Markers of coagulation activation and acute kidney injury in patients after hematopoietic cell transplantation

Hingorani, Sangeeta; Seidel, Kristy; Pao, Emily; Lawler, Richard L.; McDonald, George B.

doi:10.1038/bmt.2015.2

Cited by 11 publications

(4 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We demonstrated that XBJ promoted tube-formation in EA.hy926 human endothelial cells which could be important in attenuating aGVHD in patients after allo-HSCT. Chemotherapy and radiation conditioning cause damages in different organs and tissues, including blood vessels in the bone marrow and other organs (Hingorani et al, 2015; Perkey and Maillard, 2018). Thus, XBJ may prevent aGVHD through preventing vessel damage and enhancing vessel repair after allo-HSCT.…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology-Guided Development of a Novel Integrative Regimen to Prevent Acute Graft-vs.-Host Disease

et al. 2018

View full text Add to dashboard Cite

Lapses in the graft-vs.-host disease (GVHD) prophylaxis and side effects of current standard care following allogeneic hematopoietic stem cell transplantation (allo-HSCT) call for novel regimens. Traditional approaches targeting T cells showed limited success in preventing acute GVHD (aGVHD). System medicine showed promising results treating complex diseases such as sepsis and multi-organ dysfunction syndrome (MODS). Adapting established network pharmacology analysis methods, we aimed to develop novel integrative regimens to prevent aGVHD. Our network pharmacology analysis predicted that Xuebijing injection (XBJ) targets a series of key node proteins in aGVHD network. It also unveiled that Salviae miltiorrhizae (Danshen), an herb in Xuebijing formula, which prevented aGVHD in rats, shares five out of six key GVHD node proteins targeted by XBJ. Interestingly, network pharmacology analysis indicated Xuebijing may share multiple aGVHD targets with Cyclosporin A (CsA), a first-line drug for preventing aGVHD in the clinic. Based on current information, we hypothesized that combination of XBJ and CsA may yield superior results in aGVHD prevention than either drug alone. We performed in vitro and in vivo assays to validate the predictions by the network pharmacology analysis. In vitro assays revealed XBJ prevented platelet aggregation and NF-κB nuclear translocation in macrophages. XBJ also promoted angiogenesis in tube-formation assay. Importantly, the combination of CsA and XBJ was effective in rescuing mice subjected to lethal GVHD. XBJ contributed to the rescue through preventing NF-κB nuclear translocation, attenuating inflammation and maintaining viability of macrophages. Overall, network pharmacology is a powerful tool to develop novel integrative regimens. Combination of XBJ and CsA may shed light on preventing aGVHD.

show abstract

Section: Discussionmentioning

confidence: 99%

Network Pharmacology-Guided Development of a Novel Integrative Regimen to Prevent Acute Graft-vs.-Host Disease

et al. 2018

View full text Add to dashboard Cite

show abstract

“…53 However, one study showed no association between plasminogen-activator inhibitor type 1, tissue plasminogen activator, and d-dimer levels and subsequent kidney injury soon after transplantation. 54 Recent studies have investigated abnormalities of the coagulation cascade and the complement system. These studies implicate deletions in the gene encoding complement factor H and factor H autoantibodies in transplantation-associated thrombotic microangiopathy.…”

Section: Thrombotic Microangiopathy After Hematopoietic-cell Transplamentioning

confidence: 99%

“…13 Urinary albuminto-creatinine ratios that are measured 80 to 100 days after transplantation appear to be clinically useful in predicting both the risk of subsequent kidney dysfunction and death. 13, 54,73 A renal biopsy may be beneficial in the care of individual patients, since the results can clarify their histologic status and its correlation with the degree of macroalbuminuria. These results can also be used to identify a possible role of GVHD, endothelial injury, and chronic inflammation in the development and progression of a given lesion.…”

Section: Albuminuriamentioning

confidence: 99%

Renal Complications of Hematopoietic-Cell Transplantation

Hingorani¹

2016

N Engl J Med

170

175

View full text Add to dashboard Cite

ach year, approximately 50,000 patients worldwide undergo hematopoietic-cell transplantation. This procedure, which is used to treat a wide range of malignant and nonmalignant diseases, may involve either a myeloablative or reduced-intensity conditioning regimen; the use of alternative allogeneic donors (i.e., haploidentical or mismatched donors); cells from bone marrow, cord blood, or peripheral-blood stem cells; and new immunomodulatory agents to prevent graft-versus-host disease (GVHD) 1 (Table 1). Despite the overall improvement in outcomes after hematopoietic-cell transplantation, kidney injury remains a frequent complication and contributes to the morbidity and mortality associated with the procedure. 2-11 The onset of acute kidney injury and chronic kidney disease, which affect from 10 to 70% of transplant recipients, 2,7,12,13 varies from days after transplantation to months or years afterward. Acute injury is generally indicated by elevated levels of serum creatinine up to 100 days after transplantation, and chronic injury by elevated levels at or after 100 days. Acute kidney injury that persists for 3 months or longer is usually reclassified as chronic kidney disease. The overall health of the patient at the time of transplantation is generally assessed with use of a hematopoietic-cell transplantation-specific comorbidity index that includes the serum creatinine level. 14 In this index, which includes 17 categories of organ dysfunction, scores for organ-specific coexisting conditions range from 0 to 3, with higher scores indicating a greater severity of the condition. The risk categories are not fixed and can vary according to conditioning regimens. Scores on the comorbidity index range from 0 to 12. Higher scores on the index (the weighted sum of all the scores for organ-specific conditions and other pretransplantation characteristics) indicate a greater risk of death that is not associated with relapse. In general, patients with a score of 0 are considered to be at low risk of death that is not associated with relapse, those with a score of 1 or 2 are considered to be at intermediate risk, and those with a score of 3 or greater are considered to be at high risk. A score of 1 or more is correlated with a risk of acute post-transplantation kidney injury. 3 Such kidney injury may be caused by conditioning chemotherapy, total-body irradiation, nephrotoxic agents, infections, the hepatic sinusoidal obstruction syndrome (previously called veno-occlusive disease of the liver), transplantation-associated thrombotic microangiopathy, and GVHD. 3-7,15-19 This article reviews the causes, diagnosis, and management of complications and disorders of the kidney after hematopoietic-cell transplantation. Definition a nd Epidemiol ogy of K idne y Injur y Acute kidney injury after transplantation was initially defined as a doubling of the baseline serum creatinine level within the first 100 days after transplantation.

show abstract

“…9 In paediatric patients with malignant and non-malignant diseases, a decrease in the natural anticoagulant function as well as the inhibition of fibrinolysis, have been observed after HSCT. 10,11 In adults, coagulation system is activated already after the conditioning treatment, 4,12,13 and increased early generation of thrombin was associated with subsequent acute GVHD. 4 In this study, we aimed to clarify the behaviour of various factors of the coagulation system, also in relation to clinical factors, during and after allogeneic HSCT in a well-defined homogenous group of paediatric patients with haematological malignancies.…”

Section: Introductionmentioning

confidence: 99%

Haematopoietic Stem Cell Transplantation in Children Shifts the Coagulation System towards a Pro-Coagulant State

et al. 2018

View full text Add to dashboard Cite

Coagulation system is disturbed by several mechanisms after allogeneic haematopoietic stem cell transplantation (HSCT). We evaluated the effect of HSCT on coagulation system by various conventional and investigational methods in 30 children and adolescents who received HSCT due to haematological malignancies. Pro-thrombin fragment 1 + 2, a specific measure of thrombin generation, and von Willebrand factor, a measure of endothelial activation, increased after conditioning treatment, and remained elevated until 3 months after HSCT ( < 0.05 for all comparisons to pre-conditioning treatment). D-dimer, a measure of fibrin turnover, was elevated from the second week onwards until 4 weeks after HSCT ( < 0.05). Endogenous thrombin potential was increased after conditioning, and at 2 weeks after HSCT ( < 0.05). Furthermore, the activities of acute phase reactants fibrinogen and coagulation factor VIII were increased ( < 0.05 for all comparisons to pre-conditioning treatment) from the first week onwards up to 3 weeks and 3 months after HSCT, respectively. Taken together, paediatric patients receiving HSCT demonstrate distinct and prolonged variations in the coagulation system towards a pro-coagulant state. This shift is of importance when estimating the risk of haemostatic and thrombotic complications in these children.

show abstract

Markers of coagulation activation and acute kidney injury in patients after hematopoietic cell transplantation

Cited by 11 publications

References 30 publications

Network Pharmacology-Guided Development of a Novel Integrative Regimen to Prevent Acute Graft-vs.-Host Disease

Network Pharmacology-Guided Development of a Novel Integrative Regimen to Prevent Acute Graft-vs.-Host Disease

Renal Complications of Hematopoietic-Cell Transplantation

Haematopoietic Stem Cell Transplantation in Children Shifts the Coagulation System towards a Pro-Coagulant State

Contact Info

Product

Resources

About