Comparison of Published Guidelines for the Diagnosis and the Management of Vaccine-Induced Immune Thrombotic Thrombocytopenia
Zazzeron L, Rosovsky RP, Bittner EA, Chang MG
Critical care explorations. 2021;3(9):e0519
The development of thrombocytopenia and thrombosis after the administration of the AstraZeneca and Johnson & Johnson/Janssen vaccines has been recently described. This new condition has been called vaccine-induced immune thrombotic thrombocytopenia. The objective of this review is to summarize the clinical characteristics and therapeutic options of vaccine-induced immune thrombotic thrombocytopenia based on available published case series. Furthermore, we provide a comparison of the diagnostic pathway and treatment recommendations provided by six major medical societies. DATA SOURCES We searched MEDLINE, PubMed, and Cochrane Central Register of Controlled Trials databases. STUDY SELECTION We included case series and case reports on patients who developed vaccine-induced immune thrombotic thrombocytopenia. We also included guidelines for the diagnosis and management of vaccine-induced immune thrombotic thrombocytopenia from major medical societies. DATA EXTRACTION We examined baseline risk factors, symptoms, physical signs, laboratory and imaging findings, and treatment in patients with vaccine-induced immune thrombotic thrombocytopenia reported in the case series. We also analyzed the diagnostic and treatment recommendations provided by major societal guidelines on the management of vaccine-induced immune thrombotic thrombocytopenia. DATA SYNTHESIS Patients who developed vaccine-induced immune thrombotic thrombocytopenia were more likely to be young women (age 20-50) who were given the AstraZeneca or Johnson & Johnson/Janssen 4-28 days prior to presentation. Patients showed signs, symptoms, and imaging findings consistent with cerebral venous sinus thrombosis and splanchnic thrombosis. Laboratory findings showed thrombocytopenia, low fibrinogen, and elevate d-dimer levels, while positive platelet factor 4 antibodies were always positive. Major societal guidelines recommend avoidance of heparin and platelets. Treatment with nonheparin anticoagulants and IV immunoglobulin is also recommended. CONCLUSIONS Vaccine-induced immune thrombotic thrombocytopenia is a rare but highly morbid complication related to the administration of the AstraZeneca and Johnson & Johnson/Janssen vaccines. Clinicians should be prepared for the early identification of patients with suspicious symptoms and prompt treatment should be initiated to avoid catastrophic deterioration. Major societal guidelines provide useful recommendations for the diagnosis and management of patients with vaccine-induced immune thrombotic thrombocytopenia.
Pharmacokinetics, clot strength and safety of a new fibrinogen concentrate: randomized comparison with active control in congenital fibrinogen deficiency
Ross C, Rangarajan S, Karimi M, Toogeh GH, Apte S, Lissitchkov T, Acharya S, Manco-Johnson MJ, Srivastava A, Brand B, et al
Journal of Thrombosis and Haemostasis : Jth. 2017;16((2):):253-261
BACKGROUND Human fibrinogen concentrate (HFC) corrects fibrinogen deficiency in congenital a-/hypofibrinogenaemia. OBJECTIVES To assess pharmacokinetics (PK), effects on thromboelastometry maximum clot firmness (MCF), and safety of a new double virus-inactivated/eliminated, highly purified HFC vs. active control. PATIENTS/METHODS In this multinational, randomized, phase II, open-label, crossover study in 22 congenital afibrinogenaemia patients ≥12 years, 70 mg kg(-1) of new HFC (FIBRYGA, Octapharma AG) or control (Haemocomplettan((R)) P/RiaSTAP() , CSL Behring GmbH) were administered, followed by crossover to the other concentrate. Fibrinogen activity, PK and MCF in plasma were assessed. RESULTS The concentrates were not bioequivalent for the primary endpoint, AUCnorm (mean ratio 1.196; 90% CI: 1.117, 1.281). Remaining PK parameters (Cmaxnorm , IVR, t1/2 , MRT) reflected bioequivalence between concentrates, except for clearance (mean ratio 0.836; 90% CI: 0.781, 0.895) and Vss (mean ratio 0.886; 90% CI: 0.791, 0.994). Mean AUCnorm was significantly larger for the new HFC (1.62 +/- 0.45 vs. 1.38 +/- 0.47 h kg g L(-1) mg(-1) , p=0.0001) and mean clearance was significantly slower (0.665 +/- 0.197 vs. 0.804 +/- 0.255 mL h(-1) kg(-1) , p=0.0002). Mean MCF increased from 0 mm to 9.68 mm (new HFC) and 10.00 mm (control) 1-hour post-infusion (mean difference -0.32 mm, 95% CI -1.70, 1.07, n.s.). No deaths, thromboses, viral seroconversions or serious related adverse events occurred. CONCLUSIONS Bioequivalence was not demonstrated for AUCnorm , clearance and Vss. Larger AUCnorm and slower clearance were observed for the new HFC. Remaining pharmacokinetic parameters reflected bioequivalence to control. Safety profiles and increases in clot strength were comparable between concentrates. This article is protected by copyright. All rights reserved.