The use of 1E12, a monoclonal anti-platelet factor 4 antibody, to improve the diagnosis of vaccine-induced immune thrombotic thrombocytopenia.

BACKGROUND: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a complication of adenoviral-based vaccine against SARS-CoV-2 due to prothrombotic immunoglobulin (Ig) G antibodies to platelet factor 4 (PF4) and may be difficult to distinguish from heparin-induced thrombocytopenia (HIT) in patients treated with heparin. OBJECTIVES: We assessed the usefulness of competitive anti-PF4 enzyme immunoassays (EIAs) in this context. METHODS: The ability of F(ab')2 fragments of 1E12, 1C12, and 2E1, 3 monoclonal anti-PF4 antibodies, to inhibit the binding of human VITT or HIT antibodies to PF4 was evaluated using EIAs. Alanine-scanning mutagenesis was performed to define the amino acids involved in the interactions between the monoclonal antibodies and PF4. RESULTS: A strong inhibition of VITT IgG binding to PF4 was measured with 1E12 (median inhibition, 93%; n = 8), whereas it had no effect on the binding of HIT antibodies (median, 6%; n = 8). In contrast, 1C12 and 2E1 inhibited VITT (median, 74% and 76%, respectively) and HIT antibodies (median, 68% and 53%, respectively) binding to PF4. When a competitive anti-PF4 EIA was performed with 1E12 for 19 additional VITT samples, it strongly inhibited IgG binding to PF4, except for 1 patient, who had actually developed HIT according to the clinical history. Epitope mapping showed that 1E12 interacts with 5 key amino acids on PF4, of which 4 are also required for the binding of human VITT antibodies, thus explaining the competitive inhibition. CONCLUSION: A simple competitive anti-PF4 EIA with 1E12 could help confirm VITT diagnosis and distinguish it from HIT in patients when both diagnoses are possible.

Effectiveness and safety of biological and target synthetic drugs treatment for psoriatic arthritis: a systematic review with network meta-analysis.

BACKGROUND: Psoriatic arthritis (PA) is a chronic inflammatory systemic arthritis that can result in loss of functional capacity and joint deformation. This systematic review assessed the effectiveness and safety of biological and target synthetic drugs for treating PA. METHODS: We searched for randomized clinical trials (RCTs) that evaluated the use of Adalimumab, Etanercept, Infliximab, Golimumab, Secukinumab, Certolizumab Pegol and Tofacitinib in the main general databases and clinical trial registers databases. The primary outcomes were ACR 50, PsARC, and serious adverse events. Two independent reviewers performed study selection and data extraction. Network meta-analyses were conducted using a random effects model and frequentist approach. The CINeMA software was used to assess the certainty of evidence. RESULTS: We included 33 RCTs (n = 11,034). The results from the network meta-analysis for the ACR 50 at 6-months follow-up showed that all drugs were superior to placebo, with Secukinumab (high certainty of evidence), Infliximab (very low certainty of evidence) and Adalimumab (high certainty of evidence) ranking the highest. Regarding the PsARC (at 6-months follow-up), all drugs, except for Golimumab (very low certainty of evidence), were superior to placebo, with Etanercept (low certainty of evidence), Infliximab (low certainty of evidence) and Certolizumab Pegol (low certainty of evidence) being the most effective drugs. There were no significant differences in the risk of serious adverse events between the drugs and placebo. Golimumab (very low certainty of evidence), Secukinumab (low certainty of evidence), and Adalimumab (very low certainty of evidence) ranked the highest for safety. CONCLUSIONS: In conclusion, based on the balance between efficacy and safety, Secukinumab and Adalimumab may be the preferred options among the evaluated drugs for treating patients with PsA. However, caution is necessary when interpreting the safety findings, as they are supported by evidence of low to very low certainty. Consequently, the balance between benefits and potential risks may change as new safety evaluation studies become available. PROTOCOL REGISTRATION: PROSPERO: CRD42022315577.

Trombocitopenia aguda profunda asociada al uso de abciximab: a propósito de un caso / Acute profound thrombocytopenia associated with the use of abciximab: case report

Se presenta un paciente con angina inestable e intervención coronaria percutánea con stents, que desarrolló púrpura mucocutánea y hematoma inguinal asociados a trombocitopenia aguda profunda inducida por abciximab con nadir de 1 x 10(9)/L (1000 plaquetas/mm³), su recuperación con el tratamiento instituido y la complicación de trombosis subaguda intrastent asociada a cuenta plaquetaria funcional que requirió reintervención con angioplastía primaria y administración de tirofiban, un agente bloqueador del receptor IIb/IIIa diferente. Se realizaron estudios diagnósticos para investigar otras causas de trombocitopenia en estos pacientes que reciben heparina, antiplaquetarios como ácido acetilsalicílico y clopidogrel, asociados a bloqueadores del receptor IIb/IIIa. Se realizó una revisión de publicaciones con reporte de esta complicación.

We present the case-report of a patient with instable angina who submitted to percutaneous coronary intervention and stent place for revascularization who developed purpura and groin hematoma associated to acute profound thrombocytopenia induced by abciximab infusion with nadir platelet counts 1 x 10(9)/L (1,000 platelets/mm³), his platelet recovery with the instituted treatment and the outcome with subacute intra-stent thrombosis that was associated with functionally platelet counts that required a primary angioplasty and administration of tirofiban, a platelet glycoprotein IIb/IIIa receptor antagonist. Laboratory confirmation to exclude other causes of thrombocytopenia and its association of glycoprotein IIb/IIIa receptor antagonist with heparin, acetylsalicylic acid and clopidogrel were obtained. We perform in literature trials with this complication.

A Multicenter, Randomized, Open-Label, Therapeutic, and Exploratory Trial to Evaluate the Tolerability and Efficacy of Platelet Glycoprotein IIb/IIIa Receptor Blocker (Clotinab(TM)) in High-Risk Patients with Percutaneous Coronary Intervention

PURPOSE: This study was designed as a multicenter, randomized, open-label study to evaluate the efficacy and tolerability of Clotinab(TM). We expected to obtain same results as with ReoPro(R) in improving ischemic cardiac complications in high-risk patients who were about to undergo percutaneous coronary intervention (PCI). PATIENTS AND METHODS: Patients of 19-80 years of age with acute coronary syndrome (ACS) who were about to undergo PCI were enrolled. After screening and confirmation of eligibility, patients were randomly assigned to different groups. Clotinab(TM) was given to 84 patients (58.7+/-10.6 years, M:F=68:16)and ReoPro(R)(59.0+/-10.5 years, M:F=30:10) was given to 40 patients before PCI. The primary efficacy endpoint was the onset of major adverse cardiac event (MACE) within 30 days from day 1. The tolerability endpoints were assessed based on bleeding, thrombocytopenia, change in Hb/Hct, human antichimetric antibody development, and adverse events. RESULTS: The number of Clotinab(TM) patients experiencing MACE was 0 out of 76 per protocol (PP) patients. The MACE rate was 0%, and its 95% exact CI was [0.00-4.74%]. A major bleeding event developed in 3 patients in the ReoPro(R) group. The probability of MACE onset in Clotinab(TM) was estimated to be less than 5%. There was no clinically significant result in tolerability variables. CONCLUSION: Clotinab(TM) is an effective and safe medicine in preventing ischemic cardiac complications for high-risk patients who will receive PCI.

Hemorrhagic pericarditis with cardiac tamponade after percutaneous coronary intervention associated with the use of abciximab

Glycoprotein (GP) IIb/IIIa inhibitors, such as abciximab, are used as adjunctive therapy for percutaneous coronary intervention (PCI) in high-risk non-ST-elevation myocardial infarction (NSTEMI) and in ST-elevation myocardial infarction (STEMI), although their effects when used for STEMI are less clear. As the use of GP IIb/IIIa inhibitors becomes more widespread, determining the risks associated with them becomes more important. The major risks associated with the use of GP IIb/IIIa inhibitors are the potential for major bleeding and thrombocytopenia. This is the first reported case in Korea of hemorrhagic pericarditis resulting in cardiac tamponade associated with the use of abciximab, a commonly used GP Ilb/IIa inhibitor, following PCI.