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Clinical Medicine (London, England) May 2023Acute thrombosis and thrombocytopenia pose challenges to the clinician. Thrombocytopenia is naturally viewed as a risk factor for bleeding, and an association with acute... (Review)
Review
Acute thrombosis and thrombocytopenia pose challenges to the clinician. Thrombocytopenia is naturally viewed as a risk factor for bleeding, and an association with acute thrombosis appears paradoxical. It presents typically as a medical emergency and requires treatment to be started before having confirmatory results. This review supports the attending clinician to recognise and manage conditions that are part of the thrombotic thrombocytopenic syndrome through four illustrative clinical cases. Common themes linking the underlying pathology and treatment are explored to highlight the continued relevance of this rare, but often devastating, presentation.
Topics: Humans; Purpura, Thrombotic Thrombocytopenic; Thrombosis; Syndrome; Risk Factors
PubMed: 37236794
DOI: 10.7861/clinmed2023-0076 -
Cold Spring Harbor Molecular Case... Feb 2022Ethylmalonic encephalopathy (MIM #602473) is a rare autosomal recessive metabolic condition caused by biallelic variants in (MIM #608451), characterized by global...
Ethylmalonic encephalopathy (MIM #602473) is a rare autosomal recessive metabolic condition caused by biallelic variants in (MIM #608451), characterized by global developmental delay, infantile hypotonia, seizures, and microvascular damage. The microvascular changes result in a pattern of relapsing spontaneous diffuse petechiae and purpura, positional acrocyanosis, and pedal edema, hemorrhagic suffusions of mucous membranes, and chronic diarrhea. Here, we describe an instructive case in which ethylmalonic encephalopathy masqueraded as meningococcal septicemia and shock. Ultrarapid whole-genome testing (time to result 60 h) and prompt biochemical analysis facilitated accurate diagnosis and counseling with rapid implementation of precision treatment for the metabolic crisis related to this condition. This case provides a timely reminder to consider rare genetic diagnoses when atypical features of more common conditions are present, with an early referral to ensure prompt biochemical and genomic diagnosis.
Topics: Brain Diseases, Metabolic, Inborn; Humans; Mitochondrial Proteins; Nucleocytoplasmic Transport Proteins; Purpura; Sepsis
PubMed: 35165146
DOI: 10.1101/mcs.a006193 -
Lakartidningen Mar 2018
Topics: ADAMTS13 Protein; Anemia, Hemolytic; Female; Humans; Infant, Newborn; Perinatal Death; Pregnancy; Pregnancy Complications, Hematologic; Purpura, Thrombotic Thrombocytopenic; Thrombocytopenia; Young Adult
PubMed: 29558005
DOI: No ID Found -
British Journal of Haematology Jul 2015Fatigue is an important aspect of health-related quality of life from the patient perspective and can have significant socio-economic consequences. It is a common... (Review)
Review
Fatigue is an important aspect of health-related quality of life from the patient perspective and can have significant socio-economic consequences. It is a common feature of chronic illnesses and a significant number of both adults and children with immune thrombocytopenia (ITP) suffer from fatigue. Reliable, validated fatigue scales have been developed for use in ITP. These will facilitate future investigation of its pathogenesis and the effectiveness of intervention. Acute inflammation acts on neural and endocrine systems resulting in 'sickness behaviour', an adaptive response to infection and injury. Inflammation is also thought to cause fatigue in chronic disease and immune dysregulation in ITP appears to have a number of pro-inflammatory components. Clinicians should consider fatigue when assessing the burden of disease. Although effective ITP-directed therapy can improve fatigue, a number of fatigue-directed strategies may also need to be considered.
Topics: Fatigue; Humans; Immunosuppressive Agents; Purpura, Thrombocytopenic, Idiopathic; Quality of Life
PubMed: 25823426
DOI: 10.1111/bjh.13385 -
Blood Aug 2022
Topics: Humans; Prevalence; Purpura, Thrombotic Thrombocytopenic; Stroke
PubMed: 35980682
DOI: 10.1182/blood.2022016942 -
Frontiers in Immunology 2018Immune thrombocytopenia (ITP) is an autoimmune disease defined by low platelet counts which presents with an increased bleeding risk. Several genetic risk factors (e.g.,... (Review)
Review
Immune thrombocytopenia (ITP) is an autoimmune disease defined by low platelet counts which presents with an increased bleeding risk. Several genetic risk factors (e.g., polymorphisms in immunity-related genes) predispose to ITP. Autoantibodies and cytotoxic CD8 T cells (Tc) mediate the anti-platelet response leading to thrombocytopenia. Both effector arms enhance platelet clearance through phagocytosis by splenic macrophages or dendritic cells and by induction of apoptosis. Meanwhile, platelet production is inhibited by CD8 Tc targeting megakaryocytes in the bone marrow. CD4 T helper cells are important for B cell differentiation into autoantibody secreting plasma cells. Regulatory Tc are essential to secure immune tolerance, and reduced levels have been implicated in the development of ITP. Both Fcγ-receptor-dependent and -independent pathways are involved in the etiology of ITP. In this review, we present a simplified model for the pathogenesis of ITP, in which exposure of platelet surface antigens and a loss of tolerance are required for development of chronic anti-platelet responses. We also suggest that infections may comprise an important trigger for the development of auto-immunity against platelets in ITP. Post-translational modification of autoantigens has been firmly implicated in the development of autoimmune disorders like rheumatoid arthritis and type 1 diabetes. Based on these findings, we propose that post-translational modifications of platelet antigens may also contribute to the pathogenesis of ITP.
Topics: Humans; Purpura, Thrombocytopenic, Idiopathic
PubMed: 29760702
DOI: 10.3389/fimmu.2018.00880 -
Tidsskrift For Den Norske Laegeforening... Sep 2016Congenital thrombotic thrombocytopenic purpura (TTP) is a rare, hereditary disorder. Clinically it presents as episodic microangiopathic haemolytic anaemia and... (Review)
Review
BACKGROUND
Congenital thrombotic thrombocytopenic purpura (TTP) is a rare, hereditary disorder. Clinically it presents as episodic microangiopathic haemolytic anaemia and thrombocytopenia with varying degrees of damage to internal organs. The condition may present in neonates, but can also present for the first time in adulthood. The prevalence of congenital TTP is particularly high in Norway, and it is therefore important for Norwegian doctors to be aware of the condition. In this article we review the main characteristics of the disease, including its diagnosis and management, and introduce potential new treatments for the future.
METHOD
The article is based on a literature search in PubMed as well as the authors’ own research and clinical experience.
RESULTS
There was great variation in the severity of congenital TTP: from neonatal mortality to disease-free intervals of several years. Episodes are generally precipitated by a trigger. Acute episodes are treated with plasma infusions, and approximately half of all patients experience frequent episodes and require prophylactic infusions to avoid organ damage. The risk of episodes is greatest in neonates, during pregnancy and in association with infections.
INTERPRETATION
There is little research-based evidence regarding long-term prognosis in congenital TTP. There is also a need for guidelines to help identify candidates for prophylactic treatment. An international patient registry would provide useful information and form the basis for better guidelines on the monitoring and treatment of these patients.
Topics: ADAMTS13 Protein; Algorithms; Blood Transfusion; Humans; Norway; Purpura, Thrombotic Thrombocytopenic
PubMed: 27686205
DOI: 10.4045/tidsskr.15.1272 -
Blood Jun 2021
Topics: ADAMTS13 Protein; Humans; Purpura, Thrombotic Thrombocytopenic
PubMed: 34165543
DOI: 10.1182/blood.2021011265 -
The Journal of the Arkansas Medical... Feb 2015
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Haematologica Feb 2023
Topics: Humans; Purpura, Thrombotic Thrombocytopenic
PubMed: 35488359
DOI: 10.3324/haematol.2022.281095