An update on the pathogenesis and diagnosis of thrombotic thrombocytopenic purpura

Gómez-Seguí, Inés; Izquierdo, Cristina Pascual; Mingot‐Castellano, María Eva; Rubia, Javier de la

doi:10.1080/17474086.2023.2159803

Cited by 5 publications

(4 citation statements)

References 161 publications

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“…Next, as a control group, we used a previously published cohort of young diabetic patients after correction of ketoacidosis where we showed that microvascular hyporeactivity recovered after acidosis correction [ 14 ] Given that patients with cardiovascular risk factors are susceptible to a lower microvascular reactivity; difference between healthy subjects and iTTP patients could be even more important than differences between diabetic and iTTP patients [ 32 – 35 ]. The device used in this study only allows exploration of the skin microvasculature and we did not investigate the endothelium of key organs affected by iTTP such as the brain, heart and kidney microcirculation [ 36 , 37 ]. Finally, we did not explore the endothelium-independent vasodilation, which requires either heating or nitroprusside challenge.…”

Section: Discussionmentioning

confidence: 99%

Reversible skin microvascular hyporeactivity in patients with immune-mediated thrombocytopenic thrombotic purpura

et al. 2023

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Background Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare disease characterized by arteriolar and capillary microthrombosis precipitating organ failure. However, the contribution of endothelial dysfunction on impaired microvascular blood flow in iTTP patients has been poorly explored. This pilot observational study aimed to explore endothelial-mediated vasoreactivity in iTTP patients at admission and its changes after plasma exchange therapy (PE). Methods We conducted a prospective observational study in patients (> 18-year old) admitted in ICU for iTTP. Using laser Doppler flowmetry and acetylcholine (Ach) iontophoresis in the forearm, we recorded the skin microvascular blood flow and the endothelium-mediated vasoreactivity at admission and after PE. Demographics, biological, clinical courses, and outcomes were also collected. As a control group, we used a previously published cohort of young diabetic patients after correction of ketoacidosis. Results Eighteen confirmed iTTP patients and 34 controls were included in the study, mainly female (72%) aged 43 ± 16-year-old. At admission, 55% had neurological abnormalities, 50% cardiac issues and 27.8% an acute kidney injury. Median platelet count was 19 G/mL [10–37]. Baseline microvascular blood flow was decreased in iTTP patients when compared to controls (5.97 ± 4.5 vs. 10.1 ± 6.3 PU, P = 0.03), associated with markedly impaired endothelial-mediated skin microvascular reactivity (AUC: 9627 ± 8122 vs. 16,475 ± 11,738, P = 0.03). Microvascular reactivity improved after the first PE session (AUC: 9627 ± 8122 vs 16,558 ± 10,699, P = 0.007, respectively, baseline and post-PE1) and much more after the second session (26,431 ± 23,181, P = 0.04 post-PE1 vs post-PE2). Hemolysis biomarkers (LDH and bilirubin) negatively correlated with skin microvascular flow and vasoreactivity. Conclusion We highlighted a marked yet reversible skin endothelium-mediated microvascular hyporeactivity in iTTP patients that could participate in organ injury pathophysiology.

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Section: Discussionmentioning

confidence: 99%

Reversible skin microvascular hyporeactivity in patients with immune-mediated thrombocytopenic thrombotic purpura

et al. 2023

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“…Thrombotic thrombocytopenic purpura (TTP) is a severe, rare, and relapsing life‐threatening thrombotic microangiopathy characterized by severe thrombocytopenia, microangiopathic hemolytic anemia, and ischemic end‐organ damage resulting from microvascular platelet‐rich thrombi 156,157 . TTP is a disorder resulting from genetic or acquired severe deficiency of plasma ADAMTS13, a metalloprotease that cleaves endothelium‐derived ultralarge von Willebrand factor (vWF), leading to unrestrained adhesion of the vWF multimers to platelets and microthrombi formation, resulting in thrombocytopenia and microangiopathic hemolytic anemia 158–161 . The predominant form of TTP is acquired immune‐mediated TTP 162 .…”

Section: Venous Stroke In Patients With Blood Diseasesmentioning

confidence: 99%

“… 156 , 157 TTP is a disorder resulting from genetic or acquired severe deficiency of plasma ADAMTS13, a metalloprotease that cleaves endothelium‐derived ultralarge von Willebrand factor (vWF), leading to unrestrained adhesion of the vWF multimers to platelets and microthrombi formation, resulting in thrombocytopenia and microangiopathic hemolytic anemia. 158 , 159 , 160 , 161 The predominant form of TTP is acquired immune‐mediated TTP. 162 TTP is an infrequent cause of stroke among young adults.…”

Section: Venous Stroke In Patients With Blood Diseasesmentioning

confidence: 99%

Cerebral venous thrombosis in patients with autoimmune disease, hematonosis or coronavirus disease 2019: Many familiar faces and some strangers

et al. 2023

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BackgroundCerebral venous thrombosis, a rare stroke, is characterized by neurological dysfunction caused by bleeding and/or infarction resulting from venous sinus thrombosis, the so‐called venous stroke. Current guidelines recommend anticoagulants as first‐line therapy in the treatment of venous stroke. With complicated causes of cerebral venous thrombosis, treatment is difficult, especially when combined with autoimmune diseases, blood diseases, and even COVID‐19.AimsThis review summarizes the pathophysiological mechanisms, epidemiology, diagnosis, treatment, and clinical prognosis of cerebral venous thrombosis combined with autoimmune diseases, blood diseases, or infectious diseases such as COVID‐19.ConclusionA systematic understanding of particular risk factors that should not be neglected when unconventional cerebral venous thrombosis occurs and for a scientific understanding of pathophysiological mechanisms, clinical diagnosis, and treatment, thus contributing to knowledge on special types of venous stroke.

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“…However, an increased VWF is not enough to lead to TPP. Hence, iTTP could be triggered by several conditions, such as an abnormal immune response to viral infections, an autoimmune disorder, the onset of a malignant disease, a bone marrow transplant or the assumption of chemotherapeutic drugs [33]. In most iTTP cases, it is hard to find the triggering factor because of the wide spectrum of clinical presentations accompanying the acute events.…”

Section: Introductionmentioning

confidence: 99%

A Long-Term Follow-Up Study in Immune-Mediated Thrombotic Thrombocytopenic Purpura: What Are the Outcomes?

Bonifacio,

Roselli,

Schifone

et al. 2023

JCM

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Endothelium damage triggers the multimeric protein von Willebrand factor (VWF) release and subsequent binding to platelets, which are recruited at sites of vascular injury. A complex and fragile equilibrium between circulating levels of von Willebrand factor and its metalloprotease, ADAMTS13, is responsible for the hemostatic balance. However, the presence of autoantibodies targeting ADAMTS13 results in an increase in von Willebrand factor, mainly in its ultra-large multimers. The latter lead to platelet aggregation, the formation of thrombi and microangiopathic hemolytic anemia. This pathologic condition, known as immune-mediated thrombotic thrombocytopenic purpura (iTTP), occurs with high morbidity and a high rate of relapses. In this work, the long-term follow-up of 40 patients with iTTP is reported. We assessed ADAMTS13 activity, plasmatic VWF levels and the ADAMTS13/VWF ratio, comparing iTTP relapsing patients with remitting ones. A decrease in the ADAMTS13/VWF ratio, along with a reduced ADAMTS13 activity, could serve as predictive and sensitive biomarkers of incoming relapses.

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An update on the pathogenesis and diagnosis of thrombotic thrombocytopenic purpura

Cited by 5 publications

References 161 publications

Reversible skin microvascular hyporeactivity in patients with immune-mediated thrombocytopenic thrombotic purpura

Reversible skin microvascular hyporeactivity in patients with immune-mediated thrombocytopenic thrombotic purpura

Cerebral venous thrombosis in patients with autoimmune disease, hematonosis or coronavirus disease 2019: Many familiar faces and some strangers

A Long-Term Follow-Up Study in Immune-Mediated Thrombotic Thrombocytopenic Purpura: What Are the Outcomes?

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