Upload
wenny-artha-mulia
View
229
Download
0
Embed Size (px)
Citation preview
8/11/2019 Laporan Tutor Sken 2 Hi
1/37
1
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)
8/11/2019 Laporan Tutor Sken 2 Hi
2/37
8/11/2019 Laporan Tutor Sken 2 Hi
3/37
3
STEP 2
1. What is actually happen with Bimo?
2. How to diagnose ?
3. How to treatment ?
4. Complication ?
5. Differential Diagnose?
8/11/2019 Laporan Tutor Sken 2 Hi
4/37
4
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
8/11/2019 Laporan Tutor Sken 2 Hi
5/37
5
4. Artopati Hemofilia
5. Clasiffication of bleeding disorder
8/11/2019 Laporan Tutor Sken 2 Hi
6/37
6
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.htm8/11/2019 Laporan Tutor Sken 2 Hi
7/37
7
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
8/11/2019 Laporan Tutor Sken 2 Hi
8/37
8
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-blood8/11/2019 Laporan Tutor Sken 2 Hi
9/37
9
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.
8/11/2019 Laporan Tutor Sken 2 Hi
10/37
10
People with severe hemophilia about 60% of the hemophilia population, have
8/11/2019 Laporan Tutor Sken 2 Hi
11/37
11
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.
8/11/2019 Laporan Tutor Sken 2 Hi
12/37
12
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
8/11/2019 Laporan Tutor Sken 2 Hi
13/37
13
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.htm8/11/2019 Laporan Tutor Sken 2 Hi
14/37
14
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.
8/11/2019 Laporan Tutor Sken 2 Hi
15/37
15
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
8/11/2019 Laporan Tutor Sken 2 Hi
16/37
16
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/haemophilia8/11/2019 Laporan Tutor Sken 2 Hi
17/37
17
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/haemosiderosis8/11/2019 Laporan Tutor Sken 2 Hi
18/37
18
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-arthropathy8/11/2019 Laporan Tutor Sken 2 Hi
19/37
8/11/2019 Laporan Tutor Sken 2 Hi
20/37
20
- 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
8/11/2019 Laporan Tutor Sken 2 Hi
21/37
21
STEP 5
1. Hemostasis ?
2.
Trombositopenia and Trombosis ?
3. Coagulation disorder beside hemophilia ?
8/11/2019 Laporan Tutor Sken 2 Hi
22/37
22
STEP 6
BELAJAR DIRUMAH
8/11/2019 Laporan Tutor Sken 2 Hi
23/37
23
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
http://www.medicinenet.com/script/main/art.asp?articlekey=4941http://www.medicinenet.com/script/main/art.asp?articlekey=2502http://www.medicinenet.com/script/main/art.asp?articlekey=2502http://www.medicinenet.com/script/main/art.asp?articlekey=5260http://www.medicinenet.com/script/main/art.asp?articlekey=5531http://www.medicinenet.com/script/main/art.asp?articlekey=9939http://www.medicinenet.com/script/main/art.asp?articlekey=9939http://www.medicinenet.com/script/main/art.asp?articlekey=85652http://www.medicinenet.com/script/main/art.asp?articlekey=85652http://www.medicinenet.com/script/main/art.asp?articlekey=9939http://www.medicinenet.com/script/main/art.asp?articlekey=9939http://www.medicinenet.com/script/main/art.asp?articlekey=5531http://www.medicinenet.com/script/main/art.asp?articlekey=5260http://www.medicinenet.com/script/main/art.asp?articlekey=2502http://www.medicinenet.com/script/main/art.asp?articlekey=2502http://www.medicinenet.com/script/main/art.asp?articlekey=49418/11/2019 Laporan Tutor Sken 2 Hi
24/37
24
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.
http://www.medicinenet.com/script/main/art.asp?articlekey=15839http://www.medicinenet.com/script/main/art.asp?articlekey=158398/11/2019 Laporan Tutor Sken 2 Hi
25/37
8/11/2019 Laporan Tutor Sken 2 Hi
26/37
26
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/8/11/2019 Laporan Tutor Sken 2 Hi
27/37
8/11/2019 Laporan Tutor Sken 2 Hi
28/37
28
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.
8/11/2019 Laporan Tutor Sken 2 Hi
29/37
29
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)
8/11/2019 Laporan Tutor Sken 2 Hi
30/37
30
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.
8/11/2019 Laporan Tutor Sken 2 Hi
31/37
31
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
8/11/2019 Laporan Tutor Sken 2 Hi
32/37
32
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
8/11/2019 Laporan Tutor Sken 2 Hi
33/37
33
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
8/11/2019 Laporan Tutor Sken 2 Hi
34/37
34
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
8/11/2019 Laporan Tutor Sken 2 Hi
35/37
35
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/8/11/2019 Laporan Tutor Sken 2 Hi
36/37
36
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.
8/11/2019 Laporan Tutor Sken 2 Hi
37/37
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