Presentation Of Thrombotic Thrombocytopenic Purpura Research Articles

Thrombotic thrombocytopenic purpura presenting as stroke mimics with normal diffusion-weighted MRI

BackgroundThrombotic thrombocytopenic purpura (TTP) is a rare and fatal thrombotic microangiopathy-based hematologic disease. Stroke has been reported as atypical neurological manifestations of TTP in some cases.Case presentationA 65-year-old male presented with typical acute ischemic stroke symptoms including sudden-onset dysarthria, right-sided facial paralysis and hemiplegia. However, his CT and MRI scans were negative without showing any new ischemic lesions. He was diagnosed with TTP with severe thrombocytopenia, mild anemia, increased LDH, and low ADAMTS-13 activity. The symptoms and positive signs were rapidly resolved after administrating the plasma exchange therapy.ConclusionClinicians should consider the possibility of TTP when a patient presents with acute stroke-like symptoms and thrombocytopenia, especially in an emergency room, either with or without new stroke lesions on the brain CT and MRI.

Abstract 160: Recurrent Multi‐territorial Ischemic Stroke as an Initial Presentation of Thrombotic Thrombocytopenic Purpura

Introduction Thrombotic thrombocytopenic purpura (TTP) is a rare hypercoagulable disorder characterized by acute hemolytic anemia, thrombocytopenia, neurologic deficits, and renal failure. Here, we describe a young patient with recurrent multi‐territory stroke, with the development of thrombocytopenia later in her course. Her prior diagnosis of etiologies for her ischemic stroke was confounded by the presence of grade 3 PFO and intrinsic arteriopathy attributed to accelerated atherosclerosis due to smoking tobacco with marijuana. Methods A 42‐year‐old woman, active tobacco and marijuana smoker, and recent cryptogenic ischemic and hemorrhagic stroke involving multiple vascular territories with hypercoagulable workup pending, presented with sudden left hemiplegia. Vessel imaging demonstrated irregularity and mild narrowing of the right posterior M2/M3 MCA branches without evidence of large vessel occlusion. MRI showed evidence of evolving left frontal encephalomalacia, prior ischemic stroke on the right inferior MCA and corpus callosum, and prior hemorrhagic stroke on the right parietal and left PCA. In addition, it showed T2 hyperintensities in bilateral anterior and posterior watershed areas. Work‐up was significant for grade 3 PFO/intrapulmonary shunt. Doppler ultrasound was negative for DVT. Basic labs showed LDL 56, A1c 4.8, and TSH 1.8. Hypercoagulable work‐up returned negative. Her platelet count during the admission was initially 169, and 208 on discharge to rehab on single agent antiplatelet (81mg aspirin) and high‐dose statin. After 11 days in rehab, she returned with sudden‐onset slurred speech and right‐sided hemiplegia. Vessel imaging was again negative for LVO and showed significant multi‐vessel arteriopathy. A repeat brain MRI showed a new stroke on the left precentral gyrus, left high frontal lobe, left medial parietal lobe, and left cerebellar hemisphere. The suspected mechanism of stroke was cardioembolic although the patient’s normal left atrial size was presumed to make this mechanism less likely. A few days into admission, her platelets began to decrease. With new‐onset thrombocytopenia (lowest platelet count was 38), ADAMTS screen was ordered and returned positive. The ADAMTS inhibitor Bethesda titer was notably high, 1.4 (nl <0.4). Uncharacteristically for TTP, the patient did not have a fever, anemia (Hb 12), or renal failure (good urine output and Cr 0.7). Nonetheless, given the absence of a clear alternative attributable stroke mechanism, thrombotic thrombocytopenia was suspected as the etiology of her ischemic strokes. For acute therapy, 3‐day 1 mg/kg methylprednisolone was started and hematology service was consulted for co‐management. The patient completed four rounds of plasmapheresis while receiving 90 mg of prednisone daily. She was then started on a regimen to complete four doses of weekly rituximab. The patient improved clinically during the course of her stay and with noted improvements in platelet count and ADAMTS as well. Results N/A Conclusion A low threshold to consider atypical presentations of cryptogenic stroke such as TTP in this case should be in mind when evaluating young adults with recurrent multi‐territory ischemic stroke. Thrombocytopenia may not be present until later in the disease course representing atypical presentations of TTP. As in our case, patients may present without fever, hemolytic anemia, and renal failure.

ADAMTS13 activity testing: evaluation of commercial platforms for diagnosis and monitoring of thrombotic thrombocytopenic purpura

BackgroundADAMTS13 activity is one of the key investigations needed to diagnose thrombotic thrombocytopenic purpura, and there are a number of different assays available to measure it. HemosIL AcuStar, a chemiluminescent immunoassay, was developed and used as a quicker, automated test. In clinical practice, discrepancies between AcuStar and the gold standard FRETS-VWF73 have been documented in a manner that would affect diagnosis and treatment. ObjectivesWe aimed to identify and highlight clinical situations where this discrepancy occurs and to attempt to determine the cause. MethodTherefore, we undertook a study to compare the FRETS-VWF73 assay with AcuStar, the Technozym Activity ELISA, and Ceveron FRET assays using a mixture of 94 retrospective and prospective patient samples. ResultsWe found that although the concordance between FRETS-VWF73 and the other methods was generally very good, discrepancies were found in a small number tested on AcuStar affecting diagnosis (5 of 32) and follow-up (7 of 51). A Wilcoxon test comparing FRETS-VWF73 to the AcuStar results suggested that the AcuStar results were significantly lower in 42 samples tested on all 4 platforms. We investigated potential causes for this difference by testing the impact of high vWF levels and addition of a monoclonal ADAMTS13 autoantibody (3H9) to samples. We found no impact of high vWF levels on interassay variability but found that 3H9 reduced ADAMTS13 activity levels much more in AcuStar and ELISA assays than in FRETS assays. ConclusionBased on our findings, we would suggest that when AcuStar is used upfront to guide management, a second testing method should be used in patients with an atypical thrombotic thrombocytopenic purpura presentation or unexpectedly slow ADAMTS13 recovery.

Two ischemic stroke events within 48 h: a case report of an unusual presentation of thrombotic thrombocytopenic purpura

BackgroundThrombotic thrombocytopenic purpura (TTP) considers a rare cause of ischemic stroke (IS). We reported a case of a newly diagnosed patient with acquired immune-mediated TTP (iTTP), in whom two IS events developed during 48 h.Case presentationA 59-year-old diabetic male was presented to the hospital 24 h after symptoms onset, including left hemiparesis, dysarthria, and decreased consciousness. A brain CT scan was performed with the suspicion of acute IS, indicating infarct lesions in the right middle cerebral artery (MCA) territory. The patient was not eligible for thrombolytic therapy due to admission delay. Over the next 24 h, the patient’s neurological condition deteriorated, and the second brain CT scan showed new ischemic lesions in the left MCA territory. Initial laboratory evaluation indicated thrombocytopenia without evidence of anemia. However, in the following days, thrombocytopenia progressed, and microangiopathic hemolytic anemia (MAHA) developed. The ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity and inhibitors assay confirmed the diagnosis of iTTP. The patient underwent plasma exchange activity and inhibitors assay confirmed the diagnosis of iTTP. The patient underwent and pulse IV methylprednisolone. Rituximab was also added due to the refractory course of the disease. After a prolonged hospital course, he had considerable neurologic recovery and was discharged.ConclusionsClinicians should consider two points. First, TTP should be considered in any patient presenting with IS and having thrombocytopenia or anemia without other symptoms of TTP. Second, worsening the patient's condition during hospitalization may indicate a new stroke and should be investigated immediately.

237 - Thrombotic thrombocytopenic purpura presenting as ST-elevation myocardial infarction

237 - Thrombotic thrombocytopenic purpura presenting as ST-elevation myocardial infarction

P.89 Management of refractory thrombotic thrombocytopenic purpura presenting in the pregnancy

P.89 Management of refractory thrombotic thrombocytopenic purpura presenting in the pregnancy

Identification of Biomarkers in Patients with Thrombotic Thrombocytopenic Purpura Presenting with Large and Small Ischemic Stroke

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare blood disorder resulting in organ damage including ischemic strokes. We sought to characterize the neuroimaging patterns of stroke in a large cohort of patients with immune-mediated TTP (iTTP) and determined their associations with clinical and laboratory parameters and outcomes. Methods: We analyzed the Alabama TTP Registry who had laboratory confirmation of acute iTTP. We reviewed the neuroimaging patterns of those with ischemic stroke on MRI, clinical information, and laboratory results. Small ischemic strokes were ≤20 mm in their maximum diameter in the axial plane. Large ischemic strokes were >20 mm. Student t test, Mann-Whitney U test, and χ² test were all used for data analysis. Results: Of 108 iTTP patients, 21 had ischemic stroke on neuroimaging. The median platelet count in these patients was 12 × 10⁹/L (interquartile range, IQR, 8.8–21 × 10⁹/L), plasma ADAMTS13 activity 1.8 U/dL (IQR 0–4.5 U/dL), and the mean plasma level of anti-ADAMTS13 IgG was 6,595.8 U/mL (SD 3,448.9 U/mL). Comparison between patients with large ischemic strokes (n = 10) and small ischemic strokes (n = 11) revealed that patients with small stroke were older (p = 0.043) and had higher plasma levels of citrullinated histone 3 (p = 0.006) and histone/DNA complex (p = 0.014) than those with large strokes. There were no significant differences between 2 stroke groups in mortality or exacerbation. Conclusions: iTTP patients can present with large ischemic strokes and are usually younger. Further research should be performed in assessing different etiologies of iTTP-associated stroke based on neutrophil extracellular trap formation biomarkers (e.g., histone markers) seen in small ischemic stroke.

Dengue Fever Complicated with Thrombotic Thrombocytopenic Purpura: A Case Report and Literature Review

Thrombotic thrombocytopenic purpura (TTP) is a hematological disorder with an incidence of around 6.5 cases per million every year. It is characterized by the clot formation in blood vessels and resulting thrombocytopenia due to widespread utilization in the process. Other clinical features include hemolytic anemia, neurological abnormalities, fever, and renal failure. The cause can be either congenital or acquired secondary to infections, the use of certain drugs, and autoimmune disorders. On the other hand, Dengue fever is a viral infection that can result in multiple systemic complications including disrupted coagulation, renal dysfunction, and inflammation in the liver, brain, and myocardial pathology. In this case report, we present a rare presentation of thrombotic thrombocytopenic purpura in a patient with dengue fever. The mortality rate, in untreated cases, has been reported by up to 90%. With timely diagnosis and management with plasmapheresis, this can be reduced to 10-20%. Currently, it is important to control such an unknown outbreak of Dengue fever, as it is a serious health care issue of disease control and prevention in Pakistan.

An Unusual Presentation of Thrombotic Thrombocytopenic Purpura

An Unusual Presentation of Thrombotic Thrombocytopenic Purpura

Recurrent ischemic strokes as the initial presentation of thrombotic thrombocytopenic purpura with normal platelets: a case report. (P1.296)

Recurrent ischemic strokes as the initial presentation of thrombotic thrombocytopenic purpura with normal platelets: a case report. (P1.296)

Thrombotic thrombocytopenic purpura presenting as acute coronary syndrome

Key Clinical MessageIn patients presenting with thrombotic thrombocytopenia purpura and non‐ST elevation myocardial infarction, prompt initiation of plasma exchange takes precedence over other invasive diagnostic procedures for coronary artery disease. Such procedures should be delayed until clinical condition and laboratory parameters have been stabilized.

Atypical presentations of thrombotic thrombocytopenic purpura: a diagnostic role for ADAMTS13.

Thrombotic thrombocytopenic purpura (TTP) is an acute, life threatening disease. Only a minority of patients expresses the complete clinical presentation and unusual manifestations can occur. Demonstration of low activity levels of ADAMTS13 (<5%) is highly specific for the diagnosis of TTP. This study reports a series of five cases of TTP presenting with a thrombotic event and no hematological findings. Detailed chart reviews on these patients were conducted. We identified two patients whose first attack of TTP presented as a thrombotic episode without microangiopathic hemolytic anemia and thrombocytopenia, only to be diagnosed as TTP days later, after the appearance of hematological signs. We also describe three cases of classical TTP relapsing atypically as cerebrovascular accidents without hematological signs. Low levels of ADAMTS13 activity were detected and facilitated the diagnosis. The neurological manifestations disappeared concurrent with normalization of ADAMTS13 activity level after plasma exchange. This study underscores the importance of having a high clinical suspicion of TTP in cases of thrombosis even without hematological abnormalities in patients with previous attacks of TTP. In this clinical scenario, measurement of ADAMTS13 activity is important for diagnosis and early administration of treatment.

How I treat catastrophic thrombotic syndromes

AbstractCatastrophic thrombotic syndromes are characterized by rapid onset of multiple thromboembolic occlusions affecting diverse vascular beds. Patients may have multiple events on presentation, or develop them rapidly over days to weeks. Several disorders can present with this extreme clinical phenotype, including catastrophic antiphospholipid syndrome (APS), atypical presentations of thrombotic thrombocytopenic purpura (TTP) or heparin-induced thrombocytopenia (HIT), and Trousseau syndrome, but some patients present with multiple thrombotic events in the absence of associated prothrombotic disorders. Diagnostic workup must rapidly determine which, if any, of these syndromes are present because therapeutic management is driven by the underlying disorder. With the exception of atypical presentations of TTP, which are treated with plasma exchange, anticoagulation is the most important therapeutic intervention in these patients. Effective anticoagulation may require laboratory confirmation with anti–factor Xa levels in patients treated with heparin, especially if the baseline (pretreatment) activated partial thromboplastin time is prolonged. Patients with catastrophic APS also benefit from immunosuppressive therapy and/or plasma exchange, whereas patients with HIT need an alternative anticoagulant to replace heparin. Progressive thrombotic events despite therapeutic anticoagulation may necessitate an alternative therapeutic strategy. If the thrombotic process can be controlled, these patients can recover, but indefinite anticoagulant therapy may be appropriate to prevent recurrent events.

Atypical presentations of thrombotic thrombocytopenic purpura in middle-aged women with recurrent cerebral macrovascular thrombosis: a case report

Dear Editor, In the current clinical practice, minimal criteria to define thrombotic thrombocytopenic purpura (TTP) are the presence of signs of microangiopathic haemolytic anaemia and low platelet (PLT) count [1]. TTP relapses (20–50 % of cases) are defined as the recurrence of acute TTP symptoms 30 days after the first episode, while exacerbations occur within 30 days [2]. We here report on an atypical case of acquired TTP where minimal criteria were met only after many recurrent macrovascular ischemic events. A 42-year old Caucasian woman with a history of coronary and cerebral ischemic events was admitted on June 2013, following a recurrent transient ischemic attack (TIA). She had severe anaemia and thrombocytopenia with laboratory signs of intravascular haemolysis and mild renal impairment. In her past medical history, recurrent ischemic events occurred from 2008 to 2012, without known risk factors and regardless of treatment. The patient was treated with acetyl salicylic acid (100 mg daily) after the first ischemic event (stroke, in 2008) plus anticoagulation with warfarin after the third stroke (in 2010), with a good compliance . Screening for autoimmune disease, Factor V Leiden and Factor II (G20210A) gene mutations and circulating anticoagulants were normal. Blood cell count and peripheral blood smear did not show any significant abnormalities in the past, without evidence of schistocytes; a slight decrease in PLT count (92×109/L) was observed only once (in 2012), at that time, ADAMTS13 activity (ADAMTS-13: AC) was 65 %. At the current admission, ADAMTS-13: AC was 6 %, inhibitors were at high titer (2 Bethesda Units, BU). A genetic test for Upshaw-Schulman syndrome was normal. Therapeutic plasma exchange (TPE) and prednisone (1 mg/kg body weight) treatment was started and maintained until clinical and haematological remission [3]. TPE (Gambro®, Italy) was performed daily for 3 weeks with an increase of ADAMTS13: AC to 50 %. TTP exacerbated after 10 days, it was well controlled with weekly rituximab (375 mg/m body surface), for 4 weeks. A relapse occurred after 37 days with the patient presenting seizures: ADAMTS-13: AC, which was 54 % after the last treatment, had decreased to 6 %. A second course of weekly rituximab, followed by maintenance with azathioprine (50 mg twice daily for 10 days, then 50 mg, daily) was followed by clinical and haematological remission. Rituximab was re-administered for its previous rapid efficacy and to prevent further complications [4]. The patient is alive and free from recurrences for 18 months; azathioprine maintenance is still on course. ADAMTS13: AC is monitored every 4 months, and it ranges from 45 to 51 %; inhibitors are no longer detectable. * Alessandro Lucchesi alessandro.lucchesi@irst.emr.it

The Total Pentad: a Case Report of Thrombotic Thrombocytopenic Purpura Presenting as an Acute Cerebrovascular Accident

Thrombotic Thrombocytopenic Purpura (TTP) is a rare blood-coagulation disorder that causes extensive thrombus formation within the blood vessels. Diagnosis of the disorder is made on the basis of identification of some or all of five clinical features, described as the typical “pentad”: thrombocytopenia, microangiopathic hemolytic anemia, fluctuating neurological symptoms, renal failure, and fever. We report the case of a middle aged female who presented to an urban teaching hospital emergency department. Her initial symptoms of TTP were subtle, making it difficult to achieve a definitive early diagnosis. Awareness of the disorder allowed us to follow through on monitoring for the pentad during the initial period of hospitalization and facilitated the diagnosis, which led to prompt and appropriate treatment. The patient made a complete and sustained recovery. Since prompt institution of plasmapheresis is essential to recovery, we share this case in order to increase the possibility that TTP will be considered in the differential diagnosis of patients presenting with all or part of the total pentad.

Gastrointestinal Ischemia as the Initial Presentation of Thrombotic Thrombocytopenic Purpura

Gastrointestinal Ischemia as the Initial Presentation of Thrombotic Thrombocytopenic Purpura

A case series of atypical presentations of thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is a heterogeneous disease primarily characterized by thrombocytopenia and microangiopathic hemolytic anemia. Therapeutic plasma exchange has dramatically improved mortality, allowing for emergence of refractory, relapsing, and atypical presentations. In this article, we describe four cases of TTP presenting with minimal schistocytes, mild elevation of lactate dehydrogenase, and symptoms suggestive of macrovascular arterial involvement. With increasing reports of less common presentations of TTP, clinicians should consider this diagnosis in cases of unexplained arterial thrombosis, thrombocytopenia, or hemolytic anemia. Testing for a disintegrin and metalloprotease with thrombospondin Type 1 motif, Member 13 ADAMTS13 activity was extremely useful to help confirm the diagnosis in our series of patients.

Atypical Presentation of Thrombotic Thrombocytopenic Purpura: A Rare Entity

Atypical Presentation of Thrombotic Thrombocytopenic Purpura: A Rare Entity

A Rare Case of Thrombotic Thrombocytopenic Purpura Presenting With Pancreatitis

Thrombotic thrombocytopenic purpura (TTP) is a rare disease characterized by platelet consumption in thromboses, leading to a microangiopathic hemolytic anemia (MAHA). Thrombotic thrombocytopenic purpura involves a decrease in the activity of a metalloproteinase, ADAMTS13, which is critical in regulation of the coagulation cascade. This occurs in several conditions, and therefore, TTP is associated with a number of diseases. The decreased activity of ADAMTS13 leads to occlusive platelet thrombi, which can result in a variety of tissue manifestations. Patients normally present with nonspecific symptoms, such as fever and petechia. The classic pentad, although now extraordinarily uncommon, includes thrombocytopenia, MAHA, varying degrees of renal failure, fever, and nonlocalizable neurologic symptoms. We present a rare case in which pancreatitis was the presenting condition in a patient with acute idiopathic TTP. We discuss the pathogenesis and etiologies of these 2 diseases.

Atypical clinical presentation of thrombotic thrombocytopenic purpura just after percutaneous coronary intervention

Atypical clinical presentation of thrombotic thrombocytopenic purpura just after percutaneous coronary intervention