Campylobacter Jejuni and Thrombotic Thrombocytopenic Purpura

Canadian Journal of Gastroenterology and Hepatology, May 2019

Gastrointestinal bacterial infections could be associated with multisystem complication due to the thrombotic phenomena. This paper reports the association of Campylobacter jejuni infection and thrombotic thrombocytopenic purpura, and describes a new test for diagnosing thrombocytopenic purpura.

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Campylobacter Jejuni and Thrombotic Thrombocytopenic Purpura

CAN JGASTROENTEROL Campyl obacter jejuni an d ROMAN JAESCHKE 1 EJAN IRvlNE 1 JANE MOORE 1 jOIIN KELTON 1 0 ed fm /mbl , cwion Fehruary 6. I990 Acee/lied 1 Departments of Med1cme, Clmical E/>idemmlogy and Bwsw11srics, and Pailwlo[;Y. McMrutcr U111versi1y, Hamilwn, Onwno; and De/>arrmcnc of Medicme, St Jme/>h' , Hu,fmal, Hamilton , Oniarw Co1Tcs/mndencc and rc/irnw, Dr HJaeschke, Si)meph\ I lo:s/nwl, roml>onnc /J~. Hamilton , Onwrw L8N 4A6 Teleplume (41 6) 525 9140e,12160 Hecci1 Gastrointestinal bacterial infecttons could be associated with rnul t isystem complication due to th e th rombotic phenomena. This paper reports the association of Campylobacter jejuni infection and thrombotic thrombocytopenic purpurn, and describes a new test for diagnosing thrombocytopenic purpura. CanJ Gastroente rol 1990;4(4):154-156 CAN J vASTRl)ENTLROL Vl)l 4 No 4 MAY/jUNE 1990 - Key W o rds: Campy lo bacter jejuni, Hemolytic uremic syndrome, Thrombotic thrombocycopenic purpura Campylobacter jejuni et le purpura thrombotique thrombocytopenique RESUME: Les infections gascro- imescinales d'origine bacte rienne pourraienr etre associees a unc compl ication agissant sur Jc mu ltiples organes et Jue aux phenomenes thrombotiques. Cet art icle rapporte !'association existant enrre l'infecuon a Campylobacter jejuni et le purpura rhro mbotique thrombo? cytopenique ( PTT), er dccrit un test nouveau permettant de diagnostiquer le PTT. HROMBCX')TOPENIA AND 'iC.?111sro. cytic hemoly1ic a nemia charac? terize a group of d1 ,order, that arc uncommon but 11nportant because of their porent1ally serious out come,. Two of these disorders, th romhotic rhrom? bocytopenic purpura and hemolytic uremic syndrome, share a numher of simi la rities while ex h1b1ting some uni? que feat ures ( I) . Hemolytic urcm1e synd rome 1s charactcnzed by t hrombo? cytopenia, schistocytic hemolytic ane mia, and renal fai lure. Recent studies ha ve shown that many episode, of hemolytic uremic synd rome follow infection, often with a verotoxin? producing Escherichia coli ( 2 ). Other 111? fectious gastrointestinal organi m~. including campylobacrer, shigella and sa lmone lla, can cause hemolytic ure mic synd rome as well. Throm bonc rh rombocytopenic purpura, like hcmolync uremic syndrome, is charac? ren:eJ hy th rombocytopenra and sch1s? * C p ... Figure 1) The />artem of von Willehrand facwr obwmed with the use of crossed immuno? ekcrrophoresis. In C()mparison with conrrol (C), the 1,acient', serum (P) demonstrates lack of the large m11lumers (*) and an increased row/ level of che factor tocytic hemolytic anemia, but neurologica l lesions arc more frequent chan ren<11 impai rmen t. Recent studi es in thrombotic thrombocycopenic pur? pura have foc used upon the charac? terization of a platelet aggregating factor in the serum of these patierm ( 3-10 ). This facmr could be of patho? genetic importance if it proved to in? duce in vivo platelet aggreg,ition . In chis report the authors describe the investigation of a pat ient who had a thrombotic thrombocytopenic pur? pura preceded by an infection wh ich has more typica ll y been associated with hemolytic uremic synd rome. Th e patient had a plate let aggregating fac? tor present in her serum that h,is been described to occur in patien ts with spontaneously occurring thrombotic rhrombocytopen ic purpura. CASE PRESENTATION A 73-year-old woman h ad a t hree day history of abdo mina l discomfort with cramps, vomiting and diarrhea. She was ad mitted to hospita l and stool cultures grew Campylobacter jejuni. Treatment with erythromyc in pro? duced a pa rtia l resolution of her sy mptoms. However, over the next severa l days she had a progressive fall in both platelet count (to 18 x 109/L) and hemoglobin level (to l 05 g/L). Exten? sive red ce ll fragmenration was oh? ~erved on a peripheral blood fi lm. Coagulation tests were norma l a nd showed no evidence of disseminated intra vascu l,ir coagul ation. Blood cu l? tures were negative. Rena l function was normal :rnd a presumptive diagn osis of th rombotic thwm hocytopenic purpura was made. The patient was initia lly treated with plasma mfusion ( 100 mL/h), hut because of a fai lure to respond she was u eated wi th plas? mapheresis. A total of seven apheresis procedures of two m three plasma ex? c hanges each, usmg stored plasma, were performed. The patient did not respond and thrombocytopenia persist ? ed. On J ay 13, there was a sudden and dramatic deterioration in neurological status with coma and a right hemi ? parcsis. Compu ted tomographic inves? tigation of the brain was reported as normal. The patient a lso developed progressive oligu ric renal fail ure anJ was treated with peritoneal dialysis. Campylobacter jejuni and TTP The patient died on Jay 21 ha ving been unresponsive to p lasma infusion, plasmaphe resis, vinc ristin c, cortico? steroids, acetylsa licylic acid a n<l Ji? pyridamole. Post mo rtem exam ination demonstrated r lmeler th rombi in the sm::ill vessels of rhe heart, kidneys, pancreas, adrenals, parathyroid glands, pituitary, lymph nodes, ute rus and ovaries. G ross Hnd microscopic ex? ;:imina ri on of the brain was normal. SPECIAL LABORATORY INVESTIGATION S The mulrimcr ic pattern of the patient 's von WillehrnnJ facto r (vWF) was studi ed using crossed immuno? electrophoresis. The tota l a moun t w,h increase<l slightl y ( l. 9 iu/ mL, with upper limit of normal range 1.6), and the re was loss of large multimcrs of vWF at rhe time of the acute thromho? cytopenic episode (Figure I). To determine if there was a pl ate let aggregating facto r present, the ability of the patient's p lasma to induce the relea~c of 14C-serotonin from 14C-sero? ronin-radiolabelleJ normal platelets wa:, measure<l. Calciu m-dependent cys? tei ne protease (calpain) act ivity was confirm ed by inhibition of this reaction by known inhibitors to calpa in (leu? peptin and iodoacetic acid ). In addi? tion, the nbilit y of the ca lpa in in the patient\ serum ro cleave the glycoca li cin component of glyco? protein lb from normal platelets was measured ( 4,5 ). The patient haJ ca lpain prc~ent in the plasma during the thrombo? cytopcnic episode. Previous experi ? mc n u, have ~hown that calpain activity is nor pre~ent in patients with other thrombocytopen ic disorders inc ludi ng idiopathic thrombocyropenic purpura and dissem inated intravascular coag? ulation. Via the sa me metho<ls, ca l? pa in activity was no t detectab le in the supernata nt from the C jejuni c ul ? tures. DISCUSSION Over the past severa l years major strides have been made in the improve? me nt of o ur understanding of throm ? botic th rombocytopenic purpura and he mo lytic uremic syndrome. Although these disorders have considerable clini? cal similarities in that borh arc as? sociated wilh thrombocycopenia and schistocyric he mo lytic ane mia, dif? ferent o rga n s arc rrimarily affec ted : the brain is frequently affected in throm? hoLic thrombocytopcnic purpura versus the kidneys in hemolyLic uremic syn? drome. Stud ies examining Lhe ratho? genes is of the two diw rJe rs have focused on the diffe rences rather than the s imilarities of the disorders: hemo? lytic uremic syndrome is frequendy pre? ceded by an cntcric infection and a number of recent reports h ave doc u? mented the high frequency of a vero? toxin-producing E coli in epidemic outbreaks of this disorder. C jejuni enteritis h as also been implicated in the pathogenesis of h e molytic uremic syn? drome ( I l - 15). In contrast, thrombo tic ACKNOWLEDGEMENTS: Th i. study was partially supported hy a grant from the I lean and S troke Foundation of Ontario. rhrombocytopenic purpura is n nt usua l? ly associated with a preceding infection ( 16 ). Recent resea rch activity concern? ing thrombo tic thrombocytopcnic pur? pura has focused upo n attempts to identify the platelet aggregating factor found in these patients' plasma. O ne group h as reported a 37 kilodalcon protein that can be ne utra lized by IgG ( 6,7 ). Another group of investigators found evide nce of unregulated calpain activity in the scra o f these patients (8- I 0). The c urrent case report suggests the possibility of a link between an in? fecting coterie organism that frequent? ly triggers he mo lytic ure mic syndrome and the development and presence of ca lpain activity in the plasma. How? ever, a direct causal associa tio n could n o t be proven. Altho ugh it is like ly that C jejuni triggered the t hrombo tic thrombocytopenic purpura episode m this patient, the organism by itself does n ot produce calpain, as tested using two d ifferent bioassays. Thus, although this study suggests a li nk between the infec? tion a nd the development of throm? botic thrombocytopenic purpura via release of calpain, it does not elucidate the linkage itself. It is po~sible that an infecting organism triggers a complex immunological response that in some way results in the generation of unregu? lated calpain in the plasma of patient~ with thrombotic t h rombocytopcn,c purpu ra. The calpa in activity, in turn, could cause platelet aggregation and the clinical syndro me of thrombonc throm bocytopenic purpura. Studies ar~ c urrently underway to try a nd identify the link between infection and the generation of calpain. MEDIATORS INFLAMMATION The Scientiifc World Journal Hindawi Publishing Corporation ht p:/ www.hindawi.com Hindawi Publishing Corporation ht p:/ www.hindawi.com Hindawi Publishing Corporation ht p:/ www.hindawi.com Journal of Diabetes Research Disease Markers Journal of Hindawi Publishing Corporation ht p:/ www.hindawi.com Immunology Research PPAR Research Hindawi Publishing Corporation ht p:/ www.hindawi.com Submit your manuscr ipts http://www.hindawi.com Obesity Endocrin Journal of Ophthalmology Hindawi Publishing Corporation ht p:/ www.hindawi.com Stem Cells International Hindawi Publishing Corporation ht p:/ www.hindawi.com Evidence-Based Complementary Alternative Medicine and Journal of Oncology Disease nal and Mathematical Methods Behavioural AIDS and l. Bram l ,--:;, Kelton JG . 1lm1mbmic thrombocycopcnic purpura and the hemolytic uremic syndrome . In: Brain M , McCulloch P , eds. C urrent Therapy in Hematology-Oncology. Philadelphia: BC Decker Inc 1983: I 93-6 . 2. Aster RH . 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Lian EC-Y, Mui PT , Siddiqui FA , Ch iu A Y, C hiu LL . Inhibition of platelet-aggregating activity in thromboric thrombocytopernc purpura plasma by n ormal adult immunoglobulin G . J C lin Invest I 984;7 3:5 48 - 55 . 8. Murphy WG , Moore JC , Kelton JG . Calcium -dependent cyste ine protease activ ity in the scra of patients with thrombotic thrombocyropenic purpura . Bloo< l 1987 ; 70 : 1683 - 7 . 9 . Kelton JG , Moore J , Sanms A , Sheridan D. Detection of a plateletagglutinating factor in thrombotic thrombocyropenic purpura . Ann Inte rn Med !984; 10 1 : 589 - 93 . 10. Murphy WG , Moore JC , Barr RD , Pai MKR , Kelton JG . Relationship between platelet aggregating factor a nd von WillebrnnJ focmr in thrombotic chrnmbocytope111c purpura . Br J Haemarol 1987 ; 66 : 509 - 13 . 11. Chamovitz RN , Hanstei n Al, Alexander SR , Terry AB , Shnrt P , K.iton R. Camp )?lohaccer jej1mi-associaced hemnlytic- urem ic syndrome in a mother an<l daughter . Pediatrics 1983 ; 71 : 253 - 6 . 12. 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Roman Jaeschke, E Jan Irvine, Jane Moore, John Kelton. Campylobacter Jejuni and Thrombotic Thrombocytopenic Purpura, Canadian Journal of Gastroenterology and Hepatology, DOI: 10.1155/1990/762562