Pathology of PlateletPathology of Platelet

Presented By Wavhal S.A. Department of pathology

What is plateletWhat is platelet Are anuclear cytoplasmic particles Are anuclear cytoplasmic particles

produced by multinucleated giant cells of produced by multinucleated giant cells of bone marrow called megakaryocytes. bone marrow called megakaryocytes.

Mature megakaryocyte produces 2000-Mature megakaryocyte produces 2000-8000 platelets8000 platelets

Maturation time –Maturation time – 3 days Mean platelets survival time is about 9-10

day Normal count is 250,000. About 1/3 are trapped in the spleen.

PLETELET PHYSIOLOGYPLETELET PHYSIOLOGY

Platelets Production:Hematopoietic stem cell

Megakaryoblast

Megakaryocyte

Fragmentation

of cytoplasm

Platelets

StructureStructure

Megakaryoblast MegakaryocyteMegakaryoblast Megakaryocyte

Platelets

Thrombopoietin:Thrombopoietin:

Regulator of platelet production.Produced by the liver and kidneys.Levels are increased in thrombocytopenia, and reduced in thrombocytosis.It increases the no. & rate of maturation of the megakaryocytes.

FunctionFunction

- Required for the maintenance of integrity of capillary endothelium and acts as a first line of defense in controlling the bleeding

- Essential for the clot retraction - Play role in the inflammatory process

TestTest

Indirect count

- less accurate but practicable.

-Count the total no. Of platelets observed in relation to 100 leukocytes

Abs. no.of platelets=No. of platelets counted / 100 total leukocytes count

Direct count:

-By using 1% ammonium oxalate.

-same as like Rbcs countingTotal no. of platelets= No.of thrombocytes 1000

Test related to plateletsTest related to plateletsBleeding Time(BT)Bleeding Time(BT)Clot RetractionClot RetractionPlatelet Aggregation TestPlatelet Aggregation TestPlatelet Antibody TestPlatelet Antibody TestClotting Time(CT)Clotting Time(CT)

Platelets DisordersPlatelets Disorders

Platelet disorders are the most common cause of bleeding.

The disorder could be number (thrombocytopenia) or defective function.

THORMBOCYTOPENIATHORMBOCYTOPENIA

Loss of platelets from the circulation faster than the rate of their production by the bone marrow. So thrombocytopenia is due to:

A. Failure of platelets production,

most common cause,

Megakaryocytes are in the

bone marrow e.g. drugs.

B. rate of removal of platelets

from the circulation.

Megakaryocytes are or normal in the bone marrow I.e production is normal but platelets are destroyed e.g. by antibodies.

Causes of ThrombocytopeniaCauses of Thrombocytopenia CongenitalCongenital

• Megakaryocytic hypoplasiaMegakaryocytic hypoplasia

AcquiredAcquired

• ImmunothrombocytopeniaImmunothrombocytopenia• Thrombotic thrombocytopenicThrombotic thrombocytopenic purpurapurpura• DICDIC• DrugsDrugs• InfectionsInfections• SplenomegalySplenomegaly• Bone marrow suppression orBone marrow suppression or infiltrationinfiltration• Aplastic anaemiaAplastic anaemia

Immunothrombocytopenia (ITP)Immunothrombocytopenia (ITP)

Autoimmune disorder characterized by Autoimmune disorder characterized by platelets bound antibodies:platelets bound antibodies:Classification:Classification:• Acute:Acute: Usually in calfs, self limiting Usually in calfs, self limiting

preceded by infection usually viral.preceded by infection usually viral.• Chronic:Chronic: Usually in adults, more common in Usually in adults, more common in

female. female.Etiology: Etiology: • IdiopathicIdiopathic

Pathogenesis of Pathogenesis of ImmunothrombocytopeniaImmunothrombocytopenia

1.1. Platelets are sensitized with Platelets are sensitized with autoantibodies. autoantibodies.

2.2. Premature removal of platelets from Premature removal of platelets from the circulation by macrophages of the the circulation by macrophages of the R-E system and destroyed mainly in R-E system and destroyed mainly in the spleen. the spleen.

Acute ImmunothrombocytopeniaAcute Immunothrombocytopenia

Self limiting usually weeks.Self limiting usually weeks. In calfs,and other young animals.In calfs,and other young animals. Usually preceeded by viral infection.Usually preceeded by viral infection. Bone marrow shows normal or increased Bone marrow shows normal or increased

megakaryocytes.megakaryocytes. Due to immune complexes bound to platelets. Due to immune complexes bound to platelets.

(Complex = viral antigen-antibody complex). These (Complex = viral antigen-antibody complex). These complexes are removed by the reticuloendothelial complexes are removed by the reticuloendothelial system (RE system).system (RE system).

5-10% can go into chronic ITP. 5-10% can go into chronic ITP.

Chronic ImmunothrombocytopeniaChronic Immunothrombocytopenia

Pathogenesis:Pathogenesis:Autoimmune. Antibodies are formedAutoimmune. Antibodies are formedagainst antigens on platelet surface.against antigens on platelet surface.Clinical:Clinical:• Usually adults, young female 15-50 yrs.Usually adults, young female 15-50 yrs.

• Chronic: last months or years.Chronic: last months or years.

Laboratory FindingsLaboratory Findings

• Thrombocytopenia with giant forms. Thrombocytopenia with giant forms. Count usually 10-50,000.Count usually 10-50,000.

• Bone marrow shows normal or Bone marrow shows normal or increased megakaryocytes. increased megakaryocytes.

• Platelet bound IgG is +.Platelet bound IgG is +.• . .

Gaint cells

Other Causes of ThrombocytopeniaOther Causes of ThrombocytopeniaBone Marrow Suppression:Bone Marrow Suppression:

Due to effect of infections (viral) or toxins or due to replacement Due to effect of infections (viral) or toxins or due to replacement e.g., by malignancy e.g., leukemias, metastatic tumors, or due to e.g., by malignancy e.g., leukemias, metastatic tumors, or due to fibrosis of the bone marrow e.g., due to irradiation.fibrosis of the bone marrow e.g., due to irradiation.

DIC:DIC:• Due to consumption of platelets.Due to consumption of platelets.

Drugs:Drugs:• Due to suppression e.g., phenylbutazone, Gold, Thiazide.Due to suppression e.g., phenylbutazone, Gold, Thiazide.• Other mechanisms of action are immune, or by causing direct Other mechanisms of action are immune, or by causing direct

aggregation of platelets.aggregation of platelets.• May be accompanied by other signs e.g., fever, joint pain, rash, May be accompanied by other signs e.g., fever, joint pain, rash,

leukopenia.leukopenia.

Aplastic AnemiaAplastic Anemia

Splenomegaly:Splenomegaly:• Normally 1/3 of body platelets are in the spleen and 2/3 Normally 1/3 of body platelets are in the spleen and 2/3

in the peripheral circulation.in the peripheral circulation.• With spleen enlargement, up to 80-90% of body With spleen enlargement, up to 80-90% of body

platelets will pool in the spleen decreased platelets in platelets will pool in the spleen decreased platelets in the peripheral circulation.the peripheral circulation.

• This spleen enlargement could due to many causes, This spleen enlargement could due to many causes, e.g., thalassemia, portal hypertension, Gauchere.g., thalassemia, portal hypertension, Gaucher’’s, s, malaria, Kalaazar, lymphomas, etc.malaria, Kalaazar, lymphomas, etc.

• Life span of the platelets is normal. Life span of the platelets is normal.

• Infections• Decreased platelets can be seen with many infections, Decreased platelets can be seen with many infections,

e.g., intra-uterine infections: best examples are e.g., intra-uterine infections: best examples are congenital syphilis, toxoplasmosis, rubella, congenital syphilis, toxoplasmosis, rubella, cytomegalo virus (CMV), herpes. Also seen with other cytomegalo virus (CMV), herpes. Also seen with other infections e.g., influenza, chicken pox, rubella, infections e.g., influenza, chicken pox, rubella, infectious mononucleosis. infectious mononucleosis.

• The effect is due to suppression of bone marrow, The effect is due to suppression of bone marrow, immune mediated or due to DIC in fulminant infections. immune mediated or due to DIC in fulminant infections.

Defective Platelets FunctionDefective Platelets Function

• A defect in function is suspected if A defect in function is suspected if there is prolonged bleeding time with or there is prolonged bleeding time with or without skin or mucosal hemorrhage in without skin or mucosal hemorrhage in the presence of normal platelet count. the presence of normal platelet count.

Disorders of Platelets FunctionDisorders of Platelets Function

CongenitalCongenital

•Storage granules defectStorage granules defect

AcquiredAcquired

• DrugsDrugs• UremiaUremia• Myeloproliferative disordersMyeloproliferative disorders• Multiple myeloma Multiple myeloma

Acquired Disorders of Platelet Acquired Disorders of Platelet FunctionFunction

Causes:Causes: • Drugs e.g., AspirinDrugs e.g., Aspirin• Myeloproliferative disorder.Myeloproliferative disorder.• Paraproteinemias e.g., multiple myeloma.Paraproteinemias e.g., multiple myeloma.• Cardiopulmonary bypass.Cardiopulmonary bypass.• Autoimmune diseases e.g., SLE (Systemic Autoimmune diseases e.g., SLE (Systemic

Lupus Erythromitosis)Lupus Erythromitosis)• Uremia (renal failure). Uremia (renal failure).

Acquired Disorders of Platelet FunctionAcquired Disorders of Platelet Function(Cont…)

Drugs:Drugs: • Best example is ASPIRIN which is the MOST Best example is ASPIRIN which is the MOST

COMMON cause of acquired platelet function COMMON cause of acquired platelet function disorder.disorder.

• Aspirin irreversibly affect the cyclo-Aspirin irreversibly affect the cyclo-oxygenase enzyme. The effect last 4-7 days oxygenase enzyme. The effect last 4-7 days and it takes about 10 days before the and it takes about 10 days before the platelets are replaced.platelets are replaced.

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