A case report of vaccine-induced immune thrombotic thrombocytopenia (VITT) with genetic analysis.

The emergence of the rare syndrome called vaccine-induced immune thrombocytopenia and thrombosis (VITT) after adenoviral vector vaccines, including ChAdOx1 nCov-19, raises concern about one's predisposing risk factors. Here we report the case of a 56-year-old white man who developed VITT leading to death within 9 days of symptom onset. He presented with superior sagittal sinus thrombosis, right frontal intraparenchymal hematoma, frontoparietal subarachnoid and massive ventricular hemorrhage, and right lower extremity arterial and venous thrombosis. His laboratory results showed elevated D-dimer, C-reactive protein, tissue factor, P-selectin (CD62p), and positive anti-platelet factor 4. The patient's plasma promoted higher CD62p expression in healthy donors' platelets than the controls. Genetic investigation on coagulation, thrombophilia, inflammation, and type I interferon-related genes was performed. From rare variants in European or African genomic databases, 68 single-nucleotide polymorphisms (SNPs) in one allele and 11 in two alleles from common SNPs were found in the patient genome. This report highlights the possible relationship between VITT and genetic variants. Additional investigations regarding the genetic predisposition of VITT are needed.

Icosapent ethyl (VASCEPA®) as treatment for post-acute sequelae of SARS CoV-2 (PASC) vaccine induced injury and infection.

OBJECTIVES: As the COVID-19 pandemic continues, a prolonged post-infectious syndrome or "long COVID" has been reported. This is a multi-organ post viral syndrome that persists well after infection. Currently, there is no available treatment. Emerging evidence credits this "long COVID" syndrome to ongoing inflammatory response following resolution of symptoms during infection. An omega-three fatty acid derivative used in the treatment of hypertriglyceridemia, Icosapent Ethyl (IPE, VASCEPA®/Epadel®), was previously shown to reduce cardiovascular risk, likely via immunomodulatory effects. This study aims to evaluate the effectiveness of Icosapent Ethyl. METHODS: Following previous publications in treatment of severe acute COVID-19, we analyze two case studies of adults treated with Icosapent Ethyl. RESULTS: After experiencing the symptoms of Long Covid, both individuals analyzed across two case studies experiences a resolution of symptoms after treatment with Icosapent Ethyl. CONCLUSION: After review and analysis we conclude that Icosapent Ethyl may have been a determining factor in Long COVID symptom resolution and should be studied further.

Aortic thrombosis and acute limb ischemia after ChAdOx1 nCov-19 (Oxford-AstraZeneca) vaccination: a case of vaccine-induced thrombocytopenia and thrombosis (VITT).

INTRODUCTION: Vaccine-induced thrombocytopenia and thrombosis (VITT) is a rare but devastating adverse event associated with the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) adenoviral vaccine against the Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2). METHODS: A 49-year-old man presented to the emergency department with acute right limb ischemia (Rutherford IIB) nine days after his ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccination. CT angiography revealed significant aortic thrombosis and right femoral artery occlusion. Severe thrombocytopenia (platelet count of 23 × 103/µL), promptly elevated D-dimers (37937 ng/mL) and a reduced fibrinogen level (176 mg/dL) were remarkable. ELISA testing for anti-PF4 antibodies confirmed the diagnosis of VITT. RESULTS: An emergency revascularization of the right leg was provided via thrombectomy. High-dose intravenous immunoglobulins were administered whereafter the platelet count restored gradually. Therapeutic anticoagulation was progressively started. The postoperative course was uneventful and follow-up imaging after four weeks showed an almost complete resolution of the significant aortic thrombosis. CONCLUSION: Early recognition and appropriate counseling of VITT is advocated to pursue a good clinical outcome. Our patient presenting with severe aortic thrombosis and acute limb ischemia was successfully treated by a vascular thrombectomy along with intravenous immunoglobulins and anticoagulation therapy as the mainstay therapy.

Whole Blood Procoagulant Platelet Flow Cytometry Protocol for Heparin-Induced Thrombocytopenia (HIT) and Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT) Testing.

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.

Multiple Electrode Aggregometry (Multiplate): Functional Assay for Vaccine-Induced (Immune) Thrombotic Thrombocytopenia (VITT).

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.

Serotonin Release Assay: Functional Assay for Heparin- and Vaccine-Induced (Immune) Thrombotic Thrombocytopenia.

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.

Heparin-Induced Thrombotic Thrombocytopenia (HITT) and Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT): Similar but Different.

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.

Covax-19/Spikogen: The first exclusively Australian-developed human vaccine in four decades

Introduction/Aim: The development of safe and effective vaccines is crucial to conquering the COVID-19 pandemic. Recombinant proteins represent the best understood and reliable approach to pandemic vaccine delivery with well-established safety;however, they face challenges in design, structural characterisation, manufacture, potency testing and ensuring adequate immunogenicity. Method(s): Our team used in silico structural modelling to design a vaccine based on a stabilised spike protein extracellular domain (ECD). The insect cell expressed recombinant spike ECD was formulated with Vaxine's proprietary Advax-CpG55.2 adjuvant. Result(s): The vaccine known as Covax-19 or SpikoGen induced high titers of antibody and memory T-cells which translated to protection against SARS-CoV-2 infection in hamsters, ferrets, and aged monkeys. Despite numerous challenges along the journey, clinical trials in Iran during a major wave of delta variant infection confirmed SpikoGen vaccine was 78% effective in reducing risk of severe disease and with no evidence of vaccine-associated thrombosis, myocarditis, or sudden death, receiving marketing approval under emergency use authorisation in Iran on 6 October 2021. This made it the first recombinant spike-protein vaccine in the world to be approved, and the first Australian-developed human vaccine to receive marketing approval in four decades. Since approval millions of doses have been administered and additional trials in Australia and Iran have confirmed its effectiveness as a booster to prevent waning immunity, as well as its safety and effectiveness in children from the age of 5 years. The ongoing Australian and overseas clinical trial program is focussed on gaining better understanding the effect of dosing intervals on vaccine immunogenicity, gathering additional data on use as a booster, and development of new variant formulations. Conclusion(s): Covax-19/Spikogen is safe and effective adjuvanted recombinant protein vaccine.

On Immunological Studies at Sirius University of Science and Technology.

This short report summarizes the results of recent immunological studies performed at new Sirius University of Science and Technology. The report focuses on studying the features of the immune response to vaccination and revaccination against SARS-CoV-2, as well as on a search of potential agents to prevent infection with this virus.

Spectrum of Serious Neurological and Psychiatric Adverse Events in Indian COVID-19 Vaccine Recipients: A Systematic Review of Case Reports and Case Series.

Indian data regarding serious neurological and psychiatric adverse events, following coronavirus disease 2019 (COVID-19) vaccination, are lacking. We, therefore, systematically evaluated cases of post-vaccinal serious neurological and psychiatric adverse reactions published from India. A systematic review of cases published from India, which were archived in PubMed, Scopus, and Google Scholar databases, was performed; pre-print databases along with ahead-of-print contents were searched in addition. Retrieved articles, as on June 27, 2022, were evaluated following PRISMA guidelines. EndNote 20 web tool was used to make a PRISMA flow chart. Individual patients' data were compiled in a tabular form. The protocol of the systematic review was registered with PROSPERO (CRD42022324183). A total of 64 records describing 136 instances of serious neurological and psychiatric adverse events were identified. More than 50% (36/64) reports were from the following four states, namely, Kerala, Uttar Pradesh, New Delhi, and West Bengal. The mean age of persons developing these complications was 44.89 ± 15.77 years. In the majority, adverse events occurred within 2 weeks of administration of the first dose of COVISHIELD vaccine. Immune-mediated central nervous system (CNS) disorders were identified in 54 instances. Guillain-Barre syndrome and other immune-mediated peripheral neuropathies were reported in 21 cases. Post-vaccinal herpes zoster was recorded in 31 vaccine recipients. Psychiatric adverse events were recorded in six patients. In Indian recipients of COVID-19 vaccine, a variety of serious neurological complications were reported. The overall risk appears minuscule. Immune-mediated central and peripheral neuronal demyelinations were the most frequently reported post-vaccinal adverse events. A large number of cases of herpes zoster have also been reported. Immune-mediated disorders responded well to immunotherapy.

Thrombotic and Thromboembolic Complications After Vaccination Against COVID-19: A Systematic Review.

Thromboembolic complications after the COVID-19 vaccination have been reported from all over the world. We aimed to identify the thrombotic and thromboembolic complications that can arise after receiving various types of COVID-19 vaccines, their frequency, and distinguishing characteristics. Articles published in Medline/PubMed, Scopus, EMBASE, Google Scholar, EBSCO, Web of Science, the Cochrane Library, the CDC database, the WHO database, ClinicalTrials.gov, and servers like medRxiv.org and bioRxiv.org, as well as the websites of several reporting authorities between December 1, 2019, and July 29, 2021, were searched. Studies were included if they reported any thromboembolic complications post-COVID-19 vaccination and excluded editorials, systematic reviews, meta-analyses, narrative reviews, and commentaries. Two reviewers independently extracted the data and conducted the quality assessment. Thromboembolic events and associated hemorrhagic complications after various types of COVID-19 vaccines, their frequency, and distinguishing characteristics were assessed. The protocol was registered at PROSPERO (ID-CRD42021257862). There were 59 articles, enrolling 202 patients. We also studied data from two nationwide registries and surveillance. The mean age of presentation was 47 ± 15.5 (mean ± SD) years, and 71.1% of the reported cases were females. The majority of events were with the AstraZeneca vaccine and with the first dose. Of these, 74.8% were venous thromboembolic events, 12.7% were arterial thromboembolic events, and the rest were hemorrhagic complications. The most common reported event was cerebral venous sinus thrombosis (65.8%), followed by pulmonary embolism, splanchnic vein thrombosis, deep vein thrombosis, and ischemic and hemorrhagic stroke. The majority had thrombocytopenia, high D-dimer, and anti-PF4 antibodies. The case fatality rate was 26.5%. In our study, 26/59 of the papers were of fair quality. The data from two nationwide registries and surveillance revealed 6347 venous and arterial thromboembolic events post-COVID-19 vaccinations. COVID-19 vaccinations have been linked to thrombotic and thromboembolic complications. However, the benefits far outweigh the risks. Clinicians should be aware of these complications because they may be fatal and because prompt identification and treatment can prevent fatalities.

Immune Thrombocytopenia Following Booster Dose of the Moderna mRNA-1273 Vaccine.

Vaccine-mediated immune thrombocytopenia, although previously reported, is considered exceedingly rare. The probability of the incidence of profound thrombocytopenia following the COVID-19 mRNA-based vaccine has been less elucidated. We present the case of an 81-year-old female patient who became profoundly thrombocytopenic with bleeding manifestations six days after the Moderna mRNA-1273 vaccine administration. Fortunately, she exhibited platelet count recovery after treatment with intravenous immunoglobulins and steroid therapy. Furthermore, we show that the inherent risk of COVID-19 infection leading to thrombocytopenia significantly outweighs the vaccine's risk.

Potential mechanisms of vaccine-induced thrombosis.

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.

On Immunological Studies at Sirius University of Science and Technology.

This short report summarizes the results of recent immunological studies performed at the new Sirius University of Science and Technology. The report focuses on studying the features of the immune response to vaccination and revaccination against SARS-CoV-2, as well as on a search of potential agents to prevent infection with this virus.

Adverse reactions to COVID-19 vaccines: Differences and similarities

Background: COVID-19 virus vaccines are associated with adverse events. We aim to characterize and compare adverse reactions to different COVID-19 vaccines in a Portuguese centre. Method(s): Retrospective analysis of patients with adverse reactions to COVID-19 vaccines referred to our Immunoallergology Department between January and October 2021. The patients were divided according to the vaccine used: Pfizer/BioNTech (Pf), Moderna (M), or AstraZeneca (AZ). Result(s): 123 patients were included. 64 patients (52%) reacted to the Pf vaccine (77% women, mean age 49 years old);15 (12%) to the M vaccine (87% females, mean age 50 years old);and 44 (36%) to the AZ vaccine (75% women, mean age 64.8 years old). All groups showed a higher number of non-immediate reactions (>6h after inoculation): 59% for Pf, 60% for M, and 91% for AZ. Reactions to Pf and M were more frequently allergic-like (63% and 60%, respectively). Reactions to AZ were predominantly non-allergic (64%). The most frequently reported reactions for Pf and M were: sensation of throat tightness (Pf 31%, M 20%), urticaria (Pf 30%, M 27%), angioedema (Pf 17%, M 33%), constitutional non-specific symptoms (Pf 25%, M 27%), and local reactions on the inoculation site (Pf 20%, M 33%). There were 8 (13%) patients with suspected anaphylaxis with Pf, 3 (20%) with M, and none with AZ. The most frequently reported reactions for AZ were cardiovascular events (30%): myocardial, cerebral or pulmonary thromboembolic events (n = 6), phlebitis (n = 5), myocarditis (n = 1), and vaccine-induced immune thrombotic thrombocytopenia (n = 1). Other common reactions were constitutional non-specific symptoms (32%), local reactions on the inoculation site (18%), urticaria (23%), angioedema (14%), and non-urticaria rash (14%). Conclusion(s): Adverse reactions were more common in women. The mRNA vaccines were more frequently associated with allergic-like reactions, including anaphylaxis. In contrast, AZ vaccine was associated with nonallergic cardiovascular reactions. Up to 1/3 of patients in each group reported constitutional non-specific symptoms and local reactions on the inoculation site.

Coagulopathies after vaccination against SARS-CoV-2: The sole solution might lead to another problem

The common reported adverse impacts of COVID-19 vaccination include the injection site's local reaction followed by various non-specific flu-like symptoms. Nevertheless, uncommon cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) and cerebral venous sinus thrombosis (CVST) following viral vector vaccines (ChAdOx1 nCoV-19 vaccine, Ad26.COV2 vaccine) have been reported. This literature review was performed using PubMed and Google Scholar databases using appropriate keywords and their combinations: SARS-CoV-2, adenovirus, spike protein, thrombosis, thrombocytopenia, vaccine-induced immune thrombotic thrombocytopenia (VITT), NF-kappaB, adenoviral vector, platelet factor 4 (PF4), COVID-19 Vaccine, AstraZeneca COVID vaccine, ChAdOx1 nCoV-19 COVID vaccine, AZD1222 COVID vaccine, coagulopathy. The s and titles of each article were assessed by authors for screening and inclusion English reports about post-vaccine CVST and VITT in humans were also collected. Some SARS-CoV-2 vaccines based on viral vector, mRNA, or inactivated SARS-CoV-2 virus have been accepted and are being pragmatic global. Nevertheless, the recent augmented statistics of normally very infrequent types of thrombosis associated with thrombocytopenia have been stated, predominantly in the context of the adenoviral vector vaccine ChAdOx1 nCoV-19 from Astra Zeneca. The numerical prevalence of these side effects seems to associate with this particular vaccine type, i.e., adenoviral vector-based vaccines, but the meticulous molecular mechanisms are still not clear. The present review summarizes the latest data and hypotheses for molecular and cellular mechanisms into one integrated hypothesis demonstrating that coagulopathies, including thromboses, thrombocytopenia, and other associated side effects, are correlated to an interaction of the two components in the COVID-19 vaccine.Copyright © 2022, Iranian Pediatric Hematology and Oncology Society. All rights reserved.

Platelet-activating functional assay resolution in vaccine-induced immune thrombotic thrombocytopenia: differential alignment to PF4 ELISA platforms.

Background: Anti-platelet factor 4 (PF4) antibodies in vaccine-induced immune thrombotic thrombocytopenia (VITT) appear to be transient, with discrepant persistence depending on the platform used for detection. Objectives: We aimed to report a longitudinal study of antibody persistence using 2 ELISA platforms and 2 platelet-activating functional assays in a clinical cohort of patients with VITT referred for follow-up testing. Methods: In total, 32 Australian patients with VITT or pre-VITT, confirmed by expert adjudication, with samples referred for clinical follow-up were included. Clinical follow-up assays, including Stago and Hyphen ELISAs, procoagulant platelet flow cytometry, and modified PF4-serotonin-release assay, were performed according to the pattern of reactivity for that patient at diagnosis. Results: The median follow-up was 24 weeks after diagnosis. A general decline in anti-PF4 antibody levels and platelet-activating capacity over time was observed with a more rapid median time to resolution of 16 weeks by functional assay vs 24 weeks by Stago ELISA. Decline in platelet-activating antibody levels detected by functional assays mirrored Stago ELISA titer but not Hyphen. However, 87% of patients received a documented second vaccination and 74% received an mRNA booster with no reported adverse events. Conclusion: Anti-PF4 antibodies persist longer than functional platelet-activating antibodies in VITT but do not warrant avoidance of subsequent vaccinations. Persistence detection is assay-dependent. Stago ELISA may be a surrogate where functional assays are unavailable for follow-up testing of confirmed patients with VITT.

Whole sporozoite immunization with Plasmodium falciparum strain NF135 in a randomized trial.

BACKGROUND: Whole sporozoite immunization under chemoprophylaxis (CPS regime) induces long-lasting sterile homologous protection in the controlled human malaria infection model using Plasmodium falciparum strain NF54. The relative proficiency of liver-stage parasite development may be an important factor determining immunization efficacy. Previous studies show that Plasmodium falciparum strain NF135 produces relatively high numbers of large liver-stage schizonts in vitro. Here, we evaluate this strain for use in CPS immunization regimes. METHODS: In a partially randomized, open-label study conducted at the Radboudumc, Nijmegen, the Netherlands, healthy, malaria-naïve adults were immunized by three rounds of fifteen or five NF135-infected mosquito bites under mefloquine prophylaxis (cohort A) or fifteen NF135-infected mosquito bites and presumptive treatment with artemether/lumefantrine (cohort B). Cohort A participants were exposed to a homologous challenge 19 weeks after immunization. The primary objective of the study was to evaluate the safety and tolerability of CPS immunizations with NF135. RESULTS: Relatively high liver-to-blood inocula were observed during immunization with NF135 in both cohorts. Eighteen of 30 (60%) high-dose participants and 3/10 (30%) low-dose participants experienced grade 3 adverse events 7 to 21 days following their first immunization. All cohort A participants and two participants in cohort B developed breakthrough blood-stage malaria infections during immunizations requiring rescue treatment. The resulting compromised immunizations induced modest sterile protection against homologous challenge in cohort A (5/17; 29%). CONCLUSIONS: These CPS regimes using NF135 were relatively poorly tolerated and frequently required rescue treatment, thereby compromising immunization efficiency and protective efficacy. Consequently, the full potential of NF135 sporozoites for induction of immune protection remains inconclusive. Nonetheless, the high liver-stage burden achieved by this strain highlights it as an interesting potential candidate for novel whole sporozoite immunization approaches. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov under identifier NCT03813108.

Autoimmune Diseases Affecting Hemostasis: A Narrative Review.

Hemostasis reflects a homeostatic mechanism that aims to balance out pro-coagulant and anti-coagulant forces to maintain blood flow within the circulation. Simplistically, a relative excess of procoagulant forces can lead to thrombosis, and a relative excess of anticoagulant forces can lead to bleeding. There are a wide variety of congenital disorders associated with bleeding or thrombosis. In addition, there exist a vast array of autoimmune diseases that can also lead to either bleeding or thrombosis. For example, autoantibodies generated against clotting factors can lead to bleeding, of which acquired hemophilia A is the most common. As another example, autoimmune-mediated antibodies against phospholipids can generate a prothrombotic milieu in a condition known as antiphospholipid (antibody) syndrome (APS). Moreover, there exist various autoimmunity promoting environments that can lead to a variety of antibodies that affect hemostasis. Coronavirus disease 2019 (COVID-19) represents perhaps the contemporary example of such a state, with potential development of a kaleidoscope of such antibodies that primarily drive thrombosis, but may also lead to bleeding on rarer occasions. We provide here a narrative review to discuss the interaction between various autoimmune diseases and hemostasis.