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1.
Med. lab ; 26(3): 213-214, 2022.
Article in Spanish | WHO COVID, LILACS (Americas) | ID: covidwho-20235771

ABSTRACT

La infección viral respiratoria causada por el SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) produce la enfermedad por coronavirus 2019 o COVID-19. Hasta el 20% al 50% de los pacientes hospitalizados con COVID-19 tienen alteraciones de la coagulación (dímero D elevado, tiempo de protrombina prolongado, trombocitopenia y fibrinógeno bajo). Esta condición se caracteriza por eventos trombóticos más que hemorrágicos. De otro lado, se presenta disfunción endotelial, lo cual explica los niveles elevados de trombina, de dímero D y de otros productos de degradación de fibrina, la trombocitopenia y la prolongación de los tiempos de coagulación; estos cambios terminan por originar hipoxia, oclusión microvascular y congestión pulmonar mediada por trombosis [1]. Se ha demostrado que el tratamiento anticoagulante inicial con heparinas de bajo peso molecular reduce la mortalidad un 48% a los 7 días y un 37% a los 28 días, y logra una mejoría significativa del cociente presión arterial de oxígeno/fracción inspirada de O2 (PaO2/FiO2), al mitigar la formación de microtrombos y la coagulopatía pulmonar asociada, disminuyendo además la inflamación [2]. En el artículo titulado "Alteraciones hematológicas como consecuencia de COVID-19 y sus vacunas", se abordan las anormalidades en la coagulación como la trombocitopenia trombótica inmune inducida por las vacunas contra el SARS-CoV-2. Es importante anotar, que hoy en día la comunidad científica está de acuerdo en que sin la vacunación hubiera sido imposible lograr el control actual que se tiene de la pandemia, pero a la vez se debe tener en cuenta que cualquier inmunización tiene también efectos adversos que por lo general son leves, pero que en raras ocasiones se pueden presentar complicaciones de mayor magnitud


Subject(s)
Humans , SARS-CoV-2 , Thrombocytopenia , Blood Coagulation , Coronavirus , COVID-19 , Hematology
2.
Front Immunol ; 14: 1186000, 2023.
Article in English | MEDLINE | ID: covidwho-20236819

ABSTRACT

Coronavirus disease 2019 (COVID-19) is known to commonly induce a thrombotic diathesis, particularly in severely affected individuals. So far, this COVID-19-associated coagulopathy (CAC) has been partially explained by hyperactivated platelets as well as by the prothrombotic effects of neutrophil extracellular traps (NETs) released from neutrophils. However, precise insight into the bidirectional relationship between platelets and neutrophils in the pathophysiology of CAC still lags behind. Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare autoimmune disorder caused by auto-antibody formation in response to immunization with adenoviral vector vaccines. VITT is associated with life-threatening thromboembolic events and thus, high fatality rates. Our concept of the thrombophilia observed in VITT is relatively new, hence a better understanding could help in the management of such patients with the potential to also prevent VITT. In this review we aim to summarize the current knowledge on platelet-neutrophil interplay in COVID-19 and VITT.


Subject(s)
COVID-19 , Thrombocytopenia , Thrombosis , Vaccines , Humans , Blood Platelets , Neutrophils , COVID-19/complications , Thrombocytopenia/chemically induced , Thrombosis/etiology , Rare Diseases
3.
Neurol Neuroimmunol Neuroinflamm ; 10(4)2023 07.
Article in English | MEDLINE | ID: covidwho-20235895

ABSTRACT

OBJECTIVES: Vaccine-induced immune thrombotic thrombocytopenia (VITT), a recently described entity characterized by thrombosis at unusual locations such as cerebral venous sinus and splanchnic vein, has been rarely described after adenoviral-encoded COVID-19 vaccines. In this study, we report the immunohistological correlates in 3 fatal cases of cerebral venous thrombosis related to VITT analyzed at an academic medical center. METHODS: Detailed neuropathologic studies were performed in 3 cases of cerebral venous thrombosis related to VITT after adenoviral COVID-19 vaccination. RESULTS: Autopsy revealed extensive cerebral vein thrombosis in all 3 cases. Polarized thrombi were observed with a high density of neutrophils in the core and a low density in the tail. Endothelial cells adjacent to the thrombus were largely destroyed. Markers of neutrophil extracellular trap and complement activation were present at the border and within the cerebral vein thrombi. SARS-CoV-2 spike protein was detected within the thrombus and in the adjacent vessel wall. DISCUSSION: Data indicate that neutrophils and complement activation associated with antispike immunity triggered by the vaccine is probably involved in the disease process.


Subject(s)
COVID-19 , Thrombocytopenia , Thrombosis , Vaccines , Venous Thrombosis , Humans , COVID-19 Vaccines/adverse effects , Endothelial Cells , SARS-CoV-2 , Venous Thrombosis/etiology
4.
Methods Mol Biol ; 2663: 405-415, 2023.
Article in English | MEDLINE | ID: covidwho-2323040

ABSTRACT

Heparin-induced thrombocytopenia (HIT) represents an autoimmune process whereby antibodies are formed against heparin in complex with platelet factor 4 (PF4) after heparin administration. These antibodies can be detected by a variety of immunological assays, including ELISA (enzyme-linked immunosorbent assay) and by chemiluminescence on the AcuStar instrument. However, pathological HIT antibodies are those that activate platelets in a platelet activation assay and cause thrombosis in vivo. We would tend to call this condition heparin-induced thrombotic thrombocytopenia (HITT), although some workers instead use the truncated abbreviation HIT. Vaccine-induced (immune) thrombotic thrombocytopenia (VITT) instead reflects an autoimmune process whereby antibodies are formed against PF4 after administration of a vaccine, most notably adenovirus-based vaccines directed against COVID-19 (coronavirus disease 2019). Although both VITT and HITT reflect similar pathological processes, they have different origins and are detected in different ways. Most notable is that anti-PF4 antibodies in VITT can only be detected immunologically by ELISA assays, tending to be negative in rapid assays such as that using the AcuStar. Moreover, functional platelet activation assays otherwise used for HITT may need to be modified to detect platelet activation in VITT.


Subject(s)
COVID-19 , Thrombocytopenia , Thrombosis , Vaccines , Humans , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnosis , Heparin/adverse effects , Thrombosis/chemically induced , Antibodies , Vaccines/adverse effects , Platelet Factor 4/adverse effects
5.
Front Immunol ; 14: 1160048, 2023.
Article in English | MEDLINE | ID: covidwho-2327129

ABSTRACT

Background: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by isolated thrombocytopenia. Recently, the pathophysiology and novel drugs of ITP have been the focus of researchers with plenty of publications emerging. Bibliometrics is the process of extracting measurable data through statistical analysis of published research studies to provide an insight into the trends and hotspots. Objective: This study aimed to provide an insight into developing trends and hotspots in the field of ITP by bibliometric analysis. Methods: By using three bibliometric mapping tools (bibliometrix R package, VOSviewer, CiteSpace), we summarized the overview information of retrieved publications, as well as the analysis of keyword co-occurrence and reference co-citation. Results: A total of 3299 publications with 78066 citations on ITP research were included in the analysis. The keyword co-occurrence network identified 4 clusters relating to the diagnosis, pathophysiology, and treatment of ITP respectively. Then the reference co-citation analysis produced 12 clusters with a well-structured and highly credible clustering model, and they can be divided into 5 trends: second-line treatment, chronic ITP, novel therapy and pathogenesis, COVID-19 vaccine. Treg cells, spleen tyrosine kinase, and mesenchymal stem cells were the latest hotspots with strong burstness. Conclusion: This bibliometric analysis provided a comprehensive insight into research hotspots and trends on ITP, which would enrich the review of the ITP research.


Subject(s)
COVID-19 , Purpura, Thrombocytopenic, Idiopathic , Thrombocytopenia , Humans , Purpura, Thrombocytopenic, Idiopathic/therapy , COVID-19 Vaccines , Bibliometrics
6.
J Thromb Thrombolysis ; 56(2): 241-252, 2023 Aug.
Article in English | MEDLINE | ID: covidwho-2325921

ABSTRACT

Heparin-induced thrombocytopenia (HIT) occurs in approximately 3% of patients receiving heparinoids. About 30-75% of patients with type 2 of HIT develop thrombosis as a result of platelet activation. The most important clinical symptom is thrombocytopenia. Patients with severe COVID-19 are among those receiving heparinoids. This meta-analysis performed to picture the current knowledge and results of published studies in this field. Three search engines were searched and 575 papers were found. After evaluation, 37 articles were finally selected of which 13 studies were quantitatively analyzed. The pooled frequency rate of suspected cases with HIT in 13 studies with 11,241 patients was 1.7%. The frequency of HIT was 8.2% in the extracorporeal membrane oxygenation subgroup with 268 patients and 0.8% in the hospitalization subgroup with 10,887 patients. The coincidence of these two conditions may increase the risk of thrombosis. Of the 37 patients with COVID-19 and confirmed HIT, 30 patients (81%) were treated in the intensive care unit or had severe COVID-19. The most commonly used anticoagulants were UFH in 22 cases (59.4%). The median platelet count before treatment was 237 (176-290) x 103/µl and the median nadir platelet count was 52 (31-90.5) x 103/µl.


Subject(s)
COVID-19 , Heparinoids , Thrombocytopenia , Thrombosis , Humans , Heparin/adverse effects , Heparinoids/adverse effects , COVID-19/complications , Thrombocytopenia/diagnosis , Anticoagulants/adverse effects , Thrombosis/etiology
7.
Methods Mol Biol ; 2663: 441-461, 2023.
Article in English | MEDLINE | ID: covidwho-2324357

ABSTRACT

Heparin-induced thrombocytopenia (HIT) is a well-characterized, iatrogenic complication of heparin anticoagulation with significant morbidity. In contrast, vaccine-induced immune thrombotic thrombocytopenia (VITT) is a recently recognized severe prothrombotic complication of adenoviral vaccines, including the ChAdOx1 nCoV-19 (Vaxzevria, AstraZeneca) and Ad26.COV2.S (Janssen, Johnson & Johnson) vaccines against COVID-19. The diagnosis of HIT and VITT involve laboratory testing for antiplatelet antibodies by immunoassays followed by confirmation by functional assays to detect platelet-activating antibodies. Functional assays are critical to detect pathological antibodies due to the varying sensitivity and specificity of immunoassays. This chapter presents a protocol for a novel whole blood flow cytometry-based assay to detect procoagulant platelets in healthy donor blood in response to plasma from patients suspected of HIT or VITT. A method to identify suitable healthy donors for HIT and VITT testing is also described.


Subject(s)
COVID-19 , Thrombocytopenia , Thrombosis , Vaccines , Humans , Blood Platelets , Ad26COVS1 , COVID-19 Vaccines/adverse effects , ChAdOx1 nCoV-19 , Flow Cytometry , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnosis , Antibodies , Platelet Factor 4
8.
Methods Mol Biol ; 2663: 429-440, 2023.
Article in English | MEDLINE | ID: covidwho-2324176

ABSTRACT

Vaccine-induced immune thrombotic thrombocytopenia (VITT) was first described in 2021 and represents an adverse reaction to adenoviral vector COVID-19 vaccines AstraZeneca ChAdOx1 nCoV-19 (AZD1222) and Johnson & Johnson Ad26.COV2.S vaccine. VITT is a severe immune platelet activation syndrome with an incidence of 1-2 per 100,000 vaccinations. The features of VITT include thrombocytopenia and thrombosis within 4-42 days of first dose of vaccine. Affected individuals develop platelet-activating antibodies against platelet factor 4 (PF4). The International Society on Thrombosis and Haemostasis recommends both an antigen-binding assay (enzyme-linked immunosorbent assay, ELISA) and a functional platelet activation assay for the diagnostic workup of VITT. Here, the application of multiple electrode aggregometry (Multiplate) is presented as a functional assay for VITT.


Subject(s)
COVID-19 , Thrombocytopenia , Vaccines , Humans , ChAdOx1 nCoV-19 , Ad26COVS1 , COVID-19 Vaccines/adverse effects , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnosis , Antibodies , Electrodes , Platelet Factor 4
9.
Methods Mol Biol ; 2663: 463-477, 2023.
Article in English | MEDLINE | ID: covidwho-2324173

ABSTRACT

The serotonin release assay (SRA) has been the gold-standard assay for detection of heparin-dependent platelet-activating antibodies and integral for the diagnosis for heparin-induced thrombotic thrombocytopenia (HIT). In 2021, a thrombotic thrombocytopenic syndrome was reported after adenoviral vector COVID-19 vaccination. This vaccine-induced thrombotic thrombocytopenic syndrome (VITT) proved to be a severe immune platelet activation syndrome manifested by unusual thrombosis, thrombocytopenia, very elevated plasma D-dimer, and a high mortality even with aggressive therapy (anticoagulation and plasma exchange). While the platelet-activating antibodies in both HIT and VITT are directed toward platelet factor 4 (PF4), important differences have been found. These differences have required modifications to the SRA to improve detection of functional VITT antibodies. Functional platelet activation assays remain essential in the diagnostic workup of HIT and VITT. Here we detail the application of SRA for the assessment of HIT and VITT antibodies.


Subject(s)
COVID-19 , Thrombocytopenia , Thrombosis , Humans , Heparin/adverse effects , Serotonin , Anticoagulants/adverse effects , COVID-19 Vaccines/adverse effects , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnosis , Antibodies , Thrombosis/diagnosis , Thrombosis/etiology , Platelet Factor 4/adverse effects
11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(2): 593-597, 2023 Apr.
Article in Chinese | MEDLINE | ID: covidwho-2320913

ABSTRACT

SARS-CoV-2-induced immune thrombocytopenia (SARS-CoV-2-induced ITP) is an autoimmune disease secondary to virus infections. Its diagnosis is often based on exclusion of other possible causes of thrombocytopenia in COVID-19 patients. Common laboratory examinations include coagulation function, thrombopoietin and drug-dependent antibodies. Since both bleeding and thrombosis risks are seen in SARS-CoV-2-induced ITP patients, individual remedy is essential for the treatment of this disease. Because thrombopoietin receptor agonist(TPO-RA) has the side effect of accelerating thrombosis and may aggravate the pulmonary embolism symptoms of patients, it should be used for refractory SARS-CoV-2-induced ITP patients only. This review briefly summarizes the recent research progress in the pathogenesis, diagnosis and treatment of SARS-CoV-2-induced ITP.


Subject(s)
COVID-19 , Purpura, Thrombocytopenic, Idiopathic , Thrombocytopenia , Thrombosis , Humans , Purpura, Thrombocytopenic, Idiopathic/drug therapy , SARS-CoV-2 , COVID-19/complications , Thrombosis/drug therapy , Thrombopoietin/therapeutic use , Recombinant Fusion Proteins/therapeutic use
12.
Cell Commun Signal ; 21(1): 103, 2023 05 08.
Article in English | MEDLINE | ID: covidwho-2317587

ABSTRACT

Hematopoietic stem cells (HSCs) are known for their significant capability to reconstitute and preserve a functional hematopoietic system in long-term periods after transplantation into conditioned hosts. HSCs are thus crucial cellular targets for the continual repair of inherited hematologic, metabolic, and immunologic disorders. In addition, HSCs can undergo various fates, such as apoptosis, quiescence, migration, differentiation, and self-renewal. Viruses continuously pose a remarkable health risk and request an appropriate, balanced reaction from our immune system, which as well as affects the bone marrow (BM). Therefore, disruption of the hematopoietic system due to viral infection is essential. In addition, patients for whom the risk-to-benefit ratio of HSC transplantation (HSCT) is acceptable have seen an increase in the use of HSCT in recent years. Hematopoietic suppression, BM failure, and HSC exhaustion are all linked to chronic viral infections. Virus infections continue to be a leading cause of morbidity and mortality in HSCT recipients, despite recent advancements in the field. Furthermore, whereas COVID-19 manifests initially as an infection of the respiratory tract, it is now understood to be a systemic illness that significantly impacts the hematological system. Patients with advanced COVID-19 often have thrombocytopenia and blood hypercoagulability. In the era of COVID-19, Hematological manifestations of COVID-19 (i.e., thrombocytopenia and lymphopenia), the immune response, and HSCT may all be affected by the SARS-CoV-2 virus in various ways. Therefore, it is important to determine whether exposure to viral infections may affect HSCs used for HSCT, as this, in turn, may affect engraftment efficiency. In this article, we reviewed the features of HSCs, and the effects of viral infections on HSCs and HSCT, such as SARS-CoV-2, HIV, cytomegalovirus, Epstein-Barr virus, HIV, etc. Video Abstract.


Subject(s)
COVID-19 , Epstein-Barr Virus Infections , HIV Infections , Thrombocytopenia , Virus Diseases , Humans , SARS-CoV-2 , Herpesvirus 4, Human , Hematopoietic Stem Cells
13.
J Neurointerv Surg ; 14(9): 853-857, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-2313764

ABSTRACT

BACKGROUND: Vaccine-induced thrombosis and thrombocytopenia (VITT) is a rare complication following ChAdOx1 nCoV-19 vaccination. Cerebral venous sinus thrombosis (CVST) is overrepresented in VITT and is often associated with multifocal venous thromboses, concomitant hemorrhage and poor outcomes. Hitherto, endovascular treatments have not been reviewed in VITT-related CVST. METHODS: Patient records from a tertiary neurosciences center were reviewed to identify patients who had endovascular treatment for CVST in VITT. RESULTS: Patient records from 1 January 2021 to 20 July 2021 identified three patients who underwent endovascular treatment for CVST in the context of VITT. All were female and the median age was 52 years. The location of the CVST was highly variable. Two-thirds of the patients had multifocal dural sinus thromboses (sigmoid, transverse, straight and superior sagittal) as well as internal jugular vein thromboses. Intracerebral hemorrhage occurred in all patients; subarachnoid blood was noted in two of them, and intraparenchymal hemorrhage occurred in all. There was one periprocedural parenchymal extravasation which abated on temporary cessation of anticoagulation. Outcome data revealed a 90-day modified Rankin Scale (mRS) score of 2 in all cases. CONCLUSIONS: We demonstrate that endovascular treatment for VITT-associated CVST is feasible and can be safe in cases that deteriorate despite medical therapy. Extensive clot burden, concomitant hemorrhage, rapid clinical progression and persistent rises in intracranial pressure should initiate multidisciplinary team discussion for endovascular treatment in appropriate cases.


Subject(s)
Sinus Thrombosis, Intracranial , Thrombocytopenia , ChAdOx1 nCoV-19 , Cranial Sinuses , Female , Humans , Male , Middle Aged , Sinus Thrombosis, Intracranial/diagnostic imaging , Sinus Thrombosis, Intracranial/etiology , Sinus Thrombosis, Intracranial/therapy , Thrombocytopenia/chemically induced , Vaccination
14.
Vaccine ; 41(23): 3550-3555, 2023 05 26.
Article in English | MEDLINE | ID: covidwho-2309898

ABSTRACT

Vaccination is the most important strategy in preventing COVID-19. Vaccine efficacy and safety have been established in clinical trials but real-world data are useful to determine occurrence of adverse events in a population with heterogeneous characteristics. Knowledge on the hematologic events associated with different COVID-19 vaccines would be beneficial for patients as well as hematologists who oversee the care of these patients. This study aimed to determine the rates and outcomes of hematologic adverse events after COVID-19 vaccination in the Philippines. In this self-controlled case series, there were 268 individuals reported to have hematologic adverse events. Most received Comirnaty at 29.85%. Majority (62.31%) reported hematologic adverse events following the first dose of the vaccine. The overall event rate was 0.0182 per 10,000 vaccine doses; and lymphadenopathy was the most common hematologic adverse effect with a rate of 0.011 per 10,000 vaccine doses, followed by anemia at 0.0034 per 10,000 vaccine doses and thrombocytopenia at 0.0017 per 10,000 vaccine doses. Autoimmune cytopenias were also reported with an event rate of 0.0007 per 10,000 vaccine doses for ITP. One-hundred thirty two (49.25%) were fully recovered and 23.88% were recovering from hematologic adverse events as of the time of writing. The study showed a low rate of hematologic adverse events post COVID-19 vaccination with the seven different vaccine brands administered in the Philippines.


Subject(s)
COVID-19 , Leukopenia , Thrombocytopenia , Vaccines , Humans , COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Philippines/epidemiology , Vaccination/adverse effects , Thrombocytopenia/chemically induced
15.
Eur J Intern Med ; 105: 1-7, 2022 11.
Article in English | MEDLINE | ID: covidwho-2309780

ABSTRACT

Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare syndrome characterized by high-titer anti-platelet factor 4 (PF4) antibodies, thrombocytopenia and arterial and venous thrombosis in unusual sites, as cerebral venous sinuses and splanchnic veins. VITT has been described to occur almost exclusively after administration of ChAdOx1 nCoV-19 and Ad26.COV2.S adenovirus vector- based COVID-19 vaccines. Clinical and laboratory features of VITT resemble those of heparin-induced thrombocytopenia (HIT). It has been hypothesized that negatively charged polyadenylated hexone proteins of the AdV vectors could act as heparin to induce the conformational changes of PF4 molecule that lead to the formation of anti-PF4/polyanion antibodies. The anti-PF4 immune response in VITT is fostered by the presence of a proinflammatory milieu, elicited by some impurities found in ChAdOx1 nCoV-19 vaccine, as well as by soluble spike protein resulting from alternative splice events. Anti-PF4 antibodies bind PF4, forming immune complexes which activate platelets, monocytes and granulocytes, resulting in the VITT's immunothrombosis. The reason why only a tiny minority of patents receiving AdV-based COVID-19 vaccines develop VITT is still unknown. It has been hypothesized that individual intrinsic factors, either acquired (i.e., pre-priming of B cells to produce anti-PF4 antibodies by previous contacts with bacteria or viruses) or inherited (i.e., differences in platelet T-cell ubiquitin ligand-2 [TULA-2] expression) can predispose a few subjects to develop VITT. A better knowledge of the mechanistic basis of VITT is essential to improve the safety and the effectiveness of future vaccines and gene therapies using adenovirus vectors.


Subject(s)
COVID-19 , Purpura, Thrombocytopenic, Idiopathic , Thrombocytopenia , Thrombosis , Vaccines , Humans , Antigen-Antibody Complex , COVID-19 Vaccines/adverse effects , Ad26COVS1 , ChAdOx1 nCoV-19 , Ligands , Spike Glycoprotein, Coronavirus , COVID-19/prevention & control , Platelet Factor 4/genetics , Platelet Factor 4/metabolism , Heparin/adverse effects , Thrombocytopenia/chemically induced , Vaccines/adverse effects , Purpura, Thrombocytopenic, Idiopathic/chemically induced , Ubiquitins
16.
J Med Case Rep ; 17(1): 122, 2023 Apr 05.
Article in English | MEDLINE | ID: covidwho-2290702

ABSTRACT

BACKGROUND: Immune thrombocytopenic purpura is a condition associated with an unusual, unexplained, and sometimes very severe reduction in the level of platelets in the blood. Though documented, its association with Graves' disease is not very common and can easily be missed or misdiagnosed, leading to excessive bleeding and mortality. Treatment with steroids and antithyroid medications has been shown to be beneficial in correcting thrombocytopenia in these patients, although the response is varied. We report on a patient with Graves' disease who presents with immune thrombocytopenic purpura. CASE PRESENTATION: A 37-year-old Ghanaian female presented to our hospital's emergency department with a complaint of palpitations, difficulty breathing, easy fatigue, and headaches. She had been referred from a peripheral hospital as a case of thrombocytopenia, severe anemia, and anterior neck swelling. She was diagnosed with Graves' disease 2 years ago, became euthyroid during treatment, but defaulted. On further examination and investigation, she was diagnosed with immune thrombocytopenic purpura and was also found to have elevated free T3 and T4, and suppressed thyroid stimulating hormone. She also had high thyroid autoantibodies. She was initially started on oral prednisolone but there was no stabilization of platelets until methimazole was introduced, which improved and normalized her platelet count. CONCLUSION: The association of Graves' disease with immune thrombocytopenic purpura, though documented, is uncommon, and very few cases have been reported thus far. There have not been any reported cases in Ghana or Sub-Saharan Africa and hence, clinicians should be aware of this association when investigating immune thrombocytopenic purpura and should consider Graves' disease as a possible cause. From this study, we observed that there was no improvement in platelet count following the use of corticosteroid therapy until methimazole was started.


Subject(s)
Graves Disease , Purpura, Thrombocytopenic, Idiopathic , Thrombocytopenia , Humans , Female , Adult , Purpura, Thrombocytopenic, Idiopathic/complications , Purpura, Thrombocytopenic, Idiopathic/diagnosis , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Methimazole/therapeutic use , Ghana , Graves Disease/complications , Graves Disease/drug therapy , Thrombocytopenia/complications
17.
Am J Case Rep ; 24: e938730, 2023 Apr 23.
Article in English | MEDLINE | ID: covidwho-2300844

ABSTRACT

BACKGROUND Vaccine-induced thrombosis and thrombocytopenia is a rare immune disorder documented after adenoviral vector ChAdOx1 nCOV-19 (AstraZeneca) and Ad26.COV2-S (Janssen) vaccine administration against severe acute respiratory syndrome coronavirus 2. It is a rare adverse effect with an incidence of 1 case per 100 000 exposures. The disorder represents altered immune response with proliferation of antibodies that bind to platelet factor 4 (PF4), leading to formation of thrombi and consumptive coagulopathy. Thrombosis combined with thrombocytopenia generally occurs in the first month following vaccination and can lead to fatal outcome, even in young, previously healthy individuals. These young adults ultimately may become solid organ donors. The main concerns with vaccine-induced thrombosis and thrombocytopenia solid organ donors are anti-PF4 antibodies transmission potential, risk of early major graft thrombosis, and serious bleeding. CASE REPORT In our center, 2 kidney transplantations were performed from a single brain-dead vaccine-induced thrombosis and thrombocytopenia donor following Ad26.COV2-S COVID-19 (Janssen) vaccine in October 2021, which represents the first 2 cases of kidney transplantation from a deceased vaccine-induced thrombosis and thrombocytopenia donor after immunization with Ad26.COV2-S (Janssen) vaccine. Both recipients were closely monitored in the early post-transplantation period and after discharge from the hospital. To date, both recipients have a good functioning allograft, without any evidence of vaccine-induced thrombosis and thrombocytopenia transmission. CONCLUSIONS Our results are consistent with those of previously published cases of successful vaccine-induced thrombosis and thrombocytopenia donor solid organ transplantation. Kidney allografts transplanted from vaccine-induced thrombosis and thrombocytopenia donors can have a good overall function with favorable outcomes.


Subject(s)
COVID-19 , Kidney Transplantation , Thrombocytopenia , Thrombosis , Young Adult , Humans , COVID-19 Vaccines/adverse effects , Ad26COVS1 , Kidney Transplantation/adverse effects , ChAdOx1 nCoV-19 , Tissue Donors , Thrombocytopenia/chemically induced , Thrombosis/etiology
18.
Best Pract Res Clin Haematol ; 35(3): 101381, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-2297446

ABSTRACT

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is primarily a complication of adenoviral vector-based covid-19 vaccination. In VITT, thrombocytopenia and thrombosis mediated by anti-platelet factor 4 (PF4) antibodies can be severe, often characterized by thrombosis at unusual sites such as the cerebral venous sinus and splanchnic circulation. Like in heparin-induced thrombocytopenia (HIT) and spontaneous HIT, VITT antibodies recognize PF4-polyanion complexes and activate PF4-treated platelets but additionally bind to un-complexed PF4, a critical finding that could be leveraged for more specific detection of VITT. Intravenous immunoglobulin and non-heparin-based anticoagulation remain the mainstay of treatment. Second dose/boosters of mRNA covid-19 vaccines appear safe in patients with adenoviral vector-associated VITT. Emerging data is consistent with the possibility that ultra-rare cases of VITT may be seen in the setting of mRNA and virus-like particle (VLP) technology-based vaccinations and until more data is available, it is prudent to consider VITT in the differential diagnosis of all post-vaccine thrombosis and thrombocytopenia reactions.


Subject(s)
COVID-19 , Thrombocytopenia , Vaccines , Humans , COVID-19 Vaccines/adverse effects , Thrombocytopenia/chemically induced
19.
Vaccine ; 41(20): 3285-3291, 2023 05 11.
Article in English | MEDLINE | ID: covidwho-2293544

ABSTRACT

BACKGROUND: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but established complication of 1st dose ChAdOx1 nCoV19 vaccination (AZD1222), however this complication after dose 2 remains controversial. OBJECTIVES: To describe the clinicopathological features of confirmed cases of VITT post dose 2 AZD1222 vaccination in Australia, and to compare this cohort to confirmed cases of VITT post 1st dose. METHODS: Sequential cases of clinically suspected VITT (thrombocytopenia, D-Dimer > 5x upper limit normal and thrombosis) within 4-42 days of dose 2 AZD1222 referred to Australia's centralised testing centre underwent platelet activation confirmatory testing in keeping with the national diagnostic algorithm. Final classification was assigned after adjudication by an expert advisory committee. Descriptive statistics were performed on this cohort and comparative analyses carried out on confirmed cases of VITT after 1st and 2nd dose AZD1222. RESULTS: Of 62 patients referred, 15 demonstrated presence of antibody mediated platelet activation consistent with VITT after dose 2 AZD1222. Four were immunoassay positive. Median time to presentation was 13 days (range 1-53) platelet count 116x10^9/L (range 63-139) and D-dimer elevation 14.5xULN (IQR 11, 26). Two fatalities occurred. In each, the dosing interval was less than 30 days. In comparison to 1st dose, dose 2 cases were more likely to be male (OR 4.6, 95% CI 1.3-15.8, p = 0.03), present with higher platelet counts (p = 0.05), lower D-Dimer (p = 01) and less likely to have unusual site thromboses (OR 0.14, 95% CI 0.04-0.28, p = 0.02). CONCLUSIONS: VITT is a complication of dose 2 AZD1222 vaccination. Whilst clinicopathological features are less severe, fatalities occurred in patients with concomitant factors.


Subject(s)
COVID-19 Vaccines , Purpura, Thrombocytopenic, Idiopathic , Thrombocytopenia , Thrombosis , Female , Humans , Male , Antibodies , ChAdOx1 nCoV-19 , Purpura, Thrombocytopenic, Idiopathic/chemically induced , Thrombocytopenia/chemically induced , Vaccination/adverse effects , Vaccines , COVID-19 Vaccines/adverse effects
20.
N Engl J Med ; 384(22): 2092-2101, 2021 06 03.
Article in English | MEDLINE | ID: covidwho-2283980

ABSTRACT

BACKGROUND: Several cases of unusual thrombotic events and thrombocytopenia have developed after vaccination with the recombinant adenoviral vector encoding the spike protein antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (ChAdOx1 nCov-19, AstraZeneca). More data were needed on the pathogenesis of this unusual clotting disorder. METHODS: We assessed the clinical and laboratory features of 11 patients in Germany and Austria in whom thrombosis or thrombocytopenia had developed after vaccination with ChAdOx1 nCov-19. We used a standard enzyme-linked immunosorbent assay to detect platelet factor 4 (PF4)-heparin antibodies and a modified (PF4-enhanced) platelet-activation test to detect platelet-activating antibodies under various reaction conditions. Included in this testing were samples from patients who had blood samples referred for investigation of vaccine-associated thrombotic events, with 28 testing positive on a screening PF4-heparin immunoassay. RESULTS: Of the 11 original patients, 9 were women, with a median age of 36 years (range, 22 to 49). Beginning 5 to 16 days after vaccination, the patients presented with one or more thrombotic events, with the exception of 1 patient, who presented with fatal intracranial hemorrhage. Of the patients with one or more thrombotic events, 9 had cerebral venous thrombosis, 3 had splanchnic-vein thrombosis, 3 had pulmonary embolism, and 4 had other thromboses; of these patients, 6 died. Five patients had disseminated intravascular coagulation. None of the patients had received heparin before symptom onset. All 28 patients who tested positive for antibodies against PF4-heparin tested positive on the platelet-activation assay in the presence of PF4 independent of heparin. Platelet activation was inhibited by high levels of heparin, Fc receptor-blocking monoclonal antibody, and immune globulin (10 mg per milliliter). Additional studies with PF4 or PF4-heparin affinity purified antibodies in 2 patients confirmed PF4-dependent platelet activation. CONCLUSIONS: Vaccination with ChAdOx1 nCov-19 can result in the rare development of immune thrombotic thrombocytopenia mediated by platelet-activating antibodies against PF4, which clinically mimics autoimmune heparin-induced thrombocytopenia. (Funded by the German Research Foundation.).


Subject(s)
Autoantibodies/blood , COVID-19 Vaccines/adverse effects , Platelet Factor 4/immunology , Thrombocytopenia/etiology , Thrombosis/etiology , Adult , Autoimmune Diseases/etiology , Blood Chemical Analysis , ChAdOx1 nCoV-19 , Disseminated Intravascular Coagulation/etiology , Enzyme-Linked Immunosorbent Assay , Fatal Outcome , Female , Humans , Intracranial Hemorrhages/etiology , Male , Middle Aged , Platelet Activation , Thrombocytopenia/immunology , Thrombosis/immunology , Young Adult
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