-
British Journal of Haematology Oct 2023Defining immune thrombocytopenia (ITP) in two age groups-children and adults-overlooks the specific clinical features and needs of adolescents and young adults (AYAS)....
Defining immune thrombocytopenia (ITP) in two age groups-children and adults-overlooks the specific clinical features and needs of adolescents and young adults (AYAS). We previously reported a high risk of chronic disease at 12 months (50%); however, data on the course of chronic ITP, the risk of refractoriness and treatment strategies in AYAS are limited. Data from patients aged 12-25 years with chronic primary ITP at 12 months were extracted from three large registries between 2004 and 2021. Clinical and laboratory data were evaluated until 48 months of follow-up (FU). Refractory ITP was defined as the administration of ≥3 different lines of therapy. A total of 427 AYAS (64% female) with chronic ITP were included. Overall, 7% and 14% were classified as 'refractory' at 12 and 48 months of FU respectively. The proportion of males was greater in the refractory group than in the non-refractory group (43% vs. 35%). AYAS with refractory disease displayed lower median platelet counts, more bleeding and a higher need for treatment at initial diagnosis and FU than non-refractory patients. This study reveals that refractory ITP is uncommon in AYAS; however, AYAS with refractory ITP display a high disease burden at all time points, including at initial diagnosis.
Topics: Male; Humans; Adolescent; Female; Young Adult; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Platelet Count; Cost of Illness; Registries
PubMed: 37735549
DOI: 10.1111/bjh.19081 -
Current Opinion in Nephrology and... May 2024To present findings indicating the value of kidney biopsy in assessing prognosis and guiding clinical approach to patients with IgA vasculitis nephritis (IgAVN),... (Review)
Review
PURPOSE OF REVIEW
To present findings indicating the value of kidney biopsy in assessing prognosis and guiding clinical approach to patients with IgA vasculitis nephritis (IgAVN), including a recent international study examining the value of the Oxford (MEST-C) classification.
RECENT FINDINGS
Historically, kidney biopsies with IgAVN are scored using the International Society for Kidney Diseases in Children (ISKDC) classification. However, this classification has limited prognostic value, and most biopsies fall into just two of the six ISKDC grades. There are few studies examining the clinical value of the Oxford classification, which is well documented to be predictive of kidney outcomes in IgA nephropathy, in IgAVN. However, a recent study of 361 biopsied patients with IgAVN showed that endocapillary hypercellularity (Oxford E1) predicted a subclass of patients showing initial improvement in kidney function with immunosuppressive treatment, followed by a later decline.
SUMMARY
Kidney outcome in patients with biopsied IgAVN treated with immunosuppression is determined by clinical factors and endocapillary hypercellularity. The latter is not part of the ISKDC classification and supports including MEST-C scores in biopsy reports of IgAVN. Even patients showing a good initial response to immunosuppression require long-term follow-up due to risk of subsequent kidney function decline.
Topics: Child; Humans; IgA Vasculitis; Kidney; Glomerulonephritis, IGA; Nephritis; Biopsy
PubMed: 38411035
DOI: 10.1097/MNH.0000000000000972 -
Journal of Critical Care Aug 2023Thrombotic thrombocytopenic purpura (iTTP) and atypical hemolytic-uremic syndrome (aHUS), once in remission, may cause long-term symptoms, among which mental-health...
Post-traumatic stress disorder and quality of life alterations in survivors of immune-mediated thrombotic thrombocytopenic purpura and atypical hemolytic and uremic syndrome.
Thrombotic thrombocytopenic purpura (iTTP) and atypical hemolytic-uremic syndrome (aHUS), once in remission, may cause long-term symptoms, among which mental-health impairments may be difficult to detect. We conducted telephone interviews 72 [48-84] months after ICU discharge to assess symptoms of anxiety, depression, and posttraumatic stress disorder (PTSD) and the 36-item Short Form questionnaire (SF-36). Of 103 included patients, 52 had iTTP and 51 aHUS; 74% were female, median age was 39 y (31-54), and 39 (38%) patients were still taking treatment. Symptoms of anxiety, PTSD and depression were present in 50%, 27% and 14% of patients, respectively, with no significant difference between the iTTP and aHUS groups. Patients with PTSD symptoms had significantly greater weight gain and significantly worse perceived physical and/or emotional wellbeing, anxiety symptoms, and depression symptoms. The SF-36 physical and mental components indicated significantly greater quality-of-life impairments in patients with vs. without PTSD symptoms and in those with aHUS and PTSD vs. iTTP with or without PTSD. In the aHUS group, quality of life was significantly better in patients with vs. without eculizumab treatment. Factors independently associated with PTSD symptoms were male sex (odds ratio [OR], 0.11; 95%CI, 0.02-0.53), platelet count ≤20 G/L at acute-episode presentation (OR, 2.68; 1.01-7.38), and current treatment (OR, 2.69; 95%CI, 1.01-7.36). Mental-health screening should be routine in patients with iTTP and aHUS to ensure appropriate care.
Topics: Humans; Male; Female; Adult; Purpura, Thrombotic Thrombocytopenic; Stress Disorders, Post-Traumatic; Quality of Life; Atypical Hemolytic Uremic Syndrome; Survivors
PubMed: 36931181
DOI: 10.1016/j.jcrc.2023.154283 -
Journal of Thrombosis and Haemostasis :... Dec 2023Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare syndrome associated with adenoviral vector vaccines for COVID-19. The syndrome is characterized...
BACKGROUND
Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare syndrome associated with adenoviral vector vaccines for COVID-19. The syndrome is characterized by thrombosis, anti-platelet factor 4 (PF4) antibodies, thrombocytopenia, high D-dimer, and hypofibrinogenemia.
OBJECTIVES
To investigate abnormalities in fibrinolysis that contribute to the clinical features of VITT.
METHODS
Plasma samples from 18 suspected VITT cases were tested for anti-PF4 by ELISA and characterized as meeting criteria for VITT (11/18) or deemed unlikely (7/18; non-VITT). Antigen levels of PAI-1, factor XIII (FXIII), plasmin-αantiplasmin (PAP), and inflammatory markers were quantified. Plasmin generation was quantified by chromogenic substrate. Western blotting was performed with antibodies to fibrinogen, FXIII-A, and plasminogen.
RESULTS
VITT patients 10/11 had scores indicative of overt disseminated intravascular coagulation, while 0/7 non-VITT patients met the criteria. VITT patients had significantly higher levels of inflammatory markers, IL-1β, IL-6, IL-8, TNFα, and C-reactive protein. In VITT patients, both fibrinogen and FXIII levels were significantly lower, while PAP and tPA-mediated plasmin generation were higher compared to non-VITT patients. Evidence of fibrinogenolysis was observed in 9/11 VITT patients but not in non-VITT patients or healthy controls. Fibrinogen degradation products were apparent, with obvious cleavage of the fibrinogen α-chain. PAP complex was evident in those VITT patients with fibrinogenolysis, but not in non-VITT patients or healthy donors.
CONCLUSION
VITT patients show evidence of overt disseminated intravascular coagulation and fibrinogenolysis, mediated by dysregulated plasmin generation, as evidenced by increased PAP and plasmin generation. These observations are consistent with the clinical presentation of both thrombosis and bleeding in VITT.
Topics: Humans; Fibrinolysis; Purpura, Thrombocytopenic, Idiopathic; Fibrinolysin; Disseminated Intravascular Coagulation; COVID-19 Vaccines; Thrombocytopenia; Thrombosis; Vaccines; Fibrinogen
PubMed: 37734715
DOI: 10.1016/j.jtha.2023.09.007 -
Haematologica Oct 2023Current immune thrombocytopenia (ITP) guidelines target children and adults, leading to oversimplification. Adolescents and young adults (AYAS) comprise a separate group...
Current immune thrombocytopenia (ITP) guidelines target children and adults, leading to oversimplification. Adolescents and young adults (AYAS) comprise a separate group with distinct health and psychosocial issues. This study aimed to describe the clinical presentation and therapeutic strategies of ITP among AYAS. We analyzed data from two large ITP registries (PARC-ITP; CARMEN-France) and included newly diagnosed ITP patients (aged 12-25 years) with an initial platelet counts of <100×109/L. Patients with secondary ITP or non-immune thrombocytopenia (n=57) and pregnant women (n=10) were excluded. Of the 656 cases of AYAS with primary ITP registered from 2004 up to 2021, 12-month follow-up data were available for 72%. The initial median platelet count was 12×109/L. In 109 patients (17%), the diagnosis was incidental, without documented bleeding. Apart from gynecological bleeding, the clinical and therapeutical characteristics of females and males were similar. Platelet-enhancing drugs were reported in 66%, 45%, and 30% of patients at diagnosis, 1-6 months, and 6-12 months after diagnosis, respectively. Corticosteroids were the preferred treatment at all time points. At 12 months, 50% of all patients developed chronic ITP. In the subgroup of patients with initial severe thrombocytopenia (<20×109/L), those receiving frontline treatment had a higher remission rate at 1 year than those who followed an initial watch-and-wait strategy (53% and 32%; P<0.05). Our analysis indicates that the remission rate at 1 year may be associated with the initial treatment strategy. This hypothesis must be confirmed in prospective studies.
Topics: Male; Child; Humans; Female; Adolescent; Young Adult; Pregnancy; Purpura, Thrombocytopenic, Idiopathic; Prospective Studies; Platelet Count; Thrombocytopenia; Hemorrhage
PubMed: 37051753
DOI: 10.3324/haematol.2022.282524 -
British Journal of Haematology Oct 2023Since its first description by Evans in 1951, this syndrome has been linked to chronic immune thrombocytopenia with the concurrent or delayed onset of autoimmune... (Review)
Review
Since its first description by Evans in 1951, this syndrome has been linked to chronic immune thrombocytopenia with the concurrent or delayed onset of autoimmune haemolytic anaemia or neutropenia. For decades, the evolution of Evans syndrome (ES) has carried a poor prognosis and often resulted in chronic steroid exposure, multiple immune suppressing medications directed against T or B lymphocytes, and splenectomy. This paper presents a new view of ES based on recent advances in genomics which begin to classify patients based on their underlying molecular variants in previously described primary immune disorders. This has opened up new avenues of targeted therapy or bone marrow transplant at rather than broad long-term immune suppression or splenectomy. Importantly, recent studies of the full lifespan of ES suggest that at least 80% of those paediatric patients will progress to various clinical or biological immunopathological manifestations with age despite the resolution of their cytopenias. Those patients merit long-term follow-up and monitoring in dedicated transition programs to improve outcome at the adult age.
Topics: Adult; Humans; Child; Anemia, Hemolytic, Autoimmune; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Neutropenia
PubMed: 37735545
DOI: 10.1111/bjh.19073 -
British Journal of Haematology Oct 2023Immune thrombocytopenia (ITP) is a disorder characterized by low platelets due to increased clearance and decreased platelet production. While ITP has been characterized... (Review)
Review
Immune thrombocytopenia (ITP) is a disorder characterized by low platelets due to increased clearance and decreased platelet production. While ITP has been characterized as an acquired disorder of the adaptive immune system, the resulting platelet autoantibodies provide ancillary links to the innate immune system via antibody interaction with the complement system. Most autoantibodies in patients with ITP are of the IgG1 subclass, which can be potent activators of the classical complement pathway. Antibody-coated platelets can initiate complement activation via the classical pathway leading to both direct platelet destruction and enhanced clearance of C3b-coated platelets by complement receptors. Similar autoantibody interactions with bone marrow megakaryocytes can also result in complement injury and ineffective thrombopoiesis. The development of novel therapeutic complement inhibitors has revived interest in the role of complement in autoantibody-mediated disorders, such as ITP. A recent early-phase clinical trial of a classical complement pathway inhibitor has demonstrated efficacy in a subset of ITP patients refractory to conventional immune modulation. In this review, we will analyse the role of complement in refractory ITP.
Topics: Humans; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Complement System Proteins; Blood Platelets; Autoantibodies
PubMed: 37735550
DOI: 10.1111/bjh.19070 -
Hematology. American Society of... Dec 2023Immune thrombotic thrombocytopenic purpura (iTTP) caused by an autoantibody-mediated deficiency of ADAMTS13 and atypical hemolytic syndrome (aHUS) caused by alternative...
Immune thrombotic thrombocytopenic purpura (iTTP) caused by an autoantibody-mediated deficiency of ADAMTS13 and atypical hemolytic syndrome (aHUS) caused by alternative complement dysregulation are the most common primary thrombotic microangiopathies (TMAs). The evaluation of a patient with TMA is a medical emergency since it is critical to quickly distinguish iTTP and aHUS from other causes of TMA. Untreated iTTP is rapidly fatal, and delays in initiating complement inhibition in aHUS increase the risk of irreversible renal failure. An ADAMTS13 activity level of less than 10% is diagnostic of iTTP in the appropriate clinical setting. In settings where rapid-turnaround ADAMTS13 testing is not available, clinical features and clinical prediction tools are useful to identify patients who should receive emergent plasma exchange. We present an evidence-based approach to the initial (first 24 hours) diagnosis and management of iTTP and review the clinical and laboratory features that can be used to identify patients with aHUS who will benefit from early C5 blockade. We also discuss the potential use of complement blockade to improve outcomes in selected patients with secondary TMA.
Topics: Humans; Purpura, Thrombotic Thrombocytopenic; Thrombotic Microangiopathies; Complement System Proteins; Syndrome; Autoantibodies; Purpura, Thrombocytopenic, Idiopathic; ADAMTS13 Protein
PubMed: 38066937
DOI: 10.1182/hematology.2023000501 -
British Journal of Haematology Oct 2023Emerging evidence has demonstrated that obesity impacts multiple immune-related diseases. It remains unclear whether and how obesity alters treatment outcomes in...
Emerging evidence has demonstrated that obesity impacts multiple immune-related diseases. It remains unclear whether and how obesity alters treatment outcomes in patients with primary immune thrombocytopenia (ITP). Thus, we retrospectively investigated 214 treatment-naïve patients who received standard high-dose dexamethasone therapy in Qilu Hospital. Patients with obesity showed significantly lower overall initial response (underweight vs. normal vs. overweight vs. obese: 85.7% vs. 85.2% vs. 72.0% vs. 52.3%, p = 0.001) and initial complete response ([CR], 71.4% vs. 70.4% vs. 53.3% vs. 27.3%, p < 0.001) rates. The same trend was observed in the 6-month sustained response (63.6% vs. 52.3% vs. 35.6% vs. 22.7%, p = 0.03) and sustained CR (36.4% vs. 44.6% vs. 24.4% vs. 9.1%, p = 0.01). The Kaplan-Meier analysis revealed a shortened duration of remission in the obese group (median duration of remission, not reached vs. 16 months vs. 2 months vs. 1 month, p = 0.002). In multivariate regression analysis, obesity was independently associated with poor initial and sustained responses, and an increased risk for relapse. In conclusion, obesity is a negative predictor for outcomes of corticosteroid treatment. A stratified strategy according to body mass index status may facilitate the precision management of ITP.
Topics: Humans; Purpura, Thrombocytopenic, Idiopathic; Retrospective Studies; Adrenal Cortex Hormones; Treatment Outcome; Obesity
PubMed: 37488467
DOI: 10.1111/bjh.18997 -
British Journal of Haematology Oct 2023Immune thrombocytopenia (ITP) in children is a relatively mild and self-limited disorder with the majority of children demonstrating normalization of platelet count by... (Review)
Review
Immune thrombocytopenia (ITP) in children is a relatively mild and self-limited disorder with the majority of children demonstrating normalization of platelet count by 12 months from diagnosis. Because of this, many children with ITP can be observed without the need for treatment. When needed, treatment with either intravenous immunoglobulin (IVIG) or corticosteroids is highly effective (>80% IVIG and >95% corticosteroids). For those children who require second-line therapies, response rates of >60% are seen with both the thrombopoietin-receptor agonists and rituximab. Despite this, some children will have 'refractory' ITP (rITP) with poor or transient responses to platelet-raising therapies. Here, we review the clinical features of rITP in children, outline proposed classifications and explore potential predictors for children with rITP.
Topics: Child; Humans; Purpura, Thrombocytopenic, Idiopathic; Immunoglobulins, Intravenous; Thrombocytopenia; Platelet Count; Blood Platelets
PubMed: 37641973
DOI: 10.1111/bjh.19072