Thrombocytopenia-Associated Multiple Organ Failure and Acute Kidney Injury

Nguyen, Trung C.; Crúz, Miguel A.; Carcillo, Joseph A.

doi:10.1016/j.ccc.2015.06.004

Cited by 46 publications

(33 citation statements)

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“…Kidney tissue from some patients with HUS are reported to have vWF/platelet-rich thrombi [9] but in other studies glomerular thrombi contain fibrin and little or no vWF [42]. In the present work, we found no evidence for increased vWF following Stx-2 treatment in proportion to the number of CD-41-positive objects (platelets).…”

Section: Discussioncontrasting

confidence: 69%

“…Despite a report that Stx induces vWF secretion by human endothelial cells [41], the presence of increased vWF in the glomeruli thrombi of human eHUS is controversial [9,42].…”

Section: Discussionmentioning

confidence: 98%

“…Another form of HUS, atypical HUS (aHUS) is distinct from eHUS , while often has overlapping symptoms. aHUS is due to unregulated complement activation, in most cases secondary to identifiable mutant complement regulatory proteins [9]. Its frequency is only about one-tenth of eHUS [10].…”

Section: Introductionmentioning

confidence: 99%

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Platelet Thrombus Formation in eHUS is Prevented by Anti-MBL2

Kushak

Boyle

Rosales

et al. 2019

Preprint

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Epidemic Hemolytic Uremic Syndrome (eHUS) caused by Shiga toxin-producing bacteria is characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury that cause acute renal failure in up to 65% of affected patients. We hypothesized that the mannose-binding lectin (MBL) pathway of complement activation plays an important role in human eHUS, as we previously demonstrated that injection of Shiga Toxin-2 (Stx-2) led to fibrin deposition in mouse glomeruli that was blocked by co-injection of the anti-MBL-2 antibody 3F8.However, the markers of platelet thrombosis in affected mouse glomeruli were not delineated.To investigate the effect of 3F8 on markers of platelet thrombosis, we used kidney sections from our mouse model (MBL-2+/+ Mbl-A/C-/-; MBL2 KI mouse). Mice in the control group received PBS, while mice in a second group received Stx-2, and those in a third group received 3F8 and Stx-2. Using double immunofluorescence (IF) followed by digital image analysis, kidney sections were stained for fibrin(ogen) and CD41 (marker for platelets), von-Willebrand factor (marker for endothelial cells and platelets), and podocin (marker for podocytes). Electron microscopy (EM) was performed on ultrathin sections from mice and human with HUS.Injection of Stx-2 resulted in an increase of both fibrin and platelets in glomeruli, while administration of 3F8 with Stx-2 reduced both platelet and fibrin to control levels. EM studies confirmed that CD41-positive objects observed by IF were platelets. The increases in platelet number and fibrin levels by injection of Stx-2 are consistent with the generation of platelet-fibrin thrombi that were prevented by 3F8.

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Section: Discussioncontrasting

confidence: 69%

“…Despite a report that Stx induces vWF secretion by human endothelial cells [41], the presence of increased vWF in the glomeruli thrombi of human eHUS is controversial [9,42].…”

Section: Discussionmentioning

confidence: 98%

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Platelet Thrombus Formation in eHUS is Prevented by Anti-MBL2

Kushak

Boyle

Rosales

et al. 2019

Preprint

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“…Laboratory and clinical studies have confirmed that thrombocytopenia—associated multiple organ failure is a thrombotic microangiopathic syndrome defined by a variety of pathological changes that includes thrombotic thrombocytopenic purpura (TTP), secondary thrombotic microangiopathy (TMA), and disseminated intravascular coagulation (DIC) [18, 19]. However a case of scrub typhus with multiorgan dysfunction and immune thrombocytopenia has not been described.…”

Section: Discussionmentioning

confidence: 99%

“…Several mechanisms have been elucidated to explain thrombocytopenia in multi-organ dysfunction [18, 19]. However a case of scrub typhus with multi-organ dysfunction and immune thrombocytopenia has not been described.…”

Section: Introductionmentioning

confidence: 99%

Immune thrombocytopenia with multi-organ dysfunction syndrome as a rare presentation of scrub typhus: a case report

Ittyachen¹,

Abraham²,

Krishnamoorthy³

et al. 2017

BMC Res Notes

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BackgroundScrub typhus is an acute infectious illness caused by Orientia tsutsugamushi. It is endemic to a part of the world known as the “tsutsugamushi triangle”. Humans are accidental hosts in this zoonotic disease. About a third of patients admitted with scrub typhus have evidence of multi-organ dysfunction. Multi-organ dysfunction secondary to scrub typhus carries a high mortality rate.Case presentationWe report a 65-year old lady who was admitted in a Tertiary Care Center in the state of Kerala in India, with 7 day history of fever, myalgia and reduced urine output. Head to foot examination revealed the presence of an eschar on her chest. One week prior to the onset of her illness she had gone trekking through a hilly forest area. She was clinically suspected to have scrub typhus, which was later confirmed with laboratory tests. She developed multi-organ dysfunction syndrome secondary to this illness. Though there was an improvement in the multi-organ dysfunction, thrombocytopenia alone failed to improve. Bone marrow study was done which was suggestive of immune thrombocytopenia. Patient was given a course of steroids with which the thrombocytopenia improved.ConclusionFailure of platelet count to normalize even after there has been a general improvement of other markers of multi-organ dysfunction in scrub typhus should prompt the clinician to consider other potential causes of thrombocytopenia. An unusual finding as this calls for further research to understand the molecular mechanisms behind such an event. Further, considering the close similarity in clinical presentation of several tropical illnesses, meticulous history taking and a detailed physical examination needs to be emphasized.

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Paeoniflorin alleviates lipopolysaccharide‐induced disseminated intravascular coagulation by inhibiting inflammation and coagulation activation

Fang

et al. 2020

Drug Development Research

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Lipopolysaccharide (LPS) is a toxic component of the outer membrane of gram-negative bacteria that can activate the blood coagulation system, leading to disseminated intravascular coagulation (DIC). DIC is a syndrome characterized by thromboembolism and multiple organ failure. Herein, the beneficial effect of paeoniflorin (PF) on the alleviation of LPS-induced DIC was investigated with an experimental DIC mouse model. Briefly, mice were randomly divided into the following six groups: (1) control; (2) LPS; (3) heparin;(4) low-PF treatment; (5) medium-PF treatment; and (6) high-PF treatment. The histological morphology of the liver and kidney was observed, and the coagulation indicators (such as prothrombin time), function indicators (such as alanine transferase), and inflammatory factors (such as TNF-α) were detected. Additionally, an in vitro cell inflammation model using RAW 264.7 murine macrophages was established. Activation of the nuclear factor kappa B (NF-κB) signaling pathway and tumor necrosis factor-α (TNF-α) were determined by western blotting. Based on our findings, PF could significantly improve the histological morphology of the liver and kidney, indicating that PF protects the liver and kidney against damage induced by LPS. Additionally, PF improved the function and coagulation indicators and reduced the production of inflammatory factors. In vitro, PF inhibited the expression of TNF-α by suppressing NF-κB signaling pathway activation.Collectively, our findings support the hypothesis that PF has anti-inflammatory and anticoagulation effects for the alleviation of LPS-induced DIC. PF is thus a potential cotreatment option for DIC. K E Y W O R D S disseminated intravascular coagulation (DIC), heparin, lipopolysaccharide (LPS), paeoniflorin (PF), tumor necrosis factor-α (TNF-α)

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Thrombocytopenia-Associated Multiple Organ Failure and Acute Kidney Injury

Cited by 46 publications

References 100 publications

Platelet Thrombus Formation in eHUS is Prevented by Anti-MBL2

Platelet Thrombus Formation in eHUS is Prevented by Anti-MBL2

Immune thrombocytopenia with multi-organ dysfunction syndrome as a rare presentation of scrub typhus: a case report

Paeoniflorin alleviates lipopolysaccharide‐induced disseminated intravascular coagulation by inhibiting inflammation and coagulation activation

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