Thrombocytopenia and Intracranial Venous Sinus Thrombosis after “COVID-19 Vaccine AstraZeneca” Exposure

Background: As of 8 April 2021, a total of 2.9 million people have died with or from the coronavirus infection causing COVID-19 (Corona Virus Disease 2019). On 29 January 2021, the European Medicines Agency (EMA) approved a COVID-19 vaccine developed by Oxford University and AstraZeneca (AZD1222, ChAdOx1 nCoV-19, COVID-19 vaccine AstraZeneca, Vaxzevria, Covishield). While the vaccine prevents severe course of and death from COVID-19, the observation of pulmonary, abdominal, and intracranial venous thromboembolic events has raised concerns. Objective: To describe the clinical manifestations and the concerning management of patients with cranial venous sinus thrombosis following first exposure to the “COVID-19 vaccine AstraZeneca”. Methods: Patient files, laboratory findings, and diagnostic imaging results, and endovascular interventions of three concerning patients were evaluated in retrospect. Results: Three women with intracranial venous sinus thrombosis after their first vaccination with “COVID-19 vaccine AstraZeneca” were encountered. Patient #1 was 22 years old and developed headaches four days after the vaccination. On day 7, she experienced a generalized epileptic seizure. Patient #2 was 46 years old. She presented with severe headaches, hemianopia to the right, and mild aphasia 13 days after the vaccination. MRI showed a left occipital intracerebral hemorrhage. Patient #3 was 36 years old and presented 17 days after the vaccination with acute somnolence and right-hand hemiparesis. The three patients were diagnosed with extensive venous sinus thrombosis. They were managed by heparinization and endovascular recanalization of their venous sinuses. They shared similar findings: elevated levels of D-dimers, platelet factor 4 antiplatelet antibodies, corona spike protein antibodies, combined with thrombocytopenia. Under treatment with low-molecular-weight heparin, platelet counts normalized within several days. Conclusion: Early observations insinuate that the exposure to the “COVID-19 vaccine AstraZeneca” might trigger the expression of antiplatelet antibodies, resulting in a condition with thrombocytopenia and venous thrombotic events (e.g., intracranial venous sinus thrombosis). These patients’ treatment should address the thrombo-embolic manifestations, the coagulation disorder, and the underlying immunological phenomena.

Immune thrombocytopenia in a newborn – a clinical case in pediatrics

Annotation. The aim of the study was to analyze with the help of literature data the features of the clinical course of immune thrombocytopenia, to monitor the mechanisms of reactions, as well as to reproduce them on their own observation. Features of clinical course and differential diagnosis of immune thrombocytopenia are described. It is established that the main manifestation of this pathology is hemorrhagic syndrome, accompanied by skin hemorrhages, bleeding, possible hepatosplenomegaly, jaundice. Detection of antiplatelet antibodies is used to confirm the diagnosis.

HLA-associated antiplatelet antibodies. Literature review

В статье представлен литературный обзор изданий на тему: HLA-ассоциированные антитромбоцитарные антитела. Описывается роль HLA-антитромбоцитарных антител в развитии рефрактерности при трансфузиях тромбоконцентрата. Несмотря на совершенствование методов подготовки, хранения крови и ее компонентов, тщательное соблюдение правил переливания, к сожалению, посттрансфузионные гемолитические и негемолитические реакции и осложнения остаются частым явлением. При многократных переливаниях тромбоцитарной массы у некоторых пациентов может возникнуть рефрактерность к повторным трансфузиям тромбоцитов, связанная с развитием у них состояния аллоиммунизации. Успех заместительной терапии зависит от количества перелитых тромбоци тов и их функциональной полноценности. Эффективность переливания тромбоцитов оценивают по их приросту сразу после, через час и через сутки после переливания. На их прирост через сутки могут повлиять сопутствующие гематологические осложнения. Для минимизации риска развития рефрактерности к тромбоцитам донора и возникновения трансфузионных реакций и посттрансфузионных осложнений необходимо проводить подбор пар «донор-реципиент» с учетом оценки их совместимости по антигенам системы HLA по локусам А и В.

Features of pathogenetic mechanisms of the interaction of viruses and platelets in patients with immune thrombocytopenia (review of literature)

Annotation. One of the urgent interdisciplinar problems of modern medicine is to study the mechanisms of development of virus-induced thrombocytopenia in patients. The aim is to sum up current knowledge of viruses and platelets interaction, how viruses affect platelet and modulate adaptive immune response. A systematic review of the articles in the Pub Med database was conducted between 2007 and 2020, using search terms: platelets, thrombocytopenia, viral infection. Current data on the study of the mechanisms of platelet interaction with different types of viruses in immune thrombocytopenia in children were analyzed. We studied activation of platelets by a viral infection and how the immune response works. We know that the immune response is a cyclic multistage process involving T-lymphocytes, B-lymphocytes, macrophages, cytokines, Nk-cells. Antiplatelet antibodies are increase platelet clearance from the blood. The combination of antibodies with platelets leads to phagocytosis. In patients with immune thrombocytopenia ІgG antibodies are produced against GP/ІІ b/ІІІ or GP/І b/ІХ glycoproteins located on the platelet surface. In this situation it is possible to produce antibodies of other subclasses of ІgG, also a complement of fixing Іg G, rarelyІg А to other glycoprotein, or to other complexes Іb ІХ, Іа/ІІа. Since megakaryocytes express glycoprotein ІІb/ІІІа, Ів as well as other platelet antigens, they become a target for autoantibodies. Viruses can interact directly with platelets and megakaryocytes. In addition, platelets can be activated by viral antigen-antibody complexes and B- lymphocytes can produce antiplatelet antibodies. All of these processes are activate platelets and lead to increased consumption and remove of platelets, this causes hemorrhagic manifestation in patients.

Antiplatelet Antibodies Do Not Predict the Response to Intravenous Immunoglobulins during Immune Thrombocytopenia

Immune thrombocytopenia (ITP) is a rare autoimmune disease due to autoantibodies targeting platelet glycoproteins (GP). The mechanism of platelet destruction could differ depending on the specificity of antiplatelet antibodies: anti-GPIIb/IIIa antibodies lead to phagocytosis by splenic macrophages, in a Fcγ receptor (FcγR)-dependent manner while anti-GPIb/IX antibodies induce platelet desialylation leading to their destruction by hepatocytes after binding to the Ashwell–Morell receptor, in a FcγR-independent manner. Considering the FcγR-dependent mechanism of action of intravenous immunoglobulins (IVIg), we assumed that the response to IVIg could be less efficient in the presence of anti-GPIb/IX antibodies. We conducted a multicentric, retrospective study including all adult ITP patients treated with IVIg who had antiplatelet antibodies detected between January 2013 and October 2017. Among the 609 identified, 69 patients were included: 17 had anti-GPIb/IX antibodies and 33 had anti-GPIIb/IIIa antibodies. The response to IVIg was not different between the patients with or without anti-GPIb/IX (88.2% vs. 73.1%). The response to IVIg was better in the case of newly diagnosed ITP (odds ratio (OR) = 5.4 (1.2–24.7)) and in presence of anti-GPIIb/IIIa (OR = 4.82 (1.08–21.5)), while secondary ITP had a poor response (OR = 0.1 (0.02–0.64)). In clinical practice, the determination of antiplatelet antibodies is therefore of little value to predict the response to IVIg.