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1.

Factor income

chemicals such as insecticides and heavy metals are also associated with

Radiation

anemia associated with bone marrow damage and pansitopenia.13

Bone marrow aplasia is the result of a major acute radiation where

Drugs

the stem cells and progenitor cells damaged. Radiation can damage DNA

Aplastic anemia can occur on the basis of hypersensitivity or

which tissues with active mitosis as hematopoiesis tissue very sensitif.4,12

excessive drug dose. Practically all the drug can cause aplastic anemia in

When the stem cells were exposed to the hematopoiesis occurs aplastic

someone with a genetic predisposition. Which often causes aplastic anemia

anemia. Radiation can also affect the bone marrow stroma and cause

is chloramphenicol. Other drugs are also frequently reported are

fibrosis.2

phenylbutazone, compounds of sulfur, gold, and anticonvulsants, for

The effects of radiation on bone marrow depends on the type of radiation,

example

dose and extent of bone marrow exposure to radiation. High-energy

Infection

cytotoxic

drugs

mieleran

or

nitrosourea.2

radiation can be used as high-dose therapy with no signs of bone marrow

Aplastic anemia can be caused by viral infections such as viral

damage is not about the radiation field as long as most of the bone

hepatitis, Epstein-Barr virus, HIV and rubella. Viral hepatitis is the most

marrow. In patients who receive whole body radiation effect depends on

frequent cause. Severe pancytopenia may occur one to two months after

the dose of radiation received. Effects on bone marrow will be a little at a

infection with hepatitis. Although rarely aplastic anemia caused by

dose of less than 1 Sv (equivalent to 1 Gy or 100 rads for X-rays). Blood

hepatitis but there is a relationship between seronegative fulminant

cell count can be reduced reversibly in radiation dose between 1 and 2.5

hepatitis with aplastic anemia .. Parvovirus B19 can cause temporary

Sv (100 and 250 rads). Irreversible loss of stem cells occurs at higher

Aplastic crisis in patients with congenital haemolytic anemia (sickle cell

radiation doses. Even patients can die due to damage to the bone marrow

anemia, hereditary spherocytosis, and others). In patients who are

radiation dose of 5 to 10 Sv unless the patient receiving a bone marrow

immunocompromised which failed to produce neutralizing antibodies

transplant. Long-term exposure to low doses of external radiation can also

against parvovirus a form of chronic red cell aplasia can terjadi.8,12,13

cause anemia aplastik.13

Virus infection usually associated with minimal suppression of the

Chemical Substances

bone

Chemicals such as benzene and benzene derivatives associated with

thrombocytopenia. Viruses can cause bone marrow damage directly,

aplastic anemia and acute myelositik leukemia (AML). Some other

namely by infection and cell cytolysis of hematopoiesis or indirectly

marrow,

usually

looks

little

sparse

neutropenia

and

through the induction of secondary immune, the initiation of the


autoimmune process that causes a reduction in stem cells and progenitor

D. Pathophysiology
The cause of aplastic anemia is difficult to determine, especially

cells or stromal tissue destruction penunjang.4

since a lot of possibilities that must be removed. If no cause is found for

2. Genetic Factors

sure then classified into the causes idiopatik.10 Another opinion states that

This group is often called constitutional aplastic anemia and some of


her diturukan according to Mendell law, such as Fanconi anemia. Fanconi

the most common cause of bone marrow failure are iatrogenic due to
cytostatic chemotherapy or therapy radiasi.9,10

anemia is an autosomal recessive disorder characterized by bone marrow

Damage that occurs in aplastic anemia found on stem cells and the

hypoplasia with brown pigmentation of the skin, thumb or radius

inability of the bone marrow tissue to allow the stem cells to grow and

hypoplasia, microcephaly, mental retardation and sexual, kidney disorders

develop properly. It is closely related to the mechanisms that occur as a

and limpa.2

direct toxicity or deficiency stromal cells. Deviations immunological

3. Aplastic Anemia on condition / Other Diseases

processes that occur in aplastic anemia associated with viral infections or

In acute lymphoblastic leukemia at kdang found pancytopenia with

drugs that are used, or substances kimia.9

marrow hypoplasia tulang.2

Hematopoesis normally occurs in the bone marrow, is the

Paroxysmal Nocturnal Hemoglobinuria (PNH).

interaction between hematopoietic progenitor stem cells in the

The disease can manifest in the form of aplastic anemia. Hemolysis

microenvironment

accompanied mengkin pancytopenia including abnormalities PNH.2

Microenvironment regulates hematopoesis by reaction stimulation by

Pregnancy

growth factors hematopoetik.10,12

(microenvironment)

in

the

bone

marrow.

Cases of pregnancy with aplastic anemia have been reported, but the

Hematologic immature cells can be seen by inspection flouresent

relationship between these two conditions is not clear. In some patients,

activate citometry flow, which can detect antigen CD34 + cells and

pregnancy exacerbates existing aplastic anemia in which the situation

proteins adhsesi less than 1% of the bone marrow normal.9,13 Aplastic

would improve again after giving birth. In other cases, aplasia occurs

anemia can occur through several mechanisms, namely heterogeneous

during pregnancy with recurring events in pregnancies berikutnya.9

damage to the microenvironment, disruption of production or function and


hematopoietic growth factors, and bone marrow damage through
mechanisms imunologis.9,11

Active cytotoxic T lymphocytes, plays an important role in bone

F. Diagnosis

marrow tissue damage through the release of lymphokines such as

Diagnosis is made by a state aplastic anemia pancytopenia

interferon- (IFN-) and tumor necrosis factor (TNF-). Increased

characterized by anemia, leukopenia and thrombocytopenia in the

production of interleukin-2 initiated the expansion of polyclonal activation

peripheral blood. This condition cause complaints pale, bleeding and fever

of T cells via the Fas receptor-ligand fas cause the target cell apoptosis.

caused by infection. On physical examination, there were no

The effect of IFN- by interferon regulatory factor 1 (IRF-1), is to inhibit

hepatosplenomegaly or lymphadenopathy. In addition to the state of

gene transcription and entry into the cell cycle. IFN- also induces the

pancytopenia, the count also showed a picture of relative lymphocytosis. A

formation of nitric oxide synthase (NOS), and toxic gas production of

definitive diagnosis of aplastic anemia is determined based on the

nitric oxide (NO) which may cause toxic effects menyebar.9

examination of bone marrow aspirate showed that cells lacking an idea,

E. Clinical Manifestations

there are a lot of connective tissue and fat tissue, the system aplasi

1. Pale

eritropoetik,

2. Weakness

G. Prognosis

3. Rash

granulopoetik

and

trombopoetik.5

The prognosis of this disease are difficult to predict but generally

4. Shortness of breath

bad, because as has been stated both etiology and pathophysiology as yet

5. Easy bruising

unclear. About two-thirds of the patients died about 6 months after

6. Nose bleed

diagnosis, less than 10-20% healed without a bone marrow transplant and

7. Bleeding gums

a third patient died from bleeding and infection are not resolved. Cause of

8. dispneu

death in general is due to infection of Pseudomonas sepsis and

9. Anorexia

staphylococcus. Therefore, determining the prognosis of patients with

10. Sick throat

aplastic anemia is important because it will determine the therapeutic

11. ulceration of the mouth and pharynx

sesuai.5

12. Bleeding into the gut, brain or kidneys

Some things that can be used as guidelines in determining the


prognosis of patients with aplastic anemia is the age of the patient, picture
hypocellular or acellular bone marrow, peripheral blood picture, and the

presence or absence of secondary infection. The prognosis of patients with

Bleeding that occurs often leads to death. To prevent bleeding,

aplastic anemia is bad if discovered at a young age, the image of the bone

especially in the vital organs can be done by maintaining a platelet count

marrow acellular with a reduction in the proportion of components

above 20,000 / uL. This can be done with a transfusion of platelets

myeloid bone marrow more than 30% lymphocytes, picture peripheral

suspension. Keep in mind that the granting of suspension of platelets can

blood with the reticulocyte count <1%, leukocytes <500 / uL, and platelets

cause isoimmunization state if performed more than 10 times, and this

<20,000 / uL, accompanied by secondary infection. Among the things on

situation could affect the success of therapy. Isoimmunization can be

the top of the most well be used as guidance in determining the prognosis

prevented by administration of platelets with HLA compatible with the

was marrow picture tulang.5

patient. If the bleeding persists can be added antifibrinolisis.

H. Procedures

To cope with infections arising due to circumstances leukopenia,

Based on the pathophysiology of this disease, aplastic anemia

can be given prophylactic antibiotics and isolation treatment. Skin hygiene

therapy approach consists of supportive governance intended to address

and good dental care is very important, because infections are usually

the circumstances that caused pancytopenia, replacement stem cell

severe and often the cause of death. Aplastic anemia in patients whose

transplant or a bone-marrow suppression immunological processes that

fever is necessary to check blood cultures, sputum, urine, feces, and if

occur by using obatobat immunosuppressant.

necessary, cerebrospinal fluid. If there is a suspicion of sepsis can be given

Management of supportive

broad-spectrum antibiotics with high doses of intravenous and ensured that

Supportive governance aimed at symptoms due to circumstances

causes fever bakteni therapy continued until 10-14 days or until the

caused pancytopenia. To overcome anemia state can be administered

cultures are negative. If fever persists for up to 48 hours after being given

transfusion leukocyte-poor red cells which aims to reduce sensitization to

empirical antibiotic can be given anti jamur.5

HLA (human leukocyte antigen), decrease the possibility of transmission

On governance aplastic anemia, which is no less important is the

of hepatitis infection, cytomegalovirus and toxoplasmosis, in some cases

avoidance of materials physics and chemistry, including medicines that

prevent graft- versus host disease (GVHD). This transfusion can take place

may be the cause. If chemicals or toxic physics was discovered and still

repeatedly so to consider the side effects and dangers of transfusion such

present in the body, must be made to remove it even though it sometimes

as transfusion reactions, hemolytic and nonhemolytic, the transmission of

can not be dilakukan.5

infectious diseases, and accumulation of iron.

Management of Medical

of the genitals. Patients with androgen therapy should be periodic liver

1. Drugs

function tests, liver ultrasound examination every year, and examination of

Management of aplastic anemia with medications given to patients

bone age per tahun.5

with mild aplastic anemia, patients who did not get a suitable donor for

3. Immunosuppressant

transplantation, and patients who have a contra-indication for bone marrow

Methylprednisolone

transplants tulang.5 purpose of giving drugs to reduce morbidity, prevent

Some research suggests that low-dose methylprednisolone 2-4 mg /

complications, and eradication keganasan.5

kg body weight / day, can be used to reduce bleeding and symptoms of

2. Androgen

serum sickness. High-dose methylprednisolone provide good treatment

Androgens are used for the treatment of aplastic anemia since 1960.

response to 40% .Dosis methylprednisolone is 5mg / kg / body weight

The effects of androgen in the management of aplastic anemia to increase

intravenously for 8 days and then proceeded tappering with a dose of 1mg

the production of erythropoietin and stimulates erythroid stem cells. The

/ kg body weight / day for 9-14 days, then tappering during 15-29 day.

use of a single androgen as aplastic anemia therapy did not increase the

Corticosteroid use is limited to the state of antilymphocyte globulin is not

survival rate of patients. Research conducted in the United States, as an

available or too expensive. Side effects include peptic ulcer, edema,

adjunct therapy androgen antitymocyte globulin (ATG) also did not show

hyperglycemia, and osteonekrosis.5

a profit, while research conducted in Europe show the androgens only

antilymphocyte globulin (ALG)

improve hematologic response but did not increase the survival rate.

Antilymphocyte globulin is cytolytic T cells along with siklosponin

Androgen therapy in patients with aplastic anemia who fail to

role in inhibiting T-cell function, particularly in the production of

immunosuppressive therapy may be useful, even dangerous. Androgen

lymphokines lymphokine supresif.4,11,17 rapid administration of ALG

preparations are commonly used are methyl testosterone, testosterone

will reduce lymphocytes circulating that reduced 10%, and when the total

enantate, testosterone propionate, oksimetolon and etiokolanolon. The

lymphocyte count returned to normal means activated T lymphocytes

dose used was 2-5 mg / kg body weight / week, intramuscularly. Dose of

dwindling. ALG preparations in vitro stimulated T cell proliferation and

nandrolone decanoate given 5 mg / kg / week. Side effects that may arise

promotes

from the provision of these androgen preparations such as cholestasis,

antilymphocyte globulin can be administered at a dose of 40 mg / kg body

hepatomegaly, hepatic tumor, masculinization, baldness, and enlargement

weight / day for 12 hours followed by infusion in combination with

the

secretion

of

several

factors

pertumbuhan.4,11,17

methylprednisolone 1 mg / kg body weight / day intravenously for 4 days.

Is a cyclic polypeptide that inhibits humoral immunity, as a specific

Can also be given a dose of 20mg / kg body weight / day for 4-6 hours by

inhibitor of the T lymphocytes, preventing the formation of interleukin-2

intravenous infusion for 8 consecutive days in combination with

and interferon-y. And can inhibit immune reactions such as tissue

prednisone 40mg / m2 / day for 5 days starting on the last day

transplant rejection, GVHD, and others. The initial dose can be

administration of ALG. ALG can cause a feeling of chills, redness,

administered 8 mg / kg body weight / day orally for 14 days followed by a

thrombocytopenia and serum sickness. The success of therapy using a

dose of 15 mg / kg body weight / day in children and 12 mg / kg / day in

single

adults. The dose is then maintained at levels 200-500ug / L to avoid toxic

ALG

approximately

50%

.5

Antitymocyt Globulin (ATG)

effects. If found toxic effects, the therapy is stopped for 1-4 days followed

Antitymocyt Globulin mediation inhibit the immune response by

by a lower dose. Cyclosporine therapy with a single response only about

altering or eliminating the function of T cells reactive cell antigen. The

25%. ATG combination with cyclosporine increases the speed of

administered dose 100-200mg / kg body weight intravenously. ATG

remission

Contraindications

Cyclophosphamide (CPA)

trombositopenia.17

are
state

hypersensitivity

reactions,

study comparing the

leukopenia

system

approximately

70%

.5

between

The use of cyclophosphamide for the treatment of aplastic anemia,

governance with ATG aplastic anemia and bone marrow transplantation

beginning at the time the use of cyclophosphamide in preparation for bone

(TST) reported that in 155 adult patients with aplastic anemia treated with

marrow transplantation tulang.4 Cyclophosphamide (CPA) is a chemical

TST better compared to the use of ATG corresponding single protocol

related to nitrogen mustard. As a CPA alkaline agents involved in cross-

terbaru.18 The European blood and marrow transplant severe aplastic

link DNA may be associated with normal cell growth and neoplasma.17

anemia working party conducted a study on patients with aplastic anemia

Some researchers assert a given therapeutic dose is 50 mg / kg body

is not severe, given immunosuppressant therapy. It was concluded that use

weight / day for 4 consecutive days. But keep in mind that high doses are

of the combination of ATG and cyclosporine A is better than the

given will increase tosik serious effects and therapeutic effects posed no

cyclosporin A single group of hematologic response, quality responses and

better than the kombinasi.20 therapy study conducted on 10 patients with

death awal.5

severe aplastic anemia with CPA 45mg / kg body weight / day for 4 days,

Cyclosporin A (Cs A)

outcome

or

hematopoietic

giving

the

result

is

more

effective

than

other

conventional

immunosuppressant, in terms of improving normal hematopoesis and

prevention of relapse or secondary clonal abnormalities, although without

Bone marrow transplantation is the primary choice in patients with

conducted TST. A study of 19 patients were given CPA at a dose of 50 mg

severe aplastic anemia who had a younger brother with HLA match.

/ kg body weight / day for 4 days showed a high dose CPA therapy without

However, bone marrow transplantation allogenik available only in small

TST make free remission in patients with severe aplastic anemia. This

sebagan patients (only about 30% of patients who have the HLA-matched

study was conducted in patients who can not be done marrow transplant

siblings). The age limit for bone marrow transplantation as primary

tulang.5

therapy has not been ascertained, but the 35-year-old patient who better to

4. The combination drug therapy

receive immunosuppressive therapy due to the increasing age, increasing

A combination of immunosuppressant drugs in the treatment of

as well the incidence and severity of bone marrow donor rejection reaction

patients with aplastic anemia Iebih satisfactory result compared with a

(Graft Versus Host Disesase / GVHD). Patients with age> 40 years proved

single immunosuppressant. Combination ALG, methylprednisolone and

to

cyclosporine A resulted in a partial or total remission of 65%. Another

Patients who receive bone marrow transplants have better survival than

combination between ATG, cyclosporin A and G-CSF is reported to give

patients receiving immunosuppressive therapy. Patients with less than 50

satisfactory hematopoietic response to a decrease in mortality. Research

years of age who fail to immunosuppressive therapy (ATG), the

carried Stephen Rosenfeld et al, with a cohort in 122 patients given 40 mg

administration of a bone marrow transplant can be considered. But the

/ kg body weight / day for 4 days with ATG and 10-12 mg / kg body

survival of patients who received bone marrow transplanasi but it has been

weight / day, cyclosporin A for 6 months and short-term administration of

getting worse immunosuppressive therapy than patients who have not

corticosteroids obtained approximately half and severe aplastic anemia

received

patients have a better recovery time with a satisfactory long-term results.

In patients receiving immunosuppressive therapy are often needed

Recent research that combines ATG with cyclosporine in patients with

transfusions for several months. Transfusion of blood components are as

severe aplastic anemia showed an increase in survival rate of 7 years

far as possible be taken from donors not as a potential bone marrow donor.

satisfactory in 55% of cases. The combination of ATG and CsA is a first-

This is necessary to prevent graft rejection (graft rejection) due to

line immunosuppressive therapy for patients with aplastic anemia berat.5

antibodies formed by tansfusi.

5. Bone marrow transplantation (TST)

have

poorer

response

immunosuppressive

than

younger

therapy

patients.

altogether.

Criteria for treatment response by European groups Marrow


Transplantation (EBMT) is as follows:

- Complete Remission: free transfusion, granulocyte at least 2000 /


mm3

and

mm3.

blood is an alternative which may be a source of stem cells for the TST in

- Remission in part: not dependent on transfusions, granulocytes below

children and adults with major haematological disorders, especially if the

2000

donor and recipient related. TST complication that occurs most frequently

mm3

platelets

and

at

platelets

least

below

100,000

100,000

who underwent TST with a donor unrelated, it was concluded that the cord

mm3.

- Refractory: no improvement.

is GVHD, graft failure and infection. A retrospective study conducted Min

Bone marrow transplant in cases of severe aplastic anemia was first

CK, et al on 40 patients with aplastic anemia who do TST allogeneic

performed in 1970. Unfortunately, only 25-30% of patients receiving

obtained incidence of graft failure, acute GVHD, chronic GVHD

donors are expected. Treatment of aplastic anemia with bone marrow

respectively 22.5%, 12.8% and 23.1%. while 5% of patients had interstitial

transplantation increases the survival rate of about 60-70%. Younger

pneumonia and 2.5% pneumonia.5

patients without recurrent transfusions have a better response around 8595% because the lymphocytes of these patients have not been sensitized by

6. Long-term effects on the treatment of aplastic anemia

prior exposure to antigen. From a study conducted in 1305 patients had

Aplastic anemia treatment either with TST or by the use of

increased 5-year survival rate and 48% 7% in the years 1976-1980 to

immunosuppressants cause long-term effects on patients. Patients who

66% 6% in 1988-1992 (p <0.0001). The risk of graft-versus-host-disease

survive are at risk of malignancy. The incidence of myelodysplasia

(GVHD) and interstitial pneumonia decreased but the risk of tissue

syndromes and acute leukemia is higher than the TST. From the report of

transplant rejection does not. Another study conducted on 212 patients

studies that have been done, the impact of long-term treatment of aplastic

with aplastic anemia showed that TST causes normal hematopoiesis into

anemia are at high risk for the case of solid tumors, myelodysplastic

the causes of morbidity and mortality due to major chronic GVHD. A

syndrome and acute leukemia after treatment TST and imunosupresan.5

study of 6,691 patients who underwent allogeneic TST turned out to


recover a greater possibility, though a few years after TST mortality is
higher than the population normal.5
Difficulty of finding a suitable donor to the patient, can be
overcome by TST derived from cord blood and the study of 78 patients
who received TST cord blood and the donor were related, and 65 patients