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Journal of Thrombosis and Haemostasis :... Aug 2021Targeted therapy of immune thrombotic thrombocytopenic purpura (iTTP) requires acurate and prompt diagnosis and differentiation from complement-mediated hemolytic uremic... (Review)
Review
Targeted therapy of immune thrombotic thrombocytopenic purpura (iTTP) requires acurate and prompt diagnosis and differentiation from complement-mediated hemolytic uremic syndrome and other causes of thrombotic microangiopathy. ADAMTS-13 (A Disintegrin And Metalloprotease with ThromboSpondin-1 Domain, member 13) evaluation (activity and inhibitors or anti-ADAMTS-13 IgG) is the key for diagnosis and further management of patients with suspected iTTP during acute episode and in clinical response or remission. Clinical trial results and real-world data have demonstrated the efficacy and safety of the triple therapy consisting of therapeutic plasma exchange, caplacizumab, and immunosuppressives (e.g., corticosteroids and rituximab) for acute iTTP. Such a therapeutic strategy has significantly accelerated the normalization of platelet counts, decreased the length of stays in the intensive care unit and the hospital, but most importantly reduced the mortality rate. The present review highlights some of the important advancements for the diagnosis and management of iTTP and proposes triple therapy as the standard of care for acute iTTP today.
Topics: ADAMTS13 Protein; Humans; Plasma Exchange; Purpura, Thrombocytopenic, Idiopathic; Purpura, Thrombotic Thrombocytopenic; Standard of Care; Thrombospondin 1
PubMed: 34060225
DOI: 10.1111/jth.15406 -
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 -
Blood Advances Jan 2024Pregnancy-onset thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening disease of which diagnosis and management requires experienced multidisciplinary...
Pregnancy-onset thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening disease of which diagnosis and management requires experienced multidisciplinary teams. The mechanisms responsible for a deficiency in the disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13 (ADAMTS13) leading to pregnancy-onset TTP may be congenital or acquired, and studying ADAMTS13 conformation could be of interest. The differential diagnosis between TTP and other pregnancy-associated thrombotic microangiopathies (TMA) is often challenging. Our retrospective multicenter study highlights the significance and the challenges associated with pregnancy-onset TTP and childbirth in terms of diagnosis, obstetric management, and follow-up aspects. Among 1174 pregnancy-onset TMA enrolled in the French Registry for TMA from 2000 to 2020, we identified 108 pregnancy-onset TTP: 52 immune-mediated TTP (iTTP, 48.1%), 27 acquired TTP of unidentified mechanism (uTTP, 25%), and 29 congenital TTP (cTTP, 26.9%). Data show that maternal outcome is good (survival rate: 95%) and fetal outcome is linked to the gestational age at the onset of the disease (survival rate: 75.5%). Three distinct entities with different natural histories emerged: pregnancy-onset iTTP appears similar to idiopathic iTTP, with an open ADAMTS13 conformation, and is marked by a relapse risk independent of subsequent pregnancies; pregnancy-onset uTTP appears to have a different pathophysiology with an unexpected open ADAMTS13 conformation and a very low relapse risk independent of subsequent pregnancies; finally, pregnancy-onset cTTP is characterized by the necessity of pregnancy as a systematic and specific trigger and a need for prophylactic plasmatherapy for subsequent pregnancies. This trial was registered at www.clinicaltrials.gov as #NCT00426686, and at the Health Authority and the French Ministry of Health (P051064/PHRC AOM05012).
Topics: Pregnancy; Female; Humans; Purpura, Thrombotic Thrombocytopenic; Follow-Up Studies; Thrombotic Microangiopathies; Retrospective Studies; Recurrence
PubMed: 38039511
DOI: 10.1182/bloodadvances.2023011972 -
Clinical Medicine (London, England) May 2022New thrombocytopenia may be associated with a variety of conditions and diagnosis can be challenging. Presentation can vary from life-threatening bleeding or thrombosis...
New thrombocytopenia may be associated with a variety of conditions and diagnosis can be challenging. Presentation can vary from life-threatening bleeding or thrombosis to an incidental finding in an asymptomatic patient. New thrombocytopenia requires urgent investigation. Investigations are mainly guided by findings from the clinical history, physical examination, full blood count and blood film analysis. Aside from the actively bleeding patient, rare but life-threatening causes of thrombocytopenia must be identified early as they require urgent treatment. These include thrombotic thrombocytopenic purpura, disseminated intravascular coagulation, suspicion of new acute promyelocytic leukaemia, and vaccine-induced prothrombotic immune thrombocytopenia. Here, we discuss how to approach a patient with new thrombocytopenia, along with key differentials not to be missed.
Topics: Blood Cell Count; Disseminated Intravascular Coagulation; Hemorrhage; Humans; Purpura, Thrombotic Thrombocytopenic
PubMed: 35584828
DOI: 10.7861/clinmed.2022-0146 -
American Journal of Hematology Jan 2023Treatment for immune thrombocytopenia (ITP) in pregnancy is hampered by the lack of fetal safety evidence of maternally-administered medications. The Pregnancy...
Treatment for immune thrombocytopenia (ITP) in pregnancy is hampered by the lack of fetal safety evidence of maternally-administered medications. The Pregnancy Surveillance Program (PSP) collected patient information from 2017-2020 for pregnancy, birth outcomes, and adverse events (AEs) for 186 women exposed to romiplostim from 20 days before pregnancy to the end of pregnancy. Timing of exposure was available in 128 women. Seventy-one mothers (38%) had prepregnancy exposure to romiplostim; intrapartum exposure was known for the first (for many mothers when they discovered their pregnancy), second, and third trimesters for 74 (40%), 22 (12%), and 44 (24%) mothers, respectively, with 15 mothers exposed during >1 trimester. Among the 86 mothers with known pregnancy outcomes, 46 (53%) had at least one pregnancy-related serious AE (SAE); approximately 2/3 of SAEs were due to underlying ITP. Of 92 mothers with known birth outcomes, 60 (65%) had a normal pregnancy and 16 (17%) had complications, with both categories including term and preterm births; there were 12 (14%) spontaneous miscarriages/stillbirths, 3 (3%) ectopic pregnancies, and 1 (1%) molar pregnancy. Most abnormal births resulted from abnormal pregnancies. There were five neonatal/postnatal AEs of note: inguinal hernia, cytomegalovirus infection, trisomy 8 (third trimester single-dose romiplostim exposure), single umbilical artery without known anomalies, and development of autism at age 2 years. Seven of 12 infants with neonatal thrombocytopenia had resolution of thrombocytopenia before discharge; all 12 were discharged. Review of pregnancies in women exposed to romiplostim did not reveal any specific safety concerns for mothers, fetuses, or infants.
Topics: Infant; Infant, Newborn; Pregnancy; Female; Humans; Child, Preschool; Purpura, Thrombocytopenic, Idiopathic; Pregnant Women; Thrombocytopenia; Pregnancy Outcome
PubMed: 36156812
DOI: 10.1002/ajh.26743 -
Sultan Qaboos University Medical Journal Nov 2022
Topics: Humans; Purpura; Pigmentation Disorders; Exanthema; Eczema
PubMed: 36407701
DOI: 10.18295/squmj.1.2022.004 -
Blood Jan 2023
Topics: Pregnancy; Female; Humans; Purpura, Thrombocytopenic, Idiopathic; Cohort Studies; Thrombocytopenia; Patients
PubMed: 36602822
DOI: 10.1182/blood.2022018082 -
Clinical and Experimental Dermatology Apr 2021The current COVID-19 pandemic is caused by the SARS-CoV-2 coronavirus. The initial recognized symptoms were respiratory, sometimes culminating in severe respiratory... (Review)
Review
The current COVID-19 pandemic is caused by the SARS-CoV-2 coronavirus. The initial recognized symptoms were respiratory, sometimes culminating in severe respiratory distress requiring ventilation, and causing death in a percentage of those infected. As time has passed, other symptoms have been recognized. The initial reports of cutaneous manifestations were from Italian dermatologists, probably because Italy was the first European country to be heavily affected by the pandemic. The overall clinical presentation, course and outcome of SARS-CoV-2 infection in children differ from those in adults as do the cutaneous manifestations of childhood. In this review, we summarize the current knowledge on the cutaneous manifestations of COVID-19 in children after thorough and critical review of articles published in the literature and from the personal experience of a large panel of paediatric dermatologists in Europe. In Part 1, we discuss one of the first and most widespread cutaneous manifestations of COVID-19, chilblain-like lesions, and in Part 2 we expanded to other manifestations, including erythema multiforme, urticaria and Kawasaki disease-like inflammatory multisystemic syndrome. In this part of the review, we discuss the histological findings of COVID-19 manifestations, and the testing and management of infected children for both COVID-19 and any other pre-existing conditions.
Topics: Adolescent; Antibodies, Monoclonal, Humanized; COVID-19; COVID-19 Testing; Child; Dermatologic Agents; Exanthema; Humans; Nicolau Syndrome; Pityriasis Rosea; Purpura; SARS-CoV-2; Skin Diseases, Viral; Urticaria
PubMed: 33207021
DOI: 10.1111/ced.14483 -
Medicina Clinica Nov 2022
Topics: Humans; COVID-19; Purpura; Cryoglobulinemia
PubMed: 35995607
DOI: 10.1016/j.medcli.2022.06.011 -
Journal of Thrombosis and Haemostasis :... Jun 2023Severe deficiency in ADAMTS-13 (<10%) and the loss of von Willebrand factor-cleaving function can precipitate microvascular thrombosis associated with thrombotic...
BACKGROUND
Severe deficiency in ADAMTS-13 (<10%) and the loss of von Willebrand factor-cleaving function can precipitate microvascular thrombosis associated with thrombotic thrombocytopenic purpura (TTP). Patients with immune-mediated TTP (iTTP) have anti-ADAMTS-13 immunoglobulin G antibodies that inhibit ADAMTS-13 function and/or increase ADAMTS-13 clearance. Patients with iTTP are treated primarily by plasma exchange (PEX), often in combination with adjunct therapies that target either the von Willebrand factor-dependent microvascular thrombotic processes (caplacizumab) or the autoimmune components (steroids or rituximab) of the disease.
OBJECTIVES
To investigate the contributions of autoantibody-mediated ADAMTS-13 clearance and inhibition in patients with iTTP at presentation and through the course of the PEX therapy.
PATIENTS/METHODS
Anti-ADAMTS-13 immunoglobulin G antibodies, ADAMTS-13 antigen, and activity were measured before and after each PEX in 17 patients with iTTP and 20 acute TTP episodes.
RESULTS
At presentation, 14 out of 15 patients with iTTP had ADAMTS-13 antigen levels of <10%, suggesting a major contribution of ADAMTS-13 clearance to the deficiency state. After the first PEX, both ADAMTS-13 antigen and activity levels increased similarly, and the anti-ADAMTS-13 autoantibody titer decreased in all patients, revealing ADAMTS-13 inhibition to be a modest modifier of the ADAMTS-13 function in iTTP. Analysis of ADAMTS-13 antigen levels between consecutive PEX treatments revealed that the rate of ADAMTS-13 clearance in 9 out of 14 patients analyzed was 4- to 10-fold faster than the estimated normal rate of clearance.
CONCLUSION
These data reveal, both at presentation and during PEX treatment, that antibody-mediated clearance of ADAMTS-13 is the major pathogenic mechanism that causes ADAMTS-13 deficiency in iTTP. Understanding the kinetics of ADAMTS-13 clearance in iTTP may now enable further optimization of treatment of patients with iTTP.
Topics: Humans; Autoantibodies; Purpura, Thrombotic Thrombocytopenic; von Willebrand Factor; Purpura, Thrombocytopenic, Idiopathic; Thrombosis; ADAMTS13 Protein; Immunoglobulin G
PubMed: 36813118
DOI: 10.1016/j.jtha.2023.02.011