The Epidemiology of Immune Thrombocytopenia

Canadian Journal of Infectious Diseases and Medical Microbiology, Jul 2018

Three cases of immune thrombocytopenia (ITP) associated with human immunodeficiency virus (HIV) infection prompted a review of community-acquired thrombocytopenia in Nova Scotia from January 1980 to December 1987. Two hundred and seven patients meeting the case definition of ITP were identified. The incidence of ITP rose from 2.0×105 in 1980 to 3.3×105 in 1987. More cases of ITP in the sexually active population occurred between 1984 and 1987 than in the previous four years (P=0.034). All three cases of known HIV associated ITP were captured in the retrospective surveillance system. The study concluded that increases in community-acquired ITP in a sexually active population may be a surrogate marker of the HIV epidemic, even in geographic areas with a low seroprevalence for HIV. Serological tests for HIV infection should be a routine part of the diagnostic investigation of ITP in all sexually active patients or those with other potential risk factors for HIV infection.

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The Epidemiology of Immune Thrombocytopenia

t h r o m b o c y t o p e n i a WALTER F SCHLECH Ill 0 FRCPC 0 CHRISTINE NESDOLY 0 N ANCY MEAGHER 0 0 Dalhousie Un iversity. Faculty ofMedicine. Halifax. Nova Scotia Nova Scotia 83H 2Y9 WF ScHLECH ill, C NESDOLY, N M EAGHER, J TuRNER, D DICKEY. The epidemiology of i mmune t hrombocytopenia. Can J Infect Di s 1992;3(6) :3 1 1-314. Th ree cases of immune U1rombocyi.openia (ITP) asociated \vith human immunodeficiency vims (HlV) infe lion prompted a review of communi ty-acquired thrombocytopenia in Nova Scotia from January 1980 to D cember 1987. 1\vo hundred and seven patients meeting the case defmition of ITP were identified. The incidence of ITP rose from 2.0x 105 in 1980 LO 3.3x 105 in 1987. More cases of ITP in the sexu ally active population occu rred between 1984 and 1987 than in U1c previous four years (P=0.034). All Uwee cases of known HIV-associa ted ITP were captured in th e relro peelive surveillan ce system . The study concluded that increases in community-acquired ITP in a sexua lly active population may be a surrogate marker o f the HN epidemic. even in geographic areas \vith a low scroprevalence for HN. Serological tests for HN infection h ould be a routine part of the diagnostic investigation of lTP in all sexu ally active patients or those with oth er pol nlial risk factors for HN infection. K ey Words: Epidemiology. Human immunodeficiency virus. Immune thrombocytopenia Epidemiologie de Ia thrombocytopenie immune RESUME: Trois cas de thrombocylopenie immune associee au virus de l"immunodeficience humaine MH) ont conduit les ch erch eu rs a passer en revue les cas de Lhrombocytopenie acquise en Nouvelle-Ecosse entre janvier 1980 et decembre 1987. Deux cent sept patients on t ete identifies portcurs cl"une Lhrombocyi.openie immune. L"incidence de lh rombocylopenie immune s?est elevce de 2.0 X 105 en 1980 a 3.3 X 105 en 1987. Plus de cas de t h rombocytopenic immune dans Ia population active scxu ellem ent sont survenus entre 1984 ct 1987 que dans les qualre annees precedentes (p=0. 034). Les trois cas de thrombocytopenic imm une associee au VIH onl ele decclcs pa r un system e de con lr61c epiclemiologique r etrosp ectif. L"etudc a onclu que !"augmentation clu nombre de cas de l hrombocylopenie immune clan s une population active pourraient conslituer un indicaleur substitul cl"une epid . m ie au VIH , m em c clans les zon es geographiques ou Ia seroprevalence du VIH e t faible. Les tests serologique pour !"infection au VIH doivent faire partie integra te de Ia rech erch e diagnostique clans Ia U1rombocytopenie immune ch ez tousles patients actifs sexuellcment OU chez ceu;-c qui presentcnt un autre faclcur cle risque a l"ega rcl de !"infection au VI H. - I man ifesta tion of th e hum an immunodefic iency virus MMU E THROMBOCYTOPENIA (ITP) FIRST WAS REPO RTED AS A (HN) e pidemic in 1982 (l) and now is recognized widely as a common manifestation of acute and chronic HIV infection ( 2 ). Estimates of thrombocytopenia in human s ubj ects of known HIV seropositive cohorts are as high as 10% at a single visit ( 3 ). and thrombocytopenia has been reported in all risk groups for HIV infection ( 3 -7 ). However no studi es of commun ity-acquired ITP exist that would allow a direct compa rison of the inciden ce of ITP in HIV infection vers us that in the general population. Three cases of HIV-related ITP diagnosed in Nova Scotia prompted a study of the incidence of ITP in that province. The hypothesis was that the incidence of ITP - a relatively uncomm on h em atological condition but a common manifestation of HIV infection - would be increasing as an epiph enomenon of the spread of HIV infection in the community . CASE PRESENTATIONS Case 1: A 22-year-o ld heterosexual female noted easy bruising and increased m en strual bleeding during Sep? tember 1984. She was a dmitted in November 1984 wi th a p latelet count of 13.000/ mm3 . White blood cell count was 4800/mm3 \vi.th a nom1al differential . A bone m ar? row exam in ation demonstrated normal megakaryo? cytes. antinuclear a ntibody and anti -DNA and lupus e rythematosis tests were n egative. A diagnos is of ITP was made an d the patient was treated with platelet transfusions and prednisone (100 mg daily): a rapid resolution of thrombocytopenia resulted. In S eptembe r 1985 a human Tcelllymphotrophic virus (H1VL)-IIl titre was positive by enzyme immunoassay and Western blot. The patient rem ained asymptomatic (Centers for Dis ? ease Control [CDC] gro up Ill with a CD4 coun t of 500 in Ju ly 1989. Th e patient's on ly sexual pa rtner in 1984 had hemophilia A and h a d referred h er for evaluation after finding out that h er was HTLV-lll pos itive. In July 1989 the partner h ad CDC group Ill HIV infection wiU1 a CD4 coun t of 300. Case 2: A 26 -year-o ld male developed easy bruising in January 1985 and in July of that year was found to be U1rombocytopenic. He was hospita lized in September 1985 \vi.th a platelet count of 67.000/mm3 because of failure to maintain an ad equ ate p latele t count while off prednisone. Total white blood cell coun t was 13.300/ mm3 and U1e differential co unt was nom1al. A bone marrow aspirate revealed m egakaryocytic hyperplasia. confirming the diagnosis of lTP. The patient was treated with vinblastine. and prednisone was con tinu ed. The thrombocytopenia resolved over sL-x m onths . An HTLV111 titre was positive in September 1985. OU1er studies were not done . The patient had a s in <fle homosexu al relationship two years prior to presentation while at? tending university in central Can ada. Th ere were no other risk factors for HIV infec tion . Case 3: A 25-year-old homosexual male developed a widespread petechial rash and bleeding of the gums in April 1986. He had a positive HTLV-III antibody test, a platelet count of 8000I mm3 and a white b lood cell count of 7600/mm3 wiU1 25% atypical lymphocytes. The pa tient was h epatitis B surface antigen-positive and ha d a cytomegalovirus titre of 1:256 and a herpes s implex virus titre of 1:64 . Bone m a rrow examination s howed megalmryocytic hyperplasia, CD4 count was 480. a nd immunoglobulin (!g) G level was 28.3 (normal 6.9 to 18 .0) . lgA 4.2 (0.9 to 4.0) and IgM 4.1 (0.6 to 3.6). A diagnosis of HTLV- III -associated ITPwas made. Treat? m en t \vi.th 100 mg prednisone daily resulted in rapid resolution of thrombocytopenia. Case as certainment: Medical records at all Ha lifax hospi tals were reviewed for ICD-9 codes 287.3 (prima ry U1rombocytopenia), 287.4 (secondary U1rombocytopen ? ia) a nd 287.5 (U1rombocytopenia. unspecified). A diag? nosis of ITP was based on a platelet count of 120.000 / mm3 or less on two determinations wiU1 evidence of pe1;pheral destruction and no underlying ex.'planatory disease or condition s u ch as drug use. alcohol a buse. liver disease or other autoin1mune diseases. Bone m a r? row examination was performed in all cases. Immune complex determinations. antiplatelet a ntibody a nd s p ecific platelet-bound Ig detem1inations were not rou ? tin ely performed. Cases m eeting U1e case definition willi dates of diagnosis between 1980 and 1987 were ab? sti-acted for demograph ic information including age. sex. date of onset, county of residence, initial platelet co un t, treatinent regimen, HIV risk factors and out? come . Office records of all h ematologists in Nova Scotia were reviewed and a mailing to internists and ped? iau;cians soliciting cases of lTP was carried out. Con ? su ltation s wiU1 h ematologists and gen eral practitioners in U1e province s uggested U1at cases of suspected ITP would routinely be referred to practising h ematologists (all located Ln Ha lifax) or internists by primary care physicia ns. a nd that review of office a nd hospital records of th ese specialists only would not significantly underestimate the number of ITP cases . Nova S cotia census data obtained in 1980 with pop? ulation projections through 1987 were used to estab? lis h lTP incidence by yea r. No attempt was m a de to contact p atients identified during the survey to deter? mine risk factors for HIV infection or to determ ine wheU1er serological evaluation for HIV would be war? ranted. RESULTS Two hundred a nd seven cases of ITP were identifi ed between January 1980 and Decemb er 198 7 in Nova Scotia . Ages ranged from one montl1 to 93 years . \villi 86 cases occurring in males and 121 in females (male: female ratio 1: 1.4) . The age disti;bution of reported cases is illustrated in Figure l. Rates of ITP p e r 100,000 popula tion were deter? mined in each of tl1e age groups (Ta ble 1). In U1e first A L L c A s E s I 1 9 8 0 I 1 9 8 7 Immune thrombocytopenia and HIV infection - 20 TO 39 MALES - 20 TO 39 FEMALES c 51 - - - - - - - - - ? A s 4 1---- - - - - - - - E s 3 four years of the survey (1980-83). rates were highest in the first decade of life and in patients over 49 years of age . Rates did not significantly ch ange for these groups during the last four years of the survey (1984 87). Between 1984 and 1987, rates of!TP for the second through fourth decades of life significantly increased (P=0.034) (x2 test= 1.9 [confidence interva l l.l to 3.6]). For tl1e age group presumed to be most sexually active (ages 20 to 39) . the increase was even more striking (P=0.002) ( l test= 2 .9 [confidence interval 1.4 to 6 .0]) (Figure 2). There was little change in the male:female ratio bel:\:veen the two time periods in this o?roup al? though in the 30- to 39-year-old group. U1e ratio changed from l: 1 to 0. 7:1 in favour of m a les. All three cases of knO\~m HIV-related lTP described above were in th is age group and were identified during the reu?ospec? tive surveillance. Cases were reported from Nova Scotia's 18 counties with no differences in ITP rate between counties. There were 14 deat11s. for a case fatality rate of 6.8% . No deaths were due to possibl HIV-related conditions. DISCUSSION Before the identification of th e causative agent of acquired immune deficiency syndrome (AJDS). surrogate markers of HIV infection -such as Pneumocystis carinii pneumonia ( 8 ) and Kaposi's sarcoma ( 9 ) - iden tified groups of patients subsequently determined to h ave HIV infection . These conditions primarily are seen in immunosuppressed hosts and reflect advanced dis? ease. The epidemiology of tuberculosis. which can occur in boili normal and immunosuppressed patients. has clearly been affected by the spread of HIV infection. with increased rates of tubercu losis occurring in hyper? endemic areas for HIV infection (10). The pres nt authors postulated lliat anollier potential m arke r for HIV infection in a comm uni ty may be an increase in ITP. a common and often early manifestation of HIV infection. Previous studies of community-acquired ITP have not been reported. The province of Nova Scotia provided a unique opportun ity to per form a retrospective study of ITP incidence because of the referral patterns for th is condition. The population of Nova Scotia has been relatively stable. growing from 850 ,000 to 900.000 during U1e period of llie present study . Access to healtl1 care is exce llent. wiU1 regular a nd rapid referral to consultants for uncommon disorders. The first case of AIDS in a Nova Scotia resident was identifi ed in 1983: 72 cases have been reported to December 1990 wi.U1 a peak incidence in 1987 of 1.8 per 100 .000 popu lation. The incidence a nd prevalence of HIV infection in tl1e province is un? knO\~. altl1ough mandatory reporting requ irements for HIV infection a re in p lace. Cross-matching ITP files with reported AIDS cases did not produce additional cases of lTP or AIDS. The study suppo rts llie hypothesis fuat increases in llie lTP rate in sexually active age groups may parallel the spread of HN infection. Automated platelet counts were introduced before and during the survey. and although they may report artefactually low platelet counts. U1is would not account for U1e differences in rates seen be~veen age groups. In addition. all patients identified in U1e survey h ad clin ical findings (easy bruising or petechia) resulting in referral for diagnosis and management. The mean platelet count at onset for the patients was 13.000/mm3 . In creased availab ility of automated platelet counts therefore seems an unlikely bias towards increased rates in the study's last four years. The data, however. may und erestimate asymp? tomatic thrombocytopenia. of which some cases may be clue to immune U1rombocytopenia associated wiU1 HN infection. Changes in referral patterns with in creased avail? ab ility of h ematological or internal medicine consult? ations could also acco unt for increased recognition in U1e IaUer part of U1e survey. However, this bias would be reflected in increased rates of ITP in all age groups: clinically significant thrombocytopenia should not have been systematically under-reported in any age group in the study's first four years. Increased reporting of known HN-related !TP did not occur. and cases 1 and 2 were recognized only in retrospect after epidemiologi? cal risk factor for HN infection were ascertained. Despite U1is delayed diagnosis. all U1ree cases of !mown HN-related !TP were captured in the survey . Rates of ITP did nol differ between counties for any study period. and disproportionate cases of AIDS have not been reported from Halif<Lx county. the major urban centre in the province with 30% of U1e total population. ( ova Scotia may be atyp ical in that respect. compared with other Canadian provinces. as two of the U1ree ITP cases cited in U1is r epo r t were not from Halifax county.) The autho rs believe thai r eferral patterns did nol s igACKNOWLEDGEMENTS: The authors are gmtcful lo Drs Or? mi lle Hayne. Vincenl lng, G Ross Lan gley and Allan Pysemany for access lo patient reco rds for review. and to th e physicians in ova Scotia who responded to the SUJ-vey . The authors also thank Daureen Stover and Janice Flynn for preparation of Lhe manuscript. nificanUy change between 1980-83 and 1984-87. malting it likely U1at ch anges in ITP rates rep resent tru e changes in the incidence of disease in U1e communi ty. HN infec tion in Nova Scotia h as been seen piincipaJ ? ly in homosexual men (85% of reported AJDS cases) . The a uthors expected a change over time in the maJe:femaJe ratio for ITP in sexually ac tive age g roups. Th is change was not noted in the overall population , bul was seen in U1 e 30- to 39-year-olcl age group. in which more cases were reported in males U1an in females for U1e study's last four years. HN may be only one of several factors thai affect the overall rate of community? acquired ITP because the maJe:female ratio did not change clran1atically. It might be easier to identify U1e effect of HIV infection on rates of ITP and male:female ratio change in areas of high prevalence. The auU1ors are unaware of similar studies to s uppor t the con? clusion U1at ITP cases may be surrogate markers for HN transmission. alU1ough anecdotal case reports and case series show a male predomin ance in l-IN-positive ITP patients. The study provided support for the oullined hypo? Ulesis but other population-based studies of ITP in areas of boU1 high and low HN prevalence are needed for confirmation. Review of ITP's clinical features in U1e chart review of patients in the sexually active age group suppo rts the hypothesis; cases of ITP exh ibited the typical chronic . autoimmune form of ITP reported in l-IN-positive patients . Independent confirmation U1rough serological investigation of the cases would have strengU1ened the observation but would have been intrusive . However U1e a uth ors recommend. on U1e basis of U1e study . that serological tests for I-IN infec? tion should be a routine part ofU1e diagnostic investiga ? tion of ITP. particularly in age groups that are likely to be sexually active . 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 Obesity Endocrin BioMed Research International 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 I. Mon?is L. Distenfeld A. Amorosi E. KarpaU '"in S. Autoimmune thrombocytopenia in homosexual m en . Ann lntem Med 1982 : 96 :7 14 - 7 . 2. Ratner L. 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Walter F Schlech, Christine Nesdoly, Nancy Meagher, Janet Turner, Donalda Dickey. The Epidemiology of Immune Thrombocytopenia, Canadian Journal of Infectious Diseases and Medical Microbiology, DOI: 10.1155/1992/164259