Primary Haemostatic

Abnormalitis
Mr.Tamer Imad
Haematology department
A normal platelet count is 150 to 450 109/L.
 In this range, an individual will have properly functioning
platelets that assist in the coagulation process by creating a
platelet plug and stimulating the formation of a solid fibrin clot.
A decrease in platelet count will cause bleeding from the
mucous membranes such as:
gum bleeding (gingival bleeding).
 nose bleeding (epistaxis).
extensive bruising (ecchymoses).
 petechiae (pinpoint hemorrhages).
 Thrombocytopenia

Causes of thrombocytopenia:

1. Thrombocytopenia Related to decreased production.

2. Thrombocytopenia Related to excessive destruction.

3. Altered Distribution of Platelets.

4. Dilutional Thrombocytopenia.
 1. Thrombocytopenia Related to decreased production

Any condition that leads to bone marrow aplasia or a lack of

megakaryocytes.

Most patients with leukemia will exhibit a thrombocytopenia as

a result of infiltration of the bone marrow with blast cells.

Defects in platelet synthesis can occur in the megaloblastic

anemias that show a pancytopenia.

Cytotoxic agents or chemotherapy usually interferes with the

cell cycle, thereby reducing the number of active platelets.

Infections with several viral agents such as cytomegalovirus,

Epstein-Barr virus, varicella, and rubella and certain bacterial

infections may cause a thrombocytopenia.

 2. Thrombocytopenia Related to excessive destruction
Immune :-
1. Autoimmune (idiopathic) thrombocytopenic purpura:
Clinically may be divided into chronic and acute forms.
A. Chronic idiopathic thrombocytopenic purpura:
The highest incidence has been considered to be in women aged 15-50 years.

It is the most common cause of thrombocytopenia without anaemia or

neutropenia.

It is usually idiopathic but may be seen in association with other diseases

such as systemic lupus erythematosus (SLE), HIV infection, CLL, Hodgkin's

disease or autoimmtme haemolytic anaemia

Pathogenesis

Platelet autoantibodies are usually IgG.

The antibody is directed against antigen sites on the glycoprotein (GP) lIb-IlIa

or Ib complex.

The normal lifespan of a platelet is 7-10 days but in ITP this is reduced to a

few hours.

Total megakaryocyte mass and platelet turnover are increased in parallel to

approximately five times normal.

 B. Acute idiopathic thrombocytopenic purpura:

This is most common in children.

In approximately 75% of patients the episode follows vaccination or an

infection such as chickenpox or infectious mononucleosis.

 2. Infections:

 It seems likely that the thrombocytopenia associated with many viral and

protozoal infections is immune-mediated.

3. Post-transfusion purpura :
Thrombocytopenia occurring approximately 10 days after a blood

transfusion has been attributed to antibodies in the recipient developing

against the human platelet antigen-la (HPA-la) (absent from the patient's own

platelets) on transfused platelets. The reason why the patient's own platelets

are then destroyed is unknown.

4. Drug-induced immune thrombocytopenia :

 An immunological mechanism has been demonstrated as the cause of

many drug-induced thrombocytopenias.

 Quinine, quinidine and heparin are particularly common causes

5. Feto-maternal allo-immune thrombocytopenia:

 Non Immune :-

1. Thrombotic Thrombocytopenic Purpura:

Congenital or acquired form.

More prevalent in women than in men.

There is deficiency of a ADAMTS13 metalloprotease which breaks down

ultra large von Willebrand factor multimers (ULVWF).

thrombotic thrombocytopenic purpura (TTP) can occur in women

postpartum or near delivery8 in those who have suffered from other immune

disorders like SLE (systemic lupus erythematosus), and in those with previous

viral infections or gastric carcinomas.

2. Disseminated intravascular coagulation

Thrombocytopenia may result from an increased rate of platelet

destruction through consumption of platelets because of their

participation in DIC.
 3. Altered Distribution of Platelets
The normal spleen holds one third of the platelet volume.

Several hematological conditions may lead to an enlarged spleen as part

of their pathological process: the myeloproliferative disorders,

extramedullary hematopoiesis, and hemolytic anemias.

As the spleen enlarges, blood pools in this organ withholding platelets

from the peripheral circulation.

 4. Dilutional Thrombocytopenia
Patients transfused with massive amounts of stored blood (more than 10

units over a 24-h period) frequently show abnormal dotting and

thrombocytopenia.