Pulmonary Tuberculosis Complicated by Thrombotic Thrombocytopenic Purpura: A Case Report and Literature Review.

Thrombotic thrombocytopenic purpura is a rare but life-threatening emergency. Tuberculosis can have hematologic complications. However, concurrent tuberculosis and thrombotic thrombocytopenic purpura are extremely rare. In this study, we report a 53-year-old man who was initially treated for pulmonary tuberculosis but later developed weakness and an altered mental status. Laboratory tests revealed evidence of thrombocytopenia, acute renal insufficiency, and microangiopathic hemolytic anemia. Brain imaging identified intracranial hemorrhage. Further testing revealed low ADAMTS13 activity (1.8%) and positive anti-ADAMTS13 antibody, confirming the diagnosis of thrombotic thrombocytopenic purpura. The patient had a full recovery after anti-tuberculosis treatment, plasma exchange, and supportive care. We present this rare case and review previous relevant studies to remind clinicians about the potential connections between tuberculosis and thrombotic thrombocytopenic purpura. In patients with signs of severe thrombocytopenia and microangiopathic hemolysis, necessary diagnostic tests should be performed to eliminate the possibility of thrombotic thrombocytopenic purpura occurring concurrently with tuberculosis.

Diagnostic and Therapeutic Strategies in Evans Syndrome: A Case Report and Literature Review.

Evans syndrome (ES) is characterized by a combination of autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). Immune dysregulation, which results in the development of antibodies against blood cells, is its defining feature. ES being a diagnosis of exclusion requires a thorough workup to rule out other probable illnesses like lymphoproliferative diseases and systemic lupus erythematosus (SLE). We present the case of a 38-year-old male who experienced shortness of breath, chest discomfort, and generalized weakness. His medical history included recurrent anemia, thrombocytopenia, and pulmonary tuberculosis in remission. Hemolysis, thrombocytopenia, and a large pericardial effusion were discovered during the physical examination and investigations. An initial treatment strategy that included pericardiocentesis was performed. In combination with AIHA and ITP, the clinical and laboratory findings strongly suggested ES, which improved with prednisolone therapy. First-line treatments consist of corticosteroids and intravenous immunoglobulin; refractory cases may also require rituximab, thrombopoietin receptor antagonists, and sirolimus. Achieving remission and lowering relapse rates need careful patient monitoring and customized treatment programs.

Iatrogenic hemorrhage and extensive venous thromboembolism during iTTP treatment with caplacizumab-A case report.

Caplacizumab reduces the need for therapeutic plasma exchange (TPE) during treatment for thrombotic thrombocytopenic purpura (TTP), associates with fewer required TPE, and shortens hospital stay. It is therefore recommended as part of standard care. However, the treatment effects on hemostasis may complicate initial management. We present a case of a woman with immune-mediated TTP who developed an intrathoracic hemorrhage on caplacizumab treatment after replacement of her central venous catheter. Reduced von Willebrand factor (vWF):glycoprotein Ib mutant (GPIbM) activity was reversed using vWF concentrate and the bleeding stopped. Unfortunately, vWF substitution in combination with caplacizumab discontinuation likely contributed to subsequent extensive venous thromboembolism. Risk-reducing strategies against both bleeding and thrombosis are crucial during caplacizumab treatment, and emergency vWF substitution increases the already high risk of thrombosis associated with TPE.

Fostamatinib for immune thrombocytopenic purpura in adult patients: A systematic review and meta-analysis.

Immune thrombocytopenic purpura (ITP) is an immune disorder characterized by thrombocytopenia. Fostamatinib is an orally administered spleen tyrosine kinase inhibitor intended to treat refractory ITP. To evaluate the efficacy and safety of fostamatinib as a subsequent-line therapy for ITP in adults. We searched four electronic databases for primary studies of any design. Primary efficacy outcomes included proportions of patients achieving overall (≥30 × 109 cells/L), partial (≥50 × 109 cells/L), and stable (as defined in original studies) platelet response. Safety outcomes included rescue medication use and other adverse events. We used narrative synthesis and Mantel-Haenszel random effect meta-analysis to summarize results. Our systematic review included 11 studies for analyses (n = 722). Weighted mean proportions of patients achieving overall, partial, and stable responses with fostamatinib treatment were 0.70 [0.62, 0.76], 0.48 [0.36, 0.61], and 0.28 [0.16, 0.44], respectively. Fostamatinib was favored over placebo for partial (relative risk [RR] = 3.04, 95% confidence interval [CI] [1.53, 6.06]) and stable (RR = 6.43, 95% CI [1.58, 26.23]) responses. Patients on fostamatinib required less rescue medication and were more likely to experience hypertension. Fostamatinib is a viable subsequent-line therapy option for refractory ITP. Given the heterogeneous data and large number of small studies, these results should be interpreted cautiously.

External validation of a predictive model for aged-related skin tears in Fitzpatrick skin types I-IV cohort.

Older Australians are at increased risk of skin tears with the risk not always recognised or the injury able to be prevented. This study externally validated Rayner et al. (2019) Skin Tear Risk Prediction Model in an independent aged cohort with a Fitzpatrick skin types I-IV from across multiple residential-care sites, over a 6-month period. A total of 362 individuals aged between 65 and 102.5 years completed the study. In all, 165-residents sustained one or more skin tears. Logistic regression analysis was conducted of the five variables (gender, previous history of skin tears, previous history of falls, purpura and solar elastosis) identified in the skin tear model. The skin tear model provided 'good' to nearly 'very good discrimination' for correctly classifying residents at-risk or not-at-risk (area under the curve of 0.799 [95% confidence interval, CI: 0.75-0.84]). The skin tear model correctly predicted 75.8% (sensitivity) of participants with skin tears and 71.6% (specificity) of residents without skin tears. The model demonstrated it could work as a screening tool to identify older individuals at risk of skin tears and would benefit clinical practice as it was easy to use, was reproducible, and had good accuracy across aged-care residents with a Fitzpatrick skin type I-IV.

A Systematic Review of the Epidemiology and Disease Burden of Congenital and Immune-Mediated Thrombotic Thrombocytopenic Purpura.

Congenital (cTTP) and immune-mediated (iTTP) thrombotic thrombocytopenic purpura are serious and rare clotting disorders resulting from a deficiency in the ADAMTS13 enzyme. A systematic review was conducted using the Ovid® MEDLINE & Embase databases to synthesize the epidemiology and burden of cTTP and iTTP worldwide (from January 1, 2010, to February 6, 2020, with an update that covered the period January 1, 2020-February 11, 2022). Outcomes of interest were incidence and prevalence of TTP, incidence of acute episodes, mortality, burden of illness (eg complications, healthcare utilization, patient-reported outcomes) and disease management. A total of 221 eligible observational studies were included. The incidence rate of acute episodes ranged from 0.19-0.35 person-years in adult patients with cTTP, and 1.81-3.93 per million persons per year for iTTP in the general population. Triggers of acute episodes were similar for cTTP and iTTP, with pregnancy and infection the most commonly observed. Exacerbation in patients with iTTP varied widely, ranging from 2.4-63.1%. All-cause mortality was observed in 0-13.4% of patients with cTTP, across studies and follow-up periods, and in 1.1% (median follow-up: 0.4 years) to 18.8% (1 year) of patients with iTTP during acute episodes. Cardiovascular, renal, and neurological disease were common complications. TTP also led to work disturbances, feelings of anxiety and depression, and general activity impairment. TTP treatment regimens used were generally reflective of current treatment guidelines. The evidence identified describes a high patient burden, highlighting the need for effective treatment regimens leading to improvements in outcomes. Considerable evidence gaps exist, particularly for disease epidemiology, patient-reported outcomes, costs of disease management, and associated healthcare resource utilization. This review may help increase disease awareness and highlights the need for additional real-world studies, particularly in geographical regions outside the United States and Western Europe.

Recurrent, atraumatic acute compartment syndrome secondary to IgA vasculitis: A case report.

Acute compartment syndrome is a surgical emergency requiring rapid recognition in the emergency department to minimize morbidity and mortality. It is most commonly caused by traumatic extremity fractures, which account for about 75% of cases. Atraumatic acute compartment syndrome is substantially less common with current evidence mostly limited to case reports, and diagnosis is made more challenging by the absence of an obvious traumatic injury. We present the case of a young adult female patient with IgA vasculitis who developed recurrent, atraumatic acute compartment syndrome and was successfully managed with prompt fasciotomy. This is the first case of spontaneous intramuscular hemorrhage, a rare sequela of IgA vasculitis, leading to recurrent, atraumatic acute compartment syndrome. This case highlights the importance of both a thorough physical exam and maintaining a high suspicion for acute compartment syndrome in the absence of injury to ensure patients receive prompt surgical evaluation for definitive care.

Effect of Immune Thrombocytopenic Purpura Medications on Depression Risk: An Analysis of NHANES Data.

BACKGROUND: Immune thrombocytopenic purpura (ITP) in adults typically develops slowly and insidiously. The ITP medications might be linked to psychological disorders, but the connection is not well-understood. OBJECTIVE: This study aimed to examine the association between ITP medication use and the risk of depression among participants in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. METHODS: Using data from 70 190 NHANES participants, we conducted a cross-sectional study, excluding individuals under 18 years, with hypertension, HIV, hepatitis C, and various comorbidities. A total of 17 299 individuals were included in the analysis of this study. We identified 2 populations within this study: those using ITP medications, including prednisone, dexamethasone, and rituximab and those not using ITP drugs. Depression status was assessed using the Patient Health Questionnaire-9 (PHQ-9), and the relationship between ITP medication use and depression was analyzed through multivariate logistic regression. RESULTS: There was no significant association between ITP medication use and an increased risk of depression after adjusting for demographic and health-related variables. Notably, among the study participants, 1.8% of the non-depressed population were on ITP medication compared with 0.3% in the depressed population. The analysis revealed varying depression risks associated with different sociodemographic factors. For instance, the correlation between ITP medication and depression risk was influenced by a combination of age, race, income, and smoking status. CONCLUSION AND RELEVANCE: The study suggests that ITP medication use does not independently increase the risk of depression. This finding is crucial for guiding clinical decisions and managing patient expectations regarding ITP treatment and its psychological impacts.

Longitudinal characterization of symptoms, healthcare resource utilization, and costs among people with thrombotic thrombocytopenic purpura compared with non-thrombotic thrombocytopenic purpura controls.

AIMS: Thrombotic thrombocytopenic purpura (TTP) is an ultra-rare blood disorder, characterized by severe ADAMTS13 deficiency. Affected individuals present with potentially life-threatening acute events and may experience sub-acute and chronic TTP manifestations often resulting in long-term organ damage. Incremental symptom prevalence before, during, and after an acute event as well as healthcare resource utilization (HCRU) and costs during and after an acute event were compared between people with TTP and matched non-TTP controls. METHODS: This retrospective, matched study used data from Merative™ MarketScan® Commercial Database and Medicare Supplemental Database (from January 1, 2008, through September 30, 2021) to identify people with TTP (inpatient diagnosis for "thrombotic microangiopathy (TMA)" or "congenital TTP," and ≥1 claim for plasma exchange or infusion). People with TTP were matched (1:2) with non-TTP controls on age, sex, geographic region, index year, and select Elixhauser comorbidities. RESULTS: 255 people with TTP were matched with 510 non-TTP controls. Both cohorts had a mean age of 43.9 years; 71% were female. Overall, more people with TTP reported symptoms compared with non-TTP controls prior to (51% vs 43%), during (99% vs 52%), and after an acute event (85% vs 50%; p < 0.05 for all periods). Symptom prevalence decreased following an acute event compared with during an acute event, but remained high-85% of people with TTP experienced symptoms compared with 50% of non-TTP controls. HCRU and mean costs per patient per month were significantly higher in all care settings among people with TTP compared with non-TTP controls (p < 0.05). LIMITATIONS: Identification of patient populations may have been limited due to coding errors, as the data were obtained from an administrative claims database. CONCLUSIONS: TTP is associated with a substantial symptom burden and increased costs and HCRU during and up to almost a year after acute events, demonstrating the longitudinal burden of this disease.

Dermatoscope for the diagnosis of erythema with purpura induced by lidocaine/prilocaine cream: A case report.

BACKGROUND: Lidocaine/prilocaine (EMLA) cream is a local anesthetic that is applied to the skin or mucosa during painful therapeutic procedures with few reported side effects. CASE SUMMARY: Here, we report the use of dermatoscopy to identify a case of erythema with purpura, a rare side effect, after the application of 5% EMLA cream. CONCLUSION: We conclude that erythema with purpura is caused by irritation and toxicity associated with EMLA, but the specific mechanism by which the toxic substance affects skin blood vessels is unclear. In response to this situation and for cosmetic needs, we recommend tranexamic acid, in addition to routine therapy, to prevent changes in pigmentation in patients with dermatitis.

Managing surgical relapse risk in acquired thrombotic thrombocytopenic purpura: a systematic review.

•Thrombotic thrombocytopenic purpura (TTP) may relapse after surgery.•In a systematic review, we assessed preoperative TTP prophylaxis.•Pre-emptive ADAMTS-13 activity measurement prior to surgery may improve relapse risk.•Preoperative TTP prophylaxis may lower surgical relapse risk.

Vitamin B12 deficiency misdiagnosed as TTP: What can we learn from it?

The case report by Dwyre et al. shows that vitamin B12 deficiency may be misdiagnosed as acute thrombotic thrombocytopenic purpura. Together with similar observations, this underlines that acquired vitamin B12 deficiency-besides the inherited disorder of intracellular cobalamin metabolism, cbl C disease-should be listed as a separate entity of the thrombotic microangiopathies. Commentary on: Dwyre et al. Microangiopathic thrombocytopenia caused by vitamin B12 deficiency responding to plasma exchange. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19625.

Practical Considerations for the Use of the Rapid AcuStar® ADAMTS13 Activity Assay in the Diagnosis of Acute Thrombotic Thrombocytopenic Purpura (TTP).

Introduction: Conventional practice in the management of acute TTP entails empirical treatment of suspected cases whilst awaiting confirmatory ADAMTS13 deficiency testing. Rapid ADAMTS13 assays offer increased accessibility and rapid diagnostics. The new automated HemosIL AcuStar® ADAMTS13 assay has seen increasing use among UK TTP Specialist Centres alongside the traditional ELISA method to confirm severe ADAMTS13 deficiency. Methods: A multi-centre retrospective case-control study was performed to review patients demonstrating discrepant ADAMTS13 activity results measured using rapid (AcuStar®) and ELISA assays in parallel from September 2019 to December 2021. Cases were compared with a cohort of suspected TTP patients exhibiting no difference in assay results and in relation to their presenting characteristics and pre-test probability of a diagnosis of TTP. Results: Where the clinical index of suspicion for TTP was high at presentation, acute TTP was confirmed using the AcuStar® assay < 0.2 IU/dL and subsequently < 10 IU/dL by ELISA with zero incidence of discrepancy. For patients with low clinical suspicion of acute TTP, a discrepancy between the AcuStar® and ELISA assay results was observed in 2% of cases; 5-10 IU/dL in AcuStar®, confirmed as >20 IU/dL by ELISA. A concurrent cancer diagnosis or sepsis was observed in 40% of discrepant cases. Conclusions: Where acute TTP is strongly suspected, there is a good correlation between the rapid AcuStar® ADAMTS13 assay and the conventional ELISA assay. Where the clinical suspicion of acute TTP is low, caution should be exercised in the interpretation of the ADAMTS13 activity using the AcuStar® assay. Accurate interpretation requires robust ADAMTS13 testing algorithms to be incorporated into diagnostic pathways.

ADAMTS13 in the New Era of TTP.

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening, often immune-mediated disease that affects 2-13 persons per million per year. Hemolytic anemia, thrombocytopenia, and end-organ damage due to the formation of microthrombi are characteristic of TTP. ADAMTS13 is a disintegrin, metalloproteinase, cleaving protein of von Willebrand factor (VWF) that processes the VWF multimers to prevent them from interacting with platelets and, in turn, to microvascular thrombosis. Prompt diagnosis of TTP is critical yet challenging. Thrombotic microangiopathies have similar clinical presentation. Measurement of ADAMTS13 activity helps in the differential diagnosis. Less than 10% ADAMTS13 activity is indicative of TTP. Laboratory ADAMTS13 activity assays include incubating the test plasma with the substrate (full-length VWM multimers) and detection with direct or indirect measurement of the cleavage product. The purpose of this study is to examine the diagnostic potential, advantages, and weaknesses of the ADAMTS13 potency in TTP.

Frontline use of rituximab may prevent ADAMTS13 inhibitor boosting during caplacizumab treatment in patients with iTTP: post hoc analysis of a phase 2/3 study in Japan.

BACKGROUND: A recent Phase 2/3 study in Japanese patients showed that caplacizumab was effective in treating immune-mediated thrombotic thrombocytopenic purpura (iTTP), with a low rate of iTTP recurrence. ADAMTS13 activity is monitored weekly during caplacizumab treatment to guide discontinuation of caplacizumab and consequently avoid exacerbations or relapse. The aim of this study was to assess changes in ADAMTS13 activity/inhibitor levels during caplacizumab treatment in this patient population. METHODS: A post hoc analysis of the Phase 2/3 study in Japanese patients was conducted. Patients ≥ 18 years old with confirmed iTTP received 10 mg of caplacizumab daily in conjunction with therapeutic plasma exchange (TPE) and immunosuppression for 30 days post-TPE. Outcomes included time to recovery of ADAMTS13 activity, ADAMTS13 activity level at treatment end, incidence of ADAMTS13 inhibitor re-elevation (ie, inhibitor boosting) during treatment, time to platelet count recovery, number of days of TPE, and safety. Outcomes according to presence of inhibitor boosting were also assessed. RESULTS: Nineteen patients had confirmed iTTP and were included in this analysis. Median (95% confidence interval) time to recovery of ADAMTS13 activity to ≥ 10%, ≥ 20%, and ≥ 60% was 14.6 (5.9-24.8), 18.5 (5.9-31.8), and 47.5 (18.5-60.9) days, respectively. Median (range) ADAMTS13 activity level at caplacizumab treatment end was 62.0% (29.0-101.0). Nine patients had ADAMTS13 inhibitor boosting. Delayed response of ADAMTS13 activity was observed in patients with inhibitor boosting. The median time to platelet count response and median number of TPE days were shorter in patients with inhibitor boosting compared with patients without inhibitor boosting. Rituximab was administered to almost all patients with inhibitor boosting (88.9%), after completion of TPE. Patients without inhibitor boosting who were treated with rituximab received it prior to completion of TPE. Only one patient experienced a recurrence, which occurred shortly after caplacizumab discontinuation due to an adverse event. CONCLUSIONS: In patients with iTTP, caplacizumab with TPE and immunosuppression may reduce the risk of ADAMTS13 inhibitor boosting if rituximab is administered early in the iTTP treatment period. Early administration of rituximab in addition to caplacizumab may prevent iTTP recurrence with inhibitor boosting. TRIAL REGISTRATION: NCT04074187.

Relationship between response to first-line steroid treatment in adult immune thrombocytopenic purpura and the course of the disease.

BACKGROUND: Immune thrombocytopenic purpura, a recurrent autoimmune disease, is characterized by thrombocytopenia, purpura and hemorrhagic episodes with the main factor in the pathogenesis of this disease being autoantibodies against platelets. Since the 1950s, first-line treatment has been glucocorticoids that have indirect and direct effects on thrombocytopenia. Although the characteristics associated with the chronicization of immune thrombocytopenic purpura at the time of diagnosis have been investigated in previous studies, no study was found in the literature investigating the relationship between the response to first-line steroid treatment and the course of the disease, the aim of this study. MATERIALS AND METHODS: This retrospective, single center study revisited electronic files of patients with a diagnosis of immune thrombocytopenic purpura between September 2012 and September at the Department of Clinical Hematology, Selcuk University Faculty of Medicine 2022. The platelet count had been confirmed by peripheral blood smears of patients with a platelet count ≤30 × 109/L. The bleeding status of patients at the time of diagnosis was evaluated according to the immune thrombocytopenic purpura bleeding score. Patient responses to treatment were categorized in three groups: a platelet count ≤30 × 109/L was defined as no-response, a platelet count of 30-100 × 109/L was defined as partial response, and a platelet count >100 × 109/L was defined as complete response. Subsequently, patients in the partial or complete response groups were divided into two subgroups: patients who remained in remission for less than or more than six months. RESULTS: A total of 100 patients were included in the study; 73 % were in the young (19-65 years old) and 27 % in the old (>65 years old) age group. Most of the patients were female (69 %). Forty-one patients were hospitalized without bleeding. The complete response rate to first-line treatment was 61 %. There was no significant difference between the agents given in first-line treatment in terms of response and length of remission. CONCLUSION: The main purpose of immune thrombocytopenic purpura treatment is to prevent severe bleeding rather than bringing the platelet count to normal values. Glucocorticoids, the first step of treatment, provide high response rates. There is no significant difference between glucocorticoid agents in terms of response to treatment and long-term remission. The points to be considered in the selection of glucocorticoid agents are the side effect profiles, ease of administration and individualization of treatment.

Development of Palpable Purpura in a Patient With Infective Endocarditis: A Case Report.

Infective endocarditis (IE) can present with a variety of signs and symptoms, including skin lesions. The few papers describing a relationship between IE and vasculitis are split between IE being able to mimic vasculitis and between IE indeed being associated with a vasculitis involving the skin, kidney, gastrointestinal tract, or peripheral nerves. It is important for clinicians to distinguish between an isolated vasculitis, infective endocarditis, and IE-associated vasculitis because the treatments and outcomes are different. We report a case of a patient with a history of intravenous (IV) drug use who initially presented with chest pain, was started on vancomycin following diagnosis of methicillin-resistant Staphylococcus aureus (MRSA) IE, left against medical advice (AMA), and then returned to the hospital due to development of a purpuric rash. We contend that while he did not have a skin biopsy due to time delay, his symmetrically distributed purpura was consistent with cutaneous vasculitis. His symptoms, including his rash and an acute kidney injury (AKI), improved with antibiotics to treat the endocarditis.

Púrpura fulminante postinfecciosa: a propósito de un caso / Postinfectious purpura fulminans: A case report

La púrpura fulminante adquirida postinfecciosa es una entidad aguda y grave, poco frecuente, caracterizada por necrosis cutánea asociada a coagulopatía intravascular diseminada (CID), en ausencia de infección activa o alteraciones previas de la coagulación. Afecta fundamentalmente a la población pediátrica y, en el 90 % de los casos, está precedida por un proceso infeccioso. El mecanismo fisiopatológico es un déficit transitorio de proteína S mediado por autoanticuerpos que favorece un estado de hipercoagulabilidad. Se presenta el caso de un varón de 8 años previamente sano, con lesiones cutáneas purpúricas características de púrpura fulminante asociada a CID en ausencia de sepsis. Se constató deficiencia plasmática transitoria de proteína S. Requirió tratamiento sustitutivo con plasma fresco congelado y anticoagulación; la evolución fue favorable. La actividad de la proteína S permaneció disminuida durante 2 meses.

Acquired postinfectious purpura fulminans is a rare, acute, and severe disease characterized by skin necrosis associated with disseminated intravascular coagulation (DIC) in the absence of active infection or previous coagulation disorders. It mainly affects the pediatric population and, in 90% of cases, it is preceded by an infectious process. The pathophysiological mechanism is a transient autoantibodymediated protein S deficiency that favors a hypercoagulable state. Here we describe the case of a previously healthy 8-year-old boy with purpuric skin lesions typical of purpura fulminans associated with DIC in the absence of sepsis. A transient plasma protein S deficiency was confirmed. He required replacement therapy with fresh frozen plasma and anticoagulation; he had a favorable course. Protein S activity remained decreased for 2 months.

Hypermethylation of the FOXP3 gene regulates Tregs immunodysregulation in chronic idiopathic thrombocytopenic purpura.

BACKGROUND: Chronic idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized by a breakdown of immune tolerance; in ITP, the body's immune system mistakenly attacks and destroys platelets. This study aims to investigate the role and underlying mechanisms of FOXP3 in chronic ITP. METHODS: Flow cytometry was used to detect the proportion of CD4+CD25+FOXP3+ regulatory T cells (Tregs) in CD4+CD25+ T lymphocytes from 20 patients with chronic ITP (CITP), 20 acute ITP (AITP) controls, and 20 healthy individuals.CD4+CD25+ Treg cells were isolated from peripheral blood of patients with CITP using magnetic beads and then treated with phosphate-buffered saline solution or decitabine (a methylation inhibitor) for 48 h. The levels of interleukin-2 (IL-2), IL-10, and transforming growth factor-beta1 (TGF-ß1) in the plasma and CD4+CD25+ Treg cells were assessed by Enzyme-linked-immunosorbent serologic assay and quantitative real-time polymerase chain reaction (qRT-PCR). FOXP3 level was measured by qRT-PCR and Western blot analysis. Methylation-specific PCR (MS-PCR) was adopted to detect the status of FOXP3 methylation. RESULTS: The number of Treg cells and the contents of IL-2, IL-10, and TGF-ß1 decreased in patients with CITP, compared to the AITP control group and normal group. FOXP3 expression was reduced and FOXP3 methylation increased in patients with CITP, compared to the AITP control group and normal group. Hypermethylation of FOXP3 promoter led to decrease in FOXP3 level in Treg cells. Inhibition of FOXP3 promoter hypermethylation promoted the secretion of IL-2, IL-10, and TGF-ß1 in Treg cells. CONCLUSION: The number of Treg cells in CITP patients decreased, and the hypermethylation of FOXP3 promoter led to reduction of its expression in Treg cells, thus affecting the immune functioning of Treg cells.

Acquired Thrombotic Thrombocytopenic Purpura (TTP) Presenting With Synthetic Cannabinoid Use.

Synthetic cannabinoids (SCs) have become commercially available throughout the United States as manufacturers circumvent regulations with labels stating "not for human consumption" with misleading advertisements, resulting in the consumption of products that are not safe or regulated. We present a case report of a middle-aged woman exhibiting altered mental status secondary to SC use who was found to have severe thrombocytopenia and hemolytic anemia. She was later confirmed to have thrombotic thrombocytopenic purpura (TTP) through ADAMTS13 testing. TTP is one of several platelet-related disorders presenting with findings of hemolytic anemia and thrombocytopenia. The presence of altered mental status is typically used as a symptomatic differentiator between hemolytic uremic syndrome, immune thrombocytopenic purpura, and TTP. SCs can cause superimposed altered mental status, which, in the setting of a concomitant platelet disorder, can complicate the standard workup and prolong the time to a final diagnosis. This case serves as an essential reminder that collecting detailed social history and promptly recognizing laboratory abnormalities is critical for early recognition of TTP, as the diagnosis is time-sensitive and delays in recognition can lead to significant morbidity and mortality.