QUANTITATIVE AND QUALITATIVE DISORDERS OF PLATELET
PLATELETS
• Platelets are small, discoid shaped, a nucleated cell with a diameter of 2-4 μm and mean volume of 7-11 fl.
• They are the second most numerous cell in the blood between 150–450×10^9/L.
• Platelets remain in circulation for 8-12 days. Sites of platelets removal are spleen, liver and bone marrow.
• Approximately one-third of the total platelet mass is stored in the spleen.
• Platelets are normally produced in the bone marrow.
• Their parent cells are the megakaryocytes that are derived from megakaryoblasts through the intermediate stage of pro-megakaryocytes.
• Nearly 30% of the platelets are retained in the spleen.
• In massively enlarged spleens as much as 60-70% of the platelets may be retained
• If the spleen is removed form a healthy individual the platelet count increases by about 25-30% above the pre-splenectomy level.
PLATELETS DISORDERS
• Numerical reduction in the number of platelets in the peripheral blood is called thrombocytopenia
• Any reduction below the lower limit of normal ismthrombocytopenia, conventionally platelet count below 100X10^3/μl is viewed as clinically significant
Mechanisms of thrombocytopenia
1. Hypoproliferation of the megakaryocytes
2. Increased consumption of the platelets in the peripheral blood
3. Hypersplenism
4. Any combination of the above
1. Hypoproliferative thrombocytopenia
• This is usually a part of marrow hypoplasia irrespective of the causes. Some of the common causes of marrow hypoproliferation are:
Aplastic anemia
Megaloblastic anemias
Subleukemic acute leukemia
Myelodysplasias
2. Increased peripheral consumption
• There are two important groups of disorders that cause increased peripheral destruction of the platelets.
Immunological
(Antigen and antibody mediated consumption)
Non immunological
(Some non immunological conditions associated with platelets consumption)
Immunological consumption causes:
• Systemic lupus erythematosus
• Chronic lymphocytic leukemia
• Heparin administration
• Malaria
• HIV-AIDS
• Other viral illnesses
• Post-transfusion purpura (PTP)
• Drug – administration
Non-Immunological consumption causes:
• Other causes of isolated thrombocytopenia are less common; some of these are:
Thrombotic thrombocytopenic purpura
Disseminated intravascular coagulation
Massive transfusion with stored blood (dilutional thrombocytopenia)
Hemolytic uremic syndrome
3. Hypersplenism
• A better and a more descriptive term for hypersplenism is splenic sequestration or splenic pooling.
• Splenic sequestration is directly proportional to the size of the spleen.
• Massively enlarged spleens may trap as many as 60- 70% of the platelets that pass through them.
• Vasurlarity of the spleen also determines the number of the platelets that are retained.
Clinical features
• A Clinical manifestations of thrombocytopenia can be summarized in one word; “bleeding”.
• These are dictated by the site, amount and rate of bleeding.
• A massive hemorrhage in the brain due to acute leukemia may be fatal while nose bleed is more of a irritant and bleeding in the skin is more of a cosmetic concern.
• Hemorrhage in the eye may seriously impair the vision.
• Platelets from patients with ITP function much better than those from patients with acute leukemia or megaloblastic anemia.
Laboratory findings:
Clinical examination and history
Examination of the bone marrow smear and biopsy.
Immunological tests for the detection and characterization of antiplatelet antibodies (Antibodies detection against platelets antigens
such as GPIIb/IIIa complex and GPIb. PLA-1gG in patient)
THROMBOCYTOSIS
• Any increase beyond the upper limit of normal is called thrombocytosis.
• Platelet count up to 500X103/μl is not considered to be significant and is usually not a manifestation of any over thrombopoietic over activity in the bone marrow.
• Counts above 600X103/μl are significantly increased and are encountered in a number of hematological and non-hematological disorders
Causes of Thrombocytosis
• Platelet count over 800X103/μl with morphological changes in the platelets in conjunction with mild polymorphonuclear leukocytosis is almost diagnostic of essential thrombocythemia.
• Splenectomy is associated with thrombocytosis; the platelet count is usually around 500 X103/μl.
• There are no significant morphological abnormalities of the platelets though some large platelets may be present
• Iron deficiency anemia is sometimes accompanied by mild thrombocytosis. Platelets, in this condition are usually small in size (microthrombocytes).
• Systemic malignancy is the commonest cause of reactive thrombocytosis
• Almost 30% of the cases of thrombocytosis are due to systemic malignant disorders
• Hemorrhage is actually a potent stimulus for thrombopoiesis hence platelet count in hemorrhage is usually increased
Qualitative Disorders of platelets:
1• BERNARD-SOULIER SYNDROME
• Bernard-Soulier syndrome (BSS) is a rare autosomal recessive disorder characterized by prolonged bleeding time, thrombocytopenia and large platelets
• It is associated with a defect of platelet glycoprotein Ib-IX-V complex
• GPIb-IX-V complex binds with vWF and thrombin
• GPIb-IX-V also regulates the platelet shape and reactivity
• Abnormality of GPIb-IX-V leads to the failure of attachment of platelets with the vWF and consequently to the exposed collagen.
• This leads to bleeding manifestations.
• Symptoms of the disease include gingival bleeds, epistaxis, purpura, and menorrhagia.
• Laboratory findings show prolonged bleeding time and mild to moderately decreased platelet count.
• Clotting time remains normal. Peripheral smear shows large platelets. Bone marrow cytology shows normal megakaryocytes
2• GLANZMANN'S THROMBASTHENIA
• Abnormality of Glanzmann’s thrombasthenia is a rare autosomal recessive disorder characterized by absent or deficient membrane glycoprotein Ilb-IIIa (GPIIb-IIIa) complex, prolonged bleeding time and normal platelet count.
• GPIIb-IIIa mediates aggregation of activated platelets by binding fibrinogen, vWf and fibronectin. Absence or defects of GPIIb-IIIa lead to the failure of clot retraction; a major event of platelet aggregation.
