Caplacizumab as an add-on therapy in a 7-year-old girl with exacerbated immune-mediated thrombotic thrombocytopenic purpura, a case report and literature review.

The cornerstone treatment for immune-mediated thrombotic thrombocytopenic purpura (iTTP) in children is a combination of therapeutic plasma exchange (TPE), corticosteroids, and rituximab. Caplacizumab is an anti-von Willebrand factor (VWF) NANOBODY molecule approved as a frontline therapy of iTTP for adults and children aged ≥12 years. Using caplacizumab in children aged <12 years remains a gray area based on recommendations but with no marketing authorization. We report the first case of a pediatric patient with iTTP successfully treated with a caplacizumab dose adjustment of 5 mg daily based on ADAMTS13 activity. We also review all published cases of iTTP in children aged <12 years treated with caplacizumab. This is a 7-year-old girl with clinical thrombotic microangiopathy, in the absence of diarrhea and kidney injury. With a French score of 2 and a PLASMIC score of 7 (high risk), the diagnosis of TTP was suspected and later confirmed by severely low ADAMTS13 activity (<5%). Immune-mediated TTP was distinguished from the congenital one due to the presence of a functional ADAMTS13 inhibitor. Daily TPE and intravenous corticosteroids were started on day 0 (D0). Rituximab was added on D4, and due to refractoriness under daily TPE, we considered off-label administration of caplacizumab from D12. A clinical answer, with a significant increase in the platelet count, was observed within 48 h. A complete ADAMTS13 recovery was reached on D62. No major adverse events were observed during the treatment. She was discharged from the hospital over 3 months ago with a platelet count still within normal ranges. In the literature, we identified a total of four case reports describing five iTTP patients aged <12 years treated with caplacizumab, with a 100% success and tolerability rate. These published data attest to the efficacy and safety of the systematic use of caplacizumab and rituximab as frontline therapy in pediatric iTTP under 12 years of age. Therefore, prospective data are needed to support commercial authorization of caplacizumab in this subpopulation. Close monitoring of ADAMTS13 activity is particularly of interest among children to limit the number of caplacizumab injections.

Main features of ischemic stroke in patients with acute immune-mediated thrombotic thrombocytopenic purpura.

BACKGROUND: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a microangiopathy often characterized by acute neurological involvement including ischemic stroke (IS). The characteristics of IS in iTTP remain largely unknown. AIMS: To evaluate the epidemiology, neuroimaging patterns and risk factors of IS in iTTP patients. METHODS: We performed a cross-sectional study of patients enrolled in the Milan TTP Registry presenting with neurological signs/symptoms and underwent neuroimaging evaluation during their first acute iTTP episode. RESULTS: Seventy-eight patients were enrolled, the majority of patients were female (72 %), with a median age of 46 years. Computed tomography (CT) was performed in all patients, and magnetic resonance (MRI) was performed in 38 % of patients. IS was confirmed in 18 out of 78 patients (23 %), most of whom (70 %) showed a non-lacunar pattern with multifocal involvement. In the subgroup of patients who had MRI (n = 30), IS was identified in 12 patients (40 %) and of them 6 (50 %) had a false negative result with CT scan. Patients with IS were slightly older than those without, whereas the prevalence of cardiovascular risk factors and iTTP-related parameters were comparable between the two groups. CONCLUSION: 23 % of patients presenting with neurological manifestations at their first acute TTP episode, showed brain IS. As expected, MRI showed higher sensitivity in detecting ischemic lesions underscoring its usefulness over CT in this setting. An unexpected prevalence of non-lacunar and multifocal stroke patterns warrants further investigation. Cardiovascular risk factors and iTTP-related clinical and laboratory parameters were similarly distributed in patients with and without IS.

Purtscher-Like Retinopathy Secondary to Febrile Illnesses in Pediatric Patients: A Case Series.

PURPOSE: Purtscher-like retinopathy is a rare microvascular occlusive disease that has been reported in few literature especially in pediatric patients. The ocular manifestation is associated with various systemic disorders, though its distinct pathophysiology and appropriate therapies remain unclear. This research presents three cases of Purtscher-like retinopathy secondary to febrile illnesses in pediatric patients. METHODS: Medical history and clinical findings were retrospectively collected. RESULTS: We report a series of three pediatric patients (age range, 7-13 years) who developed Purtscher-like retinopathy, secondary to febrile illnesses, including systemic juvenile idiopathic arthritis, thrombotic microangiopathy, and COVID-19 infection. All patients received steroidal therapy to control underlying conditions and ocular disease, with visual improvement in different degrees. CONCLUSIONS: Clinician awareness of Purtscher-like retinopathy is crucial for the prompt diagnosis and treatment of pediatric patients with protracted high fevers and febrile viral illnesses.

Targeting neutrophils extracellular traps, a promising anti-thrombotic therapy for natural products from traditional Chinese herbal medicine.

Thrombi are the main cause of vascular occlusion and contribute significantly to cardiovascular events and death. Neutrophils extracellular traps (NETs)-induced thrombosis plays a vital role in thrombotic complications and it takes the main responsibility for the resistance of fibrinolysis. However, the conventional anti-thrombotic therapies are inadequate to treat NETs-induced thrombotic complications but carry a high risk of bleeding. Consequently, increased attention has shifted towards exploring novel anti-thrombotic treatments targeting NETs. Interestingly, accumulating evidences prove that natural products from traditional Chinese herbal medicines have a great potential to mitigate thrombosis through inhibiting generous NETs formation and degrading excessive NETs. In this review, we elaborated the formation and degradation of NETs and highlighted its pivotal role in immunothrombosis through interactions with platelets and coagulation factors. Since available anti-thrombotic drugs targeting NETs are deficient, we further summarized the natural products and compounds from traditional Chinese herbal medicines which exert effective actions on regulating NETs formation and also have anti-thrombotic effects. Our findings underscore the diverse effects of natural products in targeting NETs, including relieving inflammation and oxidative stress of neutrophils, inhibiting neutrophils activation and DNA efflux, suppressing granule proteins release, reducing histones and promoting DNA degradation. This review aims to highlight the significance of natural medicines in anti-thrombotic therapies through targeting NETs and to lay a groundwork for developing novel anti-thrombotic agents from traditional Chinese herbal medicines.

Incidence and risk of arterial and venous thrombotic events in Systemic Lupus Erythematosus patients: a population-based study.

OBJECTIVES: Current data on arterial and venous thrombotic events (ATE & VTE) and cardiovascular (CV) risk management in European systemic lupus erythematosus (SLE) population are limited. This study aimed to investigate the incidence and risk of thrombotic events and all-cause death in an Italian SLE cohort over the past decade, along with its pharmacotherapy. METHODS: Incident SLE cases between 2010 and 2019 were identified using administrative health databases of the Lombardy Region. The association between SLE and outcomes, compared with age- and sex-matched controls, was reported as incidence rate per 1000 person-years and as adjusted hazard ratios with 95% confidence intervals. RESULTS: Overall, 2133 SLE patients and 21 283 no-SLE individuals were included. A higher incidence rate of ATE (4.22 vs 2.26 1000 PY), VTE (1.85 vs 0.67 1000 PY,) and all-cause death (15.18 vs 6.22 1000 PY) was reported in SLE patients than in those without (p< 0.0001) as well as an increased risk of ATE (HR, 1.65; 95% CI, 1.20-2.26), VTE (HR, 2.25; 95% CI, 1.35-3.74), and all-cause death (HR, 1.81; 95% CI, 1.52-2.15). After SLE diagnoses, hydroxychloroquine and glucocorticoids were prescribed for at least 60% of patients. Additionally, a higher exposure to cardiovascular medications was also seen in SLE patients. CONCLUSION: Our findings confirmed higher risks of ATE, VTE and all-cause death in SLE patients. While increased CV medications use after SLE diagnoses suggests heightened awareness to CV risk profile, more attention is required to balance SLE disease activity with minimizing exposure to drugs associated with exacerbating CV risk.

The value of CT coronary angiography for a comprehensive assessment of left circumflex artery in Kawasaki disease: 9 years of experience from a tertiary center.

Background: Transthoracic echocardiography (TTE) has traditionally been the primary method for coronary imaging in children with Kawasaki disease (KD). We aimed to evaluate coronary artery lesions (CALs) of the left circumflex artery (LCx) in KD on computed tomography coronary angiography (CTCA). Methods: Over a 9-year period (November 2013-December 2022), 225 children with KD underwent radiation-optimized CTCA on a 128-slice dual-source platform. TTE was performed on the same day, or a day prior or after CTCA. Findings: On CTCA, LCx CALs were seen in 41/225 (18.2%) patients. However, TTE detected CALs in only one third of these patients [15/41 (36.6%)]. CTCA showed 47 LCx CALs in 41 patients-aneurysms in 39 patients (40 fusiform, 2 saccular; 7 giant aneurysms), stenoses in 3, and thrombosis in 2. Thromboses and stenoses were both missed on TTE. Proximal LCx aneurysms were seen in 39 patients-of these, 12 had distal extension. Six patients had distal LCx aneurysms without proximal involvement and 2 non-contiguous multiple aneurysms. Four (9.75%) patients had isolated LCx involvement. Based on CTCA findings, treatment protocols had to be modified in 3/41 (7.3%) patients. Interpretation: This study highlights anatomical findings of LCx involvement in KD. Isolated LCx CALs were noted in 4/41 (9.75%) patients. TTE alone proved inadequate for LCx assessment in children with KD. With abnormalities detected in 18.2% of cases, including those missed by TTE, CTCA emerges as an essential imaging modality. The findings have implications for treatment planning and follow-up strategies in children with KD. Funding: None.

Excessive cleavage of von Willebrand factor multimers by ADAMTS13 may predict the progression of transplant-associated thrombotic microangiopathy.

Background: Transplant-associated thrombotic microangiopathy (TA-TMA) is a fatal complication of hematopoietic stem cell transplantation and is characterized by severe thrombocytopenia, hemolytic anemia, and organ dysfunction. In response to several possible triggers, dynamic multimetric change in von Willebrand factor (VWF) may contribute to inducing microthrombi in circulation in TA-TMA. Objectives: By performing VWF multimer analysis and measuring VWF-degradation product (DP), we unraveled the relationship between multimeric changes in circulating VWF and the pathogenesis of TA-TMA. Methods: This study analyzed 135 plasma samples from 14 patients who underwent allogeneic hematopoietic stem cell transplantation at a single institute. VWF-associated markers, namely VWF:antigen (VWF:Ag), VWF-DP/VWF:Ag ratio, VWF:ristocetin cofactor activity, VWF:ristocetin cofactor activity/VWF:Ag ratio, and ADAMTS13 activity, were analyzed in these samples collected every 7 days. Results: There were 2 patients with definite thrombotic microangiopathy (TMA) and 6 patients who presented with probable TMA that did not progress to definite TMA. Each plasma sample was classified into 3 groups: definite TMA, probable TMA, and non-TMA. VWF multimer analysis showed the absence of high-molecular-weight VWF multimers in probable TMA, whereas the appearance of unusually large VWF multimers was observed in definite TMA. The median value of the VWF-DP/VWF:Ag ratio in probable TMA was elevated to 4.17, suggesting that excessive cleavage of VWF multimers by VWF cleaving enzyme, ADAMTS13, resulted in the loss of high-molecular-weight VWF multimers. Conclusion: During the transition from probable to definite TMA, drastic VWF multimer changes imply a switch from bleeding to thrombotic tendencies. Extensive VWF-DP and VWF multimer analyses provided novel insights.

EASIX (endothelial activation and stress index) predicts mortality in patients with coronary artery disease.

BACKGROUND: Coronary interventions reduce morbidity and mortality in patients with acute coronary syndrome. However, the risk of mortality for patients with coronary artery disease (CAD) additionally depends on their systemic endothelial health status. The 'Endothelial Activation and Stress Index' (EASIX) predicts endothelial complications and survival in diverse clinical settings. OBJECTIVE: We hypothesized that EASIX may predict mortality in patients with CAD. METHODS: In 1283 patients undergoing coronary catheterization (CC) and having a diagnosis of CAD, EASIX was measured within 52 days (range - 1 year to - 14 days) before CC and correlated with overall survival. In an independent validation cohort of 1934 patients, EASIXval was measured within 174 days (+ 28 days to + 11 years) after CC. RESULTS: EASIX predicted the risk of mortality after CC (per log2: hazard ratio (HR) 1.29, 95% confidence interval: [1.18-1.41], p < 0.001) in multivariable Cox regression analyses adjusting for age, sex, a high-grade coronary stenosis ≥ 90%, left ventricular ejection fraction, arterial hypertension and diabetes. In the independent cohort, EASIX correlated with EASIXval with rho = 0.7. The long-term predictive value of EASIXval was confirmed (per log2: HR 1.53, [1.42-1.64], p < 0.001) and could be validated by integrated Brier score and concordance index. Pre-established cut-offs (0.88-2.32) associated with increased mortality (cut-off 0.88: HR training: 1.63; HR validation: 1.67, p < 0.0001 and cut-off 2.32: HR training: 3.57; HR validation: 4.65, p < 0.0001). CONCLUSIONS: We validated EASIX as a potential biomarker to predict death of CAD patients, irrespective of the timing either before or after catheterization.

[Libman-Sachs endocarditis and ischemic stroke : A case report]. / Endocardite de Libman-Sachs et accident vasculaire cérébral ischémique : à propos d'un cas.

Libman-Sacks endocarditis is a rare cardiac manifestation of anti-phospholipid syndromes, in which non-infectious thrombotic vegetations are found on the heart valves. Most patients are asymptomatic whereas the risk of thromboembolism is considerable. Diagnostic work-up is based on questioning and clinical examination data looking for extracardiac signs, biological data and also on imaging, and, above all, echocardiography. We report the case of a 47-year-old female patient with no known history who is admitted to hospital with paresthesia of the right hemi-body associated with dysarthria. Cerebral CT scan confirms a paraventricular ischemic stroke. The etiological work-up for stroke is negative except the transesophageal echocardiogram which reveals mitral valve vegetations. Further investigations lead to the diagnosis of Libman-Sacks endocarditis. Treatment with Coumadin is started, with a target INR of between 2 and 3, as recommended. The clinical course was favourable, with stable lesions on transoesophageal echocardiography carried out later.

Venous recanalisation in the setting of post-thrombotic syndrome: An expert consensus from the French Society of Vascular Medicine (SFMV) and the French Society of Cardiovascular Imaging and Interventional Radiology (SFICV).

Several aspects of the management of post-thrombotic syndrome (PTS) are still a matter of debate, or not yet addressed in international guidelines. The objective of this expert consensus from the French Society of Vascular Medicine (SFMV) and the French Society of Cardiovascular Imaging (SFICV) was to define the main elements of diagnosis and treatment of this syndrome, and to develop a proposal for its preoperative, procedural and follow-up management. In this consensus, the following issues were addressed: clinical and ultrasound diagnosis; pre-procedural workup; indications and contraindications to venous recanalisation; procedures; clinical and duplex ultrasound reports; follow-up; long-term treatment; management of great saphenous vein incompetency; anticoagulant and antiplatelet therapy after venous stenting.

Kidney Biopsy Findings After Lung Transplantation.

Introduction: The early diagnosis of histological kidney damage after lung transplantation (LT) is of paramount importance given the negative prognostic implications of kidney disease. Methods: Three pathologists analyzed all kidney biopsies (KBs) (N = 100) performed from 2010 to 2021 on lung transplant patients in 4 Paris transplantation centers. Results: The main indication for biopsy was chronic renal dysfunction (72% of patients). Biopsies were performed at a median of 26.3 months after transplantation and 15 months after a decline in estimated glomerular filtration rate (eGFR) or the onset of proteinuria. Biopsies revealed a wide spectrum of chronic lesions involving the glomerular, vascular, and tubulointerstitial compartments. The 4 most frequent final diagnoses, observed in 18% to 49% of biopsies, were arteriosclerosis, acute calcineurin inhibitor (CNI) toxicity, thrombotic microangiopathy (TMA) and acute tubular necrosis (ATN). TMA was significantly associated with a combination of mTOR inhibitors (mTORi) or CNIs with biological signs present in only 50% of patients. The eGFR was poorly correlated with most lesions, particularly percent glomerulosclerosis, and with the risk of end-stage renal disease (ESRD). Thirty-four patients progressed to ESRD at an average of 20.1 months after biopsy. Three factors were independently associated with the risk of ESRD: postoperative dialysis, proteinuria >3 g/g and percent glomerulosclerosis >4%. Conclusion: Given the great diversity of renal lesions observed in lung transplant recipients, early referral to nephrologists for KB should be considered for these patients when they present with signs of kidney disease.

Autoantibodies to ADAMTS13 in human immunodeficiency virus-associated thrombotic thrombocytopenic purpura.

BACKGROUND AND OBJECTIVES: Thrombotic thrombocytopenic purpura (TTP) is a potentially fatal thrombotic microangiopathic disorder that can result from human immunodeficiency virus (HIV) infection. The pathogenesis involves a deficiency of the von Willebrand factor (vWF) cleaving protease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin motifs member 13) and the presence of anti-ADAMTS13 autoantibodies. However, there is insufficient information regarding the epitope specificity and reactivity of these autoantibodies. This study aimed to perform epitope-mapping analysis to provide novel insights into the specific epitopes on ADAMTS13 domains affected by autoantibodies. MATERIALS AND METHODS: The study analysed 59 frozen citrate plasma samples from HIV-associated TTP patients in South Africa, measuring ADAMTS13 activity using Technozyme® ADAMTS13 activity test, total immunoglobulin (Ig) M and IgA antibodies levels using ELISA kit and purifying IgG antibodies using NAb™ Protein G spin columns. A synthetic ADAMTS13 peptide library was used for epitope mapping. RESULTS: Overall, 90% of samples showed anti-ADAMTS13 IgG autoantibodies, with 64% of these antibodies being inhibitory, as revealed by mixing studies. Samples with ADAMTS13 antigen levels below 5% showed high anti-ADAMTS13 IgG autoantibody titres (≥50 IU/mL), whereas those with 5%-10% levels had low autoantibody titres (<50 IU/mL).The metalloprotease, cysteine-rich and spacer domains were 100% involved in binding anti-ADAMTS13 IgG antibodies, with 58% of samples containing antibodies binding to the C-terminal part of the ADAMTS13 disintegrin-like domain, indicating different pathogenic mechanisms. CONCLUSION: The metalloprotease, cysteine-rich and spacer domains are the primary targets for anti-ADAMTS13 IgG autoantibodies in patients with HIV-associated TTP. These findings suggest potential effects on the proteolytic activity of ADAMTS13, highlighting the complex nature of the pathogenic mechanisms involved.

AB040. A complication of recurrent artery of Huebner infarction after resection of an anterior cerebral artery thrombotic giant intracranial aneurysm: case report and literature review.

BACKGROUND: Giant aneurysms, comprising 3-5% of all intracranial aneurysms, pose a considerable challenge due to their heterogeneity and complex vascular anatomy. Defined as aneurysms exceeding 2.5 cm in diameter, they often develop intraluminal thrombosis. Despite advancements in neurosurgical techniques, managing giant aneurysms remains complex and highly individualized. Thrombotic giant aneurysms are particularly problematic due to their size and thrombosis potential. This case report is unique as it presents the first documented instance of recurrent artery of Heubner (RAH) infarction following surgical resection of a giant thrombotic aneurysm. CASE DESCRIPTION: A 53-year-old man with no prior systemic presented to our emergency department due to progressive left-sided weakness and slurred speech. Magnetic resonance imaging (MRI) of brain revealed a thrombotic giant intracranial aneurysm on right anterior cerebral artery (ACA). Surgical resection was performed using a right pterional craniotomy. During surgery, the aneurysm was confirmed to be completely thrombosed and was excised. Postoperatively, the patient experienced a generalized seizure and was intubated. Brain MRI revealed a new infarction in the RAH territory. Despite initial complications, the patient showed significant recovery with rehabilitation, regaining most motor functions by the 6-month follow-up. CONCLUSIONS: This case emphasizes the critical importance of comprehensive preoperative evaluation, particularly in assessing small perforating branches and collateral circulation. It highlights the challenges in managing giant aneurysms and the necessity of anticipating potential postoperative complications. This report adds valuable insights into the clinical management and surgical planning for giant aneurysms, particularly those involving the ACA and RAH.

Thrombotic Thrombocytopenia Purpura (TTP) following emergent aortic valve replacement after a complicated TAVR procedure: a case report and review of the literature.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare hematological disorder. The occurrence of TTP subsequent to an emergent aortic valve replacement after a TAVR procedure is exceedingly uncommon with only a few reported cases worldwide. CASE PRESENTATION: We report the case of a 70-year-old female patient diagnosed with aortic insufficiency. Following a transcatheter aortic valve replacement, she underwent emergency aortic valve replacement under cardiopulmonary bypass on the subsequent day due to heart valve displacement. The postoperative diagnosis revealed TTP and symptomatic treatment involving plasma exchange was administered. After demonstrating steady improvement, the patient was eventually discharged. CONCLUSION: Aortic valve replacement after TAVR is a high-risk procedure and increases susceptibility for developing secondary TTP. The diagnosis and treatment of secondary TPP is considerably challenging, and early diagnosis with symptomatic treatment including plasma exchange can increase patient survival.

Efficacy and safety of daratumumab in multiresistant immune-mediated thrombotic thrombocytopenic purpura.

The immunosuppressive treatment of immune-mediated thrombotic thrombocytopenic purpura (iTTP) in patients with intolerance or refractoriness to the B-cell depleting monoclonal antibody rituximab remains debated. Daratumumab, a plasma cell-directed monoclonal antibody targeting CD38, represents a therapeutic option, but data are scarce. The French Thrombotic Microangiopathies Reference Center conducted a nationwide survey on iTTP patients treated with daratumumab. Nine episodes from seven patients were identified. Treatment was administered for A Disintegrin And Metalloproteinase with ThromboSpondin-1 motifs, 13th member (ADAMTS13) relapses while patients were otherwise in clinical response (N = 8), or during the acute phase of the disease following rituximab intolerance (N = 1). Patients have received a median of three previous therapeutic lines. ADAMTS13 activity improved in eight cases following daratumumab administration, including three cases where ADAMTS13 normalized. ADAMTS13 relapses occurred in three patients; in two cases, retreatment with daratumumab was successful. Median ADAMTS13 relapse-free survival was not reached; 12-month ADAMTS13 relapse-free survival was 56%. Daratumumab-related adverse events occurred in five cases and were non-severe infusion-related reactions in all cases. These results suggest that daratumumab may be an effective treatment option for iTTP patients with intolerance or refractoriness to rituximab.

Familial thrombotic microangiopathy in a child with coenzyme Q10 deficiency-associated glomerulopathy.

We report a child with biallelic COQ6 variants presenting with familial thrombotic microangiopathy (TMA). A Chinese boy presented with steroid-resistant nephrotic syndrome at 8 months old and went into kidney failure requiring peritoneal dialysis at 15 months old. He presented with hypertensive encephalopathy with the triad of microangiopathic haemolytic anaemia, thrombocytopenia, and acute on chronic kidney injury at 25 months old following a viral illness. Kidney biopsy showed features of chronic TMA. He was managed with supportive therapy and plasma exchanges and maintained on eculizumab. However, he had another TMA relapse despite complement inhibition a year later. Eculizumab was withdrawn, and supportive therapies, including ubiquinol (50 mg/kg/day) and vitamins, were optimized. He remained relapse-free since then for 4 years. Of note, his elder sister succumbed to multiple organ failure with histological evidence of chronic TMA at the age of 4. Retrospective genetic analysis revealed the same compound heterozygous variants in the COQ6 gene.

The synergistic effects of Korean Red Ginseng and Cervi Parvum Cornu ameliorating FeCl3-induced arterial thrombosis by downregulating ICAM-1 and VCAM-1.

In this study, we compared antithrombotic activities of Korean Red Ginseng (KRG) and Cervi Parvum Cornu (CPC) on rats with induced thrombosis. Results indicate that KRG and CPC suppressed the arterial occlusion and the combination of KRG and CPC (KRG + CPC) treatment exhibited a synergistic effect with maximum reduction in thrombosis.

Unusual Presentation of Aggressive Atypical Hemolytic Uremic Syndrome With Brugada Syndrome.

Hemolytic uremic syndrome (HUS) is part of a spectrum of disorders known as thrombotic microangiopathies. These disorders are characterized by giving rise to platelet microthrombi, which subsequently develop hemolytic anemia and thrombocytopenia. In HUS, the kidneys are destroyed, mainly due to damage to the renal blood vessels. HUS can be typical or atypical, depending on the cause, and can lead to significant mortality rates. We herein report an unusual case of atypical HUS in a 15-year-old female who presented with fatigue, abdominal pain with nausea and vomiting, loss of appetite, and urine discoloration. Further tests showed low platelets with significant anemia. She was diagnosed with atypical HUS after discovering that she had no previous bloody diarrhea episode with a negative E. coli strain, O157:H7, alongside valid ADAMTS13 activity. The diagnosis was confirmed by genetic testing, and a variant of uncertain significance was found in the CFH gene. The patient, therefore, was started on eculizumab, and a follow-up was done once or twice a month through blood testing. She showed significant improvement. Due to non-compliance with the eculizumab treatment, the patient showed deterioration numerous times. A kidney biopsy was subsequently done, showing signs of acute to chronic thrombotic microangiopathy with moderate tubular atrophy and interstitial fibrosis. After many hemodialysis and plasma exchange sessions and being put on several treatments, such as prednisolone and rituximab, the patient faced death after one year.

A comparative study of anti-ADAMTS-13 antibody dynamics in immune-mediated thrombotic thrombocytopenic purpura.

Background: Thrombotic thrombocytopenic purpura, particularly its immune-mediated variant (iTTP), necessitates accurate diagnostic approaches for effective management. Objectives: To compare a chemiluminescence immunoassay (CLIA) and an enzyme-linked immunosorbent assay (ELISA) for testing ADAMTS-13 activity and detecting anti-ADAMTS-13 autoantibodies (AAbs) in patients with iTTP. Methods: This study involved 31 paired samples from 12 iTTP patients. ADAMTS-13 activity was measured using the HemosIL AcuStar (Instrumentation Laboratory, CLIA) and Technozym (Technoclone) activity assay (ELISA). The presence of AAbs was assessed using Technozym ADAMTS-13-INH assay (ELISA) and HemosIL AcuStar activity (CLIA) within a Bethesda assay following mixing with normal pool plasma. von Willebrand factor (VWF) multimers were analyzed using the HYDRASYS-2 SCAN system and the HYDRAGEL 5- or 11-VW Multimer kits (Sebia). VWF activity levels were measured with the HemosIL AcuStar VWF:GPIbR on the ACL AcuStar Analyzer (IL). Results: For ADAMTS-13 activity, a strong linear relationship and no bias between CLIA and ELISA were confirmed (slope = 1.01 [0.91, 1.11], intercept = 0.00 [-0.47, 0]). However, significant discrepancies were found in AAb detection during remission phases with ADAMTS-13 activity between 10% and 50%, with CLIA and ELISA showing significant divergence (P < .001, Cohen's g = 0.34). Consistently, VWF multimers and activity levels exhibited significantly different values between remission samples with ADAMTS-13 activity below 50% and above 50%. In longitudinal analysis of patients with multiple iTTP relapses, positivity to CLIA appears to precede ELISA in predicting exacerbations. Conclusion: While CLIA and ELISA might be interchangeable for assessing ADAMTS-13 activity, they are not equivalent for detecting AAbs, particularly in patients in clinical remission with ADAMTS-13 activity between 10% and 50%.