-
The Medical Journal of Australia May 2022
Topics: Facial Dermatoses; Humans; Purpura; Vomiting
PubMed: 35421901
DOI: 10.5694/mja2.51504 -
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 -
Archives of Dermatological Research Mar 2023Levamisole exposure in cocaine users is a well-recognized cause of retiform purpura, a distinctive net-like maculopapular patch. Prolonged exposure to levamisole... (Review)
Review
Levamisole exposure in cocaine users is a well-recognized cause of retiform purpura, a distinctive net-like maculopapular patch. Prolonged exposure to levamisole can lead to a serious systemic syndrome known as levamisole-induced vasculitis, most commonly involving the kidneys and lungs. More recently, retiform purpura has been observed in patients with the novel coronavirus disease of 2019 (COVID-19). Due to their overlapping dermatologic and systemic manifestations, levamisole-induced and COVID-19-induced retiform purpura may mimic one another in clinical presentation. The possibility that patients may present with one or both syndromes creates a diagnostic challenge. This review of levamisole-induced and COVID-19-induced retiform purpura highlights their corresponding and distinctive features. Additionally, we propose a unique staging system for levamisole-induced retiform purpura that may be valid for future classification of COVID-19-induced retiform purpura.
Topics: Humans; COVID-19; Levamisole; Purpura
PubMed: 34807290
DOI: 10.1007/s00403-021-02303-1 -
Transfusion Aug 2019
Review
Topics: Aged; Erythrocyte Transfusion; Female; Humans; Purpura; Skin Diseases, Vascular; Transfusion Reaction
PubMed: 31175667
DOI: 10.1111/trf.15392 -
Archives of Pathology & Laboratory... Aug 2023Immune thrombotic thrombocytopenic purpura (iTTP) is a rare but potentially fatal blood disorder resulting from acquired deficiency of plasma ADAMTS13, a metalloprotease... (Review)
Review
CONTEXT.—
Immune thrombotic thrombocytopenic purpura (iTTP) is a rare but potentially fatal blood disorder resulting from acquired deficiency of plasma ADAMTS13, a metalloprotease that cleaves endothelium-derived ultralarge von Willebrand factor. Standard of care for iTTP including therapeutic plasma exchange, caplacizumab, and immunosuppressives, known as triple therapy, has led to a significant reduction in the disease-related mortality rate. The first International Society of Thrombosis and Haemostasis TTP guideline stresses the importance of having plasma ADAMTS13 activity testing in the algorithm for diagnosis and management of iTTP. However, the predictive role of assessing plasma ADAMTS13 activity and inhibitors or other ADAMTS13-related parameters in patients with acute iTTP and during remission has not been systematically evaluated.
OBJECTIVE.—
To review and assess the predictive values of testing plasma ADAMTS13 activity, antigen, and inhibitors or anti-ADAMTS13 immunoglobulin G at various stages of disease in outcomes of iTTP.
DATA SOURCES.—
Peer-reviewed publications and personal experience.
CONCLUSIONS.—
We conclude that assessing ADAMTS13 biomarkers is not only essential for establishing the initial diagnosis, but also crucial for risk stratification and the early detection of disease recurrence. This may guide therapeutic interventions during acute episodes and for long-term follow-up of iTTP patients.
Topics: Humans; ADAMTS13 Protein; Biomarkers; Immunosuppressive Agents; Purpura, Thrombotic Thrombocytopenic; Thrombosis; von Willebrand Factor
PubMed: 36223210
DOI: 10.5858/arpa.2022-0050-RA -
British Journal of Haematology Apr 2022The 100th anniversary of the first description of Thrombotic Thrombocytopenic Purpura (TTP) as a disease by Dr. Eli Moschcowitz approaches. For many decades, TTP... (Review)
Review
The 100th anniversary of the first description of Thrombotic Thrombocytopenic Purpura (TTP) as a disease by Dr. Eli Moschcowitz approaches. For many decades, TTP remained mostly a mysterious fatal condition, where diagnosis was often post-mortem. Initially a pentad of symptoms was identified, a pattern that later revealed to be fallible. Sporadic observations led to empiric interventions that allowed for the first impactful breakthrough in TTP treatment, almost 70 years after its first description: the introduction of plasma exchange and infusions as treatments. The main body of knowledge within the field was gathered in the latest three decades: patient registries were set and proved crucial for advancements; the general mechanisms of disease have been described; the diagnosis was refined; new treatments and biomarkers with improvements on prognosis and management were introduced. Further changes and improvements are expected in the upcoming decades. In this review, we provide a brief historic overview of TTP, as an illustrative example of the success of translational medicine enabling to rapidly shift from a management largely based on empiricism to targeted therapies and personalized medicine, for the benefit of patients. Current management options and present and future perspectives in this still evolving field are summarized.
Topics: ADAMTS13 Protein; Empiricism; Humans; Molecular Targeted Therapy; Plasma Exchange; Purpura, Thrombotic Thrombocytopenic
PubMed: 35146746
DOI: 10.1111/bjh.18040 -
Transfusion Medicine Reviews Oct 2022Immune thrombotic thrombocytopenic purpura (iTTP) is a microangiopathic hemolytic anemia (MAHA) underpinned by autoreactivity against the von Willebrand factor (vWF)... (Review)
Review
Immune thrombotic thrombocytopenic purpura (iTTP) is a microangiopathic hemolytic anemia (MAHA) underpinned by autoreactivity against the von Willebrand factor (vWF) cleaving protease, ADAMTS13 (adisintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). Autoantibody mediated ADAMTS13 inhibition leads to the accumulation of ultra-large vWF multimers which activate platelets and endothelium to initiate microvascular thrombosis. In the absence of urgent therapeutic intervention, iTTP is rapidly fatal due to cumulative organ dysfunction including catastrophic neurological and cardiac sequalae. Therapeutic plasma exchange (TPE) is the mainstay of initial therapy and aims to remove pathological autoantibodies and ultra-large vWF multimers while replenishing ADAMTS13. Immunosuppression is an important treatment adjunct, as attainment of remission and successful TPE cessation is strongly associated with suppression of anti-ADAMTS13 antibody production. More recently, caplacizumab, an antibody fragment blocking the interaction between vWF multimers and platelets, has been incorporated into acute TTP management to mitigate end-organ damage while awaiting suppression of anti-ADAMTS13 activity. In most cases, remission is achieved using corticosteroids alone or in combination with the B-cell depleting antibody, rituximab. However, some patients are refractory to front-line immunosuppression in the context of 'inhibitor boosting' whereby the exposure to homologous plasma exacerbates the underlying autoimmune flare. As such cases have been observed in the context of likely effective B-cell depletion, it has been hypothesized that plasma cells (ie, terminally differentiated B-cells) may provide a therapy-resistant nidus of anti-ADAMTS13 production as has been demonstrated in other autoimmune disease settings. Autoreactive plasma cells can be targeted by conventional and novel therapeutics, including those developed for malignant plasma cells in the context of multiple myeloma. Here we review the rationale and evidence for plasma cell directed therapy in refractory iTTP, with a focus on the proteasome inhibitor, bortezomib, and the CD38 monoclonal antibody, daratumumab.
Topics: Humans; Purpura, Thrombotic Thrombocytopenic; Plasma Cells; von Willebrand Factor; Purpura, Thrombocytopenic, Idiopathic; Thrombosis
PubMed: 36396570
DOI: 10.1016/j.tmrv.2022.09.001 -
Dermatologic Therapy Apr 2022
Topics: COVID-19; COVID-19 Vaccines; Humans; Purpura; Vaccination
PubMed: 35137500
DOI: 10.1111/dth.15360 -
Archives of Disease in Childhood.... Dec 2021-A 14-year-old boy with recent antibiotic treatment for tonsillitis, presented to the emergency department with 1-week history of worsening rash and haemorrhagic bullae...
-A 14-year-old boy with recent antibiotic treatment for tonsillitis, presented to the emergency department with 1-week history of worsening rash and haemorrhagic bullae involving the bilateral legs, trunk and hands (figures 1 and 2). Laboratory results were significant for proteinuria (2+protein) and haematuria (1+, 5-10 red blood cells/high power field); 24 hours urinary protein and renal function were within normal limits. The patient had an inconclusive skin biopsy.
Topics: Adolescent; Emergency Service, Hospital; Exanthema; Humans; IgA Vasculitis; Lower Extremity; Male; Purpura
PubMed: 32576570
DOI: 10.1136/archdischild-2019-317600 -
Revista Paulista de Pediatria : Orgao... 2021To assess intermittent abdominal pain in IgA vasculitis patients and its relation to demographic data, clinical manifestations and treatments.
OBJECTIVE
To assess intermittent abdominal pain in IgA vasculitis patients and its relation to demographic data, clinical manifestations and treatments.
METHODS
A retrospective cohort study included 322 patients with IgA vasculitis (EULAR/PRINTO/PRES criteria) seen at the Pediatric Rheumatology Unit in the last 32 years. Sixteen patients were excluded due to incomplete data in medical charts. Intermittent abdominal pain was characterized by new abdominal pain after complete resolution in the first month of disease.
RESULTS
Intermittent abdominal pain was observed in 35/306 (11%) IgA vasculitis patients. The median time between first and second abdominal pain was 10 days (3-30 days). The main treatment of intermittent abdominal pain included glucocorticoid [n=26/35 (74%)] and/or ranitidine [n=22/35 (63%)]. Additional analysis showed that the frequency of intermittent purpura/petechiae (37 vs. 21%; p=0.027) and the median of purpura/petechiae duration [20 (3-90) vs. 14 (1-270) days; p=0.014] were significantly higher in IgA vasculitis patients with intermittent abdominal pain compared to those without. Gastrointestinal bleeding (49 vs. 13%; p<0.001), nephritis (71 vs. 45%; p=0.006), glucocorticoid (74 vs. 44%; p=0.001) and intravenous immunoglobulin use (6 vs. 0%; p=0.036) were also significantly higher in the former group. The frequency of ranitidine use was significantly higher in IgA vasculitis patients with intermittent abdominal pain versus without (63 vs. 28%; p<0.001), whereas the median of ranitidine duration was reduced in the former group [35 (2-90) vs. 60 (5-425) days; p=0.004].
CONCLUSIONS
Intermittent abdominal pain occurred in nearly a tenth of IgA vasculitis patients, in the first 30 days of disease, and was associated with other severe clinical features. Therefore, this study suggests that these patients should be followed strictly with clinical and laboratorial assessment, particularly during the first month of disease course.
Topics: Abdominal Pain; Child; Humans; IgA Vasculitis; Immunoglobulin A; Retrospective Studies; Rheumatology
PubMed: 34495272
DOI: 10.1590/1984-0462/2022/40/2020202