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.

[Analysis of anti-SARS-CoV-2 IgG antibody titers after mRNA booster vaccination in patients with nonmalignant hematological disorders].

In our facility, anti-SARS-CoV-2 mRNA vaccines were given to 21 patients, including 8 with aplastic anemia (AA), 3 with pure red cell aplasia (PRCA), and 10 with immune thrombocytopenic purpura (ITP), and IgG antibody titers were assessed one month after vaccinations. After receiving both a second vaccine and a booster shot, all patients with AA/PRCA treated with cyclosporine A aside from one, had IgG titers that were lower than the median levels of healthy controls. Even if prednisolone (PSL) doses did not go over 10 mg/day, ITP patients receiving PSL therapy were unable to achieve adequate levels of IgG after booster immunizations.

Impact of restrictive measures due to the Covid-19 pandemic on the incidence of immune thrombocytopenia in children: an Italian single center experience.

The COVID-19 pandemic has had a huge effect all over the world and its impact has been even more profound in the world of Healthcare. In this brief report we'd like to report about our experience in pediatric newly diagnosed thrombocytopenia and how we have seen the landscape of this disease change in the last 2 years. In particular, we believe that the use of personal protective equipment and lockdown measures have reduced the incidence of viral triggers that are supposed to be responsible for the vast majority of ITP cases. Along with these data, we found some other significant differences in the period taken into account.

COVID-19-associated immune thrombocytopenia

The coronavirus disease 2019 (COVID-19) is a contagious respiratory tract infection caused by the beta-coronavirus SARS-CoV-2. The World Health Organization declared the COVID-19 outbreak a pandemic on March 11, 2020. Since the COVID-19 pandemic started, more than 166 million patients have been tested positive worldwide with more than 3.4 million related death recorded. COVID-19 has a wide range of signs and symptoms. Hematological changes such as lymphopenia, thrombocytopenia, and coagulation distur-bances are not unusual in patients with COVID-19. However, the mechanisms causing these changes are partially comprehended. Immune thrombocytopenia was identified to be among the hematologic autoimmune diseases seen in patients infected with SARS-CoV-2. This review summarizes the evidence on COV-ID-19-associated immune thrombocytopenia and the underlying mechanisms involved in its development. © 2021, Amaltea Medical Publishing House. All rights reserved.

Evans' syndrome following vaccination with ChAdOx1 nCoV-19 in a patient with new-onset localized scleroderma.

Growing evidence suggests that COVID-19 vaccines can induce hematological conditions. Here, we report a case of Evans' syndrome, a combination of immune thrombocytopenic purpura and autoimmune hemolytic anemia following administration of the ChAdOx1 nCoV-19 vaccine. The present case further supports the notion that COVID-19 vaccines can trigger in rare cases severe persistent autoimmune-mediated hematological conditions which may predominantly occur in patients with underlying autoimmune conditions.

Possible Immunological Mechanisms in COVID-19 Patients with Immune Thrombocytopenic Purpura

Millions of people around the world were, or are still involved with COVID-19 due to infection with SARS-CoV-2. In addition to hallmark symptoms, thrombotic problems, lymphopenia, and thrombocytopenia have also been reported in COVID-19 patients, of which ITP is the most common and occurs in more than one-third of COVID-19 patients. Hyperinflammation, cytokine storms, and generally immune dysregulation in a percentage of patients develop the main consequences of diseases such as ALI, ARDS and multiple organ failure. Some of the important events in the immunopathogenesis of this disease are disruption of T-cell effector differentiation and the destructive role of Th17 lymphocytes, neutrophil function and inflammatory macrophages. NLRP3-inflammasome hyperactivity causes serious dysfunction of innate immune cells and, consequently, T lymphocytes in many inflammatory disorders, most notably in the COVID-19. A closer look at the immunopathogenesis of ITP and COVID-19 brings us to common ground. The purpose of this study was to review and summarize the findings of various studies on the immunopathogenesis of ITP and its possible causes in COVID-19. Finally, enhanced differentiation of Th17 and Th1, the cell death called as pyroptosis, hyperinflammation and dysfunction of inflammatory neutrophils and macrophages, and NLRP3-inflammasome hyperactivity are important factors in the development of thrombocytopenia in patients with COVID-19. Further studies are needed to better understand immunopathogenesis and effective treatments for ITP, especially in inflammatory disorders. © 2022, Opca Bolnica Zadar. All rights reserved.

A Systematic Review of Reported Cases of Immune Thrombocytopenia after COVID-19 Vaccination.

With the recent outbreak of the COVID-19 pandemic and emergency use authorization of anti-SARS-CoV-2 vaccines, reports of post-vaccine immune thrombocytopenia (ITP) have gained attention. With this systematic review, we aim to analyze the clinical characteristics, therapeutic strategies, and outcomes of patients presenting with ITP after receiving COVID-19 vaccination. Medline, Embase, and Ebsco databases were systematically explored from inception until 1 June 2022. Case reports and case series investigating the association between the anti-SARS-CoV-2 vaccine and ITP were included. We found a total of 66 patients. The mean age of presentation was 63 years with a female preponderance (60.6%). Sixteen patients had pre-existing ITP. The mean time from vaccine administration to symptom onset was 8.4 days. More ITP events were triggered by mRNA vaccines (BNT162b2 (n = 29) > mRNA-1273 (n = 13)) than with adenoviral vaccines (ChAdOx1-S AstraZeneca (n = 15) > Ad26.COV2-S (n = 9)). Most of the patients were treated with steroids or IVIG, or both. The overall outcome was promising, with no reported deaths. Our review attempts to increase awareness among physicians while evaluating patients presenting with thrombocytopenia after receiving the vaccine. In our solicited opinion, the rarity of these events and excellent outcomes for patients should not change views regarding the benefits provided by immunization.

Immune thrombocytopenic purpura induced by the COVID-19 vaccine after the second dose in a 78-year-old patient: A case report.

Coronavirus disease 2019 (COVID-19) has become a global pandemic, but treatment options remain limited. Up to now, vaccination has been the main strategy to prevent transmission and reduce disease severity. However, with follow-up observations after massive vaccination, immune thrombocytopenic purpura (ITP) induced by COVID-19 vaccines has attracted the attention of investigators. The present study reported the case of a 78-year-old elderly female who presented with 'oral bleeding for 2 days and scattered bleeding spots on the extremities for 1 day' after vaccination with the COVID-19 vaccine (Vero Cells), and blood routine analysis indicated a white blood cell count of 6.27x109/l, hemoglobin levels of 144 g/l and a low platelet (PLT) count of 1x109/l. Bone marrow cytomorphology showed thrombocytopenia, while no platelet-producing megakaryocytes were observed. The patient was diagnosed with ITP and given symptomatic and supportive treatment, such as prednisone acetate 1 mg/kg, recombinant human thrombopoietin, intravenous injection of human immunoglobulin 0.4 g/kg and prevention of bleeding. At 1 week after the treatment started, the patient's PLT count began to increase, and 9 days later, it returned to normal levels. The aim of the present study was to raise the awareness of medical staff regarding this disease and to increase the vigilance of the general public. At the same time, the present study also provided an effective method to manage this type of adverse reaction to the COVID-19 vaccine.

Successful Treatment of Immune Thrombocytopenic Purpura with Intracranial Hemorrhaging and Duodenal Bleeding Following SARS-CoV-2 Vaccination.

Several vaccines have been developed for coronavirus disease 2019 - caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - in record time. A few cases of immune thrombocytopenic purpura (ITP) following SARS-CoV-2 vaccination have been reported. We herein report a 90-year-old man who received the Pfizer-BioNTech SARS-CoV-2 vaccine (BNT162b2) and developed severe thrombocytopenia with intracranial hemorrhaging and duodenal bleeding, consistent with vaccine-related ITP. He was successfully treated with intravenous immunoglobulin, prednisolone, and eltrombopag and discharged without cytopenia. Vaccine-related ITP should be suspected in patients presenting with abnormal bleeding or purpura after vaccination.

Thrombocytopenia in Pregnancy: Identification and Management at a Reference Center in Pakistan.

OBJECTIVE: The study aimed to evaluate the causes of thrombocytopenia in pregnancy and its management along with the outcome in the COVID-19 era. METHODS: Recruitment for this prospective, cross-sectional observational study of thrombocytopenia in pregnancy (platelet counts <100x109/L) was done from January 2017 to August 2020 at the National Institute of Blood Diseases (NIBD) after taking the patients' informed consent. Complete clinical and lab profile of patients was also collected. RESULTS: A total of 150 pregnant women with thrombocytopenia were enrolled, with the mean age being 27.3±4.64 years. Mean platelet counts at baseline were 48.0±24. Main clinical manifestations at baseline included: anemia 65.9%, bruises 23.25%, and edema 9.3%. Causes of thrombocytopenia were gestational thrombocytopenia (GT) 72 (48%), acute fatty liver five (3.3%), pre-eclampsia in 11 (7.3%), and eclampsia seven (4.6%). Causes not specific to pregnancy included 30 (20%) cases of ITP, hepatitis C, and nutritional deficiency was reported in nine (6%) patients each. 72/150 received supportive care treatment to manage thrombocytopenia and were closely monitored and given supplements. Twenty (66.6%) ITP patients received treatment with steroids, with complete response in 70% of them seen. Overall, 38 (25.3%) women with bleeding symptoms and platelet count <50x109/L received platelet transfusions. CONCLUSION: The study shows that pre-eclampsia and eclampsia are serious conditions with a high risk for complications, while GT is a benign and the most common cause of thrombocytopenia in pregnancy which requires no active treatment. The other causes such as ITP and infections require individualized management.

SARS-Cov2 acute and post-active infection in the context of autoimmune and chronic inflammatory diseases.

The clinical and immunological spectrum of acute and post-active COVID-19 syndrome overlaps with criteria used to characterize autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Indeed, following SARS-Cov2 infection, the innate immune response is altered with an initial delayed production of interferon type I (IFN-I), while the NF-kappa B and inflammasome pathways are activated. In lung and digestive tissues, an alternative and extrafollicular immune response against SARS-Cov2 takes place with, consequently, an altered humoral and memory T cell response leading to breakdown of tolerance with the emergence of autoantibodies. However, the risk of developing severe COVID-19 among SLE and RA patients did not exceed the general population except in those having pre-existing neutralizing autoantibodies against IFN-I. Treatment discontinuation rather than COVID-19 infection or vaccination increases the risk of developing flares. Last but not least, a limited number of case reports of individuals having developed SLE or RA following COVID-19 infection/vaccination have been reported. Altogether, the SARS-Cov2 pandemic represents an unique opportunity to investigate the dangerous interplay between the immune response against infectious agents and autoimmunity, and to better understand the triggering role of infection as a risk factor in autoimmune and chronic inflammatory disease development.

COVID-19-induced immune thrombocytopenic purpura; Immunopathogenesis and clinical implications.

Following the outbreak of the COVID-19 pandemic, millions of people around the world have been affected with SARS-CoV-2 infection. In addition to the typical symptoms, thrombotic events, lymphopenia, and thrombocytopenia have been reported in COVID-19 patients. Immune thrombocytopenic purpura (ITP) is one of the thrombotic events that occur in some COVID-19 patients. Hyperinflammation, cytokine storms, and immune dysregulation in some patients are the cause to the main COVID-19 complications such as ALI (acute lung injury), acute respiratory distress syndrome (ARDS), and multiple organ failure. Disruption in the differentiation of T-cells, enhanced differentiation of Th17 and Th1, cell death (pyroptosis), hyper-inflammation and dysfunction of inflammatory neutrophils and macrophages, and hyperactivity of NLRP3-inflammasome are among the important factors that may be the cause to COVID-19-induced ITP. This study aimed to give an overview of the findings on the immunopathogenesis of ITP and COVID-19-induced ITP. Further studies are required to better understand the exact immunopathogenesis and effective treatments for ITP, especially in inflammatory disorders.

Primary Immune Thrombocytopenia and Essential Thrombocythemia: So Different and yet Somehow Similar-Cases Series and a Review of the Literature.

This article collects several published cases in which immune thrombocytopenic purpura (ITP) is followed by essential thrombocythemia (ET) and vice versa. This surprising clinical condition is possible, but very rare and difficult to diagnose and manage. We have made an attempt to analyse the possible causes of the sequential appearance of ITP and ET taking into consideration the following: alteration of the thrombopoietin (TPO) receptor, the role of autoimmunity and inflammation, and cytokine modulation. A better understanding of these interactions may provide opportunities to determine predisposing factors and aid in finding new treatment modalities both for ITP and ET patients.

Pathogenesis of Two Faces of DVT: New Identity of Venous Thromboembolism as Combined Micro-Macrothrombosis via Unifying Mechanism Based on "Two-Path Unifying Theory" of Hemostasis and "Two-Activation Theory of the Endothelium".

Venous thrombosis includes deep venous thrombosis (DVT), venous thromboembolism (VTE), venous microthrombosis and others. Still, the pathogenesis of each venous thrombosis is not clearly established. Currently, isolated distal DVT and multiple proximal/central DVT are considered to be the same macrothrombotic disease affecting the venous system but with varying degree of clinical expression related to its localization and severity. The genesis of two phenotypes of DVT differing in clinical features and prognostic outcome can be identified by their unique hemostatic mechanisms. Two recently proposed hemostatic theories in vivo have clearly defined the character between "microthrombi" and "macrothrombus" in the vascular system. Phenotypic expression of thrombosis depends upon two major variables: (1) depth of vascular wall damage and (2) extent of the injury affecting the vascular tree system. Vascular wall injury limited to endothelial cells (ECs) in sepsis produces "disseminated" microthrombi, but intravascular injury due to trauma extending from ECs to subendothelial tissue (SET) produces "local" macrothrombus. Pathogen-induced sepsis activates the complement system leading to generalized endotheliopathy, which releases ultra large von Willebrand factor (ULVWF) multimers from ECs and promotes ULVWF path of hemostasis. In the venous system, the activated ULVWF path initiates microthrombogenesis to form platelet-ULVWF complexes, which become "microthrombi strings" that produce venous endotheliopathy-associated vascular microthrombotic disease (vEA-VMTD) and immune thrombocytopenic purpura (ITP)-like syndrome. In the arterial system, endotheliopathy produces arterial EA-VMTD (aEA-VMTD) with "life-threatening" thrombotic thrombocytopenic purpura (TTP)-like syndrome. Typically, vEA-VMTD is "silent" unless complicated by additional local venous vascular injury. A local venous vessel trauma without sepsis produces localized macrothrombosis due to activated ULVWF and tissue factor (TF) paths from damaged ECs and SET, which causes distal DVT with good prognosis. However, if a septic patient with "silent" vEA-VMTD is complicated by additional vascular injury from in-hospital vascular accesses, "venous combined micro-macrothrombosis" may develop as VTE via the unifying mechanism of the "two-path unifying theory" of hemostasis. This paradigm shifting pathogenetic difference between distal DVT and proximal/central DVT calls for a reassessment of current therapeutic approaches.

Successful mRNA SARS-Cov-2 vaccine rechallenge after a first episode of immune thrombocytopenic purpura.

In 2021, the world experienced the most extensive vaccination campaign to defeat COVID-19. Many cases of idiopathic thrombocytopenia have been reported following injections of SARS-Cov-2 mRNA vaccine. We present the case of a 73-year-old woman with de novo ITP after a first injection of SARS-Cov-2 mRNA vaccine (Moderna vaccine) who experienced a successful rechallenge of SARS-Cov-2 mRNA vaccine (Pfizer vaccine) a few months later.

COVID-19 associated with immune thrombocytopenia: a systematic review and meta-analysis.

BACKGROUND: Immune thrombocytopenia, also known as immune thrombocytopenic purpura (ITP), has emerged as a significant COVID-19-associated complication. This study analyzes the published literature of case reports and case series regarding COVID-19 infection associated with ITP. METHODOLOGY: In this systematic review and meta-analysis, a systematic search was conducted through PubMed, Web of Science, and Medline through Clarivate and EBSCO to include the eligible studies. The authors utilized Review Manager 5.4 to conduct quantitative data synthesis for the condition of interest analysis. RESULTS: A total of 13 eligible case reports and case series with 42 patients were included in this study; 54.8% of them were male. The pooled mean age of all participants was (59.5 ± 19) years with a median age of 63 years. The estimated mean time from diagnosis with COVID-19 to ITP development was 18.1 ± 21 days and the mean time to recovery from ITP was 5.8 ± 4.8 days. The pooled random effect of mean platelet count in the included six studies was 14.52, CI [8.79, 20.25]. CONCLUSION: Our analysis shows that ITP secondary to COVID-19 infection is slightly more prevalent among males (54.8%). Elderly patients were more vulnerable to the disease.    Most cases developed ITP within 2-3 weeks after COVID-19 infection and recovered in less than one week from ITP.

Immune thrombocytopenia purpura flare post COVID-19 vaccine.

INTRODUCTION AND IMPORTANCE: Coronavirus disease 2019 (COVID-19) is a recently discovered disease that has yet to be thoroughly described. It is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus that can be transmitted easily from human to human, mainly by the respiratory route. The disease often presents with non-specific symptoms such as fever, headache, and fatigue, accompanied by respiratory symptoms (e.g., cough and dyspnea) and other systemic involvement. Currently, vaccination is the primary strategy to prevent transmission and reduce disease severity. However, vaccines have side effects, and the consequences of vaccination in different diseases are not well established. Moreover, the impact of SARS-CoV-2 vaccination during pregnancy is another not well-known area. CASE PRESENTATION: We present a young lady known to have ITP, which was controlled for years, presented with relapse after taking the SARS-CoV-2 vaccine during pregnancy. CLINICAL DISCUSSION: The patient had a relapse of ITP after the introduction of the first dose of the COVID-19 vaccine, which worsened further after the second dose. This suggests that patients with ITP who develop flare post-SARS-CoV-2 vaccine should have their second dose delayed, particularly if pregnant. CONCLUSION: To avoid further deterioration in platelet count, and avoid confusion due to the presence of different causes of thrombocytopenia and avoid complications related to thrombocytopenia during pregnancy which can affect the mode of delivery. THE CASE IS REPORTED IN LINE WITH THE SCARE 2020 CRITERIA: Agha RA, Franchi T, Sohrabi C, Mathew G, for the SCARE Group. The SCARE 2020 Guideline: Updating Consensus Surgical CAse REport (SCARE) Guidelines, International Journal of Surgery 2020; 84:226-230.

Simultaneous Occurrence of Cerebral Venous Sinus Thrombosis and Immune Thrombocytopenic Purpura in a Patient with a History of COVID-19 Infection.

Since the emergence of the coronavirus disease 2019 (COVID-19) pandemic, multiple but rare complications of this infection have been described, comprising cerebral venous sinus thrombosis (CVST) and immune thrombocytopenic purpura (ITP). Although these two complications have been reported as separate entities, to the best of our knowledge, their concurrent presentation has not been reported. In this case report, we present a middle-aged man with a history of COVID-19 infection who developed a sudden-onset severe occipital headache followed by right-sided blindness (right homonymous hemianopia). Upon his diagnostic workup, brain computed tomography scan with and without contrast was indicative of thrombosis of the left transverse venous sinus and hemorrhagic venous infarction. In addition, laboratory data revealed thrombocytopenia, which upon investigation confirmed a diagnosis of ITP. We postulate three pathophysiological mechanisms for this circumstance: either COVID-19 infection caused ITP and then ITP gave rise to CVST, or COVID-19 complications themselves resulted in ITP and CVST independently and simultaneously, or another plausible mechanism is immune-mediated thrombocytopenia caused by the anti-platelet 4-factor antibody, which is the proposed mechanism for CVST after the COVID-19 vaccine.

Vaccine-Associated Thrombocytopenia and Thrombosis: Venous Endotheliopathy Leading to Venous Combined Micro-Macrothrombosis.

Serious vaccine-associated side effects are very rare. Major complications of vaccines are thrombocytopenia and thrombosis in which pathogenetic mechanism is consistent with endotheliopathy characterized by "attenuated" sepsis-like syndrome, leading to the activation of inflammatory and microthrombotic pathway. In the COVID-19 pandemic, acute respiratory distress syndrome caused by microthrombosis has been the major clinical phenotype from the viral sepsis in association with endotheliopathy-associated vascular microthrombotic disease (EA-VMTD), sometimes presenting with thrombotic thrombocytopenic purpura (TTP)-like syndrome. Often, venous thromboembolism has coexisted due to additional vascular injury. In contrast, clinical phenotypes of vaccine complication have included "silent" immune thrombocytopenic purpura (ITP-like syndrome), multiorgan inflammatory syndrome, and deep venous thrombosis (DVT), cerebral venous sinus thrombosis (CVST) in particular. These findings are consistent with venous (v) EA-VMTD. In vEA-VMTD promoted by activated complement system following vaccination, "consumptive" thrombocytopenia develops as ITP-like syndrome due to activated unusually large von Willebrand factor (ULVWF) path of hemostasis via microthrombogenesis. Thus, the pathologic phenotype of ITP-like syndrome is venous microthrombosis. Myocarditis/pericarditis and other rare cases of inflammatory organ syndrome are promoted by inflammatory cytokines released from activated inflammatory pathway, leading to various organ endotheliitis. Vaccine-associated CVST is a form of venous combined "micro-macrothrombosis" composed of binary components of "microthrombi strings" from vEA-VMTD and "fibrin meshes" from vaccine-unrelated incidental vascular injury perhaps such as unreported head trauma. This mechanism is identified based on "two-path unifying theory" of in vivo hemostasis. Venous combined micro-macrothrombosis due to vaccine is much more serious thrombosis than isolated distal DVT made of macrothrombus. This paradigm changing novel concept of combined micro-macrothrombosis implies the need of combined therapy of a complement inhibitor and anticoagulant for CVST and other complex forms of DVT.

What's New in Neuraxial Labor Analgesia.

PURPOSE OF REVIEW: This article provides an update of recent practice trends in neuraxial labor analgesia. It reviews available evidence regarding management of labor pain in obstetric patients with COVID-19, serious adverse events in obstetric anesthesia to help inform risk/benefit decisions, and increasingly popular neuraxial labor analgesia techniques and adjuvants. State-of-the-art modes of epidural drug delivery are also discussed. RECENT FINDINGS: There has recently been a focus on several considerations specific to obstetric anesthesia, such as anesthetic management of obstetric patients with COVID-19, platelet thresholds for the safe performance of neuraxial analgesia in obstetric patients with thrombocytopenia, and drug delivery modes for initiation and maintenance of neuraxial labor analgesia. SUMMARY: Neuraxial labor analgesia (via standard epidural, dural puncture epidural, and combined spinal epidural techniques) is the most effective therapy to alleviate the pain of childbirth. SARS-CoV-2 infection is not, in and of itself, a contraindication to neuraxial labor analgesia or cesarean delivery anesthesia. Early initiation of neuraxial labor analgesia in patients with COVID-19 is recommended if not otherwise contraindicated, as it may reduce the need for general anesthesia should emergency cesarean delivery become necessary. Consensus regarding platelet thresholds for safe initiation of neuraxial procedures has historically been lacking. Recent studies have concluded that the risk of spinal epidural hematoma formation after neuraxial procedures is likely low at or above an imprecise range of platelet count of 70-75,000 × 106/L. Thrombocytopenia has been reported in obstetric patients with COVID-19, but severe thrombocytopenia precluding initiation of neuraxial anesthesia is extremely rare. High neuraxial blockade has emerged as one of the most common serious complications of neuraxial analgesia and anesthesia in obstetric patients. Growing awareness of factors that contribute to failed conversion of epidural labor analgesia to cesarean delivery anesthesia may help avoid the risks associated with performance of repeat neuraxial techniques and induction of general anesthesia after failed epidural blockade. Dural puncture techniques to alleviate the pain of childbirth continue to become more popular, as do adjuvant drugs to enhance or prolong neuraxial analgesia. Novel techniques for epidural drug delivery have become more widely disseminated.