DOCSLIB.ORG

Leak Syndrome and Perforin in the Induction of Vascular Evidence For

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Leak Syndrome and Perforin in the Induction of Vascular Evidence For Evidence for the Involvement of Fas Ligand and Perforin in the Induction of Vascular Leak Syndrome This information is current as Asimah Q. Rafi, Ahmet Zeytun, Michael J. Bradley, D. of October 1, 2021. Phillip Sponenberg, Randolph L. Grayson, Mitzi Nagarkatti and Prakash S. Nagarkatti J Immunol 1998; 161:3077-3086; ; http://www.jimmunol.org/content/161/6/3077 Downloaded from References This article cites 39 articles, 18 of which you can access for free at: http://www.jimmunol.org/content/161/6/3077.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on October 1, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 1998 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Evidence for the Involvement of Fas Ligand and Perforin in the Induction of Vascular Leak Syndrome1 Asimah Q. Rafi,2* Ahmet Zeytun,* Michael J. Bradley,* D. Phillip Sponenberg,† Randolph L. Grayson,‡ Mitzi Nagarkatti,† and Prakash S. Nagarkatti3* Endothelial cell injury resulting in vascular leak syndrome (VLS) is one of the most widely noted phenomenons in a variety of clinical diseases. In the current study we used IL-2-induced VLS as a model to investigate the role of cytolytic lymphocytes in the cytotoxicity of endothelial cells. Administration of IL-2 (75,000 U/mouse, three times a day for 3 days) into BL/6 wild-type mice triggered significant VLS in the lungs, liver, and spleen. Interestingly, perforin-knockout (KO) mice exhibited a marked decrease in IL-2-induced VLS in all three organs tested. Also, Fas ligand-defective (gld) mice and Fas-deficient (lpr) mice exhibited de- creased VLS in the liver and spleen, but not in the lungs. The decreased VLS seen in perforin-KO, gld, and lpr mice was not due to any defect in lymphocyte migration or homing to various organs because histopathologic studies in these mice demonstrated Downloaded from significant and often greater perivascular infiltration of lymphocytes compared with the IL-2-treated wild-type mice. Ultrastruc- tural studies of the lungs demonstrated significant damage to the endothelial cells in IL-2-treated wild-type mice and decreased damage in perforin-KO mice. IL-2 administration caused up-regulation of CD44 in all strains of mice tested and triggered increased LAK activity against an endothelial cell line in wild-type and gld mice, but not in perforin-KO mice. The current study demonstrates for the first time that perforin and Fas ligand may actively participate in endothelial cell injury and induction of VLS in a variety of organs. The Journal of Immunology, 1998, 161: 3077–3086. http://www.jimmunol.org/ t sites of chronic inflammation as seen in a variety of and pulmonary edema (8, 9). Such toxicity results from increased infections, autoimmune diseases, graft-vs-host disease, capillary leak, also known as vascular leak syndrome (VLS).3 A A and during treatment of cancer patients with high doses number of cytokines used as hemopoietic growth factors are also of IL-2, significant damage to the endothelial cells has been known known to trigger VLS (9). The exact mechanism of cytokine-trig- to occur, which leads to severe toxicity or pathogenesis associated gered endothelial cell damage and induction of VLS is not clear. with the disease. For example, in murine lymphocytic choriomen- Several recent studies have suggested that VLS may result from ingitis viral infection, massive delayed-type hypersensitivity reac- actual damage to the endothelial cells caused by cytotoxic lym- tion occurs in the cerebrospinal fluid. It has been speculated that phocytes (10, 11). In contrast, some types of endothelial cell dam- by guest on October 1, 2021 virally activated CD81 T cells kill the endothelial cells, leading to age may result from participation of neutrophils and complement massive extravasation of monocytes and CD41 T cells via the components (12). The fact that CTL are involved in the induction subarachnoid space (1). In multiple sclerosis, damage to the blood- of VLS was demonstrated in a recent study from our laboratory in brain barrier has been known to occur after injury to the endothe- which administration of a CTL clone into a syngeneic irradiated lial cells by cytotoxic T cells (2). Also, in autoimmune disease mouse along with IL-2 led to a significant induction of VLS in models involving vasculitides, the lesions have been associated vivo (13). with infiltration of lymphocytes and macrophages at the vascular In the current study we used VLS as a model to study the en- wall structure (3). Such types of vasculitis have been described in dothelial cell damage seen after IL-2 administration. To directly human and murine autoimmune diseases (4, 5). Similarly, in arte- test the involvement of cytotoxic lymphocytes in endothelial cell riosclerosis, endothelial cell damage and inflammatory cell activa- injury leading to the induction of VLS, we used perforin-knockout tion have been shown to contribute to the further development of (KO) and Fas ligand (FasL)-defective, gld mice, inasmuch as per- the cardiovascular disease (6, 7). forin and FasL have been characterized as two important effector Although IL-2 therapy has yielded encouraging results in the molecules involved in cytotoxicity mediated by CTL and NK/LAK treatment of certain types of cancer, its use is limited by dose- cells (14). The results demonstrated that the VLS was markedly dependent toxicity characterized by weight gain, dyspnea, ascites, decreased in all organs tested in perforin-KO mice and was sig- nificantly decreased in the liver and spleen of gld mice, thereby supporting the hypothesis that VLS results from direct cytotoxicity Departments of *Biology, ‡Plant Pathology, Physiology, and Weed Science, and †Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary of endothelial cells by cytotoxic lymphocytes. Medicine, Virginia Tech, Blacksburg, VA 24061 Received for publication December 5, 1997. Accepted for publication May 11, 1998. Materials and Methods The costs of publication of this article were defrayed in part by the payment of page Mice charges. This article must therefore be hereby marked advertisement in accordance Four to six-week-old female C57BL/6 mice were purchased from the Na- with 18 U.S.C. Section 1734 solely to indicate this fact. tional Institutes of Health (Bethesda, MD). Age-matched B6/gld/gld B6/ 1 This work was supported in part by grants from the American Cancer Society (IM lpr/lpr and perforin-KO mice were bred in our animal facilities. The per- 747) and the National Institutes of Health (AI101392 and HL058641), and by a Gina forin-KO mice were provided by W. K. Clark (University of California, Finzi Memorial Student Fellowship from the Lupus Foundation of America (to A.R.). 2 Address correspondence and reprint requests to Dr. Prakash S. Nagarkatti, Depart- ment of Biology, Virginia Tech, Blacksburg, VA 24061. E-mail address: 3 Abbreviations used in this paper: VLS, vascular leak syndrome; KO, knockout; [email protected] FasL, Fas ligand; PE, phycoerythrin. Copyright © 1998 by The American Association of Immunologists 0022-1767/98/$02.00 3078 VASCULAR LEAK SYNDROME IN FasL-DEFECTIVE AND PERFORIN-DEFICIENT MICE Los Angeles, CA) (15). It should be noted that gld and lpr mice used at 4 Histology to 6 wk of age did not exhibit any lymphoproliferative disease. For histopathologic studies, groups of five separate mice were injected with Cell lines IL-2 or PBS as described above, and on day 4, lungs and liver were fixed in 10% formalin solution. The organs were embedded in paraffin, sec- YAC1, a NK-sensitive Moloney virus-induced lymphoma, and TME-3H3, tioned, and stained with hematoxylin and eosin. Perivascular infiltration an SV40-transformed endothelial cell line, were maintained in vitro by was scaled by counting the number of lymphocytes infiltrating the vessel serial passages, as previously described (13, 16). and averaging the minimum and maximum ranges for each group. Three samples were used for lung, and 10 samples were used for the liver. Antibodies Electron microscopy studies Monoclonal MEL-14 (lymphocyte homing receptor; rat IgG) and anti- Tissue samples were fixed in 5% glutaraldehyde/4.4% formaldehyde/ LFA-1 (M17/4; rat IgG) were grown in vitro as described previously (17). 2.75% picric acid in 0.05 M sodium cacodylate buffer, pH 7.4; washed in The FITC-CD3, PE-CD44, PE-CD8, FITC-CD4, and Jo2 (anti-Fas) mAbs a sodium cacodylate buffer; postfixed in osmium tetroxide; embedded in were purchased from PharMingen (San Diego, CA). FITC-conjugated Polybed 812 resin (Polysciences, Warrington, PA); and studied with an F(ab9) goat anti-Syrian hamster IgG was purchased from Jackson Immu- 2 electron microscope. noResearch Laboratories (West Grove, PA). [125I]BSA was purchased from ICN (Costa Mesa, CA). Statistical analysis ILs The VLS data in different strains of mice were compared using analysis of variance, and p , 0.05 was considered statistically significant. Recombinant IL-2 was provided by Hoffmann-La Roche (Nutley, NJ) and Dr. C. Reynolds (National Institutes of Health). Results VLS induction in wild-type, perforin-KO, FasL-defective (gld), Downloaded from Detection of surface molecules using immunofluorescence and Fas-deficient (lpr) mice analysis To directly test whether VLS seen following injection of IL-2 is Splenic T cells and LN cells were analyzed for CD3 and CD44 expression caused by cytolytic effector molecules such as perforin and FasL, by staining the cells with FITC-CD3- and PE-CD44-labeled Abs for 30 min on ice followed by washing three times.
Load more

Recommended publications
  • COVID-19 Vaccine Janssen: Contraindication in Individuals with Previous Capillary Leak Syndrome and Update on Thrombosis with Thrombocytopenia Syndrome
    Janssen Sciences Ireland UC Address: Airton Road, Tallaght, D24 WR89 Tel: +353 1 466 5200 Fax: +353 1 431 1058 www.janssen.ie 19the July 2021 COVID-19 Vaccine Janssen: Contraindication in individuals with previous capillary leak syndrome and update on thrombosis with thrombocytopenia syndrome Dear Healthcare Professional, Janssen-Cilag International NV in agreement with the European Medicines Agency and the Health Products Regulatory Authority (HPRA) would like to inform you of the following: Summary Capillary leak syndrome (CLS): • Very rare cases of capillary leak syndrome (CLS) have been reported in the first days after vaccination with COVID-19 Vaccine Janssen, in some cases with a fatal outcome. A history of CLS has been reported in at least one case. • COVID-19 Vaccine Janssen is now contraindicated in individuals who have previously experienced episodes of CLS. • CLS is characterised by acute episodes of oedema mainly affecting the limbs, hypotension, haemoconcentration and hypoalbuminaemia. Patients with an acute episode of CLS following vaccination require prompt recognition and treatment. Intensive supportive therapy is usually warranted. Thrombosis with thrombocytopenia syndrome (TTS): • Individuals diagnosed with thrombocytopenia within 3 weeks after vaccination with COVID-19 Vaccine Janssen should be actively investigated for signs of thrombosis. Similarly, individuals who present with thrombosis within 3 weeks of vaccination should be evaluated for thrombocytopenia. • TTS requires specialised clinical management. Healthcare professionals should consult applicable guidance and/ or consult specialists (e.g., haematologists, specialists in coagulation) to diagnose and treat this condition. Background on the safety concern COVID-19 Vaccine Janssen suspension for injection is indicated for active immunisation to prevent COVID-19 caused by SARS-CoV-2, in individuals 18 years of age and older.
    [Show full text]
  • Capillary Leak Syndrome
    The Medicine Forum Volume 17 Article 8 2016 Case Report: Uncontrolled Anasarca: Capillary Leak Syndrome Ankita Mehta, MD Thomas Jefferson University Hospital, [email protected] Mansi Shah, MD Jefferson Hospital Ambulatory Practice, Thomas Jefferson University Hospital, [email protected] Follow this and additional works at: https://jdc.jefferson.edu/tmf Part of the Internal Medicine Commons, and the Oncology Commons Let us know how access to this document benefits ouy Recommended Citation Mehta, MD, Ankita and Shah, MD, Mansi (2016) "Case Report: Uncontrolled Anasarca: Capillary Leak Syndrome," The Medicine Forum: Vol. 17 , Article 8. DOI: https://doi.org/10.29046/TMF.017.1.009 Available at: https://jdc.jefferson.edu/tmf/vol17/iss1/8 This Article is brought to you for free and open access by the Jefferson Digital Commons. The Jefferson Digital Commons is a service of Thomas Jefferson University's Center for Teaching and Learning (CTL). The Commons is a showcase for Jefferson books and journals, peer-reviewed scholarly publications, unique historical collections from the University archives, and teaching tools. The Jefferson Digital Commons allows researchers and interested readers anywhere in the world to learn about and keep up to date with Jefferson scholarship. This article has been accepted for inclusion in The Medicine Forum by an authorized administrator of the Jefferson Digital Commons. For more information, please contact: [email protected]. Mehta, MD and Shah, MD: Case Report: Uncontrolled Anasarca: Capillary Leak Syndrome ONCOLOGY Case Report: Uncontrolled Anasarca: Capillary Leak Syndrome Ankita Mehta, MD, and Mansi Shah, MD INTRODUCTION progression of her pancreatic cancer. She was ultimately discharged home with hospice care.
    [Show full text]
  • Common Terminology Criteria for Adverse Events
    Common Terminology Criteria for Adverse Events Version 3.0 Index Cancer Therapy Evaluation Program NATIONAL INSTITUTES OF HEALTH National Cancer Institute http://ctep.cancer.gov/ 10/22/2003 Public Health Service Cancer Therapy Evaluation Program National Institutes of Health National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) - Index Terms Report Bethesda, Maryland 20892 -- A -- abdomen ENDOCRINE HEPATOBILIARY/PANCREAS Adrenal insufficiency 17 Liver dysfunction/failure (clinical) 34 GASTROINTESTINAL Pancreatitis 34 Colitis 19 PAIN Distension/bloating, abdominal 20 Pain --Select 55 Enteritis (inflammation of the small bowel) 21 VASCULAR Fistula, GI --Select 22 Portal vein flow 70 Typhlitis (cecal inflammation) 27 HEMORRHAGE/BLEEDING abducens Hemorrhage, GI --Select 31 See: CN VI HEPATOBILIARY/PANCREAS abnormal Pancreatitis 34 BLOOD/BONE MARROW INFECTION Myelodysplasia 4 Colitis, infectious (e.g., Clostridium difficile) 35 CONSTITUTIONAL SYMPTOMS Infection (documented clinically or microbiologically) with 35 Odor (patient odor) 11 Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L) --Select Infection with normal ANC or Grade 1 or 2 neutrophils -- 35 ENDOCRINE Select Neuroendocrine: 17 Infection with unknown ANC --Select 36 ADH secretion abnormality (e.g., SIADH or low ADH) Neuroendocrine: 17 MUSCULOSKELETAL/SOFT TISSUE gonadotropin secretion abnormality Soft tissue necrosis --Select 46 Neuroendocrine: 17 PAIN growth hormone secretion abnormality Neuroendocrine: 17 Pain --Select 55 prolactin hormone secretion abnormality
    [Show full text]
  • Life-Threatening Capillary Leak Syndrome
    on Tec ati hn nt o la lo p g s i e n s a r & Journal of Yi-Zhi et al., J Transplant Technol Res 2015, S4 T R f e o l s DOI: 10.4172/2161-0991.1000S4-003 a e a n ISSN:r 2161-0991 r c u h o J Transplantation Technologies & Research CaseResearch Report Article OpenOpen Access Access EditorialResearchCase Report Article OpenOpen Access Access Life-threatening Capillary Leak Syndrome in an Adult with Refractory Acute Myeloid Leukemia during Allogeneic Transplantation: a Case Report and Review of Literature Yi-Zhi J, Lai-Quan H, Gui-Ping S, Yan D, He-Sheng H and Dong-Ping H* Department of Hematology, The Affiliated Yijishan Hospital of Wannan Medical College, Wuhu, China Abstract Background: Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers the possibility of cure for hematological malignancies, various complications have been described. Capillary leak syndrome (CLS) has been previously observed in HSCT patients. CLS is a rare disease characterized by recurrent episodes of generalized edema and severe hypotension along with hypoproteinemia. Case Report: A 27-year-old Chinese man, diagnosed with refractory acute myeloid leukemia, was treated with a haploidentical stem cell transplant combined with an unrelated umbilical cord blood unit. The patient developed fatal CLS during the 9th day of the conditioning therapy. Conclusion: Since it is difficult to distinguish between CLS and other early complications during allo-HSCT, our report highlights the need for rigorous investigation of identifying CLS and the increasing need of insightful diagnosis to manage any incidence of CLS.
    [Show full text]
  • Necrotizing Soft-Tissue Infections
    11/1/2020 Necrotizing Fasciitis ▪Is a surgical diagnosis characterized by friability of the superficial fascia, Necrotizing dishwater-gray exudate, and a notable Soft-Tissue absence of pus. Infections N ENGL J MED 2017;377:2253-65. 1 2 Necrotizing fasciitis type I: Necrotizing fasciitis type II ▪ Polymicrobial infection involving aerobic ▪ Often associated with gas in the tissue ▪ A monomicrobial infection. and anaerobic organisms. and thus is difficult to distinguish from gas gangrene ▪ Seen in the elderly or in those with ▪ Among gram-positive organisms, group A streptococcus is the underlying illnesses. ▪ Nonclostridial anaerobic cellulitis and most common pathogen, followed by MRSA. synergistic necrotizing cellulitis are type ▪ Predisposed I variants. Both occur in patients with ▪ May occur in any age group and in those without underlying illness ▪ Diabetic or decubitus ulcers diabetes and typically involve the feet, ▪ Hemorrhoids with rapid extension into the leg ▪ Aeromonas hydrophila (freshwater laceration) ▪ Rectal fissures ▪ Necrotizing fasciitis should be ▪ Vibrio vulnificus (saltwater laceration, ingestion of raw oysters, ▪ Episiotomies considered in patients with systemic cirrhosis) ▪ Colonic or urologic surgery or gynecologic manifestations of sepsis, such as procedures. tachycardia, leukocytosis, acidosis, or ▪ Necrotizing group A streptococcal and clostridial infections are marked hyperglycemia mediated by bacterial exotoxins and the host response ▪ Ludwigs- submandibular ▪ Lemierre’s –thrombophlebitis of jugular ▪ Fournier’s-urethral breach 3 4 Invasive Group A Streptococcal Soft-Tissue Infections Invasive Group A Streptococcal Soft-Tissue Infections (Streptococcus Continued pyogenes) ▪ Infection with a defined portal of bacterial entry: Infection that arises spontaneously in the deep tissue, without an overt wound or lesion: ▪ In 50% of patients with group A streptococcal necrotizing fasciitis or myonecrosis, are without a portal ▪ S.
    [Show full text]
  • Signal AR on Embolic and Thrombotic Events with COVID-19 Vaccine
    20th April 2021 EMA/268126/2021 Pharmacovigilance Risk Assessment Committee (PRAC) Signal assessment report on Embolic and Thrombotic events (SMQ) with COVID-19 Vaccine Janssen (Ad26.COV2-S [recombinant]) EPITT no:19689 Confirmation assessment report 3rd April 2021 Adoption of first PRAC Recommendation 9th April 2021 Submission of responses by MAH 15th April 2021 Preliminary assessment report 19th April 2021 Deadline for comments 19th April 2021 (8pm CET) Updated Rapporteur assessment 20th April 2021 (9am Adoption of 2nd PRAC recommendation 20th April 2021 Submission of responses by MAH 22nd April 2021 Rapporteur assessment 30th April 2021 Deadline for comments 30th April 2021 (8pm CET) Updated Rapporteur assessment report 3rd May 2021 Adoption of 3rd PRAC recommendation 06th May 2021 Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Ne therla nds Address for visits and deliveries Refer to www.ema.europa.eu/how-to-fi nd-us An agency of the European Union Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000 © Euro pe an Me dici ne s Age ncy, 2021. Reproduction is authorised provided the source is acknowledged. Administrative information Active substance(s) (invented name) COVID-19 Vaccine (Ad26.COV2-S [recombinant]) – COVID-19 Vaccine Janssen suspension for injection (Other viral vaccines) Strength(s) All Pharmaceutical form(s) All Route(s) of administration All Indication(s) COVID-19 Vaccine Janssen is indicated for active immunisation to prevent COVID-19 caused by SARS-CoV-2 in individuals
    [Show full text]
  • Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of Dalantercept, an Activin Receptor–Like Kinase-1 Ligand Trap, in Patients with Advanced Cancer
    Published OnlineFirst October 30, 2013; DOI: 10.1158/1078-0432.CCR-13-1840 Clinical Cancer Cancer Therapy: Clinical Research Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of Dalantercept, an Activin Receptor–like Kinase-1 Ligand Trap, in Patients with Advanced Cancer Johanna C. Bendell1, Michael S. Gordon2, Herbert I. Hurwitz3, Suzanne F. Jones1, David S. Mendelson2, Gerard C. Blobe3, Neeraj Agarwal4, Carolyn H. Condon5, Dawn Wilson5, Amelia E. Pearsall5, Yijun Yang5, Ty McClure5, Kenneth M. Attie5, Matthew L. Sherman5, and Sunil Sharma4 Abstract Purpose: The angiogenesis inhibitor dalantercept (formerly ACE-041) is a soluble form of activin receptor–like kinase-1 (ALK1) that prevents activation of endogenous ALK1 by bone morphogenetic protein-9 (BMP9) and BMP10 and exhibits antitumor activity in preclinical models. This first-in-human study of dalantercept evaluated its safety, tolerability, pharmacokinetics, pharmacodynamics, and antitu- mor activity in adults with advanced solid tumors. Experimental Design: Patients in dose-escalating cohorts received dalantercept subcutaneously at one of seven dose levels (0.1–4.8 mg/kg) every 3 weeks until disease progression. Patients in an expansion cohort received dalantercept at 0.8 or 1.6 mg/kg every 3 weeks until disease progression. Results: In 37 patients receiving dalantercept, the most common treatment-related adverse events were peripheral edema, fatigue, and anemia. Edema and fluid retention were dose-limiting toxicities and responded to diuretic therapy. No clinically significant, treatment-related hypertension, proteinuria, gross hemorrhage, or gastrointestinal perforations were observed. One patient with refractory squamous cell cancer of the head and neck had a partial response, and 13 patients had stable disease according to RECISTv1.1, eight of whom had prolonged periods (12 weeks) of stable disease.
    [Show full text]
  • Veno-Occlusive Disease (VOD) AKA Hepatic Sinusoidal Obstruction Syndrome (SOS) Mira A
    Veno-Occlusive Disease (VOD) AKA Hepatic Sinusoidal Obstruction Syndrome (SOS) Mira A. Kohorst, MD MD Anderson Cancer Center Disclosures • No financial disclosures • No discussion of off-label use of medication Roadmap • Pathophysiology • Risk factors • Clinical presentation • Diagnosis • Treatment • Critical care management • Summary PATHOPHYSIOLOGY Injury to the hepatic venous endothelium (sinusoidal endothelial cells and zone 3 hepatocytes) – conditioning chemotherapy, gemtuzumab/inotuzumab, radiation (>30 Gy) Hepatocytes Space of Disse Sinusoid Sinusoidal endothelial cells Richardson PG et al. Expert Opin Drug Saf 2013;12:123–36 Activation of endothelial cells → ↑thrombosis, ↓fibrinolysis, ↑inflammation, ↓cytoskeletal structure → Narrowing of sinusoids Richardson PG et al. Expert Opin Drug Saf 2013;12:123–36 Increased thrombosis and decreased thrombolysis → VOD/SOS Richardson PG et al. Expert Opin Drug Saf 2013;12:123–36 RISK FACTORS Risk Factors Corbacioglu, Jabbour, and Mohty. Biology of Blood and Marrow Transplantation (2019) 25:1271-80. Risk Factors • Pediatric patients have a 2- to 3-fold higher incidence than adults, estimated at 20-30% – Infants 30% (as high as 60%) – Osteopetrosis 60% – Neuroblastoma 30% – Macrophage activating syndromes 30% – Thalassemia 30% Strouse et al. Biology of Blood and Marrow Transplantation (2018). Corbacioglu et al. Expert Rev Hematol (2012). Cesaro et al. Haematologica (2005). CLINICAL PRESENTATION Clinical Presentation Faraci et al. Biology of Blood and Marrow Transplantation. Oct 2018. Clinical Presentation • Weight gain (fluid retention) – first • Can see thrombocytopenia and platelet refractoriness • Hyperbilirubinemia/jaundice, transaminitis – Anicteric in ~30% of pediatric patients • Firm, painful hepatomegaly with ascites • Renal insufficiency (hepatorenal syndrome) in 50% – Need for dialysis in 25% • Multiorgan failure, hepatic encephalopathy, death Corbacioglu et al.
    [Show full text]
  • Systemic Capillary Leak Syndrome Associated with Hypovolemic Shock
    Saugel et al. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 2010, 18:38 http://www.sjtrem.com/content/18/1/38 CASE REPORT Open Access SystemicCase report Capillary Leak Syndrome associated with hypovolemic shock and compartment syndrome. Use of transpulmonary thermodilution technique for volume management Bernd Saugel*1, Andreas Umgelter1, Friedrich Martin2, Veit Phillip1, Roland M Schmid1 and Wolfgang Huber1 Abstract Systemic Capillary Leak Syndrome (SCLS) is a rare disorder characterized by increased capillary hyperpermeability leading to hypovolemic shock due to a markedly increased shift of fluid and protein from the intravascular to the interstitial space. Hemoconcentration, hypoalbuminemia and a monoclonal gammopathy are characteristic laboratory findings. Here we present a patient who suffered from SCLS with hypovolemic shock and compartment syndrome of both lower legs and thighs. Volume and catecholamine management was guided using transpulmonary thermodilution. Extended hemodynamic monitoring for volume and catecholamine management as well as monitoring of muscle compartment pressure is of crucial importance in SCLS patients. Backround care unit (ICU) (hospital B) after emergency decompres- Systemic Capillary Leak Syndrome (SCLS) is a rare disor- sive fasciotomy in another hospital (hospital A) the previ- der characterized by unexplained, often recurrent, non ous day (fig. 1). sepsis-related episodes of increased capillary hyperper- On admission to hospital A the previous day the patient meability leading to hypovolemic shock due to a mark- had presented with severe muscle pain in the legs and a 2- edly increased shift of fluid and protein from the week history of flu-like illness and sore throat with fever intravascular to the interstitial space.
    [Show full text]
  • Cardiac Tamponade Caused by Pericardial Effusion in a Patient with Systemic Capillary Leak Syndrome
    Netherlands Journal of Critical Care Submitted July 2017; Accepted November 2017 CASE REPORT Cardiac tamponade caused by pericardial effusion in a patient with systemic capillary leak syndrome W.L. Zoetman1, J.E. Paramarta2, C. Bouman1, B.T. Sanou3, A.P.J. Vlaar1,2 Departments of 1Intensive Care Medicine, 2Internal Medicine and 3Anaesthesiology, Academic Medical Center, Amsterdam, the Netherlands Correspondence A.P.J. Vlaar - [email protected] Keywords - intensive care, critically ill, capillary leakage, shock, tamponade Abstract We present a patient with systemic capillary leak syndrome show any abnormalities, in particular no abnormal haemoglobin (SCLS), complicated by obstructive shock due to cardiac phenotyping. No treatment was initiated, follow-up of the tamponade. anaemia was performed in the outpatient clinic. Methods: SCLS is a rare disease characterised by hypotension, hypoalbuminaemia, haemoconcentration and generalised Table 1. Laboratory values illustrating the course of SCLS oedema. Several severe complications have been described, Laboratory test Out-patient ER ICU admis- ICU day 1 ICU day 2 clinic sion including acute kidney injury, rhabdomyolysis, compartment Haemoglobin (g/dL, 12.4 20.9 16.3 14.8 11.1 syndrome and death. We present a patient with SCLS, 13.7-16.9) complicated by rapidly progressive pericardial effusion with Haematocrit (L/L, 0.38 0.62 - - 0.32 cardiac tamponade, for which a lifesaving pericardiocentesis 0.35-0.4) was performed. Because SCLS is often confused with septic Creatinine (µmol/L, 52 118 172 175 169 shock and anaphylactic shock, an obstructive shock may be 65-95) easily missed. Albumin (g/L, 44 - <10 27 28 35-50) Although SCLS is a very rare disorder, it is important to be aware Creatinine kinase 264 149 44377 81622 of its existence and the possible life-threatening complications, (U/L) including cardiac tamponade, in order to improve the outcome for the patient.
    [Show full text]
  • Severe Cerebral Involvement Due to Idiopathic Systemic Capillary Leak Syndrome Ali Riza Gunes,€ Peter Berlit & Ralph Weber
    CASE REPORT Severe cerebral involvement due to idiopathic systemic capillary leak syndrome Ali Riza Gunes,€ Peter Berlit & Ralph Weber Department of Neurology, Alfried-Krupp-Hospital Essen, Alfried-Krupp-Str. 21, 45131 Essen, Germany Correspondence Key Clinical Message Ali Gunes,€ Department of Neurology, Alfried- Krupp-Hospital Essen, Alfried-Krupp-Str. 21, The idiopathic systemic capillary leak syndrome (ISCLS) is a rare disorder, 45131 Essen, Germany. characterized by recurrent attacks of hypotension, hypoalbuminemia, and Tel: +4920143441439; hemoconcentration, which is often misdiagnosed due to overlapping features Fax: +492014342377; with other diseases. Even though cerebral involvement is uncommon, a broad E-mail: [email protected] awareness is crucial, because of its life-threatening character. Funding Information Dr. Gunes€ received funding for trips from Keywords Boehringer Ingelheim for the Annual Meeting coma, critical care, neurology, systemic disease. 2014 of the German Neurological Society and from Bayer Vital for the MS-School Marburg 2014. Dr. Weber received honoraria for oral presentation from Boehringer Ingelheim, Bristol-Myers Squibb, Covidien, and from serving on a scientific advisory board of Covidien. Dr. Weber received funding for trips from Bayer Vital for the European Stroke Conference 2011 and Boehringer Ingelheim for the Annual Meeting 2012 of the German Neurological Society. Prof. Peter Berlit received honoraria for lecturing from Bayer, Biogen, CSL Behring, Desitin, Merck Serono, MSD, Novartis. Received: 9 September 2015; Revised: 25 December 2015; Accepted: 5 February 2016 doi: 10.1002/ccr3.525 Case the absence of albuminuria, hemoconcentration (hemat- ocrit 55%), and a known IgG monoclonal gammopathy. We report the case of a 43-year-old woman who was The initial MR of the brain showed contrast agent referred to our hospital with coma of unknown origin.
    [Show full text]
  • Kidney Dysfunction After Hematopoietic Cell Transplantation—Etiology, Management, and Perspectives
    Hematol Oncol Stem Cell Ther (2018) 11, 195– 205 Available at www.sciencedirect.com ScienceDirect journal homepage: www.elsevier.com/locate/hemonc REVIEW Kidney dysfunction after hematopoietic cell transplantation—Etiology, management, and perspectives Dorota Jagus´a, Karol Lis b, Longin Niemczyk a, Grzegorz W. Basak b,* a Department of Nephrology, Dialysis and Internal Medicine, Medical University of Warsaw, Warsaw, Poland b Department of Hematology, Oncology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland Received 4 February 2018; received in revised form 26 April 2018; accepted 12 July 2018 Available online 29 July 2018 KEYWORDS Abstract Acute kidney injury; Kidney dysfunction is a common complication of hematopoietic cell transplantation (HCT) with Chronic kidney disease; proven negative impact on early and long-term mortality. Causes of this complication are Hematopoietic cell diverse, usually overlapping, and poorly understood. Therefore, management implicates multi- transplantation directional investigations and simultaneous treatment of suspected causes. The etiology is fre- quently unconfirmed due to a lack of specific markers and prevalence of contraindications to renal biopsy among HCT recipients. Herein, we provide a summary of etiology and propose an algorithm for evaluation of kidney injury after HCT. We also map out the most urgent areas for research that aim to identify patients at risk of severe renal injury and develop nephropro- tective strategies. Ó 2018 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc- nd/4.0/). Contents Introduction . 196 Etiology . 197 Kidney injury before HCT . 197 Prerenal AKI.
    [Show full text]