Thrombotic thrombocytopenic purpura following ChAdOx1 nCov-19 vaccination: A case report.

Vaccine-associated thrombotic thrombocytopenic purpura (TTP) is a rare type of acquired TTP recently reported after COVID-19 vaccination. Merely four cases are ascribed to the ChAdOx1 nCoV-19 vaccine in the medical literature till the preparation of this study. In this case report, we describe a 43-year-old man who developed symptoms of TTP four days after receiving the second dose of the ChAdOx1 nCoV-19 vaccine. Peripheral blood smear demonstrated multiple schistocytes. Given a high plasmic score, he received plasma exchange, corticosteroids, and rituximab, and later, low ADAMTS 13 activity and high-titer ADAMTS inhibition antibody confirmed the diagnosis of COVID-19 vaccine-associated TTP. COVID-19 vaccine-associated TTP is an infrequent consequence of SARS-CoV-2 vaccination but with a substantial mortality rate which must be considered as one of the crucial differential diagnoses of post-COVID-19 vaccine thrombocytopenia besides vaccine-induced immune thrombotic thrombocytopenia and Immune thrombocytopenic purpura.

Kidney Limited Complement-Mediated Thrombotic Microangiopathy- a Challenging Case

Introduction: Complement-mediated thrombotic microangiopathy (CM-TMA) is a rare disease characterized by microangiopathic hemolytic anemia (MAHA), thrombocytopenia and organ injury. The absence of hemolysis and thrombocytopenia is rare. We present a case of kidney limited CM-TMA successfully treated with eculizumab. Method(s): A 36 year-old man with poorly controlled hypertension, obesity, CKD (baseline creatinine (sCr) 2,6mg/dL, albuminuria 150mg/g), hyperlipidemia, obstructive sleep apnea, hyperuricemia, SARS-CoV-2 infection 3 months earlier, and family history of CKD of unknown etiology (father started kidney replacement therapy (KRT) at young age) presented to the ER with high blood pressure and right hemiplegy. Head CT scan showed left thalamo-capsular hemorrhage. Oftalmologic exam was normal. Laboratory findings were: hemoglobin (Hb) 12.5g/dL, elevated white cell count (17.900/uL), platelet count 214.000/uL, sCr 4.3mg/dL, lactate dehydrogenase (LDH) 303U/L. Urine dipstick revealed protein+ and Hb++. Chest X-ray showed signs of pneumonia. The patient was admitted in ICU and mechanically ventilated. After 3 weeks, renal function recovered to its baseline (sCr 1.5mg/dL, no proteinuria) without KRT, and the patient was transferred to the medical ward. Several infectious complications prolonged hospital stay. After 3 months, a new mild SARS-CoV-2 infection was detected. At this time: Hb 9.9g/dL, platelets 220.000/uL, sCr 2.2mg/dL. Six days later the patient showed Hb 9.5 g/dL, without reticulocytosis, platelets 195.000/uL, sCr 6.3mg/dL, LDH 348U/L, normal haptoglobin, no schizocytes on blood smear. After 3 days, the patient was anuric and sCr increased to 10mg/dL, prompting KRT. Kidney ultrasound showed no abnormalities. Autoimmunity study was negative, normal C3/C4, no monoclonal gammopathy, and negative viral serologies. Kidney biopsy (KB) was performed as the etiology of AKI remained unclear. Light microscopy revealed thickned glomerular capillary walls with subendothelial expansion forming double contouring, arteriolar intimal expansion and fibrin thrombi occluding the vascular lumina. Scarse C3 deposition was observed in capillary walls. Since the morphological features were consistent with TMA, secondary causes were excluded and primary causes also investigated: ADAMTS13 activity, complement factor B and I were within normal range, slight decrease of factor H with normal anti factor H antibody. The molecular studies of complement genes were performed by NGS-based gene panel revealing a rare heterozygous missense mutation on gene CFB, c.1189G>A (p.Asp397Asn), described as a genetic risk factor of CM-TMA in the presence of a trigger. Result(s): Treatment with eculizumab was started and the patient showed signs of kidney recovery allowing KRT suspension 1 month later (sCr 5.53mg/dL). Of note, the patient never presented MAHA or thrombocytopenia. After 5 months, renal function improved to sCr 3.9mg/dL. Conclusion(s): We report a case of CM-TMA with isolated kidney injury without laboratory hallmarks of TMA. Patients usually require a secondary trigger for the disease to manifest, and in this case SARS-CoV-2 infection may have been the causative agent. A mutation in gene CFB may have predisposed the patient to the outcome. KB was crucial for diagnosis and prompted the treatment with eculizumab with partial recovery without the need for chronic KRT. No conflict of interestCopyright © 2023

Clinical Analysis of 15 Adult Patients with Thrombotic Thrombocytopenic Purpura

Introduction: Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy characterized by severe thrombocytopenia, microangiopathic hemolytic anemia, and organ ischemia ascribable to platelet-rich microthrombi. TTP is related to a severe deficiency in ADAMTS13, the specific von Willebrand factor-cleaving metalloprotease. The aim of our study is to analyze the clinical characteristics, treatment and outcome of patients with TTP. Method(s): We retrospectively analyzed 15 patients with TTP treated Farhat Hached hospital, Sousse, Tunisia, from2004 to 2021. Result(s): Among the 15 patients, there were 7 males and 8 females, with a median age of 45,5 (30~72) years. Two of them had evolutive cancer and 1 had covid-19 vaccination 3 months earlier. Twelve patients had neurological presentations (80%), 4 had mucocutaneous bleeding and 2 had fever. Biology showed thrombopenia, mechanical hemolytic anemia in all patients and renal failure in 2 patients. No abnormalities in coagulation tests were detected. The ADAMTS13 activity was performed in only 3 patients (Due to test unavailability) showing a level <=10% in all 3 patients. All patients were treated with plasma exchange/ plasma infusion + glucocorticoid, combined with rituximab in 2 cases. Ten patients showed complete remission, 1 relapsed within the first year, 2 died and 2 others were lost to follow-up. Discussion/Conclusion: Most TTP patients presented with the triad of microangiopathic anemia, thrombocytopenia, and neurologic abnormalities and improved with plasma therapy.

Thrombotic Thrombocytopenic Purpura (TTP) secondary to Covid-19 infection in a patient with Systemic Lupus Erythematosus (SLE)

Background: Covid-19 infection has caused a global pandemic in the recent years and although initially it was considered mainly a respiratory ailment it has proven over time to cause a constellation of complications across various systems such as hematological, immune, cardiovascular, gastrointestinal, and neurological. Method(s): We report a case of a lupus patient with Covid-19 infection who presented initially with fever and gum bleeding with a negative dengue serology and negative HIV serology. Result(s): A 45-year- old lady with a 30-year history of SLE was admitted to our hospital with Covid 19 infection. She had relatively stable disease over the past few years but was admitted to the hospital with complaints of fever, gum bleeding and shortness of breath with no chest x-ray changes. Her oxygen saturations were 95% under room air and her vital signs were stable. Laboratory examinations revealed raised white cell count (11.63) with neutrophilia and elevated C-reactive protein (2.84mg/dl). Her platelet count was low at 113 when compared to her baseline of 549. An urgent peripheral blood film showed an incidental finding of Stomato-ovalocytosis with mild anaemia however there was no features of haemolysis. She was initially treated as acquired Immune thrombocytopenia provoked by Covid-19 infection and was started on IV hydrocortisone. She had a lack of response as evident of a further decline in her platelet counts and the following day, she developed rapid decline in her renal function wherein her creatinine increased from 83 to 207. An urgent ultrasound doppler of the kidneys to rule out acute renal vein thrombosis was organised however it showed normal patent renal vessels. Peripheral blood films were repeated which showed minimal schistocytes and the diagnosis was clinched with the Adamst13 activity levels being less than 0.2%. She was started on 20g IVIG per day with plasma exchange however succumbed to the illness. Conclusion(s): The diagnosis of TTP classically involves the recognition of the pentad of fever, microangiopathic hemolytic anemia, thrombocytopenia, acute renal failure, and neurological abnormalities however 60% of patients do not fulfil the pentad. It is essential to recognize that Covid-19 is an acquired cause of TTP, and a high index of suspicion must be maintained for early treatment institution.

Semi-selective plasma filtration applied to the treatment of acquired thrombotic thrombocytopenic purpura following bnt162b2 administration.

Following the widespread use of anti SARS-CoV-2 vaccines, there have been reports of thrombocytopenia developing after the administration of different types of vaccine. We report a case of a 63-year-old male who developed neurological symptoms after receiving the second dose of the bnt162b2 vaccine. Blood tests performed upon admission to the Emergency Department revealed severe thrombocytopenia and microangiopathic hemolytic anemia. ADAMTS13 activity was undetectable and antibody titer was high. Due to the rapid neurological deterioration, steroid therapy with prednisone was started at an initial dose of 1 mg/kg/day. Rituximab therapy was started to prevent the formation of new antibodies. Given the slow response to this therapy, we added Caplacizumab, (a monoclonal antibody anti-Von Willebrand factor) in order to inhibit platelet hyperaggregation, combined with standard plasma exchange. The patient experienced repeated episodes of intolerance to fresh frozen plasma (FFP). Switching from plasma exchange to plasma filtration, remission was attained in this unusual case of vaccine-related thrombocytopenia with microangiopathic hemolytic anemia.

Hemolysis and COVID-19 infection: A fatal combination - An interesting series of three cases

COVID-19 has wreaked havoc ever since its inception and with the protean manifestations of the disease, it is imperative that progressively data are added to the literature. COVID-19 infection is a multisystem disorder with a wide range of clinical symptomatology. Recent information garnered has laid emphasis on pathological changes at microvascular level causing thrombotic/hemostatic defects, leading to the assorted clinical presentation. We present a consortium of three confirmed COVID-19 cases whose hospital course got convoluted with grave hematological complications in the form of hemolytic uremic syndrome and autoimmune hemolytic anemia. Regrettably, all three patients succumbed to their illness.

Thrombotic Microangiopathy in a Patient With COVID-19 Infection and Metastatic Cholangiocarcinoma.

This is a case report of a 63-year-old African American female with a past medical history most significant for metastatic cholangiocarcinoma that presented for evaluation of persistent shortness of breath. Initial workup was remarkable for refractory anemia, moderate schistocytes on peripheral smear and lab work suggestive of a hemolytic anemia. Due to concern for thrombotic thrombocytopenic purpura (TTP), she subsequently underwent several rounds of plasma exchange without significant improvement. Secondary to progressive renal failure, patient eventually had a renal biopsy with findings remarkable for thrombotic microangiopathy (TMA). Simultaneously, patient was also diagnosed with coronavirus disease 2019 (COVID-19) infection. After a few weeks of supportive care, she was stable for discharge. Unfortunately, she did become dialysis dependent. Prior to hospital admission, she was being treated for metastatic cholangiocarcinoma and had received chemotherapy with gemcitabine. Her last chemotherapy session was approximately 3 weeks prior to her first hospitalization. Furthermore, although her hemolytic work did suggest TMA, it was not consistent with the diagnosis of TTP. She was transferred to a tertiary care center where hemolytic labs were trended, and supportive care was maximized. In light of the current COVID-19 pandemic, it is crucial to further investigate the pathophysiology of TMA in patients with active malignancies and COVID-19 infections. To our knowledge, this is the first case of TMA in a patient with both metastatic cholangiocarcinoma and COVID-19 infection.