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Hematological Disorders

in Geriatric Patients
Sahyuddin
Tutik Harjianti
A. Fachruddin Benyamin
SubDiv of Hematology & Medical Oncology
Dept of Internal Medicine, Medical Faculty
Hasanuddin University

I. Introduction :

Specific disorders/diseases in geriatric


Related to aging process, natural &
physiologically
Specific health problems
Should be managed properly

II. Age & Diseases Relationship :


Evidence :
1. Degenerative diseases
2. Bone & Joint diseases
3. Malignancy
4. Others

III. Basic Concept of Aging :

a. Genetic process
b. Somatic mutation error in
transcription & translation process
c. Immune system defect
d. Free radicals cell destruction
tissue destr organ destr.

Sel Normal
Gain of function
mutations of tyrosine
kinases

Loss of function of Loss of Apoptosis


transcription factors
needed for differen. eg.:

eg. FLT3, c-KIT


mutations
N- & K-RAS
mutations
BCR-ABL
TEL-PDGFR

eg. AML1-ETO
CBF-SMMHC
PML-RAR

enhanced
Normal
proliferation

enhanced
Normal
differentiati
on

Bcl-2 over expression

Suppressio
Normal
apoptosis
n
apoptosis
GgnImun
Sistem
surveilence
imun

IV. Hematological Disorders


in Geriatric Patients :
1. Iron defc Anemia
2. Megaloblastic Anemia
3. Chronic Lymphocytic Leukemia
4. Multiple Myeloma
5. Myelodysplastic Syndrome

Aging in Hematopoetic System :

Bone marrrow : dynamic elements


Production & replication continously
Old age : involution of BM
decrease of BM reserve
Cause : - micro-environmental
- humoral factors

ALL

CLL
nave

Lymphomas

MM

germinal center

B-lymphocytes
Lymphoid
progenitor

AML

Hematopoietic
stem cell

Myeloid
progenitor

Plasma
cells
T-lymphocytes

Myeloproliferative disorders
Neutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells

B-cell development
CLL

stem
cell
lymphoid
progenitor

mature
naive
B-cell

memory
germinal B-cell
center
B-cell

MM

progenitor-B

ALL

pre-B
immature
B-cell

Bone marrow

DLBCL,
FL, HL

plasma cell

Lymphoid tissue

1. Iron Defc Anemia

Cause : chronic blood-loss (mostly)


G I tract - ulcer,varices,colorectal,malign.
- drug ( ASA, NSAID)
Effects : - Decrease of working capacity
- Predisposition to infection

2. Megaloblastic Anemia

a : B12 defc & Folate defc


(Gastrectomy,malabsorption,diverticle,
Crohn disease, lymphoma,drugs etc.)
Hyperthyroidism, malignancy
b : Pernicious anemia
Peak : 60 y.o
Auto-immune,atrophy (achlorhydria)

Deficiency
Cyanocobalamin

B12 : all of it made from diet


A food ingredients may from animal.
Absorbtion : 5 ug / days
Cofactor at 2 important reaction in a
body

Division of Hematology & Medical Oncology Dept. of Internal Medicine

Deficiency
Cyanocobalamin
An important
sign :
3. Level of Vit B12 <100 pg/ ml

1. macrocytic Anemia

sign

2. Peripheral blood smear:


macro-ovalocyte & hypersegmented neutrophil

Division of Hematology & Medical Oncology Dept. of Internal Medicine

Macrocytic
Division of Hematology & Medical Oncology Dept. of Internal Medicine

Normocytic

The Cause
1.
2.

2.

3.
4.

Deficiency vit B12 (diet)


The decrease production of intrinsic factor (Anemia
perniciosa, post-gastrectomy)
The decrease absorbtion of vit B12 at the ileum
(Post-op, Crohn ds)
Helmynthyasis (tape-worm)
Deficiency Transcobalamin II

Division of Hematology & Medical Oncology Dept. of Internal Medicine

Physiology

Vit B12 come in from IT binding with intrinsic


factor (made from parietal mucosa gaster cell)
abs in ileum terminal by spesific receptor
come in to the plasma liver .
There are 3 protein transporter in the plasma :
Trans-cobalamin I, II & III (by leukocyte).
Only Trans-cobalamin II that can transport vit
B12 into the cell.

Division of Hematology & Medical Oncology Dept. of Internal Medicine

Division of Hematology & Medical Oncology Dept. of Internal Medicine

Phatogenesis

Hepar consist 2.000 5.000 ug vit B12

Need : 3 5 ug / hari

Defs vit B12 will be happen in 3 years after


no more absorpsi.

Defs caused by diet less vit B12 vary rare


( vegetarian )

Example :

Gastrectomy the area produce


factor intrinsik will decrease
Over-growth bactery in intestinal
Reseksi ileum the area of
absorpsi vit B12 will decrease
Helmenthyasis
Crohns disease ileum
destruction
the area of absorpsi vit B12 will
decrease

3. Leukemia
AML : 80 % adult age
Median age : 55 y.o.
Increase of incidence = age
Problem : - Poor prognosis
- Low remission rate
(low tolerance to chemotx, infection etc)

4. Chronic Lymphocytic Leukemia

CLL : Most often found leukemia in USA.


Mostly > 60 y.o.
90 % > 50 y.o.

5. Myelodysplastic Syndromes

MDS : abnormal proliferation of single


clone in bone-marrow.
Defects : maturation & proliferation
BMP : usually hypercellular
Peripheral blood smear : cytopenia
Clinic : anemia,infection,bleeding
MDS may progresses to Acute Leukemia

MDS :

Median age : male


female

74,1 y.o
78,2 y.o

6. Multiple Myeloma

MM : malignant growth of plasma cell.


Median age : 62 y.o.
Abnormal plasma cell secreting monoclonal Ig (in serum & urine)
1. Bone-marrow failure
2. Increased plasma volume
3. Increased plasma viscosity

MM :
4. Supressed normal Ig production
5. Bone destruction bone-pain etc.
6. Kidney function disorder

* Gbr. klinis
_________________________________
Peny. lanjut usia (median : 60 th)
Anemia, LED tinggi
Nyeri tulang : costa, vertebra
Fraktur patologik : colum femoris
Ggl ginjal, kompresi med.spinalis

* Gbr. Klinis (2)


_________________________________
Sindr.hiperviskositas :
perdrh.mukosa,
nausea, vertigo, ggn visus, ggn
jiwa.
Pucat, nyeri tulang, neuropati
Ggl jantung kongestif

* Laboratorium
_________________________________
Anemia ( normokrom )
LED sangat tinggi ( mis. 150 / 160
)
Hiperkalsemia ( Ca >> )
Proteinuria (Bence Jones protein)
Elektroforesis protein serum
abnormal
(spike monoclonal pd beta atau

Serum Protein
Electrophoresis
Normal

Monoclonal Protein in Myeloma

Kyle RA and Rajkumar SV. Cecil Textbook of Medicine, 22nd Edition, 2004

Thank You

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