dr. Siti Syarifah, M.

Biomed

Faculty of Medicine
University of Sumatera Utara
Medan, April 2016
 ANEMIA
ž Common complication in persons with HIV
disease
ž Before 1996 & HAART – associated with
poor outcomes
ž 70% to 90% patients affected over the course
of HIV disease
ž 10% to 20% present with anemia on initial
visit
 Definition
— A decrease in the RBC count, hemoglobin and/or
Hematocrit values resulting in a lower ability for
the blood to carry oxygen to body tissues .
PATOPHYSIOLOGY
HEMOGLOBIN
PATHOPHYSIOLOGY
 PARAMETERS
— Men: Hct < 42% (Hb < 14)
— Women: Hct <37% (Hb <12)
— Grade & Hb:
— I Mild 10 – Normal
— II Moderate 8.0 –9.9
— III Severe 6.5 – 7.9
— IV Very Severe <6.5
Ø Eritrosit blood count
CLASSIFICATION
I . W.H.O .
1. ANEMIA DEFICIENCY
-Iron
-Folic Acid
-Cyanocobalamine (Vit B12)
1. ANEMIA HEMOLITIC.
2. ANEMIA POST HEMORRHAGIC .
3. ANEMIA APLASTIC .
 RISK FACTORS
— Poor socio economic class
— Multiparity
— Teenage pregnancy
— Menstrual problem
 IRON DEFICIENCY ANEMIA
— Decrease of iron (Fe) in the body
— Morphology: micrositic hypochromic
— Decrease of synthesis hemoglobin
— Iron forms:
Ferum (Fe)
àIon Fero (Fe2+)
§ àIon Feri (Fe3+)
§ Gastric/ intestinal ulcer of tumor,
pregnancy, bleeding, insufficient intake
Distribution of Iron in the body
PHYSIOLOGIS

§Hemoglobin
§Myoglobin
§Redox reaction enzymatic
(ENZIM : SITOKROM, KATALASE, PEROKSIDASE)

Total iron
4 – 5 gr
RESERVE

— Ferritin
— Tansferin
— Hemosiderin
EPITHELIAL DISORDER IN IRON DEF ANEMIA
SITE FINDING
1 NAIL FLATTENING
KOILONYCHIA
2 TONGUE SORENESS
PAPILLARY ATROPHY
FILLIFORM PAPIL (-)
3 MOUTH ANGULAR STOMATITIS
4 HYPOPHARYNX DYSPHAGIA
ESOPHAGEAL WEBS
5 STOMACH ACHLORHYDRIA
GASTRITIS
Ferrous agents
— Ferrous fumarate, ferrous gluconate, ferrous
sulfate, polysaccharide-iron complex.
— Clinical Use: Iron Deficiency.
— MOA: Replaces the iron necessary for RBC’s to
transport oxygen.
— Pharmacokinetics: Route of administration: p.o.;
Eliminated in the feces, urine and sweat.
— Side effects: Gastrointestinal complaint
— Contraindications: Patients with Peptic Ulcer disease,
Ulcerative Colitis and Hemolytic Anemia.
— Drug Interactions: Antacids may inhibit absorption.
 Iron salts
Ferrous sulfate –least expensive – treatment of choice
Ferrous salts (sulfate, fumarate, gluconate, succinate)
are absorbed about three times as well as ferric
salts.
Vitamin C increases absorption - Ascorbic acid, 200
mg or more, increases absorption by at least 30%
(with increased incidence of side effects too)
 Ferrous agents
— Iron Dextran
— Clinical Use: Iron Deficiency.
— MOA: Replaces the iron necessary for RBC’s to
transport oxygen.
— Pharmacokinetics: Route of administration: i.m. or i.v.;
Eliminated in the feces, urine and bile.
— Side effects: Flushing and dizziness.
— Contraindications: Patients with liver disease and
asthma.
Parenteral iron
Iron dextran injection (INFED, DEXFERRUM, HIBIRON)
An effective alternative when oral therapy fails
Indications: malabsorption, severe oral iron intolerance,
as a routine supplement to total parenteral nutrition
and in patients with renal disease who are receiving
erythropoietin
Acute hypersensitivity, including anaphylactic reactions,
can occur in from 0.2% to 3% of patients.
IV is preferred – more reliable response
Im route – more local side effects – skin discoloration,
long-term discomfort, concern about malignant
change at injection site
NON PHARMOCOLOGICAL MANAGEMENT:
q Tea and coffee inhibit iron absorption when consumed with a
meal or shortly after a meal.

q Vitamin C (ascorbic acid) is also a powerful enhancer of iron

absorption from nonmeat foods when consumed with a meal.
The size of the vitamin C effect on iron absorption increases
with the quantity of vitamin C in the meal.

ž Germination and fermentation of cereals and legumes improve

the bioavailability of iron by reducing the content of phytate, a
substance in food that inhibits iron absorption.

ž Promote and support exclusive breastfeeding for about 6

months followed by breastfeeding with appropriate
complementary foods, including iron-rich through the second
year of life.
Anemia due to Folic Acid Deficiency
Folic Acid deficiency as a
result of :
— intestinal disease or
— pregnancy (increased
demand on the system).
FOLIC ACID
— Leafy vegetables, liver
— Min.requirement 5 μg/d
— Insufficient intake, malabsorption in gastrointestinal
disease, pregnancy
— Antiepileptic drugs (pheytoin, phenobarbital)
— Anemia megaloblastic and mucosal damage
— In pregnancy: neural tube defect
Anemia due to Vitamin B 12 Deficiency

— Vitamin B 12 deficiency may develop as a result of

the absence of intrinsic factor.
— Source: meat,eggs, milk
— The deficiency may result in pernicious anemia
and irreversible nerve damage.

— Cyanocobalamin, Crystalline
— Hydroxycobalamin, Crystalline
VIT B12 AND FOLAT
Folate and Vitamin B12 Interaction
methionine homocysteine
remethylation

DNA Synthesis
Vit-B12 = cobalamin

Folic 5-methyl
Dietary intake THF THF
acid
MTHFR

5,10-methyleneTHF
 ERYTROPOIESIS
IN BONE MARROW
Folic Acid
— pharmacology:
— Clinical Use: Folic acid Deficiency in alcoholism and
malabsorptive syndromes.
— MOA: Replaces the folic acid necessary for DNA
synthesis, cell proliferation and development.
— Pharmacokinetics: Route of administration: p.o.,
or i.m. ; Eliminated in the feces, urine and breast
milk
— Side effects: Flushing and allergy.
Folic acid therapy
§ Rule out underlying cobalamin deficiency

§ In acutely ill – folate, pteroylglutamic acid injection

(5 mg/ml) – 1-5 mg im

§ 1-2 mg oral but up to 5 mg day in malabsorption

syndrome
Cyanocobalamin,
hydroxycobalamine
— Pharmacology:
— Clinical Use: Vitamin B 12 Deficiency or intrinsic factor
deficiency.
— MOA: Converted to methylcobalamin or
deoxyadenosylcobalamin, cofactors for biochemical
reactions which is essential for growth, cell replication,
hematopoiesis.
— Pharmacokinetics: Route of administration: p.o., or
i.m. ; Eliminated in the feces, urine and breast milk
— Adverse effects: Urticaria.
— Contraindications: Patients with optic nerve damage.
— Drug Interactions: Absorption decreased by alcohol.
Medications that may result in anemia
— Antiretroviral — Antibiotic
— Zidovudine — Trimethoprim-
— Gancyclovir sulfamethoxazole
— Foscarnet — Sulfonamides
— Alpha-interferon — Dapsone
— Ribavirin — Antineoplastic
— Cidofovir — Hydroxyurea
— Antifungal — Antiparasitic
— Amphotericin B — Pyrimethamine
— Flucytosine — Pentamidine
HEMOSTASIS
PENGHENTIAN DARAH

@ PRIMER
PENGHENTIAN PERDARAHAN

@ SEKUNDER
PEMBEKUAN DARAH
HEMOSTASIS PRIMER

• SEGERA SETELAH LUKA, TROMBOSIT

MELEKAT PADA JARINGAN IKAT KOLAGEN

• TERBENTUK SUMBAT TROMBOSIT

HEMOSTASIS SEKUNDER
• SUMBAT TROMBOSIT TIDAK DAPAT
MENUTUP LUKA SELAMANYA

( SUMBAT KUAT DIBUTUHKAN )

• SUMBAT BEKUAN FIBRIN & TROMBUS

• SEMUA FAKTOR PEMBEKUAN IKUT SERTA
Mekanisme pembekuan darah (hemostasis).

Luka kerusakan
Trombosit
(leukosit) Tromboplastin (F.III)
Sel-sel jaringan Jaringan
+ ion Ca (Fa IV)

( F II ) protrombin Trombin

( F.I ) Fibrinogen fibrin

Sel-sel Clot (beku)

darah
 MEKANISME HEMOSTASIS
KONTAK PERMUKAAN

KERUSAKAN JARINGAN
XII XII a

XI XI a III THROMBOPLASTIN

IX IX a VII a VII

X Xa X

XIII
PROTROMBIN TROMBIN

Phosfolipid

XIII a
HASIL
FIBRIN TAK FIBRIN URAI
FIBRINOGEN FIBRIN
STABIL STABIL

PLASMINOGEN PLASMIN

AKTIVATOR PLASMINOGEN
FAKTOR – FAKTOR KOAGULAN
FAKTOR SINONIM
I Fibrinogen
II Preotrombin
III Tissue thromboplastin
IV Ca+
V Labile factor
VII Proconvertin
VIII Anti hemophilic globulin
IX Chrismast factor
X Stuart factor
XI Plasma thromboplastin antecedent
XII Hageman factor
XIII Fibrin stibilizing factor
HMWK High - molecular - weight – kininogen
PRE-K Prekalikrein
Ka Kallikrein
pl Platelet phospholipid
Anticoagulant Drugs

ì Heparin

ì Warfarin

ì Coumarin

Zain-Hamid,R; Faculty of Medicine,

Universitas Sumatera Utara.
 Intrinsic Pathway Extrinsic Pathway
Blood Vessel Injury Tissue Injury

XIIa Tissue Factor

XII
Recall !
Thromboplastin
XI XIa

IX IXa VIIa VII

X Xa X

Prothrombin Thrombin
Factors affected
By Heparin Fibrinogen Fribrin monomer
Vit. K dependent Factors Fibrin polymer
Affected by Oral Anticoagulants XIII
Why anticoagulants ?
— To reduce the coagulability of blood
— Blood clots – Thrombus
— Arterial Thrombosis:
— Adherence of platelets to arterial walls – “White” in color -
Often associated with MI, stroke and ischemia
— Venous Thrombosis:
— Develops in areas of stagnated blood flow (deep vein
thrombosis), “Red” in color- Associated with Congestive
Heart Failure, Cancer, Surgery
— Thrombus dislodge from arteries and veins and become an
embolus
— Venous emboli can block arterioles in the lung and
pulmonary circulation
— Thromboembolism
Heparin Actions
• Indirect acting - Activates plasma antithrombin III (AT III)
• Heparin-AT III complex inactivates clotting factors - Xa, IIa,
IXa, XIIa and XIIIa, but not VIIa (extrinsic pathway)
– At low conc. Xa mediated conversion of Prothrombin to thrombin
affected
– Overall, Xa and IIa mediated conversion of fibrinogen to fibrin
• AT III (suicide inhibitor) – binds to clotting factors slowly to
form stable complex. Heparin enhances it by
1. Heaprin creates scaffolding to bind each (clotting factors)
other with AT III
2. A specific polysaccharide in heparin binds to AT III and
induce conformational changes – bind factors
 Heparin mechanism of action
Heparin

Antithrombin III
Thrombin
Heparin – Contd.
• Adverse effects:
1. Bleeding due to overdose – haematuria is 1st sign
2. Thrombocytopenia – aggregation of platelets
3. Hypersensitivity – urticaria, rigor, fever and
anaphylaxis etc.
4. Alopecia and osteoporosis
• Contraindications: Bleeding disorders, Severe
hypertension, GIT ulcer, Piles, malignancy, Ocular &
neurosurgery, Chronic alcoholism, cirrhosis etc.
• Aspirin and antiplatelet drugs - caution
 ANTIPLATELET DRUGS
(ANTITHROMBOTIC)
— Drugs which interferes with platelet function and used in
prophylaxis of thromboembolic disorders.
— Drugs: Aspirin, Dipyridamole, Ticlodipine, Clopidogrel
and Prasugrel
— Aspirin as antiplatelet:
— Irreversible Inhibition of COX 1 and TX synthase
— Suppress TXA2 (generated by platelets) in low doses (75-150 mg) –
till fresh platelets are formed – prolonged bleeding time
— Suppress COX-1 and decrease PGI2 synthesis in vessel wall – but
endothelial cells immediately re-synthesize fresh enzyme
— Also inhibits release of ADP from platelets and their sticking to
each other – but not to adhesion to damaged vessel walls
 Antithrombotic drugs - Clopidogrel
• Similar MOA to Ticlodipine – irreversible blockade of platelet
function
– Safer and better tolerated than Ticlodipine
• Advantages over Aspirin in Ischaemia – lower incidence of ischaemic
events
• Synergistic action with aspirin – prevention of Ischaemic episodes
• Kinetics: Prodrug like Ticlodipine, 50% absorbed orally
– Only a fraction slowly activated in liver by CYP2C19 slow acting
– CYP2C19 – genetic polymorphism - interindivdual variability in
antiplatelet action
– Takes 5-7 days for action
• ADRs: Bleeding most common, neutropenia and thrombocytopenia
rarely
• Dose: 75 mg OD