated heparin (UFH) for the prevention of thrombotic events in patients on venovenous (VV) extracorporeal membrane oxygenation (ECMO). However, data in patients bridged to lung transplantation are limited. In this case series, we describe the outcomes of six patients who were transitioned from UFH to bivalirudin during their course of VV ECMO support as a bridge to lung transplantation. All six patients were on VV ECMO support until transplant, with a median duration of 73 days. Bivalirudin demonstrated a shorter time to first therapeutic activated thromboplastin time (aPTT) level. Additionally, time in therapeutic range was longer while patients were receiving bivalirudin compared to UFH (median 92.9% vs. 74.6%). However, major bleeding and thrombotic events occurred while patients were receiving either anticoagulant. Based on our experience, bivalirudin appears to be a viable option for anticoagulation in VV ECMO patients bridged to lung transplantation. Larger studies evaluating the optimal anticoagulation strategy in patients bridged to transplant are needed.

Percutaneous Coronary Intervention with Procedural Unfractionated Heparin without Activated Clotting Time Guidance: A Unique Opportunity to Assess Thrombotic and Bleeding Events.

Background: Rates of major bleeding and intraprocedural thrombotic events (IPTE) in the setting of percutaneous coronary intervention (PCI) using weight-adjusted unfractionated heparin (UFH) without activated clotting time (ACT) monitoring are not known. Methods: We reviewed 2,748 consecutive patients who underwent coronary angiography at our tertiary care university hospital between January 2017 and December 2020. All patients who underwent PCI with weight-adjusted UFH without ACT guidance were considered for further analysis. Major bleeding complications occurring within 48 hours of PCI were collected from patients' medical records. IPTE were collected independently by two interventional cardiologists after review of coronary angiograms. Results: There were 718 patients included in the analysis (65.4 ± 12.2 years old; 81.3% male). In total, 45 patients (7.8%) experienced a major bleed or IPTE. The most common IPTE were slow/no reflow (1.5%) and coronary artery dissection with decreased flow (1.1%). Other IPTE occurred in <1% of cases. Major bleeding occurred in 11 patients (1.5%), of whom 8 required blood transfusion and 3 required vascular intervention. Bleeding complications were more common with femoral compared with radial access (6.6% vs. 0.2%, P < 0.001). Conclusion: Weight-adjusted UFH use during PCI without ACT monitoring was related to low rates of major bleeding or IPTE.