Long-term follow-up of patients with congenital thrombotic thrombocytopenia purpura receiving a plasma-derived factor VIII (Koate) that contains ADAMTS13.

BACKGROUND: Hereditary thrombotic thrombocytopenia purpura (hTTP) is an ultra-rare disorder resulting from an inherited deficiency of ADAMTS13, a von Willebrand factor (VWF)-cleaving metalloprotease. The plasma-derived factor VIII/VWF Koate (FVIII/VWFKoate ) has been shown to contain ADAMTS13, allowing for its use to treat hTTP at home by the patient/caregiver. AIM: Based on prior demonstration of safe and effective use of FVIII/VWFKoate in eight patients with hTTP, we conducted a retrospective study to gather additional data regarding the use of FVIII/VWFKoate for hTTP. METHODS: This was a multicentre, retrospective, noninterventional chart review of patients who had received FVIII/VWFKoate for the management of hTTP. Data collected included demographics, medical history, relevant family history, past use and tolerability of fresh frozen plasma, and details regarding FVIII/VWFKoate therapy. RESULTS: The cohort included 11 patients (seven males, four females) with hTTP, ranging in age at study entry from 2 to 28 years. The average duration of FVIII/VWFKoate therapy was 4.8 years (range, 0.5-6.5 years). Among nine patients using FVIII/VWFKoate as prophylaxis, the normalized annual rate of breakthrough TTP episodes ranged from 0.2 to 1.1 episodes/year. All nine patients who received FVIII/VWFKoate prophylaxis had thrombocytopenia recorded at baseline, while eight (88.9%) did not have thrombocytopenia after using FVIII/VWFKoate . There was one AE (unspecified) attributed to FVIII/VWFKoate . CONCLUSION: These data suggest that FVIII/VWFKoate is a safe and well-tolerated source of the missing ADAMTS13 enzyme in patients with hTTP, producing a marked reduction in thrombocytopenia prevalence, low frequency of TTP episodes, and with the added benefit of self- or caregiver-administration.

Characteristics and outcome of breast cancer-related microangiopathic haemolytic anaemia: a multicentre study.

BACKGROUND: Cancer-related microangiopathic haemolytic anaemia (MAHA) is a rare but life-threatening paraneoplastic syndrome. Only single cases or small series have been reported to date. We set up a retrospective multicentre study focusing on breast cancer-related MAHA. METHODS: Main inclusion criteria were known diagnosis of breast cancer, presence of schistocytes and either low haptoglobin or cytopenia and absence of any causes of MAHA other than breast cancer, including gemcitabine- or bevacizumab-based treatment. Patient characteristics, treatments and outcome were retrieved from digital medical records. RESULTS: Individual data from 54 patients with breast cancer-related MAHA were obtained from 7 centres. Twenty-three (44%) patients had a breast tumour with lobular features, and most primary tumours were low grade (grade I/II, N = 39, 75%). ER+/HER2-, HER2+ and triple-negative phenotypes accounted for N = 33 (69%), N = 7 (15%) and N = 8 (17%) cases, respectively. All patients had stage IV cancer at the time of MAHA diagnosis. Median overall survival (OS) was 28 days (range 0-1035; Q1:10, Q3:186). Independent prognostic factors for early death (≤ 28 days) were PS > 2 (OR = 7.0 [1.6; 31.8]), elevated bilirubin (OR = 6.9 [1.1; 42.6]), haemoglobin < 8.0 g/dL (OR = 3.7 [0.9; 16.7]) and prothrombin time < 50% (OR = 9.1 [1.2; 50.0]). A score to predict early death displayed a sensitivity of 86% (95% CI [0.67; 0.96]), a specificity of 73% (95% CI [0.52; 0.88]) and an area under the curve of 0.90 (95% CI [0.83; 0.97]). CONCLUSIONS: Breast cancer-related MAHA appears to be a new feature of invasive lobular breast carcinoma. Prognostic factors and scores may guide clinical decision-making in this serious but not always fatal condition.

A life-threatening case of pregnancy-related atypical Haemolytic uremic syndrome and successful treatment with Eculizumab.

BACKGROUND: Pregnancy-related Atypical Haemolytic Uremic Syndrome (P-aHUS) is a rare condition affecting genetically predisposed women during pregnancy. It is often difficult to diagnose and has a significant impact on maternal and foetal outcomes. It is characterised by microangiopathic haemolytic anaemia and kidney injury from thrombotic microangiopathy. CASE PRESENTATION: A 27-year-old female of Lebanese descent presented at 36 weeks' gestation with foetal death in-utero (FDIU) with placental abruption on a background of previously normal antenatal visits. She was coagulopathic and anaemic with anuric acute kidney injury, requiring emergency Caesarean section, intubation and dialysis. Her coagulopathy rapidly resolved, however, her anaemia and renal dysfunction persisted. A diagnosis of P-aHUS was made, and she was empirically treated with Eculizumab. Her ADAMTS13 level was normal, effectively excluding thrombotic thrombocytopenic purpura. Within 2 weeks of treatment her haematological parameters improved, and her renal function began to recover and within 2 months she became dialysis independent. CONCLUSION: This case highlights the challenges of a timely diagnosis of P-aHUS from other pregnancy-related diseases. Although our patient is dialysis-independent, her risk of relapse remains high with subsequent pregnancies. Currently we are awaiting her genetic sequencing to complete her assessment for underlying mutations and are determining the safest approach to a future planned pregnancy.

Microangiopathy in Cancer: Causes, Consequences, and Management.

Thrombotic microangiopathy (TMA) is a syndrome involving fragmentation haemolysis, thrombocytopenia, and thrombosis. A range of disorders including cancer may have TMA as a clinical manifestation. TMA in cancer may be caused by several mechanisms, including systemic microvascular metastases, but may also be due to extensive bone marrow involvement with cancer or secondary necrosis. Chemotherapeutic agents may also cause associated TMA through a range of different mechanisms. Gemcitabine, platinum-based drugs, mitomycin C, and proteasome inhibitors are known to cause TMA in cancer patients. Transplant-associated TMA (TA-TMA) may affect either solid organ or HSCT patients. TA-TMA remains a difficult complication to address due to its high mortality rate, lack of standard diagnostic criteria, and limited therapeutic options. The challenge of cancer-associated TMA is furthered by the fact that plasma exchange is ineffective in its management.

Thrombotic microangiopathies in critically ill children: The MATUCIP registry in Spain.

INTRODUCTION: Thrombotic microangiopathies (TMA) are rare diseases usually presenting with renal, haematological, neurologic and cardiovascular involvement and nonspecific but severe symptoms. A registry of TMA cases managed in Spanish paediatric intensive care units (the MATUCIP Registry) was established with the aim of gaining knowledge on their clinical characteristics, diagnosis and acute-phase treatment. METHODS: We conducted a prospective multicentre observational study in 20 paediatric intensive care units (PICUs) in Spain from January 2017 to December 2021 in children aged more than 1 month with TMAs, who were followed up through the discharge from the PICU. RESULTS: The sample included 97 patients (51.5% female) with a median age of 2.6 years (interquartile range [IQR], 1.6-5.7). The initial manifestations were gastrointestinal (74.2%), respiratory (14.4%), fever (5.2%), neurologic (3.1%) and other (3.1%). At admission, 75.3% of patients had microangiopathic haemolytic anaemia, 95.9% thrombocytopenia and 94.8% acute kidney injury. Of the total sample, 57.7% of patients received a diagnosis of Shiga toxin-associated haemolytic uraemic syndrome (HUS), 14.4% of Streptococcus pneumoniae-associated HUS, 15.6% of atypical HUS, 10.3% of secondary TMA and 2.1% of thrombotic thrombocytopenic purpura. Eighty-seven patients (89.7%) developed arterial hypertension, and 49.5% gastrointestinal, 22.7% respiratory, 25.8% neurologic and 12.4% cardiac manifestations. Also, 60.8% required renal replacement therapy and 2.1% plasma exchange. Twenty patients received eculizumab. The median PICU stay was 8.5 days (IQR, 5-16.5). Two children died. CONCLUSIONS: The MATUCIP registry demonstrates the clinical variability of TMA cases requiring admission to the PICU. Knowledge of the presentation and outcomes of TMAs can facilitate early aetiological diagnosis. This registry can help improve our understanding of the clinical spectrum of these diseases, for which there is a dearth of published data.

Reference range for ADAMTS13 antigen, activity and anti-ADAMTS13 antibody in the healthy adult Singapore population

INTRODUCTION: ADAMTS13 (a disintegrin-like and metalloproteinase with a thrombospondin Type 1 motif, member 13) plays a fundamental role in the regulation of haemostasis and thrombosis. Its deficiency leads to an accumulation of ultra-large von Willebrand multimers, inducing spontaneous platelet aggregation, thrombosis in the microvasculature, and thrombotic thrombocytopenic purpura (TTP), a condition with 90% mortality when left untreated. Prompt quantification of ADAMTS13 antigen, activity and autoantibody plays a crucial role in the diagnosis and management of TTP and can help differentiate it from other thrombotic microangiopathies (TMAs). Reference ranges for ADAMTS13 are generally derived from Caucasian patients. Given that polymorphism in the ADAMTS13 gene can be associated with variable ADAMTS13 levels, we aimed to establish the first reference range in Singapore and provide a crucial laboratory test for institutions here and elsewhere. METHODS: 150 healthy voluntary donors (75 men, 75 women) aged 21-60 years, with an ethnic mix mirroring Singapore's population profile, were recruited. ADAMTS13 antigen, activity and autoantibody levels were measured using the fluorescence resonance energy transfer-vWF73 and enzyme-linked immunosorbent assay methodologies. RESULTS: Levels (activity 0.65-1.79 IU/mL, antigen 0.36-1.17 IU/mL, autoantibody 1.4-12.5 U/mL) were not statistically different between the genders and various age groups. CONCLUSION: TTP and TMAs are encountered in a wide range of specialties. The availability of new assays in Singapore will aid clinicians in the timely management of these conditions. Standardising reference ranges established for Singapore against World Health Organization standards allows harmonisation of measurements between laboratories and for future research collaborations.

Co-existence of Thrombotic Thrombocytopenic Purpura and Megaloblastic Anaemia: A Case-Based Review.

Introduction: Thrombotic thrombocytopenic purpura is a rare and fatal thrombotic microangiopathy characterised by a pentad of microangiopathic haemolytic anaemia, thrombocytopenia, renal abnormalities, neurological abnormalities, and fever. Due to ineffective erythropoiesis, vitamin-B12 deficiency may rarely present as haemolytic anaemia. Case report: We report a case of a 42-year-old vegetarian female presenting as vitamin B12 deficiency anaemia found to have concomitant TTP, responding to plasmapheresis, corticosteroids, and rituximab therapy. Discussion: In this case of vitamin B12 deficiency with co-existent TTP, we hypothesise vitamin B12 deficiency as a contributory or precipitating factor for TTP. We reviewed similar cases in the literature to support this hypothesis. Timely detection of TTP and the initiation of treatment is of utmost importance as TTP has a high mortality when left untreated. The possible relationship with Vitamin B12 deficiency needs further exploration.

Thrombotic Thrombocytopenic Purpura: A Tale of Two Cases.

Microangiopathic hemolytic anaemia, thrombocytopenia, renal failure, neurologic abnormalities, and fever form the pentad of thrombotic thrombocytopenic purpura (TTP). Early diagnosis is crucial because TTP responds well to plasmapheresis therapy but is associated with substantial mortality if left untreated. A substantial percentage of patients with TTP used to die from systemic microvascular thrombosis in the brain and the heart. However, since plasma exchange therapy became a mainstay in the treatment of TTP, mortality has reduced considerably. Diagnosing TTP can be difficult due to the vast range of symptoms and the absence of clearly defined diagnostic criteria. Hemolytic uremic syndrome and disseminated intravascular coagulation are a close differential of TTP. Here we report two patients with TTP who achieved remission when treated with steroids, plasmapheresis and were free of disease relapse till about two months during follow-up in the outpatient department.

Post-partum occurrence of Wunderlich syndrome and microangiopathic haemolytic anaemia (MAHA): a case report.

This is a case of a 27-year-old primigravida with monochorionic diamniotic twin gestation who was admitted to the hospital for induction of labour. Her postpartum course was complicated by microangiopathic haemolytic anemia (MAHA). The etiology for the MAHA was initially thought to be secondary to pre-eclampsia and vitamin B12/folate deficiency. However, she had persistent anemia and further workup demonstrated that she had a left renal cell carcinoma (RCC) with perinephric haemorrhage consistent with Wunderlich syndrome. This case was intriguing because of its unusual presentation and the several diagnostic and therapeutic challenges along the way. Abbreviations: MAHA: microangiopathic haemolytic anaemia; RCC: renal cell carcinoma; BP: blood pressure; WS: Wunderlich syndrome; CT: computed tomography; LFTs: liver function tests; LDH: lactate dehydrogenase; HELLP: haemolysis elevated liver enzymes, low platelets; DIC: disseminated intravascular coagulation; PLASMIC: score for TTP - includes platelet count <30 x 109/L, evidence of haemolysis (reticulocyte count >2.5%, haptoglobin undetectable, or indirect bilirubin >2mg/dL), active cancer, history of solid organ transplant, mean corpuscular volume (MCV) <90fL, INR <1.5, creatinine <2mg/dL. Each item is sored as being present (YES) or not (NO). Absence of active cancer and solid organ transplant gets scored with a point each. The total points are added up to categorize the severity and risk of TTP. Low risk <4, Intermediate 5, high risk >6; TTP: thrombotic thrombocytopenic purpura; APLA- anti-phophospholipid antibody; BMI: body mass index; TMAs: thrombotic microangiopathies; HUS: haemolytic uremic syndrome; vWF: von Willebrand factor.

Microangiopathic Haemolytic Anaemia in a Young Male Patient With Oesophageal Carcinoma.

Microangiopathic haemolytic anaemia (MAHA) in patients with various solid cancers and haematological malignancies has been reported, but to our knowledge, there has been no clearly reported case of MAHA in a young patient with oesophageal adenocarcinoma. MAHA is a subgroup of haemolytic anaemias characterised by destruction of red blood cells as they traverse small-calibre blood vessels. Its most defining features are anaemia and presence of fragmented red blood cells in the circulation. MAHA associated with cancer is now a well-recognized paraneoplastic syndrome, seen in various solid tumours and haematological malignancies, the most common being gastric, breast and lung carcinoma. The development of MAHA associated with any malignant process is usually an ominous condition, not only because of the fact that no convincing treatment has been discovered to date, but also because it invariably almost always occurs in disseminated cancers as a late presentation. The prompt identification of the signs and symptoms suggestive of intravascular haemolysis, the deliberation of the cause of such symptoms and the concurrent ruling out of related conditions which may mimic MAHA symptoms such as haemolytic uremic syndrome and thrombotic thrombocytopenic purpura are crucial to ensure successful treatment. The patient is a 33-year-old male patient of Asian descent who had oesophageal adenocarcinoma that had metastasized to the peritoneal cavity and para-aortic lymph nodes. The patient was admitted with bilateral extensive deep vein thrombosis, and was later found to have pulmonary embolism as well. A few days after his admission, he suddenly developed shortness of breath, severe chest pain and was diagnosed with cancer-associated MAHA. His sudden, rapid clinical deterioration, and the inability to intervene successfully was a traumatizing experience for his doctors and relatives alike.

Thrombotic microangiopathy following saw-scaled viper (Echis carinatus) envenoming in Sri Lanka.

The saw-scaled viper (Echis carinatus) is considered as a highly venomous snake in Sri Lanka. The clinical manifestations are localized pain and swelling, coagulopathy and renal impairment. Thrombotic microangiopathy is rarely reported as a complication of saw-scaled viper envenoming. The clinical manifestations of thrombotic microangiopathy include thrombocytopenia, microangiopathic haemolytic anaemia and acute kidney injury. The consumption coagulopathy of post-envenoming could be followed by a syndrome consistent with thrombotic microangiopathy. We describe a patient with thrombotic microangiopathy following saw-scaled viper systemic envenoming which was managed with antivenom and supportive therapy. The dead snake which was brought by patient was identified by medical professional as saw-scaled viper (E. carinatus) based on morphological features. This case illustrates a rare manifestation thrombotic microangiopathy following saw-scaled viper envenoming.

Usefulness of automated fragmented red blood cell percentage in the diagnosis of paediatric haemolytic uraemic syndrome.

INTRODUCTION: Presence of schistocytes in peripheral blood smear supporting haemolysis is important for diagnosis and decision-making in paediatric haemolytic uraemic syndrome (HUS). High observer dependency and requirement of expertise for peripheral smear evaluation propels us to think of other modalities to overcome these issues. We envisage that newer techniques like automated fragmented red blood cell percentage (FRC %), whose role has been described in transplant associated HUS and thrombotic thrombocytopenic purpura, can serve the purpose. METHODS: Twenty-eight children with HUS after excluding secondary causes were enrolled in this study. Blood samples were analysed for FRC% at admission, using SYSMEX XN-1000 (Japan) haematology analyser, and simultaneously, schistocytes in peripheral smear were reported by a single expert haematopathologist. RESULTS: Median age was 56 months ranging from 2 to 140 months. FRC% was elevated in 85.8% (n-24/28) with a mean of 4.56 ± 3.1%. FRC% had a sensitivity of 95.4% (C.I: 77.16% to 99.88%) in children who had FRC% >1.49% with an accuracy of 85.71% (C.I: 67.33% to 95.97%). However, specificity was only 50% (C.I: 11.81% to 88.19%) with a positive likelihood ratio of 1.91. Receiver-operator curve showed an AUC value of 0.841. CONCLUSION: We suggest automated FRC% as a rapid and highly sensitive index for screening of paediatric HUS; however, a peripheral blood film examination is a must in cases with count >2% to avoid false positives as the index has low specificity.

[Breast cancer-related thrombotic microangiopathy: A review]. / Cancer du sein et microangiopathies thrombotiques paranéoplasiques.

Thrombotic Microangiopathies (TM) have been described since the 1960s. They are characterized by presence of mechanical haemolytic anemia associated with peripheral thrombocytopenia. TM in cancer can be related to several causes, whose cancer himself: cancer-related microangiopathic haemolytic anaemia (MAHA). Incidence of cancer related MAHA remains unknown. Cancer-related MAHA are mainly observed in mucin-producer adenocarcinomas, such as gastric (half of reported cases) and breast cancer. We conducted a review of all original published cases of TM reported in breast cancer, and we specifically investigated BC-MAHA cases. A Medline search identified 158 MAHA cases including 118 BC-MAHA, and 40 drug-related MAHA. Most of BC-MAHA occur in disseminated cancers, mainly with medullar involvement, and/or bone metastasis. Patients typically suffer from poor general state, bone pain, and/or dyspnea. Laboratory abnormalities such as myelemia or erythromyelemia in peripheral blood are frequently observed. Incidence of coagulation disorders is increased, compared to other MAHA causes. BC-MAHA prognosis is dramatically poor. Treatments classically used in other MAHA causes, such as plasmapheresis or immunoglobulins, are inefficient. Urgent anti-neoplastic therapy may be the only effective treatment, associated to symptomatic therapies (transfusions, blood pressure control).

Thrombotic microangiopathy with renal injury: an approach for the general physician

Thrombotic microangiopathy with renal dysfunction is a haematological and renal emergency warranting urgent diagnosis and intervention. As the potential underlying causes may be complex, assessment and management can be challenging for treating clinicians, and a timely and collaborative approach between general physicians, haematologists and nephrologists may be extremely helpful in order to optimise clinical outcomes. This paper will aim to build an understanding of different potential presentations of thrombotic microangiopathies and provide a practical framework for diagnosis and management, using a case-based discussion format, for acute and general physicians. Some aspects of subsequent specialist management are also discussed.

Gemcitabine-induced haemolytic uremic syndrome, although infrequent, can it be prevented: A case report and review of literature.

Gemcitabine is an antineoplastic used to treat several malignancies including pancreatic cancer. Its toxicity profile is well known with myelotoxicity, increased vascular permeability and peripheral oedema as most frequent adverse events. However, several cases of acute renal failure have been reported and haemolytic uremic syndrome (HUS) seems to be the underlying process. The cause of HUS remains unknown but its consequences can be lethal. Therefore, a high grade of suspicion is crucial to diagnose it and promptly treat it. This hopefully will reduce its morbidity. HUS is characterized by progressive renal failure associated with microangiopathic haemolytic anaemia and thrombocytopenia. The primary event is damage to endothelial cells and thrombotic microangiopathy (TMA) is the histopathological lesion. TMA affects mainly renal microvasculature. However, some cases evolve with central nervous or cardiovascular systems involvement. We present here a case of gemcitabine-induced HUS, with renal and cardiovascular system affected at the time of diagnosis which to our knowledge this is the first time of such case to be reported.

Practice guidelines for the emergency treatment of thrombotic microangiopathy. / Guía práctica de tratamiento urgente de la microangiopatía trombótica.

BACKGROUND AND AIM: The term thrombotic microangiopathy (TMA) involves a heterogeneous group of diseases that can be overwhelming or invalidating, with an acute development, characterised by microangiopathic haemolytic anaemia and thrombocytopaenia. Its management during its initial hours is essential to improving the prognostic of these patients. The aim of this review is to give recommendations about the optimisation of TMA initial treatment and to accelerate the aetiological diagnosis. PATIENTS AND METHODS: We provide a practice guideline based on four steps for the initial management of TMA: diagnosis of suspicion, syndromic confirmation, emergent treatment and complementary tests. RESULTS: The detection of microangiopathic haemolytic anaemia (characterised by elevated reticulocytes, LDH and indirect bilirubin, negative direct Coombs test and schistocytes in peripheral blood), and thrombocytopaenia not explained by other secondary aetiologies confirm the syndromic diagnosis of microangiopathic haemolytic anaemia and thrombocytopaenia (MAHAT). These patients require admission to an Intensive Care Unit to initiate plasma exchange therapy as soon as possible, ideally within the first 4-8hours. Prior to this, samples for ADAMTS13 and complement study should be obtained. Finally, it is important to request the complementary tests necessary to have a correct aetiological diagnosis. CONCLUSIONS: Adherence to the agreed recommendations in this guideline will improve therapeutic results by facilitating cooperation between different specialists involved in TMA management.

Where are we with haemolytic uremic syndrome? / Síndrome hemolítico urémico: estado actual.

Haemolytic uremic syndrome (HUS) is characterised by microangiopathic haemolytic anaemia with acute kidney injury. It is currently classified into two main categories: Shiga-toxin producing E. coli-hemolytic uremic syndrome (STEC-HUS) and atypical haemolytic uremic syndrome (aHUS). Endothelial cell damage is the common pathway in HUS to developing thrombotic microangiopathy. Atypical HUS includes primary, secondary and aHUS due to metabolic diseases. In the majority of aHUS cases, hyperactivity of the alternative complement pathway plays a central role. Therefore, treatment is based on complement inhibitors like eculizumab, a drug that has revolutionised the natural history of the disease. Relapses are frequent after kidney transplant and thus confer a poor prognosis.

Microangiopatías trombóticas en niños críticamente enfermos. Registro español MATUCIP / Thrombotic microangiopathies in critically ill children: The MATUCIP registry in Spain

Introducción: Las microangiopatías trombóticas (MAT) son entidades infrecuentes que suelen causar afectación renal, hematológica, neurológica y cardiovascular, con síntomas inespecíficos pero graves. Con la finalidad de mejorar el conocimiento de sus características clínicas, el proceso diagnóstico y el tratamiento en la fase aguda, se ha creado el registro de MAT en las unidades de cuidados intensivos pediátricos (UCIP) de España (Registro MATUCIP). Pacientes y métodos: Estudio observacional, multicéntrico, realizado en 20 UCIP españolas desde enero de 2017 hasta diciembre de 2021 que incluyó niños mayores de 1mes con diagnóstico de MAT y seguimiento hasta el alta de la UCIP. Resultados: Se incluyeron 97 pacientes (51,5% mujeres), con una mediana de edad de 2,6años (RIQ: 1,6-5,7). La clínica inicial fue de tipo gastrointestinal (74,2%), respiratoria (14,4%), cuadro febril (5,2%), neurológica (3,1%) y otras (3,1%). Al ingreso, el 75,3% presentaban anemia hemolítica microangiopática, el 95,9% trombocitopenia y el 94,8% daño renal agudo. Fueron diagnosticados de síndrome hemolítico urémico (SHU) asociado a Escherichia coli productora de toxina Shiga el 57,7%, SHU por Streptococcus pneumoniae el 14,4%, SHU atípico el 15,6%, MAT secundaria el 10,3% y púrpura trombótica trombocitopénica el 2,1%. Desarrollaron hipertensión arterial el 89,7%, manifestaciones digestivas el 49,5%, respiratorias el 22,7%, neurológicas el 25,8% y cardiacas el 12,4%. El 60,8% requirieron depuración extrarrenal y el 2,1%, plasmaféresis. Recibieron eculizumab 20 pacientes. La mediana de estancia en la UCIP fue de 8,5días (RIQ: 5-16,5). Dos niños fallecieron. (AU)

Introduction: Thrombotic microangiopathies (TMA) are rare diseases usually presenting with renal, haematological, neurologic and cardiovascular involvement and nonspecific but severe symptoms. A registry of TMA cases managed in Spanish paediatric intensive care units (the MATUCIP registry) was established with the aim of gaining knowledge on their clinical characteristics, diagnosis and acute-phase treatment. Patients and methods: We conducted a prospective multicentre observational study in 20 paediatric intensive care units (PICUs) in Spain from January 2017 to December 2021 in children aged more than 1month with TMAs, who were followed up through the discharge from the PICU. Results: The sample included 97 patients (51.5% female) with a median age of 2.6years (interquartile range [IQR]: 1.6-5.7). The initial manifestations were gastrointestinal (74.2%), respiratory (14.4%), fever (5.2%), neurologic (3.1%) and other (3.1%). At admission, 75.3% of patients had microangiopathic haemolytic anaemia, 95.9% thrombocytopenia and 94.8% acute kidney injury. Of the total sample, 57.7% of patients received a diagnosis of Shiga toxin-associated haemolytic uraemic syndrome (HUS), 14.4% of Streptococcus pneumoniae-associated HUS, 15.6% of atypical HUS, 10.3% of secondary TMA and 2.1% of thrombotic thrombocytopenic purpura. Eighty-seven patients (89.7%) developed arterial hypertension, and 49.5% gastrointestinal, 22.7% respiratory, 25.8% neurologic and 12.4% cardiac manifestations. Also, 60.8% required renal replacement therapy and 2.1% plasma exchange. Twenty patients received eculizumab. The median PICU stay was 8.5days (IQR: 5-16.5). Two children died. (AU)

Reference range for ADAMTS13 antigen, activity and anti-ADAMTS13 antibody in the healthy adult Singapore population

INTRODUCTION@#ADAMTS13 (a disintegrin-like and metalloproteinase with a thrombospondin Type 1 motif, member 13) plays a fundamental role in the regulation of haemostasis and thrombosis. Its deficiency leads to an accumulation of ultra-large von Willebrand multimers, inducing spontaneous platelet aggregation, thrombosis in the microvasculature, and thrombotic thrombocytopenic purpura (TTP), a condition with 90% mortality when left untreated. Prompt quantification of ADAMTS13 antigen, activity and autoantibody plays a crucial role in the diagnosis and management of TTP and can help differentiate it from other thrombotic microangiopathies (TMAs). Reference ranges for ADAMTS13 are generally derived from Caucasian patients. Given that polymorphism in the ADAMTS13 gene can be associated with variable ADAMTS13 levels, we aimed to establish the first reference range in Singapore and provide a crucial laboratory test for institutions here and elsewhere.@*METHODS@#150 healthy voluntary donors (75 men, 75 women) aged 21-60 years, with an ethnic mix mirroring Singapore's population profile, were recruited. ADAMTS13 antigen, activity and autoantibody levels were measured using the fluorescence resonance energy transfer-vWF73 and enzyme-linked immunosorbent assay methodologies.@*RESULTS@#Levels (activity 0.65-1.79 IU/mL, antigen 0.36-1.17 IU/mL, autoantibody 1.4-12.5 U/mL) were not statistically different between the genders and various age groups.@*CONCLUSION@#TTP and TMAs are encountered in a wide range of specialties. The availability of new assays in Singapore will aid clinicians in the timely management of these conditions. Standardising reference ranges established for Singapore against World Health Organization standards allows harmonisation of measurements between laboratories and for future research collaborations.

Exchange transfusion for neonate with haemolytic uremic syndrome.

INTRODUCTION: Haemolytic uremic syndrome (HUS) is one of the most common causes of acute renal failure in children but it is uncommon in newborns. To our knowledge only five cases have been reported so far (probably underreported). The known modalities of treatment include transfusion of plasma and plasmapheresis. We report a case of neonatal HUS for whom we performed an exchange transfusion to good effect. CASE DESCRIPTION: A term vaginally born baby, meconium stained and floppy at birth presented with severe anaemia in the first few hours of life. The baby later on developed renal failure and blood picture was suggestive of severe thrombocytopenia and microangiopathic haemolytic anaemia. No extra renal manifestations of birth asphyxia were noted. A double volume exchange transfusion was performed relatively early and subsequently platelet and haemoglobin stabilised and renal failure improved. DISCUSSION AND EVALUATION: The clinical impression in this case was convincing of neonatal HUS, likely attributable to birth asphyxia but needs to be differentiated from disseminated intravascular coagulation (DIC) and thrombotic thrombocytopenic purpura (TTP). The coagulation profile is usually normal in HUS but it is abnormal in DIC, whereas in TTP one would find hyperbilirubinemia, increased creatinine, haemolysis etc. TTP is rare but not very uncommon in infancy. Congenital TTP is attributed to an inherent deficiency of ADAMTS-13, which is a vWF-cleaving metalloprotease. Irrespective of the etiology of HUS in our case, a dramatic response was observed with exchange transfusion. Transfusion of fresh frozen plasma (FFP) and plasmapheresis are known treatment modalities. FFP replaces the missing or altered complement factors and plasmapheresis removes antibodies, immune complexes and toxins. An exchange transfusion combines both these functions. CONCLUSIONS: In the absence of facilities for plasmapheresis, exchange transfusion is a good alternative.