Title Učestalost i utjecaj hipovitaminoze D na novootkrivenu imunu trombocitopeniju u djece
Title (english) Incidence and effect of hypovitaminosis D on newly diagnosed immune thrombocytopenia in children
Author Davor Petrović
Mentor Joško Markić (mentor)
Committee member Ozren Polašek (predsjednik povjerenstva)
Committee member Igor Aurer (član povjerenstva)
Committee member Boris Filipović-Grčić (član povjerenstva)
Granter University of Split School of Medicine Split
Defense date and country 2022-01-12, Croatia
Scientific / art field, discipline and subdiscipline BIOMEDICINE AND HEALTHCARE Clinical Medical Sciences Pediatrics
Universal decimal classification (UDC ) 616 - Pathology. Clinical medicine
Abstract Imuna trombocitopenija (ITP) stečena je autoimuna bolest karakterizirana izoliranom
trombocitopenijom koju definiramo brojem trombocita u perifernoj krvi <100 x 109
/L. ITP se
očituje naglim razvojem krvarenja u prethodno zdravog djeteta. Promjene po koži u vidu
petehija, hematoma i ekhimoza nalaze se u 60% djece, dok se krvarenja u sluznicama i
organima pojavljuju u 40% djece.
Vitamin D (VD) je prohormon koji se proizvodi iz 7-dehidrokolesterola pod utjecajem
ultraljubičastog zračenja. Aktivni oblik VD-a regulira apsorpciju kalcija i fosfata iz crijeva,
mobilizaciju kalcija iz kostiju te reapsorpciju kalcija u bubrezima. U zadnjih nekoliko godina
posebno se istražuje uloga VD-a u imunom i upalnom odgovoru. VD je regulator
hematopoetskog sustava, modulira aktivaciju i proliferaciju limfocita, potiče diferencijaciju
monocita te inhibira lučenje nekoliko citokina u T stanicama. Nadoknada VD-a potiče Th1
posredovani autoimuni odgovor, a nedostatak VD-a usmjerava imuni odgovor prema gubitku
tolerancije. Pronađena je povezanost između hipovitaminoze D i veće pojavnosti autoimunih
bolesti, među kojima su i autoimune citopenije.
Cilj istraživanja bio je pronaći poveznicu između razine 25-hidroksivitamina D (25(OH)D)
i težine kliničke slike novootkrivenog ITP-a koristeći IBLS i SMOG sustave bodovanja
krvarenja. Također, analizirali smo i odnos između razine 25(OH)D i broja trombocita u
vrijeme dijagnoze ITP-a. Analiziran je i odnos dobi i spola bolesnika s razinom 25(OH)D i
vrijednosti SMOG ocjene. Utjecaj tjelesne mase na razinu VD-a smo analizirali korelacijom
između z vrijednosti indeksa tjelesne mase (ITM) i razine 25(OH)D.
Ispitanici su 60 pedijatrijskih bolesnika iz obalne Hrvatske s novodijagnosticiranim ITPom. Težinu kliničke slike procijenili smo korištenjem IBLS i SMOG sustava bodovanja
krvarenja.
Pronašli smo statistički značajnu negativnu korelaciju između razine 25(OH)D i SMOG
ocjene (p=0,002) kao i 25(OH)D i IBLS ocjene (p=0,048). Djeca s nižim razinama 25(OH)D
su imala više vrijednosti SMOG i IBLS sustava bodovanja krvarenja, odnosno teža krvarenja
u vrijeme dijagnoze novootkrivenog ITP-a. Uspoređujući razinu 25(OH)D s djelovima SMOG
ocjene, nađeno je da bolesnici s nižim razinama 25(OH)D imaju teža krvarenja u koži
(p<0,0001) i organima (p=0,01). Nismo pronašli povezanost između razine 25(OH)D i broja
trombocita. Utvrdili smo statistički značajnu negativnu korelaciju između razine 25(OH)D i
dobi bolesnika (p=0,001), kao i statistički značajnu pozitivnu korelaciju između vrijednosti
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SMOG ocjene i dobi bolesnika (p=0,02). Nije pronađena povezanost između razine 25(OH)D
i z vrijednosti ITM-a.
Ova studija je pokazala da hipovitaminoza D utječe na težinu kliničke slike
novootkrivenog ITP-a u djece. Stoga bi terapija s pripravkom VD-a mogla biti jedna od novih
terapijskih opcija za liječenje ITP-a, a za što su potrebna daljnja istraživanja.
Abstract (english) mmune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by
isolated thrombocytopenia defined as platelet count in peripheral blood <100 x 109
/L. ITP
manifests with sudden purpura and hematoma in previously healthy children. Skin changes
such as petechiae and purpura can be found in 60% of children, whereas mucous membrane
and organ bleeding can be found in 40% of children.
Vitamin D (VD) is a pro-hormone produced from 7-dehydrocholesterol when being
exposed to radiation of ultraviolet light. The active form of VD affects the absorbance of
calcium and phosphate in the intestine, calcium mobilization in bones and reabsorbance of
calcium in the kidneys. In recent years the importance of VD has been examined in immune
and inflammatory response. VD is also the regulator of the hematopoietic system, it modulates
activation and proliferation of lymphocytes, induces differentiation of monocytes and inhibits
secretion of several cytokines in T-cells. It has been demonstrated that supplementation with
VD is beneficial for Th1- mediated autoimmune response, and that VD insufficiency turns
immune response towards loss of tolerance. Scientists have found connection between
hypovitaminosis D and higher incidence of autoimmune diseases, including autoimmune
cytopenias.
Aim of this study was to find correlation between values of 25-hydroxyvitamin D
(25(OH)D) and severity of clinical presentation of newly diagnosed ITP using IBLS and
SMOG bleeding scores. We also analyzed correlation between 25(OH)D values and platelet
count. As our secondary outcome we assessed the correlation between the patient gender and
age with SMOG score value, and also correlation of the same variables with 25(OH)D values.
Influence of body mass on the VD values and clinical severity of ITP we analyzed with a
correlation between body mass index (BMI) z score and 25(OH)D values.
Medical records of 60 pediatric patients with newly diagnosed immune thrombocytopenia
in the coastal region of Croatia were evaluated. The severity of bleeding was assessed using
two bleeding scores, ITP Bleeding Scale (IBLS) and Skin-Mucosa-Organ-Gradation (SMOG).
We found statistically significant negative correlation between 25(OH)D values and
SMOG score (p=0,002), and between 25(OH)D values and IBLS score (p=0,048). Children
with lower 25(OH)D values had higher values of the SMOG and IBLS scores and respectively
more severe bleeding at the diagnosis of ITP. With further analysis of main domains of SMOG
score, we found that patients with lower 25(OH)D value had more severe bleeding in the skin
(p<0,0001) and organs (p=0,01). We did not find any statistically significant correlation
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between 25(OH)D value and platelet count. However, there was statistically significant
negative correlation between 25(OH)D value and patients age (p=0,001), as well as statistically
significant positive correlation between SMOG score and patients age (p=0,02). We did not
find statistically significant correlation between 25(OH)D value and BMI z score.
In conclusion, our findings suggest that hypovitaminosis D influences the severity of the
clinical presentation of ITP in children at the initial diagnosis of the disease. Therefore, therapy
with VD could be a new potential option for treatment of ITP but for that further studies are
needed.
Keywords
hipovitaminoza D
imuna trombocitopenija
djeca
ITP
Keywords (english)
hypovitaminosis D
immune thrombocytopenia
children
ITP
Language croatian
URN:NBN urn:nbn:hr:171:181363
Promotion 2022
Study programme Title: Translational Research in Biomedicine - TRIBE Study programme type: university Study level: postgraduate Academic / professional title: doktor/doktorica znanosti, interdisciplinarna područja znanosti (doktor/doktorica znanosti, interdisciplinarna područja znanosti)
Type of resource Text
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Created on 2022-02-02 14:15:04