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8/11/2019 Laporan Tutor Sken 2 Hi

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Scenario 2

Bleeding in Tooth Expulsion

Bimo, 9 years old, accompanied by his mother to put off his tooth. After expulsion, the blood is

not stopping. Then, Bimo is taken care in the hospital to observe the bleeding. When he learned

to walk, Bimo often got knee swelling if he felt down, also he easily got bruise when he got

minor trauma. His uncle also have similar condition. In physical examination theres no

organomegaly found. The laboratory findings result that aPTT 80 second (refferal score 31-47

second) and platelet count 200.000/L (referral score 150.000-400.000/L)


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STEP 2

1. What is actually happen with Bimo?

2. How to diagnose ?

3. How to treatment ?

4. Complication ?

5. Differential Diagnose?


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STEP 3

1. Hemophilia is a bleeding disorder that slows the blood clotting process. People with this

condition experience prolonged bleeding or oozing following an injury, surgery, or having a

tooth pulled. In severe cases of hemophilia, continuous bleeding occurs after minor trauma or

even in the absence of injury (spontaneous bleeding). Serious complications can result from

bleeding into the joints, muscles, brain, or other internal organs. Milder forms of hemophilia

do not necessarily involve spontaneous bleeding, and the condition may not become apparent

until abnormal bleeding occurs following surgery or a serious injury.

The major types of this condition are

A. Hemophilia A (also known as classic hemophilia or factor VIII deficiency)

B. hemophilia B (also known as Christmas disease or factor IX deficiency).

Although the two types have very similar signs and symptoms, they are caused by

mutations in different genes. People with an unusual form of hemophilia B, known as

hemophilia B Leyden, experience episodes of excessive bleeding in childhood but have

few bleeding problems after puberty.

2. Anamnesis

- Physical examination

- Laboratorium examination

3. Suportif treatment

- Alternate coagulation treatment


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4. Artopati Hemofilia

5. Clasiffication of bleeding disorder


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STEP 4

1. Hemophilia is a rare hereditary (inherited) bleeding disorder in which blood cannot clot

normally at the site of a wound or injury. The disorder occurs because certain blood clotting

factors are missing or do not work properly. This can cause extended bleeding from a cut or

wound. Spontaneous internal bleeding can occur as well, especially in the joints and muscles.

Hemophilia affects males much more often than females.

There are two types of inherited hemophilia:

1. Hemphilia A , the most common type, is caused by a deficiency of factor VIII, one of the

proteins that helps blood to form clots.

Hemophilia A is caused by an inherited X-linked recessive trait, with the defective gene

located on the X chromosome. Females have two copies of the X chromosome, so if the

factor VIII gene on one chromosome doesn't work, the gene on the other chromosome

can do the job of making enough factor VIII. Males, however, have only one X

chromosome, so if the factor VIII gene on that chromosome is defective, they will have

hemophilia A. Thus, most people with hemophilia A are male.

If a woman has a defective factor VIII gene, she is considered a carrier. This means the

defective gene can be passed down to her children. In a woman who carries the defective

gene, any of her male children will have a 50% chance of having hemophilia A, while

any of her female children will have a 50% chance of being a carrier. All female children
http://www.nlm.nih.gov/medlineplus/ency/article/002051.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/002051.htm


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of men with hemophilia carry the defective gene. Genetic testing is available for

concerned parents.

Risk factors for hemophilia A include:

Family history of bleeding

Being male

Rarely, adults can develop a bleeding disorder similar to hemophilia A. This may happen

after giving birth (postpartum), in people with certain autoimmune diseases such as

rheumatoid arthritis, in people with certain types of cancer (most commonly lymphomas

and leukemias), and also for unknown reasons (called "idiopathic"). Although these

situations are rare, they can be associated with serious, even life-threatening bleeding.

Clinical Classification of Hemophilia A

Severity Factor Level

Mild > 5% to 35% of normal

Moderate 1% to 5% of normal

Severe < 1% of normal


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2. Hemophilia B hemophilia is caused by a deficiency of factor IX. Hemophilia B is a rare

genetic bleeding disorder in which affected individuals have insufficient levels of a blood

protein called factor IX. Factor IX is a clotting factor. Clotting factors are specialized

proteins that are essential for clotting, the process by which blood clumps together to

plug the site of a wound to stop bleeding. Individuals with hemophilia B do not bleed

faster or more profusely than healthy individuals, but, because their blood clots poorly,

they have difficulty stopping the flow of blood from a wound. This may be referred to as

prolonged bleeding or a prolonged bleeding episode. Hemophilia B can be mild,

moderate or severe. In mild cases, prolonged bleeding episodes may only occur aftersurgery or dental procedures. In more severely affected individuals, symptoms may

include prolonged bleeding from minor wounds, painful swollen bruises, and unexplained

(spontaneous) bleeding into vital organs as well as joints and muscles . Hemophilia B is

caused by disruptions or changes (mutations) to the F9 gene on the X chromosome. The

disorder is almost always fully expressed in males only, although some females who

carry the gene may have mild or ,rarely, severe symptoms of bleeding. Hemophilia B is

also known as factor IX deficiency or Christmas disease.

Hemophilia B is the second most common type of hemophilia. It can also be known as

factor IX deficiency, or Christmas disease. It was originally named Christmas disease

for the first person diagnosed with the disorder back in 1952.

It is largely an inherited disorder in which one of the proteins needed to form blood clots

is missing or reduced. In about 30% of cases, there is no family history of the disorder

and the condition is the result of a spontaneous gene mutation.
http://www.webmd.com/heart/anatomy-picture-of-bloodhttp://www.webmd.com/drugs/drug-1081-coagulation+factor+ix+iv.aspxhttp://www.webmd.com/a-to-z-guides/blood-clotshttp://www.webmd.com/skin-problems-and-treatments/guide/bruises-articlehttp://www.webmd.com/skin-problems-and-treatments/guide/bruises-articlehttp://www.webmd.com/a-to-z-guides/blood-clotshttp://www.webmd.com/drugs/drug-1081-coagulation+factor+ix+iv.aspxhttp://www.webmd.com/heart/anatomy-picture-of-blood


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Hemophilia B is far less common than Hemophilia A. Occurring in about one in 25,000

male births, hemophilia B affects about 3,300 individuals in the United States. All races

and economic groups are affected equally.

When a person with hemophilia is injured, he does not bleed harder or faster than a

person without hemophilia, he bleeds longer. Small cuts or surface bruises are usually not

a problem, but more traumatic injuries may result in serious problems and potential

disability (called "bleeding episodes").

Normal plasma levels of FIX range from 50% to 150%. There are different levels ofhemophilia: mild, moderate, and severe, depending on the amount of clotting factor in the

blood:

People with mild hemophilia have 5% up to 50% of the normal clotting factor in

their blood. Most patients usually have problems with bleeding only after serious

injury, trauma or surgery. In many cases, mild hemophilia is not diagnosed until aninjury, surgery or tooth extraction results in prolonged bleeding. The first episode

may not occur until adulthood. Women with mild hemophilia often experience

menorrhagia, heavy menstrual periods, and can hemorrhage after childbirth.

People with moderate hemophilia about, 15% of the hemophilia population, have 1%

up to 5% of the normal clotting factor in their blood. They tend to have bleeding

episodes after injuries and some without obvious cause. These are called spontaneous

bleeding episodes.


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People with severe hemophilia about 60% of the hemophilia population, have


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The symptoms of hemophilia vary depending on whether the person has the mild, moderate,

or severe form of the disorder. For people with severe hemophilia, bleeding episodes occur

more often and with little provocation. Sometimes, bleeding begins for no apparent reason.

For those with moderate hemophilia, prolonged bleeding tends to occur after a more

significant injury. People with the mild form of hemophilia might have unusual bleeding only

after a major injury, surgery, or trauma.

People with hemophilia may also have internal bleeding (inside the body), especially in the

muscles and joints, such as the elbows, knees, hips, shoulders, and ankles. Often there is no

pain at first, but if it continues, the joint may become hot to the touch, swollen, and painful to

move. Continued bleeding into the joints and muscles can cause permanent damage, such as

joint deformity and reduced mobility (ability to get around).

Bleeding in the brain is a very serious problem for those with severe hemophilia, and may be

life-threatening. Signs of bleeding in the brain may include changes in behavior, excessive

sleepiness, persistent headaches and neck pain, double vision, vomiting, and convulsions or

seizures.

Severely affected hemophilic patients with less than 1% of normal levels of factor VIII or IX

have severe and often unprovoked (spontaneous) bleeding, with joint hemorrhage being

especially prominent in the knees, elbows, ankles, shoulders, wrists, and hips, in decreasing

order of frequency. There is some overlap between severe and moderate hemophilia when the

latter is about 1% of normal; however, at 5% of normal, bleeding, including hemarthroses,

usually occurs only with trauma. Mildly affected patients have very few hemorrhagic

episodes, which are almost always precipitated by trauma or surgery.


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Soft tissue bleeding is common in patients with severe hemophilia, with bleeding in skeletal

muscle being most common, and hemorrhage into the central nervous system (CNS) or

retroperitoneum and around or into vital organs being most dangerous. Bleeding around the

airway, for example, can lead to asphyxiation unless treated promptly. Two areas that do not

seem prone to excessive bleeding are the myocardium and the phallus .[3]

2. A doctor will perform a physical examination to rule out other conditions. If you have

symptoms of hemophilia, the doctor will obtain information about your familys medicalhistory, since this disorder tends to run in families.

Blood tests are then performed to determine how much factor VIII or factor IX is present in

your blood. These tests will show which type of hemophilia you have, and whether it is mild,

moderate, or severe, depending on the level of clotting factors in the blood:

People who have 5-30% of the normal amount of clotting factors in their blood have mild

hemophilia.

People with 1-5% of the normal level of clotting factors have moderate hemophilia.

People with less than 1% of the normal clotting factors have severe hemophilia

The diagnosis of hemophilia A is established by measuring the level of plasma factor VIII

activity by using a one-stage or chromogenic assay. The latter assay is considered by some to

be more accurate, but it is less widely available in clinical laboratories in the United States .[1]

The "normal" range of factor VIII in our clinical coagulation laboratory is from 54% to


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161%, but the median value is about 100% 5%. Carriers of hemophilia A have about 50%

levels of factor VIII.

Hemophilia B is established by measuring the level of factor IX using a chromogenic or one-

stage assay; the range of normal in our laboratory is from 44% to 139%, but the median

levels are 100% 5% .[2] Carriers of hemophilia B have about 50% levels of this factor on

average.

The broad range of normal levels is due to laboratory variations, inflammation, liver

dysfunction, and probably genetic factors. Repeat measurements of either factor VIII or IXshould be performed to get a true estimate of the levels of each factor. Carriers of hemophilia

A and B may be symptomatic when factor VIII or IX levels are below 50%, which may occur

as a result of extreme lyonization.

Laboratorium examination :

Low serum factor VIII activity

Normal prothrombin time

Normal bleeding time

Normal fibrinogen level

Prolonged partial thromboplastin time (PTT)

PT

APTT

CT

Darah lengkap
http://www.nlm.nih.gov/medlineplus/ency/article/003678.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003652.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003656.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003650.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003653.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003653.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003650.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003656.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003652.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/003678.htm


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3. Suportif treatment

a. Avoid the injury

b. Avoid bleeding acut

- Rest

- Compress ice

- Elevate bleeding area

c. Kortikostreoid

- Prednisone 0,5 mg 1 mg

d.

Analgetik ,except aspirin

The treatment will depend on the type and severity of the disorder. The treatment is usually

replacement therapy, in which concentrates of the clotting factors VIII or IX are given as

needed to replace the blood clotting factors that are missing or deficient. These blood factor

concentrates can be made from donated human blood that has been treated and screened to

reduce the risk of transmitting infectious diseases, such as hepatitis and HIV. Recombinantclotting factors, which are not made from human blood, are also available to further reduce

the risk of infectious disease.

During replacement therapy, the clotting factors are injected or infused (dripped) into a

patients vein. Usually, people with mild hemophilia do not require replaceme nt therapy

unless they are going to have surgery. In cases of severe hemophilia, treatment may be given

as needed to stop bleeding when it occurs. Patients who have very frequent bleeding episodes

may be candidates for prophylactic factor infusions; that is, infusions given two or three

times per week to prevent bleeding from occurring.


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People with severe hemophilia are more likely to experience serious bleeding problems,

including bleeding. Replacement therapy can reduce or prevent joint or muscle damage

caused by internal bleeding.

Alternate coagulation treatment

Some people with the mild or moderate form of hemophilia type A can be treated with

desmopressin (DDAVP), a synthetic (man-made) hormone that helps to stimulate the release

of factor VIII and another blood factor that carries and binds to it. Sometimes DDAVP is

given as a preventive measure before a person with hemophilia has dental work or

participates in sports. DDAVP is not effective for people with type B hemophilia or severe

hemophilia type A.

Hemophilia is at least 2 distinct diseases -- namely, hemophilia A (classic hemophilia or

factor VIII deficiency) and hemophilia B (Christmas disease or factor IX deficiency). Each

results from mutations at the factor VIII or IX loci on the X chromosome, and each occurs in

mild, moderate, and severe forms. A similar level of deficiency of factor VIII or IX results in

clinically indistinguishable disease because the end result is deficient activation of factor X

by the factor Xase complex (FVIIIa/FIXa/calcium and phospholipid).

Other blood clotting factor deficiencies can be similar to hemophilia A and B as far as

bleeding symptoms are concerned, but these disorders are secondary to mutations at specific

loci on autosomal chromosomes. They are usually referred to more specifically as factor II

(hypoprothrombinemia), V, VII, X, and XI deficiency, afibrinogenemia, and


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dysfibrinogenemia, or as "hemophilioid" disorders. For purposes of this report, the term

"hemophilia" will be limited to a discussion of factor VIII and IX deficiency.

Treatment of hemophilia requires factor VIII or factor IX intravenous replacement therapy.

The exception is that hemostasis in some patients with mild hemophilia A may be managed

using desmopressin acetate (DDAVP) if they have been demonstrated to respond to this

agent. Purified concentrates of factor VIII and IX can be obtained either from human plasma

or by recombinant techniques and are considered to be safe and effective.

4.

Haemophilic arthropathy refers to permanent joint disease occurring in haemophiliasufferers as a long-term consequence of repeated haemarthrosis. Around 50% of patients

with haemophilia will develop a severe arthropathy. 1

Epidemiology

Haemophilia is an x-linked recessive disease affecting males. Haemarthroses may be

spontaneous or result from minor trauma and typically first occurs before the age of two

and continues to occur into adolescence. It is usual for the same joint to be involved

repeatedly. In adulthood haemarthroses are uncommon, however proliferative chronically

inflamed synovium results in the development of haemophilic arthopathy

Distribution

Haemophilic arthropathy is often monoarticular or oligoarticular. Large joints are most

commonly involved in the following order of frequency: 2

knee
http://radiopaedia.org/articles/haemophiliahttp://radiopaedia.org/articles/haemophilia


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elbow

ankle

hip

shoulder

Pathology

There is synovial hyperplasia, chronic inflammation, fibrosis, and haemosiderosis. The

synovium mass erodes cartilage and subchondral bone leading to subarticular cyst

formation.3

Radiographic featur es

Plain film

symmetrical loss of joint cartilage involving all compartments equally

periarticular erosions and subchondral cysts

periarticular osteoporosis : from hyperaemia

epiphyseal enlargement : from hyperaemia

osteophytosis and sclerosis : due to secondary degenerative disease

appearances can be similar to juvenile rheumatoid arthritis

joint effusion seen in setting of haemarthrosis

knee 3

o widened intercondylar notch

o squared inferior margin of the patella

o bulbous femoral condyles
http://radiopaedia.org/articles/haemosiderosishttp://radiopaedia.org/articles/missing?article%5Btitle%5D=juvenile+rheumatoid+arthritishttp://radiopaedia.org/articles/missing?article%5Btitle%5D=juvenile+rheumatoid+arthritishttp://radiopaedia.org/articles/haemosiderosis


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o flattened condylar surfaces

o Arnold-Hilgartner classification 4

elbow 2

o enlarged radial head

o widened trochlear notch

ankle 1

o talar tilt : relative undergrowth of the lateral side of the tibial epiphysis leads to a

pronated foot

MRI

good for detection of early disease

thickened synovium with low signal due to haemosiderin susceptibility effect :

siderotic synovitis

enhancing synovium due to synovitis

joint effusion

cartilage loss and erosions can be well seen

Nuclear medicine

bone scan

o sensitive for detecting areas of disease over entire skeleton

o follow-up scans can monitor treatment response

radiosynoviorthes
http://radiopaedia.org/articles/arnold-hilgartner-classification-haemophilic-arthropathyhttp://radiopaedia.org/articles/siderotic-synovitishttp://radiopaedia.org/articles/siderotic-synovitishttp://radiopaedia.org/articles/arnold-hilgartner-classification-haemophilic-arthropathy


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- Myeloma

- Polisitemia

b. Herediter

- Von willebrand disease

3. Coagulation disordes

a. Herediter :

- Rare disorders

b.

Adapted :- Defisiensi vitamin k

- DIC

- Liver disease

- Drug induced

4. Vascular disorders

a. Defisiensi vitamin c

b. Paraproteinemia

c. Aging


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STEP 5

1. Hemostasis ?

2.

Trombositopenia and Trombosis ?

3. Coagulation disorder beside hemophilia ?


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STEP 6

BELAJAR DIRUMAH


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STEP 7

1. Trombocitopenia

Thrombocytopenia is a lower than normal number of platelets in the blood.

Platelets are one of the components of the blood along with white and red blood cells.

Platelets play an important role in clotting and bleeding. Platelets are made in the bone

marrow similar to other cells in the blood such as, white blood cells and red blood cells.

Platelets originate from megakaryocytes which are large cells found in the bone marrow. The

fragments of these megakaryocytes are platelets that are released into the blood stream. The

circulating platelets make up about two third of the platelets that are released from the bone

marrow. The other one third is typically stored (sequestered) in the spleen.

Platelets, in general, have a brief 7 to 10 days life in the blood, after which they are removed

from the blood circulation. The number of platelets in the blood is referred to as the platelet

count and is normally between 150,000 to 450,000 per micro liter (one millionth of a liter) of

blood. Platelet counts less than 150,000 are termed thrombocytopenia. Platelet counts greater

that 450,000 are called thrombocytosis.

The function of platelets is very important in the clotting system. Platelets are a part of a very

complicated pathway. They circulate in the blood vessels and become activated if there is

any bleeding or injury in the body. Certain chemicals are released from the injured blood

vessels or other structures that signal platelets to become activated and join the other

components of the system to stop the bleeding. When activated, the platelets become sticky
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and adhere to one another and to the blood vessel wall at the site of the injury to slow down

and stop the bleeding by plugging up the damaged blood vessel or tissue (hemostasis) .

It is important to note that, even though, the platelet numbers are decreased in

thrombocytopenia, their function usually remains completely intact. Other disorders exist that

can cause impaired platelet function despite normal platelet count.

Low platelet count in severe cases may result in spontaneous bleeding or may cause delay in

the normal process of clotting. In mild thrombocytopenia, there may be no adverse effects in

the clotting or bleeding pathways.

If for any reason your blood platelet count falls below normal, the condition is called

thrombocytopenia. Normally, you have anywhere from 150,000 to 450,000 platelets per

microliter of circulating blood. Because each platelet lives only about 10 days, your body

continually renews your platelet supply by producing new platelets in your bone marrow.

Thrombocytopenia has many possible causes.

1. Trapping of platelets in the spleen

The spleen is a small organ about the size of your fist located just below your rib cage

on the left side of your abdomen. Normally, your spleen works to fight infection and

filter unwanted material from your blood. An enlarged spleen which can be caused

by a number of disorders may harbor too many platelets, causing a decrease in the

number of platelets in circulation.
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Thrombotic thrombocytopenic purpura (TTP). TTP is a rare condition that

occurs when small blood clots suddenly form throughout your body, using up large

numbers of platelets.

Hemolytic uremic syndrome. This rare disorder causes a sharp drop in platelets,

destruction of red blood cells and impairment of kidney function. Sometimes it can

occur in association with a bacterial Escherichia coli (E. coli) infection, such as

may be acquired from eating raw or undercooked meat.

Medications. Certain medications can reduce the number of platelets in your

blood by confusing the immune system and causing it to destroy platelets.Examples include heparin, quinidine, quinine, sulfa-containing antibiotics,

interferon, anticonvulsants and gold salts

Thrombocytosis

This condition occurs if another disease, condition, or outside factor causes the platelet count

to rise. For example, 35 percent of people who have high platelet counts also have cancer

mostly lung, gastrointestinal, breast, ovarian, and lymphoma. Sometimes a high platelet

count is the first sign of cancer.

Other conditions or factors that can cause a high platelet count are:

Iron-deficiency anemia (uh-NEE-me-uh)

Hemolytic (HEE-moh-lit-ick) anemia

Absence of a spleen (after surgery to remove the organ)
http://www.nhlbi.nih.gov/health/health-topics/topics/ida/http://www.nhlbi.nih.gov/health/health-topics/topics/ha/http://www.nhlbi.nih.gov/health/health-topics/topics/ha/http://www.nhlbi.nih.gov/health/health-topics/topics/ida/


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Hemostasi have 3 steps :

I. Vascular phase - Cutting or damaging blood vessels leads to vascular spasm of the smooth

muscle in the vessel wall. This produces a vasoconstriction which will slow or even stop

blood flow. This response will last up to 30 minutes and is localized to the damaged area.

II. Platelet phase - Damaged endothelial cells lining the blood vessel release von

Willebrand's Factor. This substance makes the surfaces of the endothelial cells "sticky".

This condition may, by itself, be enough to close small blood vessels. In larger blood

vessels, platelets begin to stick to the surfaces of endothelial cells. This effect is calledPlatelet Adhesion.

The platelets that adhere to the vessel walls now begin to secrete Adenosine diphosphate

(ADP) which is released from "stuck" platelets. This material causes the aggregation of

nearby free platelets which attach to the fixed platelets and each other. Thisaggregation of

platelets leads to the formation of a platelet plug.

This clumping of platelets serves a number of functions:

1. It can plug the break in a small blood vessel.

2. Aggregated platelets release Platelet Thromboplastin (Factor III) which activates the

clotting process.

3. Clumped platelets provide a surface essential for the clotting process.Along with ADP,

the clumped platelets secrete thromboxane, a powerful vasoconstrictor.


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III. Coagulation Phase - Begins 30 seconds to several minutes after phases I and II have

commenced.

A. The overall process involves the formation of the insoluble protein Fibrin from the

plasma protein Fibrinogen through the action of the enzyme Thrombin. Fibrin forms

a network of fibers which traps blood cells and platelets forming a thrombus or clot.

B. This process depends on the presence in the blood of 11 different clotting factors

(proteins) and calcium (Factor IV). Ultimately, these factors will generate the

production of Prothrombin Activator (Factor X). Depending on the initial trigger forthe clotting reactions, there are two pathways leading to the formation of the

thrombus; the Extrinsic Pathway and the Intrinsic Pathway.

Extrinsic Pathway - Is initiated with material outside of or "extrinsic" to the blood.

This material, Tissue Thromboplastin (Factor III), is released by damaged tissue cells.

Factor III permits the clotting process to take a chemical shortcut. As a result, theextrinsic pathway is a very rapid process, i.e., within 12 to 15 seconds. However, the

production of Thrombin is low and the resulting clot is small. This pathway is most

effective as a "quick patch" process.

1. Damaged tissue releases Tissue Thromboplastin (Factor III).

2. Tissue Thromboplastin activates Factor VII (Calcium dependent step).

3. Factor VII activates Factor X - Prothrombin Activator (Calcium dependent step)


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Intrinsic Pathway - Is initiated by the blood coming in contact with exposed

collagen in the blood vessel wall, i.e., material within the blood or blood vessel wall.

This process is considerably slower (5 to 10 minutes) but results in the formation of

larger amounts of thrombin. This allows the formation of larger clots.

1. Factor XII is activated by making contact with exposed collagen underlying the

endothelium in the blood vessel wall.

2. Factor XII activates Factor XI.

3. Factors XII and XI (contact activation product) jointly activate Factor IX.

4. Factor IX activates Factor VIII.

5. Factor VIII together with Calcium ions and Factor III from platelets (Platelet

Thromboplastin) activate Factor X - Prothrombin Activator. Since Factor III is

released from activated platelets, the completion of the Intrinsic Pathway depends onthere being an adequate number of platelets in circulation.

It should be noted that both pathways lead to the same reaction, namely, the

activation of Factor X - Prothrombin Activator. From this point on, both pathways

follow the same course to Fibrin formation. For this reason the steps from Factor X

activation to Fibrin formation are referred to as the Common Pathway.


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Common Pathway

1. Factor X (active) engages in a series of reactions with Factor V, Calcium ions

and phospholipids derived from platelets. This composite of clotting factors and

their reactions is referred to as the Factor V Complex or Prothrombin Activator.

2. Factor V Complex initiates the conversion of Prothrombin to active form of the

enzyme Thrombin.

3. Thrombin accelerates the formation of Fibrin threads from Fibrinogen (Factor I).

FACTOR NAME SOURCE PATHWAY

I Fibrinogen Liver Common

II Prothrombin (enzyme) Liver * Common

III Thromboplastin Released by

damaged cellsExtrinsic

III Thromboplastin Released by platelets Intrinsic

IV Calcium ions Bone and gut Entire process

VProaccererin

(heat labile cofactor)

Liver and PlateletsExtrinsic and

Intrinsic

VII Proconvertin (enzyme) Liver * Extrinsic

VIII Anti-hemolytic Platelets and Intrinsic


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factor(cofactor) endothelium

IX

Christmas factor(plasma

thromboplastin component) Liver * Intrinsic

XStuart Prower factor

(enzyme)Liver *

Extrinsic and

Intrinsic

XIPlasma thromboplastin

antecedent (enzyme)Liver Intrinsic

XII Hageman factor LiverIntrinsic; also

activates plasmin

XIIIFibrin stabilizing factor

Liver Retards fibrinolysis

*vitamin K dependent

IV. Clot Retraction - After 2 or 3 days, the clot begins to contract. Platelets in the clot

contain contractile proteins. These proteins pull the edges of the wound together

and reduces the chance of further hemorrhage. This activity also assists the repair

processes.

V. Fibrinolysis - Dissolution of the clot. The breakdown of the clot is due to the

production of a powerful proteolytic enzyme Plasmin. Plasmin is formed through

the same chemical pathway that produces thrombin. These reactions demonstrate


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that materials which induce clot formation (Thrombin and Factor XII) will

eventually assist in the breakup of the clot.

ANTICOAGULANT COMPONENTS OF HEMOSTASIS

1. Smooth, intact endothelium - an undamaged endothelial lining prevents the

initiation of hemostasis.

2. Thrombin adsorption to fibrin - 9O% of thrombin formed during hemostasis is

adsorbed to fibrin preventing the diffusion of thrombin to surrounding areas.

3. Heparin - released from mast cells (tissue basophils) inactivates thrombin.

4. Activated thrombin - stimulates endothelial cells to release a prostaglandin,

prostacyclin. Prostacyclin prevents adherence of platelets to surrounding,

uninjured endothelial cells, inhibits

the aggregation of platelets and produces vasodilation.

5. Fibrinolytic system - is turned on as a direct outcome of the clotting process.

Hageman factor (XII) activates plasminogen forming the fibrin digesting enzyme

plasmin.

3. a. DIC is widespread intravascular activation of the coagulation system ("runaway

hemostasis") caused by a disruption in the intricate control mechanisms of hemostasis. DIC

is not a specific disease, but the sequelae of many pathologic conditions with various

effects on the hemostatic system (See Table). These conditions lead to release of

proinflammatory cytokines, uncontrolled thrombin generation, widespread microvascular


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thrombosis, impairment of anticoagulant pathways, activation or impairment of the

fibrinolytic system, and other effects. Tissue damage and the deposition of fibrin also result

in the release and activation of plasminogen activators and the generation of plasmin in

amounts that overwhelm its inhibitor, (antiplasmin). Plasmin degrades factors VIII, V, and

I and produces fibrin/fibrinogen degradation products. These substances, as well as the

products of incompletely polymerized fibrin, impair platelet function and normal fibrin

polymerization. Microvascular thrombosis leads to tissue ischemia, necrosis, and organ

dysfunction, and the release of tissue factor, which further accelerates the process. In acute

DIC, the consumption of platelets and clotting factors occurs more rapidly than they can bereplenished and bleeding results. The bleeding can be severe or even fatal. Chronic DIC

(compensated DIC, nonovert DIC ) occurs when time or int ensity of the trigger

mechanism is such that the the regulatory mechanisms of coagulation are able to control

systemic activation of coagulation, and the liver and bone marrow are able replace the

missing coagulation factors and platelets.

The following table lists the pathogenic mechanism of DIC in different diseases.

Diseasem and DIC Pathogenic Factors

Tissue damage, trauma

Release of thromboplastic substances with activation of extrinsic coagulation pathway.

Increased proinflammatory cytokines with TF-mediated coagulation activation,suppression of anticoagulation, and PAI-1mediated inhibition of fibrinolysis.

Shock


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Decreased blood flow with loss of hemodilution. Ischemia and multiple organ failure.

Acute leukemia

Tumor cell-related factors with procoagulant and fibrinolytic properties, cytokine

release by leukemia cells, effect of chemotherapy, infectious complications.

b. Von Willebrand disease (VWD) is a bleeding disorder. It affects your blood's ability to

clot. If your blood doesn't clot, you can have heavy, hard-to-stop bleeding after an injury.

The bleeding can damage your internal organs. Rarely, the bleeding may even cause

death.

In VWD, you either have low levels of a certain protein in your blood or the protein

doesn't work well. The protein is called von Willebrand factor, and it helps your blood

clot.

Normally, when one of your blood vessels is injured, you start to bleed. Small blood cellfragments called platelets (PLATE-lets) clump together to plug the hole in the blood

vessel and stop the bleeding. Von Willebrand factor acts like glue to help the platelets

stick together and form a blood clot.

Von Willebrand factor also carries clotting factor VIII (8), another important protein that

helps your blood clot. Factor VIII is the protein that's missing or doesn't work well in

people who have hemophilia, another bleeding disorder.
http://www.nhlbi.nih.gov/health/health-topics/topics/hemophilia/http://www.nhlbi.nih.gov/health/health-topics/topics/hemophilia/


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VWD is more common and usually milder than hemophilia. In fact, VWD is the most

common inherited bleeding disorder. It occurs in about 1 out of every 100 to 1,000

people. VWD affects both males and females, while hemophilia mainly affects males.

The three major types of VWD are called type 1, type 2, and type 3.

Type 1

People who have type 1 VWD have low levels of von Willebrand factor and may have

low levels of factor VIII. Type 1 is the mildest and most common form of VWD.

About 3 out of 4 people who have VWD have type 1.

Type 2

In type 2 VWD, the von Willebrand factor doesn't work well. Type 2 is divided into

subtypes: 2A, 2B, 2M, and 2N. Different gene mutations (changes) cause each type,

and each is treated differently. Thus, it's important to know the exact type of VWD

that you have.

Type 3

People who have type 3 VWD usually have no von Willebrand factor and low levelsof factor VIII. Type 3 is the most serious form of VWD, but it's very rare.


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REFERENCE

Hematologi onkologi anak. Cetakan ke 3. Balai penerbit IDAI. 201

Hoffbrand A.V. Pettit J.E. Moss P.A.H. Kapita selekta hematologi. Ed 4. Jakarta: EGC.

2005. P 245-9

Niemann KMW. Diseases Related to The Hemotopoietic System. In : Lovell WW,

Winter RB, Eds. Pediatric Orthopaedics; 2nd ed. Philadelphia : J.B. Lippincott, 1986; 195

211

Sudoyo AW, Setiyohadi B, Alwi I, Simadibrata M, Setiati S. Buku Ajar Ilmu Penyakit

Dalam Edisi IV 2006, Pusat Penerbitan Departemen Ilmu Penyakit Dalam Fakultas

Kedokteran Universitas Indonesia, Jakarta

laporan tutor sken 2 hi

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