1.
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
Abstract
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.
2.
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
Abstract
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.
3.
Selective augmentations of intratumoral 5-fluorouracil concentration by local immunotherapy with OK-432 and fibrinogen
Amano M, Sekimoto M, Monden T, Tomita N, Ohue M, Haba A, Sakita I, Tamaki Y, Monden M
Diseases of the Colon & Rectum. 2000;43((3)):402-7.
Abstract
PURPOSE Pyrimidine nucleoside phosphorylase is an enzyme that converts 5'-deoxy-5-fluorouridine into its active metabolite, 5-fluorouracil. In colorectal cancer tissue pyrimidine nucleoside phosphorylase has been proven to be produced by macrophages in the cancer stroma despite presence of the cancer cells. We reported that local immunotherapy with OK-432 and fibrinogen induced aggregation of macrophages in the cancer stroma and enforced their pyrimidine nucleoside phosphorylase expression. Thus it was hypothesized that if colon cancer were treated with 5'-deoxy-5-fluorouridine, the 5-fluorouracil concentration in cancer tissues would be enhanced by local immunotherapy. The present study was conducted to investigate whether local immunotherapy for colon cancer could increase the intratumoral 5-fluorouracil concentration in patients given chemotherapy with 5'-deoxy-5-fluorouridine. METHODS Twenty patients with resectable colorectal cancer were examined in this study. They were given 5'-deoxy-5-fluorouridine (600 mg/day) orally for seven days preoperatively. Nine randomly selected patients underwent intratumoral injection of OK-432 mixed with fibrinogen, which was performed on the third preoperative day (OK-432 and fibrinogen plus 5'-deoxy-5-fluorouridine group); eleven patients were given oral 5'-deoxy-5-fluorouridine only (5'deoxy-5-fluorouridine group). The 5-fluorouracil concentration in tumor tissue and normal colon mucosa tissue was measured, and the influence of the local immunotherapy was assessed. RESULTS The 5-fluorouracil concentration in the cancer tissue was increased by the local immunotherapy, whereas that in the normal colon mucosa was not influenced. Thus, the influence of local immunotherapy was selective to the cancer tissue where the mixture of OK-432 and fibrinogen was injected. CONCLUSION In patients with colorectal cancer, selective high 5-fluorouracil concentration in the cancer tissue could be achieved by a combination of 5'-deoxy-5-fluorouridine and local immunotherapy with a mixture of OK-432 and fibrinogen.