scholarly journals Thrombotic events and COVID-19 vaccines

2021 ◽  
Vol 25 (9) ◽  
pp. 701-707
Author(s):  
C. Brazete ◽  
A. Aguiar ◽  
I. Furtado ◽  
R. Duarte
Keyword(s):  
Immune Thrombocytopenia ◽  
Large Scale ◽  
Viral Vector ◽  
Vaccine Safety ◽  
Severe Thrombocytopenia ◽  
The European Union ◽  
Vein Thrombosis ◽  
Post Marketing Surveillance ◽  
Post Marketing ◽  
Vaccination Campaigns

COVID-19 vaccines are considered promising agents in the control of the pandemic. Although their safety was assessed in randomised clinical trials, severe adverse events (AEs) have been reported after large-scale administration. This study aims to evaluate thromboembolic AEs reported after vaccination in a real-world context and how they led to the interruption of vaccination campaigns. We also review the benefits and risks of the vaccines approved in the European Union and provide recommendations. A review of the literature was performed using Medline/PubMed electronic database as well as institutional and pharmacovigilance official reports. Our findings show that vaccine-induced prothrombotic immune thrombocytopenia has been suggested as a very rare AE associated with viral vector vaccines. Unusual thrombotic events combined with moderate-to-severe thrombocytopenia were reported mainly in women under 60 years of age. As safety signals emerged, Vaxzevria and Janssen´s COVID-19 vaccine campaigns have been paused while investigations proceed. On the other hand, the number of deep vein thrombosis and pulmonary embolism reports have not increased. Post-marketing surveillance indicated that mRNA vaccines are safe and should continue to be used. The thrombotic events report rate is not increased in people over 60 years. As they are at greater risk for COVID-19 complications and death, no vaccine restrictions are recommended in this group. Risk factors for vaccine-induced prothrombotic immune thrombocytopenia should be established so that evidence-based decisions can be made. Systematic monitoring of COVID-19 vaccine safety is essential to ensure that the benefits of vaccination outweigh the risks.

scholarly journals Fondaparinux

2013 ◽  
pp. 44-52
Author(s):  
G. Airoldi ◽  
M. Campanini
Keyword(s):  
Dose Range ◽  
Factor Xa ◽  
Pharmacokinetic Profile ◽  
Tolerability Profile ◽  
Severe Thrombocytopenia ◽  
Medical Patients ◽  
Post Marketing Surveillance ◽  
Major Orthopedic Surgery ◽  
Post Marketing ◽  
Low Incidence

AIM OF THE STUDY To review the best evidence-based knowledge about the clinical pharmacology and use of fondaparinux. DESIGN OF THE STUDY Narrative review. RESULTS Fondaparinux is a synthetic pentasaccharide anticoagulant that binds selectively with high affinity to antithrombin and catalyses the inactivation of factor Xa, which results in a dose-dependent inhibition of thrombin generation. Fondaparinux does not bind to platelets or inhibit platelet aggregation, does not cross-react with antibodies to heparin-PF4 complexes (HIT antibodies) and has no effects on the activated partial thromboplastin time, prothrombin time and antithrombin levels. Fondaparinux shows a linear and highly predictable pharmacokinetic profile in humans, with very limited intraindividual and interindividual variability, which makes routine monitoring and dose adjustments unnecessary for the majority of the population. After subcutaneous iniection fondaparinux undergoes complete and dose-independent absorption; it is not significantly metabolized by the liver and does not interfere with cytochrome P450-mediated transformation of other drugs. Fondaparinux is almost entirely excreted unchanged in the urine with a half-life of approximately 17 hours, allowing for once-daily dosing. Its plasma clearance is reduced in patients with moderate or severe renal insufficiency. In the clinical trials and post-marketing surveillance fondaparinux shows an excellent tolerability profile, with a low incidence of major bleeding across a wide dose range and no cases of severe thrombocytopenia or heparin-induced thrombocytopenia (HIT). CONCLUSIONS Fondaparinux has been approved in many countries for use in thromboprophylaxis after major orthopedic surgery and in medical patients, and for the treatment of sintomatic venous thromboembolism (deep venous thrombosis and hemodynamically stable pulmonary embolism) and acute coronary syndromes (unstable angina, and acute miocardial infartion, with or without ST elevation). In these clinical settings fondaparinux is at least as effective and safe as unfractionated heparin or low molecular weight heparins, and may be easier to use.

Post-marketing surveillance of live-attenuated Japanese encephalitis vaccine safety in China

Vaccine ◽  
2014 ◽  
Vol 32 (44) ◽  
pp. 5875-5879 ◽  
Author(s):  
Yali Wang ◽  
Duo Dong ◽  
Gang Cheng ◽  
Shuyan Zuo ◽  
Dawei Liu ◽  
...  
Keyword(s):  
Japanese Encephalitis ◽  
Vaccine Safety ◽  
Japanese Encephalitis Vaccine ◽  
Post Marketing Surveillance ◽  
Post Marketing

scholarly journals Drug-Immune Thrombocytopenia with Thrombosis versus Heparin-Induced Thrombocytopenia: A Critical Clinical Controversy

2015 ◽  
Vol 5 (2) ◽  
pp. 152-159
Author(s):  
Hassan Al-Jafar ◽  
Anas Al-Yousef ◽  
Somaya Al-Shatti ◽  
Khalifa Al-Banwan
Keyword(s):  
Immune Thrombocytopenia ◽  
Recurrent Infection ◽  
Severe Thrombocytopenia ◽  
Drug Induced ◽  
Clinical Issue ◽  
Heparin Induced Thrombocytopenia ◽  
Vein Thrombosis ◽  
Below The Knee ◽  
Febrile Episodes ◽  
End Stage

Heparin-induced thrombocytopenia (HIT) is a type of drug-induced immune thrombocytopenia (DITP). DITP is a rare and challenging clinical issue, especially when it is associated with thrombosis. A 62-year-old woman was admitted to our institution with end-stage renal failure. She received heparin for hemodialysis. Six days later, she became febrile and was treated with vancomycin and amikacin antibiotics. Two days after starting the vancomycin, she developed severe thrombocytopenia with extensive gangrenous deep vein thrombosis in her right leg, which required a below-the-knee amputation. The HIT test yielded positive results when heparin was already stopped, but her platelet count did not regenerate even after 3 months of heparin-free treatment. Courses of vancomycin treatment were given during several febrile episodes over the long period of severe thrombocytopenia. The patient was given both anti-immune thrombocytopenia and anticoagulant treatments because of both severe persistent thrombocytopenia and recurrent thrombotic episodes. The patient died as a result of severe thrombocytopenia, recurrent infection, and blood loss from the amputation site. Vancomycin is known to cause DITP, thrombosis, and immune complexes. DITP is a bleeding disorder, whereas HIT is a controversial thrombotic disorder. HIT tests can be influenced by cross-reacting antibodies and many other factors. Thus, there is no single method that can be considered 100% effective in confirming the HIT diagnosis. Anticoagulants must be used with great caution in patients with suspected DITP. Treatment of HIT-positive cases requires both clinical correlation and experience rather than reliance on HIT tests alone.

scholarly journals Safety and efficacy of etelcalcetide, an intravenous calcimimetic, for up to 52 weeks in hemodialysis patients with secondary hyperparathyroidism: results of a post-marketing surveillance in Japan

2020 ◽  
Vol 25 (1) ◽  
pp. 66-79
Author(s):  
Keitaro Yokoyama ◽  
Masafumi Fukagawa ◽  
Takashi Shigematsu ◽  
Takashi Akiba ◽  
Ken Yoshikawa ◽  
...  
Keyword(s):  
Secondary Hyperparathyroidism ◽  
Large Scale ◽  
Target Range ◽  
Safety And Efficacy ◽  
Laboratory Test Results ◽  
Post Marketing Surveillance ◽  
Starting Dose ◽  
Nutrition Disorders ◽  
Post Marketing

Abstract Background Etelcalcetide is a second-generation calcimimetic for the management of secondary hyperparathyroidism (SHPT) in patients on dialysis. We performed a post-marketing surveillance (PMS) to obtain information on the safety and efficacy of etelcalcetide in clinical practice in Japan. Methods This PMS enrolled SHPT patients who started initial treatment with etelcalcetide between April 1, 2017 and February 28, 2018 in Japan. Safety [adverse drug reactions (ADRs)] and efficacy [serum intact parathyroid hormone (iPTH), corrected calcium (cCa), phosphorous (P), and alkaline phosphatase (ALP)] were recorded for up to 52 weeks or until treatment discontinuation. Treatment decisions were at the physician’s discretion. Results Of 1226 patients enrolled across 282 centers, safety and efficacy data were available for 1195 and 1192, respectively, while 933 continued treatment to Week 52. The starting dose was 5 mg in 82.0% of patients. There were 218 ADRs in 169 patients (14.1%). Metabolism and nutrition disorders (8.8%), adverse laboratory test results (1.8%), and gastrointestinal disorders (1.6%) were the most frequent classes of ADRs. Hypocalcemia-related ADRs occurred in 104 patients (8.7%). The percentage of patients with iPTH levels within the target range (60–240 pg/mL) steadily increased from 19.5% at Week 0 to 64.1% at Week 52 or last dose. cCa, P, and ALP levels remained well controlled. Conclusion This was the first real-world, large-scale, long-term observational PMS of etelcalcetide in Japan. We did not observe any new safety concerns. Etelcalcetide was associated with clinically relevant improvements in serum iPTH and maintenance of serum cCa, P, and ALP levels.

scholarly journals Design and Baseline Data for a Prospective Observational Study of Rivaroxaban in Patients with Venous Thromboembolism in Japan (XASSENT)

TH Open ◽  
2021 ◽  
Author(s):  
Ikuo Fukuda ◽  
Atsushi Hirayama ◽  
Kazuo Kawasugi ◽  
Takao Kobayashi ◽  
Hideaki Maeda ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Venous Thromboembolism ◽  
Patient Characteristics ◽  
Open Label ◽  
Phase 3 ◽  
Vein Thrombosis ◽  
Post Marketing Surveillance ◽  
Post Marketing ◽  
History Of ◽  
Deep Vein

Background The efficacy and safety of rivaroxaban have been demonstrated in phase 3 trials of patients with venous thromboembolism (VTE; pulmonary embolism [PE] and deep vein thrombosis [DVT]). Data regarding rivaroxaban treatment of VTE in routine Japanese clinical practice remain limited. Objectives XASSENT will evaluate rivaroxaban treatment of VTE in real-world Japanese clinical practice. We report the study design and baseline patient characteristics. Methods XASSENT (NCT02558465) is a an open-label, prospective observational, post-marketing surveillance cohort study in patients receiving rivaroxaban treatment for VTE. Enrolment took place between November 2015 and March 2018. XASSENT will follow patients for up to 2 years. Primary outcome variables: major bleeding and symptomatic recurrent VTE. Statistical analyses are exploratory and descriptive. Results Baseline patient characteristics at June 2020 (n=2,299) are presented (58.2% female; mean age 66.7 years; mean weight 60.9kg). The population encompasses patients with wide-ranging characteristics including older age, low weight, and renal dysfunction. Most participants (67.6%) had a history of VTE risk factors at baseline. Half of the population (50.4%) had DVT only; 41.4% had DVT with PE; 8.2% had PE only. Overall, 68.4% were inpatients and 77.1% had symptomatic VTE. Rivaroxaban was prescribed for initial treatment in 84.6% of patients and maintenance treatment in 15.4%. Most were prescribed the approved dose of rivaroxaban for initial (30mg daily; 84.4%) or maintenance (15mg daily; 81.9%) treatment of VTE in Japan. The most common reason for selecting non-recommended dose was ‘elderly’. Conclusions Results from XASSENT will complement phase 3 trial data and inform clinical practice.

Challenges in Treating Extensive Deep Vein Thrombosis with Severe Thrombocytopenia in Patients with Antiphospholipid Syndrome—A Follow-up of 2 Years

2019 ◽  
Author(s):  
Lee Kai Wei ◽  
Ashish Anil Sule
Keyword(s):  
Deep Vein Thrombosis ◽  
Antiphospholipid Syndrome ◽  
Lower Limb ◽  
Immune Thrombocytopenia ◽  
Femoral Vein ◽  
Severe Thrombocytopenia ◽  
Bleeding Events ◽  
Superficial Femoral Vein ◽  
Vein Thrombosis ◽  
Deep Vein

AbstractThrombocytopenia is one of the most common manifestations of antiphospholipid syndrome (APS). There is little evidence or definitive guidelines regarding the treatment of APS with thrombocytopenia. We describe a patient with APS and moderate-to-severe thrombocytopenia and the challenges of balancing anticoagulation with thrombocytopenia. A 19-year-old male patient presented with right lower limb swelling to the emergency department with a history of gradually worsening right leg swelling for 1 week and was diagnosed with right leg proximal deep vein thrombosis. Ultrasound Doppler of the right lower limb revealed complete venous thrombosis from the level of the popliteal vein to the distal superficial femoral vein. Subsequently, he was found to have triple-positive APS and moderate-to-severe immune thrombocytopenia, with a platelet count nadir of 31 × 10 to the ninth power/L. He was started on anticoagulation with warfarin. The severe thrombocytopenia was not treated with immunosuppressants and the platelets fluctuated in the range of moderate-to-severe thrombocytopenia but did not develop any rethrombotic or bleeding events. His platelets varied from 31 × 10 to the ninth power/L to 106 × 10 to the ninth power/L. This case report demonstrates that it may be safe to hold off treatment for thrombocytopenia in APS, even in cases of severe thrombocytopenia. Treatment with immunosuppressants may be instituted only when platelet levels fall below 20 × 10 to the ninth power/L or when there is clinically significant bleeding, as in primary immune thrombocytopenia.

Post Marketing Surveillance of in vitro Diagnostic System in the European Union

2020 ◽  
Vol 07 ◽  
Author(s):  
Himadri Singh
Keyword(s):  
European Union ◽  
Medical Device ◽  
Diagnostic System ◽  
The European Union ◽  
Post Marketing Surveillance ◽  
In Vitro Diagnostic ◽  
Clinical Benefits ◽  
Post Marketing ◽  
And Performance

: Advances in medical device technology and regulatory authorization adapt to changing requirements and market conditions. The assessment of safety and performance in real world scenario will help us in understanding of clinical benefits and help in evolution of the medical device and in vitro diagnostic devices. The paradigm shift in evaluation of medical devices and in vitro diagnostic devices will ensure that the device deliver intended benefits. This articles discusses the new approach of the post marketing surveillance in the context of new in vitro diagnostic regulation in the European Union.

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