Measuring the neuropsychological consequences of thrombotic thrombocytopenic purpura: a rapid literature review

Thrombotic thrombocytopenic purpura and its diagnosis

Retrospective Analysis of Patients Afflicted with Thrombotic Thrombocytopenic Purpura: A Single Institutional Experience.

Randomized clinical trials in thrombotic thrombocytopenic purpura: where do we go from here?

The Novel Use of Daratumumab for Pediatric TTP: A Case Series of Two Pediatric Patients with Refractory TTP

Despite improvements in our understanding of the pathophysiology of thrombotic thrombocytopenic purpura (TTP), little data exist regarding the long-term sequelae following a diagnosis of TTP. We present the results of a comprehensive evaluation of neurologic injury that included a magnetic resonance imaging (MRI), a neurocognitive testing, and an evaluation of health-related quality of life. Twenty-seven patients with a history of idiopathic TTP functioning normally in their activities of daily living were recruited from existing patient cohorts at both the Ohio State University (n 5 12) (Columbus) and the University College London Hospitals (n 5 15) (London, UK). Nine of 23 (39%) of the MRI studies were abnormal; 17/27 (63%) patients demonstrated neurocognitive impairment, particularly in tests of visual learning and memory. Health-related quality of life scores were also significantly lower than age- and gender-matched US norms for both the composite mental component score and physical component score. These data suggest that the prevalence of neurologic findings in TTP patients in remission is quite high and is largely undetected by routine clinical evaluations. Further longitudinal study will be required to define the risk for neurologic injury and the long-term prognosis in patients previously diagnosed with TTP.

Validation of the Plasmic Score and Development of a Novel Predictive Model for Thrombotic Thrombocytopenic Purpura: Exploring Socioeconomic Disparities and Outcomes

277 A Rare Case of Rebif Induced Thrombotic Thrombocytopenic Purpura

Treatment delay and outcomes in elderly thrombotic thrombocytopenic purpura patients: A nationwide analysis.

Impact of Residual Effects and Complications of Thrombotic Thrombocytopenic Purpura (TTP) on Daily Living: A Qualitative Study

Validation of the Plasmic Score for Predicting ADAMTS13 Activity < 10% in Patients Admitted to Hospitals in Alberta with Suspected Thrombotic Thrombocytopenic Purpura

Assessment of the Plasmic Score Utility for Classification of Pediatric Thrombotic Microangiopathies

Introduction: Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy characterized by severely reduced activity of the von Willebrand factor cleaving protease ADAMTS13. It is characterized by small vessel platelet rich thrombi causing thrombocytopenia, microangiopathic hemolytic anemia, and multi organ damage. TTP can be acquired via an immune mediated process due to autoantibodies against ADAMTS13 or hereditary due to variations in the ADAMTS13 gene. Immune TTP has been linked to several pharmacologic agents; the antifungal Terbinafine being anecdotally reported as a potential precipitant. TTP is a medical emergency and can be fatal if not treated promptly. We report a case of immune-mediated TTP in a patient with recent Terbinafine use. Case Presentation: A 39 year old female with rosacea presented to the hospital with one week of nausea, vomiting and syncope, which started after a 21-day course of Terbinafine for tinea corporis. Physical exam revealed scattered petechiae, purpura and pallor. Lab studies were remarkable for hemoglobin 9 g/dL, platelets 20,000 uL, LDH 1,680 uL, undetectable haptoglobin, elevated reticulocyte count, creatinine and troponin. Coagulation studies and antiglobulin testing were normal. Peripheral blood smear showed thrombocytopenia and 1-6 schistocytes per high power field. Brain imaging with CT and MRI confirmed subcentimeter intraparenchymal hemorrhages in parietal, frontal and temporal lobes. ADAMTS13 levels were less than 5% and ADAMTS13 antibody levels greater than 90%. She underwent plasmapheresis and was transferred to a tertiary care center for evaluation of enrollment in clinical trials. She experienced a full recovery, with normalization of platelet levels following the discontinuation of Terbinafine Discussion: Our patient was diagnosed with acquired immune-mediated TTP with multi organ involvement after Terbinafine use. She had severe thrombocytopenia, hemolytic anemia, presence of ADAMTS13 autoantibodies and decreased ADAMTS13 activity-hallmarks of immune TTP. Normal coagulation tests and negative direct antiglobulin testing helped rule out disseminated intravascular coagulation and other hemolytic anemias. The absence of alternative triggers and recent initiation of Terbinafine led to high clinical suspicion of drug-induced TTP. While TTP associated with drug exposure is increasingly recognized, TTP triggered by antifungal agents like Terbinafine are rare. This case highlights the necessity for comprehensive meta-analysis of drug-induced TTP along with pharmacovigilance databases to clarify associations and help clinicians recognize potential triggers. Conclusion: This is a case of immune-mediated TTP in an otherwise healthy 39 year old female following Terbinafine use. Though instances of Terbinafine induced TTP are rare, cases such as this provide foundation for plausibility.

Introduction: Thrombotic Thrombocytopenic Purpura (TTP) is a rare life-threatening condition that is imperative to recognize early as the estimated mortality is 10 – 20% despite therapy. Here we describe a 47-year-old female with metastatic breast cancer who acquired TTP. Case: A 47-year-old woman with angioinvasive ductal carcinoma diagnosed three weeks prior presented with rapidly progressive weakness, fatigue, tachycardia, dyspnea, and anorexia. Her physical exam was unremarkable except for lethargic appearance. She had thrombocytopenia with 22,000 platelets and hemoglobin of 12.9 g/dL; nucleated red blood cells, atypical lymphocytes, metamyelocytes, myelocytes, basophils, and monocytes were elevated. She had a high anion gap metabolic acidosis with elevated creatinine, increased LDH and bilirubin, and low haptoglobin levels. Peripheral smear reduced suspicion of TTP due to few scattered schistocytes. Worsening thrombocytopenia was accompanied by worsening metabolic and respiratory acidosis, anemia, and further deterioration in renal function. Plasmapheresis was initiated following identification of high-density schistocytes on peripheral smear, suggestive of TTP. Despite this, she rapidly deteriorated with subsequent respiratory failure, intubation, and cardiac arrest. Postmortem ADAMTS13 level was 40.7%, suggestive of acquired TTP. Discussion: In cancer patients there are two primary etiologies of TTP: 1) chemotherapy, 2) malignancy itself. In the case of malignancy driven TTP, it is suspected that bone marrow invasion and secondary myelofibrosis play crucial roles. In the presented case, labs suggested bone marrow invasion, and nuclear medicine bone scan showed increased radiotracer uptake in the proximal humeri, distal femora, right sacrum, and proximal left tibia. Hemolytic anemia, renal failure, thrombocytopenia, and schistocytes on peripheral smear raised concern for TTP.Plasmapheresis remains the cornerstone of therapy for TTP. Despite intervention the mortality for cancer patients who develop TTP remains high. One study reports 75% mortality for cancer patients treated with plasmapheresis without chemotherapy due to high rates of TTP recurrence; average survival was 1 month. One patient had remission of TTP and survived 31 months when chemotherapy and plasmapheresis were combined.TTP remains diagnostically challenging due to ADAMTS13 levels requiring several days to result. It requires high clinical suspicion due to high mortality despite therapy. The PLASMIC score and peripheral smear can assist with risk stratification. However, several cases report TTP despite absence of schistocytes, while others report presence of schistocytes without TTP. Therefore, the full clinical picture is imperative when evaluating patients for TTP, particularly in cancer patients where symptoms of metastatic disease and TTP may overlap.

Is ADAMTS-13 deficiency specific for thrombotic thrombocytopenic purpura? No

Rituximab for Prevention of Recurrent Pregnancy Related Thrombotic Thrombocytopenic Purpura in High Risk Patients with Previous Episodes of Thrombotic Thrombocytopenic Purpura during Pregnancy