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1.
J Korean Med Sci ; 37(10): e75, 2022 Mar 14.
Article in English | MEDLINE | ID: covidwho-1742199

ABSTRACT

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but life-threatening complication. VITT strongly mimics heparin-induced thrombocytopenia (HIT) and shares clinical features. Heparin is commonly used to prevent coagulation during hemodialysis. Therefore, nephrologists might encounter patients needing dialysis with a history of heparin exposure who developed thrombotic thrombocytopenia after vaccination. A 70-year-old male presented with acute kidney injury and altered mental status due to lithium intoxication. He needed consecutive hemodialysis using heparin. Deep vein thrombosis of left lower extremity and accompanying severe thrombocytopenia of 15,000/µL on 24 days after vaccination and at the same time, nine days after heparin use. Anti-platelet factor 4 antibody test was positive. Anticoagulation with apixaban and intravenous immunoglobulin (IVIG) infusion resolved swelling of his left calf and thrombocytopenia. There were no definitive diagnostic tools capable of differentiating between VITT and HIT in this patient. Although VITT and HIT share treatment with IVIG and non-heparin anticoagulation, distinguishing between VITT and HIT will make it possible to establish a follow-up vaccination plan in a person who has had a thrombocytopenic thrombotic event. Further research is needed to develop the tools to make a clear distinction between the clinical syndromes.


Subject(s)
/adverse effects , Heparin/adverse effects , Purpura, Thrombocytopenic, Idiopathic/etiology , Renal Dialysis/adverse effects , Thrombocytopenia/etiology , Aged , Anticoagulants/adverse effects , Autoantibodies/blood , Diagnosis, Differential , Humans , Immunoglobulin G/blood , Lithium/toxicity , Male , Platelet Count , Platelet Factor 4/immunology , Purpura, Thrombocytopenic, Idiopathic/blood , Purpura, Thrombocytopenic, Idiopathic/diagnosis , Renal Dialysis/methods , Thrombocytopenia/blood , Thrombocytopenia/diagnosis
5.
Hematology Am Soc Hematol Educ Program ; 2021(1): 621-627, 2021 12 10.
Article in English | MEDLINE | ID: covidwho-1566500

ABSTRACT

Early in the pandemic, COVID-19-related increases in rates of venous and arterial thromboembolism were seen. Many observational studies suggested a benefit of prophylactic anticoagulation for hospitalized patients using various dosing strategies. Randomized trials were initiated to compare the efficacy of these different options in acutely ill and critically ill inpatients as the concept of immune-mediated inflammatory microthrombosis emerged. We present a case-based review of how we approach thromboembolic prophylaxis in COVID-19 and briefly discuss the epidemiology, the pathophysiology, and the rare occurrence of vaccine-induced thrombotic thrombocytopenia.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19/complications , Purpura, Thrombocytopenic, Idiopathic/etiology , Thrombosis/etiology , Anticoagulants/therapeutic use , Blood Coagulation/drug effects , COVID-19/blood , Critical Illness , Humans , Male , Middle Aged , Purpura, Thrombocytopenic, Idiopathic/blood , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Risk Factors , Thrombosis/blood , Thrombosis/drug therapy
6.
Blood Coagul Fibrinolysis ; 32(7): 427-433, 2021 Oct 01.
Article in English | MEDLINE | ID: covidwho-1526210

ABSTRACT

Immune thrombocytopenia is a haematological, autoimmune disorder characterized by elevated platelet demolition due to the presence of antiplatelet autoantibodies derived from B cells and to an irregular, deficient process of platelets production in bone marrow. In this review, after a brief presentation of 'old' strategies used nowadays yet, we focused on new drugs used in the treatment of immune thrombocytopenia and their mechanism of action and posology, basing on the last scientific literature. The observation that CoViD-19 can be associated with immune thrombocytopenia is also put in evidence. Particular attention will be dedicated on the concept that the ideal treatment should represent a solution not only for the failure of normal processes of production and survival of platelets, but also it should improve quality of life of patients, with minimum adverse events. Anyway, despite enormous advances of the last years, further investigations are necessary in order to define scrupulously long-term efficacy of new molecules proposed.


Subject(s)
Purpura, Thrombocytopenic, Idiopathic/drug therapy , Aminopyridines/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/complications , COVID-19/immunology , Histocompatibility Antigens Class I , Humans , Immunosuppressive Agents/therapeutic use , Morpholines/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Purpura, Thrombocytopenic, Idiopathic/etiology , Purpura, Thrombocytopenic, Idiopathic/immunology , Pyrimidines/therapeutic use , Receptors, Fc/antagonists & inhibitors , Receptors, Thrombopoietin/agonists , SARS-CoV-2/immunology , Syk Kinase/antagonists & inhibitors , Thiazoles/therapeutic use , Thiophenes/therapeutic use
9.
J Clin Apher ; 37(1): 117-121, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1473857

ABSTRACT

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a newly described hematologic disorder, which presents as acute thrombocytopenia and thrombosis after administration of the ChAdOx1 nCov-19 (AstraZeneca) and Ad26.COV2.S (Johnson & Johnson) adenovirus-based vaccines against COVID-19. Due to positive assays for antibodies against platelet factor 4 (PF4), VITT is managed similarly to autoimmune heparin-induced thrombocytopenia (HIT) with intravenous immunoglobulin (IVIG) and non-heparin anticoagulation. We describe a case of VITT in a 50-year-old man with antecedent alcoholic cirrhosis who presented with platelets of 7 × 103 /µL and portal vein thrombosis 21 days following administration of the Ad26.COV2.S COVID-19 vaccine. The patient developed progressive thrombosis and persistent severe thrombocytopenia despite IVIG, rituximab and high-dose steroids and had persistent anti-PF4 antibodies over 30 days after his initial presentation. As such, delayed therapeutic plasma exchange (TPE) was pursued on day 32 of admission as salvage therapy, with a sustained improvement in his platelet count. Our case serves as proof-of-concept of the efficacy of TPE in VITT.


Subject(s)
/adverse effects , Plasma Exchange/methods , Purpura, Thrombocytopenic, Idiopathic/therapy , Vaccination/adverse effects , Humans , Male , Middle Aged , Platelet Count , Platelet Factor 4/immunology , Purpura, Thrombocytopenic, Idiopathic/etiology
11.
Int J Mol Sci ; 22(19)2021 Oct 06.
Article in English | MEDLINE | ID: covidwho-1457948

ABSTRACT

Novel coronavirus SARS-CoV-2 has resulted in a global pandemic with worldwide 6-digit infection rates and thousands of death tolls daily. Enormous efforts are undertaken to achieve high coverage of immunization to reach herd immunity in order to stop the spread of SARS-CoV-2 infection. Several SARS-CoV-2 vaccines based on mRNA, viral vectors, or inactivated SARS-CoV-2 virus have been approved and are being applied worldwide. However, the recent increased numbers of normally very rare types of thromboses associated with thrombocytopenia have been reported, particularly in the context of the adenoviral vector vaccine ChAdOx1 nCoV-19 from Astra Zeneca. The statistical prevalence of these side effects seems to correlate with this particular vaccine type, i.e., adenoviral vector-based vaccines, but the exact molecular mechanisms are still not clear. The present review summarizes current data and hypotheses for molecular and cellular mechanisms into one integrated hypothesis indicating that coagulopathies, including thromboses, thrombocytopenia, and other related side effects, are correlated to an interplay of the two components in the vaccine, i.e., the spike antigen and the adenoviral vector, with the innate and immune systems, which under certain circumstances can imitate the picture of a limited COVID-19 pathological picture.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Thrombocytopenia/etiology , Thrombosis/etiology , Adenoviridae/immunology , Animals , COVID-19/immunology , COVID-19 Vaccines/immunology , Genetic Vectors/adverse effects , Genetic Vectors/immunology , Humans , Purpura, Thrombocytopenic, Idiopathic/etiology , Purpura, Thrombocytopenic, Idiopathic/immunology , Spike Glycoprotein, Coronavirus/adverse effects , Thrombocytopenia/immunology , Thrombosis/immunology , Vaccination/adverse effects
14.
Blood ; 138(22): 2256-2268, 2021 12 02.
Article in English | MEDLINE | ID: covidwho-1443788

ABSTRACT

SARS-CoV-2 vaccine ChAdOx1 nCoV-19 (AstraZeneca) causes a thromboembolic complication termed vaccine-induced immune thrombotic thrombocytopenia (VITT). Using biophysical techniques, mouse models, and analysis of VITT patient samples, we identified determinants of this vaccine-induced adverse reaction. Super-resolution microscopy visualized vaccine components forming antigenic complexes with platelet factor 4 (PF4) on platelet surfaces to which anti-PF4 antibodies obtained from VITT patients bound. PF4/vaccine complex formation was charge-driven and increased by addition of DNA. Proteomics identified substantial amounts of virus production-derived T-REx HEK293 proteins in the ethylenediaminetetraacetic acid (EDTA)-containing vaccine. Injected vaccine increased vascular leakage in mice, leading to systemic dissemination of vaccine components known to stimulate immune responses. Together, PF4/vaccine complex formation and the vaccine-stimulated proinflammatory milieu trigger a pronounced B-cell response that results in the formation of high-avidity anti-PF4 antibodies in VITT patients. The resulting high-titer anti-PF4 antibodies potently activated platelets in the presence of PF4 or DNA and polyphosphate polyanions. Anti-PF4 VITT patient antibodies also stimulated neutrophils to release neutrophil extracellular traps (NETs) in a platelet PF4-dependent manner. Biomarkers of procoagulant NETs were elevated in VITT patient serum, and NETs were visualized in abundance by immunohistochemistry in cerebral vein thrombi obtained from VITT patients. Together, vaccine-induced PF4/adenovirus aggregates and proinflammatory reactions stimulate pathologic anti-PF4 antibody production that drives thrombosis in VITT. The data support a 2-step mechanism underlying VITT that resembles the pathogenesis of (autoimmune) heparin-induced thrombocytopenia.


Subject(s)
Antigen-Antibody Complex/immunology , Autoantibodies/immunology , COVID-19/prevention & control , Capsid Proteins/adverse effects , Drug Contamination , Genetic Vectors/adverse effects , HEK293 Cells/immunology , Immunoglobulin G/immunology , Platelet Factor 4/immunology , Purpura, Thrombocytopenic, Idiopathic/etiology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/adverse effects , Adenoviridae/immunology , Animals , Antigen-Antibody Complex/ultrastructure , Autoantibodies/biosynthesis , Capillary Leak Syndrome/etiology , Capsid Proteins/immunology , Cell Line, Transformed , /immunology , Dynamic Light Scattering , Epitopes/chemistry , Epitopes/immunology , Extracellular Traps/immunology , Extravasation of Diagnostic and Therapeutic Materials/etiology , Genetic Vectors/immunology , HEK293 Cells/chemistry , Humans , Imaging, Three-Dimensional , Immunoglobulin G/biosynthesis , Inflammation , Mice , Microscopy/methods , Platelet Activation , Proteomics , Purpura, Thrombocytopenic, Idiopathic/blood , Purpura, Thrombocytopenic, Idiopathic/immunology , Sinus Thrombosis, Intracranial/diagnostic imaging , Sinus Thrombosis, Intracranial/immunology , Spike Glycoprotein, Coronavirus/immunology , Virus Cultivation
18.
Br J Haematol ; 196(2): 351-355, 2022 01.
Article in English | MEDLINE | ID: covidwho-1373796

ABSTRACT

The COVID-19 pandemic has created many challenges in the management of immune thrombocytopenic purpura (ITP). The recommendation for avoidance of steroids by WHO led to the off-licence use, supported by NHS England, of thrombopoietin mimetics (TPO-RA) for newly diagnosed or relapsed ITP. This is a real-world prospective study which investigated the treatment patterns and outcomes in this setting. Twenty-four hospitals across the UK submitted 343 cases. Corticosteroids remain the mainstay of ITP treatment, but TPO-RAs were more effective. Incidental COVID-19 infection was identified in a significant number of patients (9·5%), while 14 cases were thought to be secondary to COVID-19 vaccination.


Subject(s)
COVID-19/epidemiology , Pandemics , Purpura, Thrombocytopenic, Idiopathic/therapy , Adolescent , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/adverse effects , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Aged, 80 and over , Autoimmune Diseases/complications , COVID-19/blood , COVID-19 Vaccines/adverse effects , Combined Modality Therapy , Comorbidity , Connective Tissue Diseases/complications , Contraindications, Drug , Disease Management , Female , Hemorrhage/epidemiology , Hemorrhage/etiology , Hospitals, District/statistics & numerical data , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Neoplasms/complications , Off-Label Use , Platelet Transfusion , Prospective Studies , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Purpura, Thrombocytopenic, Idiopathic/epidemiology , Purpura, Thrombocytopenic, Idiopathic/etiology , Tertiary Care Centers/statistics & numerical data , Thromboembolism/epidemiology , Thromboembolism/etiology , Thrombopoietin/agonists , Tranexamic Acid/therapeutic use , Treatment Outcome , United Kingdom/epidemiology , Young Adult
19.
N Engl J Med ; 385(18): 1680-1689, 2021 10 28.
Article in English | MEDLINE | ID: covidwho-1352005

ABSTRACT

BACKGROUND: Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a new syndrome associated with the ChAdOx1 nCoV-19 adenoviral vector vaccine against severe acute respiratory syndrome coronavirus 2. Data are lacking on the clinical features of and the prognostic criteria for this disorder. METHODS: We conducted a prospective cohort study involving patients with suspected VITT who presented to hospitals in the United Kingdom between March 22 and June 6, 2021. Data were collected with the use of an anonymized electronic form, and cases were identified as definite or probable VITT according to prespecified criteria. Baseline characteristics and clinicopathological features of the patients, risk factors, treatment, and markers of poor prognosis were determined. RESULTS: Among 294 patients who were evaluated, we identified 170 definite and 50 probable cases of VITT. All the patients had received the first dose of ChAdOx1 nCoV-19 vaccine and presented 5 to 48 days (median, 14) after vaccination. The age range was 18 to 79 years (median, 48), with no sex preponderance and no identifiable medical risk factors. Overall mortality was 22%. The odds of death increased by a factor of 2.7 (95% confidence interval [CI], 1.4 to 5.2) among patients with cerebral venous sinus thrombosis, by a factor of 1.7 (95% CI, 1.3 to 2.3) for every 50% decrease in the baseline platelet count, by a factor of 1.2 (95% CI, 1.0 to 1.3) for every increase of 10,000 fibrinogen-equivalent units in the baseline d-dimer level, and by a factor of 1.7 (95% CI, 1.1 to 2.5) for every 50% decrease in the baseline fibrinogen level. Multivariate analysis identified the baseline platelet count and the presence of intracranial hemorrhage as being independently associated with death; the observed mortality was 73% among patients with platelet counts below 30,000 per cubic millimeter and intracranial hemorrhage. CONCLUSIONS: The high mortality associated with VITT was highest among patients with a low platelet count and intracranial hemorrhage. Treatment remains uncertain, but identification of prognostic markers may help guide effective management. (Funded by the Oxford University Hospitals NHS Foundation Trust.).


Subject(s)
COVID-19 Vaccines/adverse effects , Purpura, Thrombocytopenic, Idiopathic/etiology , Thrombosis/etiology , Adolescent , Adult , Aged , Anticoagulants , Autoantibodies/blood , COVID-19/prevention & control , Female , Humans , Immunoglobulins, Intravenous/therapeutic use , Intracranial Hemorrhages/etiology , Intracranial Hemorrhages/mortality , Male , Middle Aged , Multivariate Analysis , Platelet Count , Platelet Factor 4/immunology , Prospective Studies , Purpura, Thrombocytopenic, Idiopathic/mortality , Purpura, Thrombocytopenic, Idiopathic/therapy , Risk Factors , Thrombosis/drug therapy , Thrombosis/mortality , United Kingdom/epidemiology , Young Adult
20.
J Cardiovasc Med (Hagerstown) ; 23(2): 71-74, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1348429

ABSTRACT

Currently, the world is coping with the COVID-19 pandemic with a few vaccines. So far, the European Medicine Agency has approved four of them. However, following widespread vaccination with the recombinant adenoviral vector-based Oxford-AstraZeneca vaccine, available only in the United Kingdom and Europe, many concerns have emerged, especially the report of several cases of the otherwise rare cerebral sinus vein thrombosis and splanchnic vein thrombosis. The onset of thrombosis particularly at these unusual sites, about 5--14 days after vaccination, along with thrombocytopenia and other specific blood test abnormalities, are the main features of the vaccine side effects. The acronym vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) has been coined to name this new condition, with the aim of highlighting the difference from the classic heparin-induced thrombocytopenia (HIT). VIPIT seems to primarily affect young to middle-aged women. For this reason, the vaccine administration has been stopped or limited in a few European countries. Coagulopathy induced by the Oxford-AstraZeneca vaccine (and probably by Janssen/Johnson & Johnson vaccine as well in the USA) is likely related to the use of recombinant vector DNA adenovirus, as experimentally proven in animal models. Conversely, Pfizer and Moderna vaccines use mRNA vectors. All vaccine-induced thrombotic events should be treated with a nonheparin anticoagulant. As the condition has some similarities with HIT, patients should not receive any heparin or platelet transfusion, as these treatments may potentially worsen the clinical course. Aspirin has limited rational use in this setting and is not currently recommended. Intravenous immunoglobulins may represent another potential treatment, but, most importantly, clinicians need to be aware of this new unusual postvaccination syndrome.


Subject(s)
/adverse effects , Intracranial Thrombosis/etiology , Purpura, Thrombocytopenic, Idiopathic/etiology , /adverse effects , Adenoviridae/immunology , Humans
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