Persistence of endothelial thrombomodulin in a patient with infectious purpura fulminans treated with protein C concentrate

Bendapudi, Pavan K.; Robbins, Alissa K.; LeBoeuf, Nicole R.; Pozdnyakova, Olga; Bhatt, Ami S.; Duke, Fujiko; Sells, Ryan E.; McQuiston, John R.; Humrighouse, Ben W.; Rouaisnel, Betty; Colling, Meaghan; Stephenson, Kathryn E.; Saavedra, Arturo; Losman, Julie-Aurore

doi:10.1182/bloodadvances.2018024430

Cited by 12 publications

(16 citation statements)

References 22 publications

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“…Dysfunction of protein C, an anticoagulant component of the coagulation cascade, often is cited as a crucial derangement leading to the development of a prothrombotic state in acute infectious PF. 21 Serum protein S and antithrombin deficiency also can play a role. 22 Specific in vitro examination of C canimorsus has revealed a protease that catalyzes N-terminal cleavage of procoagulant factor X, resulting in loss of function.…”

Section: A B Cmentioning

confidence: 99%

Purpura Fulminans in an Asplenic Intravenous Drug User

Nyers¹

2021

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Capnocytophaga species are fastidious, slowgrowing microorganisms. It is important, therefore, to maintain a high degree of suspicion and alert the microbiology laboratory to increase the likelihood of isolation.• Patients should be cautioned regarding the need for prophylactic antibiotics in the event of an animal bite; asplenic patients are at particular risk for infection.• In patients with severe purpura fulminans and a gangrenous limb, it is important to allow adequate time for demarcation of gangrene and not rush to amputation.

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Section: A B Cmentioning

confidence: 99%

Purpura Fulminans in an Asplenic Intravenous Drug User

Nyers¹

2021

Cutis

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“…AIPF is caused by various pathogens including Neisseria meningitidis , Streptococcus pneumoniae , Haemophilus influenzae , Staphylococcus aureus , and rickettsiae. The mechanism of purpura fulminans is poorly understood; however, a recent study revealed a severe deficiency in protein C caused by the loss of thrombomodulin on the endothelial surface during an early disease stage [103, 104]. Because of the strong association with DIC, laboratory tests show thrombocytopenia, a prolonged prothrombin time, an increased d-dimer level, and a decreasing fibrinogen level.…”

Section: Main Textmentioning

confidence: 99%

Sepsis-associated disseminated intravascular coagulation and its differential diagnoses

et al. 2019

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Disseminated intravascular coagulation (DIC) is a common complication in sepsis. Since DIC not only promotes organ dysfunction but also is a strong prognostic factor, its diagnosis at the earliest possible timing is important. Thrombocytopenia is often present in patients with DIC but can also occur in a number of other critical conditions. Of note, many of the rare thrombocytopenic diseases require prompt diagnoses and specific treatments. To differentiate these diseases correctly, the phenotypic expressions must be considered and the different disease pathophysiologies must be understood. There are three major players in the background characteristics of thrombocytopenia: platelets, the coagulation system, and vascular endothelial cells. For example, the activation of coagulation is at the core of the pathogenesis of sepsis-associated DIC, while platelet aggregation is the essential mechanism in thrombotic thrombocytopenic purpura and endothelial damage is the hallmark of hemolytic uremic syndrome. Though each of the three players is important in all thrombocytopenic diseases, one of the three dominant players typically establishes the individual features of each disease. In this review, we introduce the pathogeneses, symptoms, diagnostic measures, and recent therapeutic advances for the major diseases that should be immediately differentiated from DIC in sepsis.

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“…A deficiency of thrombomodulin impairs activation of protein C so that coagulation proceeds unchecked, leading to DIC. 5 In vitro studies have suggested two possible mechanisms for the loss of thrombomodulin activity in response to infections. While few studies have suggested downregulation of thrombomodulin gene activity in response to infections, other recent studies support a posttranscriptional mechanism that involves cleavage of the protein from the endothelial surface.…”

Section: Introductionmentioning

confidence: 99%

“…While few studies have suggested downregulation of thrombomodulin gene activity in response to infections, other recent studies support a posttranscriptional mechanism that involves cleavage of the protein from the endothelial surface. [5][6][7] The syndrome has been described predominantly in children but also in adults, with high mortality rates. 8,9 Patients develop fever, shock, and systemic consumptive coagulopathy with progression to multisystem organ failure.…”

Section: Introductionmentioning

confidence: 99%

“…The underlying infection causes attenuation of thrombomodulin—a cofactor of thrombin that activates protein C and plays a role in endogenous anticoagulation. A deficiency of thrombomodulin impairs activation of protein C so that coagulation proceeds unchecked, leading to DIC 5 . In vitro studies have suggested two possible mechanisms for the loss of thrombomodulin activity in response to infections.…”

Section: Introductionmentioning

confidence: 99%

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Acute purpura fulminans—a rare cause of skin necrosis: A single‐institution clinicopathological experience

et al. 2020

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Background: Purpura fulminans, an uncommon syndrome of intravascular thrombosis with hemorrhagic infarction of the skin, is often accompanied by disseminated intravascular coagulation (DIC) and multi-organ failure, and may ultimately lead to death. Methods: Herein, we document 13 skin biopsies from 11 adult patients with the clinical diagnosis of sepsis and confirmed histopathologic diagnosis of intravascular thrombosis and/or DIC, compatible with acute infectious purpura fulminans (AIPF). Detailed history and clinical examination were performed, and the lesions were correlated with histopathologic findings. Any underlying medical disease was taken into consideration. Results: There were 5 males and 6 females with lower extremity or peri-incisional purpuric skin lesions. The most important comorbidities identified were a history of surgical procedure or neoplasm, although 4 patients had no relevant underlying history. Most skin biopsies revealed focal epidermal ischemia or necrosis and 3 showed full-thickness epidermal necrosis. In the underlying dermis, there were fibrin thrombi in superficial and deep blood vessels with acute inflammation. Changes of an inflammatory destructive vasculitis were identified in 5 cases. No bacteria or fungi were identified on histopathology. Conclusions: AIPF is a rapidly-progressing medical emergency which may be identified by histopathology in culture-negative cases. Biopsies may show neutrophilic infiltrate without infective organisms.

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Persistence of endothelial thrombomodulin in a patient with infectious purpura fulminans treated with protein C concentrate

Cited by 12 publications

References 22 publications

Purpura Fulminans in an Asplenic Intravenous Drug User

Purpura Fulminans in an Asplenic Intravenous Drug User

Sepsis-associated disseminated intravascular coagulation and its differential diagnoses

Acute purpura fulminans—a rare cause of skin necrosis: A single‐institution clinicopathological experience

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