Vaccine-induced immune thrombotic thrombocytopenia after vaccination against Covid-19: A clinical dilemma for clinicians and patients.

The coronavirus disease 2019 (Covid-19) pandemic has had devastating effects on public health worldwide, but the deployment of vaccines for Covid-19 protection has helped control the spread of SARS Coronavirus 2 (SARS-CoV-2) infection where they are available. The common side effects reported following Covid-19 vaccination were mostly self-restricted local reactions that resolved quickly. Nevertheless, rare vaccine-induced immune thrombotic thrombocytopenia (VITT) cases have been reported in some people being vaccinated against Covid-19. This review summarizes the thromboembolic events after Covid-19 vaccination and discusses its molecular mechanism, incidence rate, clinical manifestations and differential diagnosis. Then, a step-by-step algorithm for diagnosing such events, along with a management plan, are presented. In conclusion, considering the likeliness of acquiring severe SARS-CoV-2 infection and its subsequent morbidity and mortality, the benefits of vaccination outweigh its risks. Hence, if not already initiated, all governments should begin an effective and fast public vaccination plan to overcome this pandemic.

Late-Onset Vaccine-Induced Immune Thombotic Thrombocytopenia (VITT) with Cerebral Venous Sinus Thrombosis.

OBJECTIVES: Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare complication after adenoviral vector vaccination against COVID-19 reported up to 24 days after ChAdOx1 nCOV-19 (AZD1222) vaccination. This report describes a case with a significantly later onset of VITT with cerebral venous sinus thrombosis. CASE DESCRIPTION: We report a 42-year-old woman presenting to the emergency department 53 days after AZD1222 vaccination with sudden onset sensory aphasia and an 18-day history of headache. Cranial computed tomography (CT) showed acute intracranial hemorrhage and CT venogram demonstrated thrombosis of the left vein of Labbé and transverse and sigmoid sinus. D-dimers were elevated and despite a normal platelet count, platelet-activating anti-PF4 antibody testing was positive, confirming the diagnosis of VITT. The patient was treated with intravenous immunoglobulins and argatroban, and was discharged without any neurological deficit on day 12. CONCLUSION: Our report of VITT with symptom onset on day 35 and diagnosis of cerebral sinuous thrombosis on day 53 after AZD1222 vaccination significantly enhances the time window during which VITT may occur.

Case of Suspected SARS-CoV-2 Vaccine-induced Immune Thrombotic Thrombocytopenia: Dilemma for Organ Donation.

Several vaccines were developed and rolled out at an unprecedented rate in response to the coronavirus disease-2019 (COVID-19) pandemic. Most vaccines approved globally by WHO for emergency use to combat the pandemic were deemed remarkably effective and safe. Despite the safety, rare incidences of vaccine-induced thrombosis and thrombocytopenia (VITT), sometimes known as vaccine-induced prothrombotic thrombocytopenia (VIPIT), have been reported. We report a case of young female with prothrombotic conditions and suspected VITT who developed catastrophic cerebral venous sinus thrombosis (CVST) and progressed to brain death. We highlight hurdles of organ retrieval from a brain-dead patient with suspected SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia. There is limited data and lack of substantial evidence regarding transplantation of organs from brain-dead patients with suspected VITT. How to cite this article: Tiwari AM, Zirpe KG, Gurav SK, Bhirud LB, Suryawanshi RS, Kulkarni SS. Case of Suspected SARS-CoV-2 Vaccine-induced Immune Thrombotic Thrombocytopenia: Dilemma for Organ Donation. Indian J Crit Care Med 2022;26(4):514-517.

Possible COVID-19 MRNA Vaccine-Induced Case of Unilateral Central Retinal Vein Occlusion.

PURPOSE: To report a case of a patient with central retinal vein occlusion (CRVO), 2 weeks after the first dose of a COVID-19 mRNA vaccine. RESULTS: A 35-year-old man presented with decreased vision on his right eye, 2 weeks after receiving the first dose of COVID-19 mRNA vaccine. During examination, signs of right CRVO were found. We started general checkup of the patient, extended with laboratory tests specific for VIPIT. No exact cause of the thromboembolic episode could be documented. With the applied therapy, symptoms resolved completely. CONCLUSION: CRVO after COVID-19 mRNA vaccination is reported only in one case in the literature. In our case, the young age of the patient, the close onset of the symptoms to the vaccination and the negative systemic, immunologic and hematologic tests are suggesting a vaccine-induced thrombotic mechanism. We propose further investigation of vaccine-induced thrombotic mechanisms and also close follow of the reported cases.

Thromboembolism after Astra Zeneca COVID-19 vaccine: Not always PF4- antibody mediated.

Cases of thromboembolic events in 2021 flared up the discussion about the safety of Astra Zeneca's AZD1222 vaccine. We hereby report three cases of pulmonary embolism (PE), one case of extended portal vein thrombosis, and one case of combined portal vein thrombosis and PE within 2 weeks after vaccination with the Astra Zeneca AZD1222 vaccine in a 60-year-old, a 50-year old, a 33-year-old, a 30-year old, and a 40-year-old male in that year. All patients were healthy before. In three patients, we observed thrombocytopenia and to some extent unusually low antibody levels for the Spike Protein (S-protein), while the other two had normal thrombocyte counts. Only one patient had anti-platelet factor 4 (PF4)-antibodies detectable as it has been described in the "heparin-induced thrombocytopenia (HIT)-like" disease of "vaccine-induced prothrombotic immune thrombocytopenia" (VIPIT) and we therefore assume that heterogeneous mechanisms led to PE. Therefore, we advise to collect and report more cases, in order to determine the age-related risks of vaccination balanced against the benefits of immunity to SARS-COV-2 for the AZD1222 vaccine in order to gain knowledge for the next pandemic.

Branch retinal vein occlusion following ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccine.

PURPOSE: To present a case of branch retinal vein occlusion (BRVO) following ChAdOx1 nCoV-19 (Oxford-AstraZeneca) Vaccine. METHODS: Case report. RESULTS: A 60-year old otherwise healthy Caucasian male, presented to the ophthalmology emergency clinic complaining of sudden, painless vision loss in his right eye of 24 h" duration. The patient had received Vaxveria seven days prior. The clinical and fundus examination of the right eye established the diagnosis of BRVO. CONCLUSION: The present case descibes the occurrence of BRVO soon after the vaccination with the Oxford-AstraZeneca vaccine. The close temporal relationship between the BRVO incidence and the vaccination is reinforced by the lack of othe subjective cause to justify the episode.

Cerebral Sinus Thrombosis and Immune Thrombocytopenia Post COVID-19 Vaccination: A Case Report and Narrative Review.

Vaccine-induced immune thrombocytopenia and thrombosis (VITT) following the adenoviral vector COVID-19 vaccine is a rare adverse event. Although the risk of VITT following the COVID-19 vaccine appears to be low, early diagnosis and management can be lifesaving. We present a case of VITT in a young female who presented with persistent headaches and fevers followed by anisocoria and right-sided hemiplegia. Initial imaging was unremarkable, and labs showed thrombocytopenia and elevated d-dimers. Repeat imaging revealed thrombosis in the left transverse and superior sagittal sinuses, and she was diagnosed with VITT. She received combined treatment with intravenous immunoglobulins and systemic anticoagulation, resulting in an increased platelet count and resolution of her neurological symptoms.

An Unusual Case of Combined Thrombosis and Amegakaryocytopenia Resembling Thrombosis With Thrombocytopenia Syndrome Following COVID-19 Infection in an Unvaccinated Patient.

As a global community, we have learned that the manifestations of severe acute respiratory syndrome coronavirus 2 (SAR-CoV-2), infection, or coronavirus disease 2019 (COVID-19), extends far beyond respiratory compromise. Thrombocytopenia is thought to occur secondary to increased platelet consumption. Platelet activation and platelet-mediated immune inflammation contribute towards the thromboembolic complications seen in COVID-19 patients. In this report, the authors present the unusual case of a 75-year-old female with a history of COVID-19 infection who presented with a transient ischemic attack, thrombocytopenia, and amegakaryocytopenia.

COVID-19 Vaccine-Induced Pro-thrombotic Immune Thrombocytopenia (VIPIT): State of the Art.

In 2020, as the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic spread rapidly throughout the world, scientists worked relentlessly to develop and test the safety and effectiveness of potential vaccines. Usually, the vaccine development process involves years of investigation and testing prior to gaining approval for use in practice. A pathogenic PF4-dependent syndrome, unrelated to the use of heparin therapy, may be manifested following the administration of viral vector vaccines. It leads to severe clot formation at unusual sites approximately in 1 out of 110.000 vaccinated persons. This side effect, although rare, represents a newly devastating clotting phenomenon manifested in otherwise healthy young adults, who are often female. An in-depth description of the specific biological mechanisms implicated in the syndrome is here summarized.

Transjugular intrahepatic portosystemic shunt, local thrombaspiration, and lysis for management of fulminant portomesenteric thrombosis and atraumatic splenic rupture due to vector-vaccine-induced thrombotic thrombocytopenia: a case report.

INTRODUCTION: Recombinant adenoviral vector vaccines against severe acute respiratory syndrome coronavirus 2 have been observed to be associated with vaccine-induced immune thrombotic thrombocytopenia. Though vaccine-induced immune thrombotic thrombocytopenia is a rare complication after vaccination with recombinant adenoviral vector vaccines, it can lead to severe complications. In vaccine-induced immune thrombotic thrombocytopenia, the vector vaccine induces heparin-independent production of platelet factor 4 autoantibodies, resulting in platelet activation and aggregation. Therefore, patients suffering from vaccine-induced immune thrombotic thrombocytopenia particularly present with signs of arterial or venous thrombosis, often at atypical sites, but also signs of bleeding due to disseminated intravascular coagulation and severe thrombocytopenia. We describe herein a rare case of fulminant portomesenteric thrombosis and atraumatic splenic rupture due to vaccine-induced immune thrombotic thrombocytopenia. This case report presents the diagnosis and treatment of a healthy 29-year-old male Caucasian patient suffering from an extended portomesenteric thrombosis associated with atraumatic splenic rupture due to vaccine-induced immune thrombotic thrombocytopenia after the first dose of an adenoviral vector vaccine against severe acute respiratory syndrome coronavirus 2 [ChAdOx1 nCoV-19 (AZD1222)]. Therapeutic management of vaccine-induced immune thrombotic thrombocytopenia initially focused on systemic anticoagulation avoiding heparin and the application of steroids and intravenous immune globulins as per the recommendations of international societies of hematology and hemostaseology. Owing to the atraumatic splenic rupture and extended portomesenteric thrombosis, successful management of this case required splenectomy with additional placement of a transjugular intrahepatic portosystemic shunt to perform local thrombaspiration, plus repeated local lysis to reconstitute hepatopetal blood flow. CONCLUSION: The complexity and wide spectrum of the clinical picture in patients suffering from vaccine-induced immune thrombotic thrombocytopenia demand an early interdisciplinary diagnostic and therapeutic approach. Severe cases of portomesenteric thrombosis in vaccine-induced immune thrombotic thrombocytopenia, refractory to conservative management, may require additional placement of a transjugular intrahepatic portosystemic shunt, thrombaspiration, thrombolysis, and surgical intervention for effective management.

Post COVID-19 Vaccine Related Cerebral Venous Sinus Thrombosis and Thrombocytopenia.

During the height of the COVID-19 pandemic, there was great relief with the global mass rollout of the Covid-19 vaccination programs. While they have proven to be safe and effective, the gradual emergence of side effects to the vaccines has undermined public trust in the vaccination program and, whilst rare, can lead to significant morbidity and mortality. The most serious was the emergence of vaccine-induced immune thrombocytopenia and thrombosis (VITT), also known as thrombosis with thrombocytopenia syndrome (TTS) or vaccine-induced prothrombotic immune thrombocytopenia (VIPIT). VITT is a serious and often fatal complication of some COVID vaccines that seem more prevalent in younger people and women. We present a case of a 48-year-old woman who presented with VITT following COVID vaccination.

Models for SARS-CoV-2 associated thrombocytopenia associated with hemophagocytic histiocytes.

A subset of COVID-19 patients is experiencing secondary immune thrombocytopenia, also called immune thrombocytopenic purpura (ITP) or secondary hemophagocytic lymphohistiocytosis (HLH). The pathogenesis of SARS-CoV-2 associated thrombocytopenia is unknown. Very rare cases of vaccine induced prothrombotic immune thrombocytopenia (VIPIT) are occurring associated with COVID-19 vaccines. COVID-19 VIPIT is associated with autoantibodies targeting platelet factor 4 (PF4) for COVID-19 adenovirus vaccines. Herein, four models for hemophagocytic histocytes contributions to the etiology of thrombocytopenia associated with SARS-CoV-2 are proposed. One of the models proposes potential involvement of hemophagocytic histocytes targeting platelets bound by autoantibodies consistent with observed PF4 autoantibodies in COVID-19 VIPIT.

Thrombosis with Thrombocytopenia Syndrome (TTS) following AstraZeneca ChAdOx1 nCoV-19 (AZD1222) COVID-19 vaccination - A risk-benefit analysis for people < 60 years in Australia.

The AstraZeneca ChAdOx1 nCoV-19 (AZD1222) vaccine is associated with Thrombosis with Thrombocytopenia Syndrome (TTS) in 3/100,000 vaccinations with high fatality rates reported in many countries. We conducted a risk-benefit analysis for Australians aged 18-59 years, comparing the risk of vaccination versus infection, and rate of TTS to other vaccines which prompted policy change following rare adverse events - rotavirus, smallpox and oral polio vaccines. COVID-19 deaths over 12 months range from 0 to 417 in current and future worst case scenarios. In the past 15 months 20 COVID-19 deaths occurred in people < 60 years compared to 890 deaths over 60 years. The estimated possible number of TTS cases is 347, with vaccine-related deaths ranging from 17 to 153if 80% of adults 18-59 years are vaccinated. The reported rate of TTS is in the same range as rare but serious adverse events associated with other vaccines that have been subject to policy change. In Australia, the potential risks of the AZD1222 vaccine in younger adults, who are at low risk of dying from COVID-19, may outweigh the benefits.

Successful treatment of vaccine-induced prothrombotic immune thrombocytopenia (VIPIT).

Cases of unusual thrombosis and thrombocytopenia after administration of the ChAdOx1 nCoV-19 vaccine (AstraZeneca) have been reported. The term vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) was coined to reflect this new phenomenon. In vitro experiments with VIPIT patient sera indicated that high-dose intravenous immunoglobulins (IVIG) competitively inhibit the platelet-activating properties of ChAdOx1 nCoV-19 vaccine induced antibodies. Here, we report a case of a 62-year-old woman who had received this vaccine and developed VIPIT. She visited the emergency ward because of petechiae and hematomas. In the laboratory work-up, thrombocytopenia, low fibrinogen, elevated D-dimer, and positivity in the platelet factor 4/heparin-enzyme-immunoassay were present. Signs and symptoms of thrombosis were absent. Upon immediate therapy with non-heparin anticoagulation, high-dose IVIG, and prednisolone, laboratory parameters steadily improved and the patient was discharged from hospital without thrombotic complications. We conclude that early initiation of VIPIT treatment results in a swift response without thrombotic complications.

COVID-19 vaccine-induced immune thrombotic thrombocytopenia: A review of the potential mechanisms and proposed management.

With over 600 million coronavirus (COVID-19) vaccine doses administered globally, adverse events are constantly monitored. Recently however, reports of thrombosis and thrombocytopenia following vaccination with the ChAdOx1 nCoV-19 vaccine have emerged. This paper aims to review the available literature and guidelines pertaining to vaccine-induced immune thrombotic thrombocytopenia (VITT) and the proposed guidelines, while offering a potential approach that unifies the available evidence. While the risk of VITT remains extremely low and the benefits outweigh the risks, experimental studies are needed to clarify the pathophysiology behind VITT and possibly decrease the risk of thrombosis and other adverse events occurring. However, treatment should not be delayed in suspected cases, and IV immunoglobulin and non-heparin anticoagulation should be initiated.

Vaccine induced thrombotic thrombocytopenia: The shady chapter of a success story.

The recognition of the rare but serious and potentially lethal complication of vaccine induced thrombotic thrombocytopenia (VITT) raised concerns regarding the safety of COVID-19 vaccines and led to the reconsideration of vaccination strategies in many countries. Following the description of VITT among recipients of adenoviral vector ChAdOx1 vaccine, a review of similar cases after Ad26.COV2·S vaccination gave rise to the question whether this entity may constitute a potential class effect of all adenoviral vector vaccines. Most cases are females, typically younger than 60 years who present shortly (range: 5-30 days) following vaccination with thrombocytopenia and thrombotic manifestations, occasionally in multiple sites. Following initial incertitude, concrete recommendations to guide the diagnosis (clinical suspicion, initial laboratory screening, PF4-polyanion-antibody ELISA) and management of VITT (non-heparin anticoagulants, corticosteroids, intravenous immunoglobulin) have been issued. The mechanisms behind this rare syndrome are currently a subject of active research and include the following: 1) production of PF4-polyanion autoantibodies; 2) adenoviral vector entry in megacaryocytes and subsequent expression of spike protein on platelet surface; 3) direct platelet and endothelial cell binding and activation by the adenoviral vector; 4) activation of endothelial and inflammatory cells by the PF4-polyanion autoantibodies; 5) the presence of an inflammatory co-signal; and 6) the abundance of circulating soluble spike protein variants following vaccination. Apart from the analysis of potential underlying mechanisms, this review aims to synopsize the clinical and epidemiologic features of VITT, to present the current evidence-based recommendations on diagnostic and therapeutic work-up of VITT and to discuss new dilemmas and perspectives that emerged after the description of this entity.