INFLAMATUAR BARSAK HASTALIĞINDA ANEMİYE...
Transcript of INFLAMATUAR BARSAK HASTALIĞINDA ANEMİYE...
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INFLAMATUAR BARSAK
HASTALIĞINDA ANEMİYE YAKLAŞIM
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ANEMİ
Kırmızı kan hücrelerin esas ölçümlerinde azalma
Hemoglobin konsantrasyonu
Hematokrit
Eritrosit sayısı
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Yaş veya cinsiyete göre Hb (g/dl) Hb (mmol/l)
Çocuk (0.5–5.0 yaş) 11.0 6.8
Çocuk (5–12 yaş) 11.5 7.1
Genç (12–15 yaş) 12.0 7.4
Kadın (>15 yaş) 12.0 7.4
Gebe kadın 11.0 6.8
Erkek (>15yaş) 13.0 8.1
WHO Anemi tanımlaması
(Hb; 1 g/dL = 0.6206 mmol/L)
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ANEMİ
ÜRETİM
SORUNU?
HAYATTA
KALMA/YIKIM?
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RETİKÜLOSİT DEĞERI
Düzeltilmiş retikülosit = Hasta retikülositi x (Hasta Hct/45)
Retikülosit index (RPI) = düzeltilmiş ret.sayısı
olgunlaşma süresi
Olgunlaşma süresi = Hct
%45 için 1
%35 1.5
%25 2
%15 2.5
Mutlak ret. sayısı = ret. x eritrosit sayısı
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MCV 100-80
MCV <80
MCV >100
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Ott C, et al. Gastroenterology Research and Practice 2012
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Manuela Voegtlin et al. Journal of Crohn's and Colitis (2010) 4, 642–648
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2008 İSVEÇ
Rejler M, et al. Scandinavian Journal of Gastroenterology. 2012; 47: 937–942
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IBH DA ANEMİ
Akut Masif kanama (%3-20)
Kronik
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IBH DA ANEMİ NEDENLERİ
Sık
nedenler
Demir eksikliği
Kronik hastalık anemisi
Nadir B12 eksikliği
Folat eksikliği
İlaca bağlı (AZT, 6-MP, 5-ASA, sulfasalazin)
Çok nadir Hemoliz
MDS
Aplastik anemi
Gashe G, et al. Gut 2004;53:1190–1197
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Duodenum Ca, Mg, Fe, Çinko
Jejunum Disakkarid, Protein,
yağda eriyen vitamin A, D
Suda eriyen vitamin B1, B2, B6,
C , folik asid
İleum yağ , B12 , safra tuzları
Kolon Su ve elektrolit
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JEJUNO-ILEO-KOLOSTOMI
(SALIM KOLON-ILEOÇEKAL REZEKSIYON)
safra tuzu diyaresi , yağlı ishal ve B12 eksikliği olabilir
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Goodhand et al. Inflamm Bowel Dis 2012
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Goodhand et al. Inflamm Bowel Dis 2012
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Crohn’da kümülatif
B12 eksikliği %15 (95%CI 9.7-20%) vs %2.8 (95%CI 0.8-9.8) (p=0.007).
Folat eksikliği %22 (95%CI 16-28%) vs %4.3(95%CI 1.4-12%)(p=0.001).
B12/folat eksikliği olanlarda %23’ü makrositik anemi (95%CI 14-35%).
Multivaryant analizde
B12 eksikliği için ileal rezeksiyon (OR 2.5; 95% CI 1.1-6.2; p=0.04),
Folat eksikliği için hastalık aktivitesi (OR 2.4; 95% CI 1.1-5.1; p=0.02)
risk faktörü. Fernando Bermejo, et al. AGA 2011 Abstract
180 Crohn hastası, 70 ülseratif kolit hastası 24 aylık takip
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Vasilopoulos S, et al.J Clin Gastroenterol 2001; 33: 132–6.
Koutroubakis IE, et al. Dig Dis Sci 2000; 45: 2347–51.
Chowers Y, et al. Am J Gastroenterol 2000; 95:3498–502.
Düşük vitamin B12 ve folik asid
düzeyleri
Yüksek homosistein ile birliktedir.
Bu da tromboemboli riskini artırır
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Stefanie Kulnigg-Dabsch, et al. PLoS ONE 2012
Demir eksikliği IBH da sekonder trombositozda
önemli bir nedendir
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iron sucrose n = 122,
ferric carboxymaltose n = 130
iron sulphate n = 56
Stefanie Kulnigg-Dabsch, et al. PLoS ONE 2012
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Rejler M, et al. Scandinavian Journal of Gastroenterology. 2012; 47: 937–942
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AZT
6-MP 6-MMP
İnaktif metabolit
6-TİOÜRİK ASİD
İnaktif metabolit
HGPRT
TPMT XO
6-TI 5’MP
IMPDH
6-TG NÜKLEOTİD
AKTİF METABOLİT
6-MTI 5’MP
Toplumun %90 normal enzim aktivitesine sahip
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417 IBH HASTASI (%58 ÜK) , ort 42 ay takip (6-288 ay),
AZT kullanma süresi ort 33 ay;
Major toksisite %4 Bırakma oranı %20
(%40’ı yan etki nedeni ile)
Uyanikoglu A, et al. Eu J Hepato-Gastroenterol 2012
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KRONİK HASTALIK ANEMİSİ SIKLIĞI W
eis
s G
, et
al. N
EJM
2005
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Eritrosit
K.İ’de eritrosit
üretimi
Plasma Fe
havuzu
Makrofajların
eritrosit
yıkımı
KC
Fe giriş Fe çıkış
Fe 20 mg/gün
1-2 mg/gün
Fe 20 mg/gün
Transferrin
1-2 mg/gün
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DİYETTEN ALINAN DEMİR
ENTEROSİT
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Weis
s G
, e
t al. N
EJM
2005
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Weiss G, et al. NEJM 2005
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Weiss G, et al. NEJM 2005
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We
iss G
, e
t al. N
EJM
2005
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IV MPR 40 mg/gün
Siklosporin 2 mg/kg/gün IV
5-ASA 3 gr/gün PO
AZT 150 mg/gün
Remisyon ile çıkartıldı
ESR 82/saat
CRP 40.4 mg/dl
WBC 23600 /mm3
PNL 22200 /mm3
Lenfosit 600 /mm3
Hb 12.1 g/dL MCV 85.8fL
Hct %34.2
Plt 495000 /mm3
Ferritin 114 ng/dL
LDH 299 IU/L
25 yaşında erkek, Ülseratif Pankolit (SEO:210; orta aktiviteli)
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TANIDAN 18 AY SONRA
ESR 120/saat
CRP 20 mg/dl
WBC 4300 /mm3
PNL 2700 /mm3
Lenfosit 1300 /mm3
Hb 9.1 g/dL MCV 82fL
Hct %27
Plt 200000 /mm3
LDH 1795 IU/L
T protein 10.8 g/dL
Albumin 3.69 g/dL
Ferritin 73.8 ng/dL Ig G lambda tipi monoklonal gamopati
1. Ülseratif pankolit
2. Hodgkin dışı lenfoma
WHO sınıflaması:
Diffüz büyük B hücreli lenfomanın immunoblastik-plasmablastik
varyantı
EBV pozitif
Evre IV B (SE)
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543 IBH (265 ÜK, 268 CH,10 INDETERMINE KOLIT).
Anemi sıklığı %16.8
Biyokimyasal demir eksikliği %49.5. ( ÜK %14.3, CH
19.5% ;p=0.102).
%29 oral replasman
%2, IV demir replasmanı
Sudeep Tanwar, et al. AGA 2011 Abstract
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GASCHE SKC, et al. Aliment Pharmacol Ther 2006
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Ott C . Gastroenterol Res and Prac 2012
Demir eksikliği saptanmasına rağmen 1/3 hasta tedavi edilmiyor
%70 anemik hastanın
%34.4’ünde demir, ferritin ve transferrin saturasyonu ölçülmüş
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Ott C . Gastroenterol Res and Prac 2012
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GASCHE SKC, et al. Aliment Pharmacol Ther 2006
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ORAL DEMIR PREPARATLARı
Demir sülfat (tardyferon)
Demir fumarat (vifer)
Demir glukonat (ferroglukonat)
Yetiskinlerde günlük doz genellikle 180 mg elemanter
demir
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Ülser alanında Fe, hidroksi radikallerinin
oluşumuna neden olur
Fenton reaksiyonu:Fe2+ + H2O2 fi Fe3+ + OH• + OH
Hidroksil radikalleri organik moleküllerin
yıkımınada neden olur ve mukozal hasarı
artırıp hastalık aktivitesini
artırabilir
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IV DEMIR
Demir sükroz (Venofer)
Demir glukonat (Ferrlecit)
Demir dekstran (Cosmofer)
Toplam Fe dozu (mg)= ağırlık (kg) x Normal-hasta Hb farkı x 2,4 + 500
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Demir sükroz
(7 mg/kg) (tek infüzyonda 500 mg aşılmamalı)
Tek infüzyonda 200 mg Fe , 100 mL serum sale içinde
Haftada 2 , Daha sonra haftada bir
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RAYKO EVSTATIEV et al. CLIN GASTROENTEROLAND HEPATOL 2013;11:269–277
500 mg demir, 250mL 0.9% saline solusyonda
( Ferinject-ferrik-karboksi-maltoz) veya placebo (0.9% saline solusyon).
Anemi nüksü tedavi grubunda daha azdı (HR, 0.62; 95% CI, 0.38 –1.00; P .049).
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2 GR DEMIR SÜKROZ 8 HAFTADA VERILMIŞ
Gasche C, et al. Ann Intern Med 1997;126:782–7.
Gasche C , et al.Digestion 1999;60:262–7.
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Hb düzelmesi
İlaç bırakılması
Lee TW, et al.Journal of Crohn's and Colitis (2012) 6, 267–275
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DÜŞÜK DOZ ORAL DEMIRDE YÜKSEK DOZ
KADAR ETKIN YAN ETKI AZ
Rizvi S, et al.Am J Gastroenterol 2011;106:1872–1879
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IV DEMIR KLINIK AKTIVITE INDEKSINDE DEĞIŞIKLIK YAPMAZ
Rizvi S, et al.Am J Gastroenterol 2011;106:1872–1879
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Gasche C. Gut 2004
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Gu
t 2
01
1;6
0:5
71
e60
7.
do
i:1
0.1
13
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ut.
20
10
.22
415
4
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ECCO GUIDELINE 2012
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TRANSFÜZYON
Hb (g/dL) Hasta özelliği ve anemi tipi
<5 Kronik anemi, risk yok
<6 Semptomatik kronik anemi, risk yok
Akut anemi genç hasta
<7 Asemptomatik kronik anemi, risk faktörü var
Akut anemi cerrahi ve kritik hasta
<8 Akut anemi, cerrahi hasta, >65 yaş
<9 Akut anemi organ disfonksiyonu
<10 Masif transfüzyon gerektiren ciddi hasta
>10 Transfüzyon yapma
Gisbert JP, et al. World J Gastroenterol 2009
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NE ZAMAN DEMİR REPLASMANI?
Anemi saptandığında
(Hb erkek <13 g/dl, kadında <12 gr/dl)
NE ZAMAN DURDURACAĞIZ?
Hb normale gelince
Depo demir doldurulunca
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ÖZET
IBH ‘da anemi ; Malabsorbsiyon, Malnutrisyon, İnflamasyon,
İntestinal rezeksiyon ve İlaç etkilerine bağlı kompleksdir.
En sık demir eksikliği görülür
Anemi saptandığında depolar doluncaya kadar replasman
yapılmalıdır
Özellikle aktif dönemde IV replasman tercih edilmelidir.
Özellikle ameliyatlı Crohn hastalarında B12, folik asid kontrol
edilmeli ve eksik tamamlanmalıdır