COVID-19 vaccine (mRNA BNT162b2) and COVID-19 infection-induced thrombotic thrombocytopenic purpura in adolescents.

The mRNA COVID-19 vaccine and COVID-19 infection caused by the SARS-CoV-2 virus may be immunologic triggers for the development of thrombotic thrombocytopenic purpura (TTP). There is not yet literature that discusses TTP induced by COVID-19 vaccination or infection in pediatric or adolescent patients. We describe three adolescents presenting with TTP (both de novo and relapsed disease) following administration of the Pfizer COVID-19 vaccine or after COVID-19 infection. Our observations demonstrate that the Pfizer-BioNTech mRNA vaccine and COVID-19 infection can act as triggers for the development/relapse of both congenital and acquired TTP.

Potential for Recombinant ADAMTS13 as an Effective Therapy for Acquired Thrombotic Thrombocytopenic Purpura.

OBJECTIVE: The metalloprotease ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) regulates the size of von Willebrand factor multimers. A deficiency in ADAMTS13 activity is associated with the life-threatening disease thrombotic thrombocytopenic purpura (TTP). The vast majority of patients have acquired TTP, where circulating anti-ADAMTS13 autoantibodies are causative for the decreased ADAMTS13 activity. Current treatment consists of plasma exchange, but improved therapies are highly warranted. APPROACH AND RESULTS: We have developed a new rat model mimicking various aspects of acquired TTP to investigate the therapeutic efficacy of human recombinant ADAMTS13. A polyclonal antibody against ADAMTS13 completely blocked endogenous rat ADAMTS13 activity in Sprague-Dawley rats. When TTP was triggered using recombinant von Willebrand factor, the animals displayed severe TTP-like symptoms, such as thrombocytopenia, hemolytic anemia, and von Willebrand factor-rich thrombi in the kidneys and brain. Subsequent injection of 400, 800, or 1600 U/kg recombinant ADAMTS13 prevented full development of these symptoms. Analysis of plasma samples confirmed that recombinant ADAMTS13 was able to override circulating anti-ADAMTS13 inhibitory antibodies, resulting in restoration of ADAMTS13 activity and degradation of ultralarge von Willebrand factor multimers. CONCLUSIONS: Recombinant ADAMTS13 was shown to be effective in averting severe acquired TTP-like symptoms in rats and holds promising value for the treatment of this severe and life-threatening disease in humans.

Vitamin B12 Deficiency Mimicking Thrombotic Thrombocytopenic Purpura: A Case Report and Review of Literature.

Vitamin B12 (cyanocobalamin) deficiency can lead to ineffective erythropoiesis, intramedullary hemolysis, and, in severe cases, neurologic deficits. Some of those findings are also features of thrombotic microangiopathies, specifically thrombotic thrombocytopenic purpura (TTP), and the distinction between both entities could sometimes be challenging. While the treatment of the former consists of enteral or parenteral repletion, the treatment of TTP is more complex and time-sensitive. For that reason, refining diagnostic strategies is crucial to avoid misdiagnosis and unnecessary interventions. Here is an example of a potential life-threatening hemolysis caused by vitamin B12 deficiency with acute onset neurologic symptoms, which resolved with B12 repletion.

COVID-Induced Thrombotic Thrombocytopenic Purpura: A Case Report and Treatment-Focused Review.

Thrombotic thrombocytopenic purpura (TTP) is a rare disease that is part of a vast spectrum of thrombotic microangiopathies (TMAs). Despite the rarity of TTP, clinicians must maintain a high suspicion of this disease. The condition is characterized by fever, low platelets, hemolytic anemia, renal abnormalities, and neurological dysfunction. However, all these symptoms are not necessarily present in all the patients. In this review, we describe a case of a 51-year-old female who presented to the emergency department (ED) with chief complaints of dizziness and lightheadedness, subsequently leading to a diagnosis of TTP, caused as a result of COVID-19. This review raises awareness so that there is early recognition of any hematological manifestations associated with COVID-19, reducing the morbidity and mortality associated with the disease. Due to the unpredictability of COVID-19 and its complications, robust research is needed to understand the mechanism and determine which patients are more at risk for adverse outcomes.

Acquired Thrombotic Thrombocytopenic Thrombocytopenia Presenting As Urinary Tract Infection and Perianal Abscess: A Case Review.

Thrombotic thrombocytopenic purpura (TTP) is a rare but potentially life-threatening hematologic disorder characterized by hemolytic anemia, thrombocytopenia, renal failure, fever, and neurologic dysfunction. While cases often do not present with all five characteristics (<5%), TTP can be hereditary or acquired, often due to a deficiency or dysfunction of the ADAMST13 enzyme. Here, we describe a case of infection-induced acquired TTP in a middle-aged male with urinary tract infection (UTI) and perianal abscess. Suspicion arose from hematologic abnormalities, fever, thrombocytopenia, acute renal failure, and the presence of an underlying infection. A PLASMIC score of 6 (indicating a 72% probability of ADAMTS13 deficiency) prompted ADAMTS13 level testing, revealing levels <5% with the presence of an inhibitor, confirming TTP diagnosis. Treatment with high-dose steroids and daily plasma exchange yielded a swift platelet response, necessitating only two to three days of plasma exchange. In addition, incision and drainage of the perianal abscess were performed. The patient was discharged on daily prednisone and initiated on four doses of weekly Rituximab to mitigate recurrence risk. This case underscores the importance of early suspicion and treatment in infectious triggers such as UTI/perianal abscess, offering crucial diagnostic and prognostic insights.

Adult Vitamin B12 Deficiency-Associated Pseudo-Thrombotic Microangiopathy: A Systematic Review of Case Reports.

Cobalamin-deficient thrombotic microangiopathy or vitamin B12 deficiency presenting as pseudo-thrombotic microangiopathy is a rare disorder that can be misdiagnosed as thrombotic thrombocytopenic purpura. Patients with this condition are at risk of receiving unnecessary plasmapheresis with a potential delay in appropriate therapy with vitamin B12 supplementation. There are no established diagnostic criteria for this condition in clinical practice. We performed a systematic review of case reports published between January 2018 and January 2023 to analyze the clinical characteristics, risk factors, and patterns of laboratory markers to improve the diagnostic criteria for this condition.

Diabetic Ketoacidosis Complicated by Thrombotic Thrombocytopenic Purpura: A Rare Association.

Thrombotic thrombocytopenic purpura (TTP) is a rare and potentially life-threatening blood disorder caused by a deficiency or dysfunction of ADAMTS13 and can occur secondary to various conditions, including autoimmune diseases, infections, medications, pregnancy, and malignancies. Diabetic ketoacidosis (DKA) inducing TTP is uncommon and not widely reported in the literature. Herein, we report a case of TTP induced by DKA in an adult patient. His clinical picture, serological, and biochemical results confirmed the diagnosis of TTP induced by DKA, and his clinical course did not improve despite normalization of glucose level, plasmapheresis, and aggressive management. Our case report emphasizes the importance of considering TTP as a potential complication of DKA.

Non-ST-Segment Elevation Myocardial Infarction As Initial Thrombotic Event of Thrombotic Thrombocytopenic Purpura: A Rare Challenging Case.

Thrombotic thrombocytopenic purpura (TTP) is a rare autoimmune and devastating blood disorder that results in micro-clots throughout the body, leading to tissue damage and organ dysfunction resulting in widespread microangiopathic hemolytic anemia, thrombocytopenia, fever, and neurological symptoms. TTP patients commonly manifest renal and neurological symptoms; however, cardiovascular involvement is not widely reported in the literature. We report a case of non-ST-segment elevation myocardial infarction (NSTEMI) as an initial manifestation of TTP. Although rare, TTP complications must be considered among other possible causes of unexpected thrombocytopenia during acute phase treatment of acute coronary syndrome because of high morbidity and mortality.

Role of the PLASMIC Score in the Management of Thrombotic Thrombocytopenic Purpura.

We report the case of a middle-aged male presenting with fatigue and abdominal pain. Prompt investigations demonstrated microangiopathic hemolytic anemia and thrombocytopenia on a peripheral blood smear. Thrombotic thrombocytopenic purpura was suspected based on the PLASMIC score. The patient significantly improved with therapeutic plasma exchange and prednisone within the next few days. The disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 levels reduction is a definitive hallmark leading to microvascular thrombosis. However, some medical centers in the United States do not promptly have quick allowance to the levels. Hence, the PLASMIC score becomes imminent in initiating immediate management and preventing life-threatening complications.

A Case of Thrombotic Thrombocytopenic Purpura and ST-Elevation Myocardial Infarction: An Unusual Correlation.

Thrombotic thrombocytopenic purpura (TTP) is a rare and potentially devastating blood disorder depicted by thrombocytopenia, fever, widespread small vessel hemolytic anemia, and neurological symptoms. The involvement of the renal and neurological systems is frequently reported in TTP; however, TTP-induced acute coronary syndrome is not widely reported. We describe a case of myocardial infarction induced by TTP in a patient who presented with the typical manifestation of acute coronary syndrome. Echocardiogram revealed a myocardial injury, and detailed investigations revealed increased levels of troponin I, lactate dehydrogenase, diminished levels of haptoglobin and von Willebrand factor-cleaving protease, and schistocytes on peripheral smear, suggestive of TTP-induced myocardial infarction. His condition was stabilized after commencing plasmapheresis, steroids, and rituximab. The initial steps in the management of this patient involve the prompt administration of steroids and the urgent start of plasmapheresis to increase platelet count.

Pseudo-Thrombotic Thrombocytopenic Purpura Due to Severe Vitamin B12 Deficiency: A Case Report.

Vitamin B12 deficiency is common in vegetarians, as meat is a common source of vitamin B12. In this case presentation, a patient presented to his primary care doctor with signs of severe vitamin B12 deficiency anemia. He had elevated lactate dehydrogenase levels, indirect bilirubin, and schistocytes on the blood smear, all pointing toward a hemolytic process. A severe vitamin B12 deficiency was deemed the cause of this hemolytic anemia after ruling out other causes. We highlight the importance of knowing more about this pathogenesis to avoid unnecessary workup and management for an elementary disorder that can result from severe B12 deficiency.

Tacrolimus-Induced Thrombotic Microangiopathy After Orthotopic Heart Transplant: A Case Report.

Tacrolimus (FK 506) is a calcineurin inhibitor and is commonly used as an immunosuppressant after a solid organ transplant. One of the serious adverse effects of tacrolimus is thrombotic microangiopathy (TMA) which has a high mortality rate. TMA leads to vascular thrombosis, eventually leading to ischemia of end organs. It is diagnosed clinically and based on the laboratory parameters. Early detection of TMA and prompt treatment can change the course. Drug-induced TMA has a poor prognosis as compared to idiopathic TMA. We present here the case of a 47-year-old male who developed tacrolimus-induced TMA after an orthotopic heart transplant and he was treated with the currently available treatment. He ultimately died after 40 days of hospitalization.

Acquired Thrombotic Thrombocytopenic Purpura in a Newly Diagnosed HIV Patient: A Case Report and Literature Review.

Thrombotic thrombocytopenic purpura (TTP) is a rare but a potentially fatal condition. Although the majority of TTP cases are of unknown etiology, certain viral infections, malignancies, and medications have been linked to the acquired form of the illness. Regardless of the underlying etiology, TTP remains a great challenge diagnostically and therapeutically. TTP remains a very uncommon complication of HIV. We reviewed the current literature to better understand the relationship between HIV and TTP and address some of the major obstacles that may impede or delay the correct diagnosis. Here, we present a case of a 28-year-old male with complaints of light-headedness, fatigue, and gingival bleeding. He was found to have severe anemia and thrombocytopenia. He tested positive for the HIV and was then diagnosed with TTP. Despite needing endotracheal intubation for airway protection, he clinically improved with packed red blood cells, plasmapheresis, and highly active antiretroviral therapy.

Life-Threatening Microangiopathy or Vitamin Deficiency: A Case Report of the Clinical Manifestations of Pseudo-Thrombotic Microangiopathic Anemia.

Hemolytic anemia with thrombocytopenia and organ damage raises suspicion for thrombotic microangiopathy (TMA), a pathology that results in thrombosis within the small vessels secondary to endothelial injury. While usually attributed to atypical hemolytic uremic syndrome (aHUS) or thrombotic thrombocytopenic purpura (TTP), an increasingly recognized and treatable entity is pseudo-thrombotic microangiopathic anemia (pseudo-TMA) secondary to severe vitamin B-12 deficiency. While TMA often requires expensive diagnostic testing and can lead to invasive treatment options such as plasma exchange, immunosuppression, and/or complement cascade blocking, pseudo-TMA requires only vitamin supplementation. Therefore, the prompt and accurate diagnosis of this entity is important for the clinician to recognize in order to avoid unnecessary health costs and institute appropriate treatment. We present the case of a 51-year-old male without any past medical history, who presented with generalized weakness, dyspnea on exertion, and decreased exercise tolerance for several months and was found to have severe microangiopathic anemia with work-up concerning for TTP. After stabilization, he was found to have severe B-12 deficiency secondary to newly diagnosed pernicious anemia and was treated with subcutaneous B-12 injections with improvement in clinical symptoms and laboratory parameters. This presentation highlights the need for prompt diagnosis and high clinical suspicion for vitamin deficiencies as a source of pseudo-microangiopathy.

A Case of COVID-19 Induced Thrombotic Thrombocytopenic Purpura.

Thrombotic Thrombocytopenic Purpura (TTP) is a challenging thrombotic diathesis which requires prompt diagnosis and therapeutic intervention in order to avoid life-threatening consequences. There are two forms of TTP, congenital and acquired, with the acquired form constituting about 90% of cases. Both forms are associated with a deficiency of ADAMTS-13, a metalloproteinase enzyme responsible for cleaving ultra-large von Willebrand factor (uLvWF), preventing its pathologic accumulation. Within the last year, many of the diverse and serious effects of the COVID-19 virus have come to recognition, with some of the most dire consequences involving devastating vascular and hematologic complications. As with many viruses, it seems that the endothelium and the vasculature are often prime targets. Here, we report a case of a 30 year old male who was diagnosed with TTP approximately one week after a positive COVID-19 test result. He responded appropriately to plasma exchange (PLEX), caplacizumab, and steroids. We believe it is important to investigate a potential link between these two conditions, as TTP has significant morbidity and mortality risk if left unattended. We hope that our report will contribute to a better understanding of this potential link.

Prevalence of the age-related diseases in older patients with acquired thrombotic thrombocytopenic purpura.

BACKGROUND: The prevalence of older patients with acquired thrombotic thrombocytopenic purpura (TTP) is increasing. There is scarce information on the prevalence of multimorbidity, polypharmacy and age-related diseases in aging TTP patients. This study aimed to evaluate the prevalence of multimorbidity and polypharmacy in a population of acquired TTP patients aged 65 years or more compared with a group of age-matched controls. METHODS: Acquired TTP patients enrolled in the Milan TTP registry from December 1st 1999 to March 31th 2018 and aged 65 years or more at the date of last follow-up were evaluated. Controls were Italian healthy individuals recruited from 2006 to March 31th 2018 among friends and non-consanguineous relatives of patients tested for thrombophilia screening at the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center of Milan. RESULTS: 36 TTP patients and 127 age-matched controls were included. Compared with controls, TTP patients had a higher prevalence of multimorbidity and polypharmacy. They also showed a higher prevalence of autoimmune diseases, osteoporosis and arterial hypertension and were more chronically treated with corticosteroids and antiplatelets for primary cardiovascular prevention. All these results were confirmed after adjusting for sex. Compared with the general elderly population, TTP patients showed a higher prevalence of ischemic heart disease and stroke. CONCLUSIONS: Our findings suggest that a careful comprehensive geriatric assessment of acquired TTP patients is necessary. It is important to look for other autoimmune diseases and such age-related comorbidities as osteoporosis, arterial hypertension, ischemic heart disease and cerebrovascular disease.

ADAMTS13 and anti-ADAMTS13 autoantibodies in thrombotic thrombocytopenic purpura - current perspectives and new treatment strategies.

A deficiency in ADAMTS13 (A Disintegrin And Metalloprotease with ThromboSpondin type-1 repeats, member 13) is associated with thrombotic thrombocytopenic purpura (TTP). Congenital TTP is caused by a defect in the ADAMTS13 gene resulting in decreased or absent enzyme activity; acquired TTP results from autoantibodies that either inhibit the activity or increase the clearance of ADAMTS13. Despite major progress in recent years in our understanding of the disease, many aspects around the pathophysiology of TTP are still unclear. Newer studies expanded the TTP field from ADAMTS13 and inhibitory antibodies to immune complexes, cloned autoantibodies, and a possible involvement of other proteases. Additionally, several new treatment strategies supplementing plasma-exchange and infusion are under investigation for a better and more specific treatment of TTP patients. In this review, we discuss the recent insights in TTP pathophysiology and describe upcoming therapeutic opportunities.