Idiopathic

Thrombocytopenic Purpura

(ITP)

Dr yogendra vijay

RESIDENT DOCTOR ,BLOOD TRANSEFUSION AND IMUNOHAEMATOLOGY

SMS MEDICAL COLLAGE ,JAIPUR RAJASTHAN

(druogendravijay23@gmail.com)

Idiopathic thrombocytopenic

purpura (ITP),

immune thrombocytopenia,

primary immune thrombocytopenia,

primary immune thrombocytopenic

purpura

autoimmune thrombocytopenic

purpura

Idiopathic thrombocytopenic purpura is a blood

disorder characterized by an abnormal decrease

in the number of platelets in the blood. can

result in easy bruising, bleeding gums and internal

bleeding.

"Idiopathic" means the cause is unknown.

"Thrombocytopenia" means a decreased number

of platelets in the blood.

"Purpura" refers to the purple discoloring of the

skin, as with a bruise.

There are two forms of ITP:

Acute thrombocytopenic purpura — This is most commonly seen in

young children (2 to 6 years old). The symptoms may follow a viral

illness, such as chickenpox. Acute ITP usually has a very sudden onset

and the symptoms usually disappear in less than six months (often

within a few weeks). The disorder usually does not recur. Acute ITP is

the most common form of the disorder.

Chronic thrombocytopenic purpura — The onset of the disorder can

happen at any age, and the symptoms can last a minimum of six months

to several years. Adults have this form more often than children, but it

does affect adolescents. Chronic ITP can recur often and requires

continual follow-up care with a blood specialist .

pathophysiology

In approximately 60 percent of cases, antibodies against platelets can be detected.

Most often these are membrane glycoproteins IIb-IIIa or Ib-IX, and are of the (IgG)

type.

The coating of platelets with IgG renders them susceptible

to opsonization and phagocytosis by splenic macrophages, as well by Kupffer cells in

the liver

. The IgG autoantibodies are also thought to damage megakaryocytes, the precursor

cells to platelets,

Recent research now indicates that impaired production of

the hormone thrombopoietin, which is the stimulant for platelet production, may be a

contributing factor to the reduction in circulating platelets.

The stimulus for auto-antibody production in ITP is probably abnormal T

cell activity. Preliminary findings suggest that these T cells can be influenced by drugs

that target B cells, such as rituximab.

In most cases, the cause of ITP is unknown and It is not

contagious.

Often, the child may have had a virus or viral

infection about three weeks before developing ITP. It

is believed that the body, when making antibodies

against a virus, "accidentally" also made an antibody

that can stick to the platelet cells. The body

recognizes any cells with antibodies as foreign cells

and destroys them. That is why ITP is also referred to

as immune thrombocytopenic purpura.

The bone marrow responds to the low number of platelets and

produces many more to send out to the body. in the bone marrow

many young platelets that have been produced. However, the blood test

results of the circulating blood would show a very low number of

platelets.

The body is producing the cells normally, but the body is also

destroying them. In most cases, other blood tests are normal except for

the low number of platelets. ITP platelets usually survive only a few

hours, in comparison to normal platelets which have a lifespan of 7 to

10 days.

Platelets are essential for the formation of a blood clot. Blood clots

consist of a mass of fibers and blood cells. Platelets travel to a damaged

area and stick together to form a plug, whenever a person is cut, for

example. If there are not enough platelets, a clot cannot be formed,

resulting in more bleeding.

Signs and symptoms

Normal platelet count is in the range of 150,000 to 450,000. In a child with ITP, the platelet

count is generally less than 100,000. By the time significant bleeding occurs, the child may

have a platelet count of less than 10,000. The lower the platelet count, the greater the risk

of bleeding.

Because platelets help stop bleeding, the symptoms of ITP are related to increased

bleeding.

Purpura - the purple color of the skin after blood has "leaked" under it. A bruise is blood

under the skin. Children with ITP may have large bruises from no known trauma. Bruises

can appear at the joints of elbows and knees just from movement.

Petechia - tiny red dots under the skin that are a result of very small bleeds.

Nose bleeds

Bleeding in the mouth and/or in and around the gums

Blood in the vomit, urine or stool

Bleeding in the head - this is the most dangerous symptom of ITP. Any head trauma that

occurs when there are not enough platelets to stop the bleeding can be life threatening.

Testing and diagnosis

The diagnosis of ITP is a process of exclusion.

First, it has to be determined that there are no blood abnormalities other than a low

platelet count, and no physical signs other than bleeding. Then, secondary causes (5–

10 percent of suspected ITP cases) should be excluded.

secondary causes include leukemia,

medications (e.g., quinine,heparin),

lupus erythematosus,

cirrhosis,

HIV, hepatitis C, congenital causes, antiphospholipid syndrome, von Willebrand

factor deficiency,

Despite the destruction of platelets by splenic macrophages, the spleen is normally not

enlarged.

In fact, an enlarged spleen should lead to a search for other possible causes for the

thrombocytopenia.

Bleeding time is usually prolonged in ITP patients. a normal bleeding time does not

exclude a platelet disorder.

Bone marrow examination may be performed on patients over the age

of 60 and those who do not respond to treatment, or when the diagnosis

is in doubt.

On examination of the marrow, an increase in the production of

megakaryocytes may be observed and may help in establishing a

diagnosis

A complete blood count (CBC), which measures the size, number, and

maturity of different blood cells

Additional blood and urine tests, which measure bleeding time and

detect possible infections

Careful review of the child's medications

A bone marrow aspiration may be performed to look at child's

production of platelets and to rule out any abnormal cells your child's

bone marrow could be producing that could lower platelet counts.

Treatment-

Not all children with ITP require treatment. Many

children spontaneously recover in about 2 to 4 day

Steroids, which help prevent bleeding by decreasing

the rate of platelet destruction. Steroids, if effective,

will result in an increase in platelet counts seen

within two to three weeks.

Initial treatment usually consists of the administration

of corticosteroids,

in urgent situations, infusions of

dexamethasone or methylprednisolone may be used,

while oral prednisone or prednisolone may suffice in

less severe cases

Anti-D

Another option, suitable for Rh-positive, non-splenectomized patients is

intravenous administration of Rho(D) immune globulin [Human; Anti-D].

The mechanism of action of anti-D is not fully understood. However, following

administration, anti-D-coated red blood cell complexes saturate Fcγ receptor sites

on macrophages, resulting in preferential destruction of red blood cells (RBCs),

therefore sparing antibody-coated platelets.

Steroid-sparing agents

Immunosuppresants such as mycophenolate mofetil and azathioprine

vincristine, a chemotherapy agent,and vinca alkaloid, has significant side-

effects and To be used with caution, especially in children.

Intravenous immunoglobulin (IVIg) may be infused in some cases. it is costly and

produces improvement that generally lasts less than a month.

Thrombopoietin receptor agonists

- are pharmaceutical agents that stimulate platelet production in the bone

marrow. Two such products are currently available:

•Romiplostim (trade name Nplate) is a thrombopoiesis stimulating Fc-

peptide fusion protein that is administered by subcutaneous injection.

• romiplostim is effective in treating chronic ITP, especially in relapsed

post-splenectomy patients.

•Eltrombopag (trade name Promacta ) is an orally-administered agent with

an effect similar to that of romiplostim. It too has been demonstrated to

increase platelet counts and decrease bleeding in a dose-dependent

manner.

Side effects of thrombopoietin receptor agonists include headache, joint

or muscle pain, dizziness, nausea or vomiting, and an increased risk of

blood clots.

Surgery

Splenectomy may be considered, as platelets which have been bound by

antibodies are taken up by macrophages in the spleen .

The procedure is potentially risky in ITP cases due to the increased

possibility of significant bleeding during surgery.

Platelet transfusion

Platelet transfusion alone is normally not recommended except in an

emergency, and is usually unsuccessful in producing a long-term platelet

count increase. This is because the underlying autoimmune mechanism

that is destroying the patient's platelets will also destroy donor platelets.

H. pylori eradication

In adults, particularly those living in areas with a high prevalence ,

identification and treatment of this infection has been shown to improve

platelet counts in a third of patients.

Experimental and novel agents

•Dapsone is an anti-infective sulfone drug. In recent

years, Dapsone has also proved helpful in treating

lupus, rheumatoid arthritis and used as second-line

treatment for ITP. The exact mechanism by which

Dapsone assists in ITP is unclear.

•The off-label use of rituximab, a chimeric monoclonal

antibody against the B cell surface antigen CD20, has

been shown in preliminary studies to be an effective

alternative to splenectomy in some patients.

•Promising results have been reported with kinase

inhibitor tamatinib fosdium

thanks