PLATELETSPLATELETS

PLETELET PHYSIOLOGYPLETELET PHYSIOLOGY

Platelets Production:Hematopoietic stem cell

Megakaryoblast

Megakaryocyte

Fragmentation

of cytoplasm

Platelets

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.

PLATELET CIRCULATIONPLATELET CIRCULATION

Normal count is 250,000. Normal life span 7-10 days. About 1/3 are trapped in the spleen.

STRUTURESTRUTURE

Mucopolysacch.

coat

Granules

Dense core

granules

Mucopolysacch. Coat: Glycoprotein content which are important for interaction of platelets with each other or aggregating agents.

Granules:- Dense core:

FunctionFunction

Formation of mechanical plug during normal hemostatic response to vascular injury.

The main steps involved are: adhesion, release, aggregation.

PLATELETS ADHESIONPLATELETS ADHESION

Adhesion of platelet to subendothelial collagen.

Dependent on the VW factor (Von Willebrand part of Fact VIII). Also dependent on glyoproteins.

RELEASE (SECRETION)RELEASE (SECRETION)

Collagen exposure results in the release of granules contents (ADP, serotonin, fibrinoen).

Collagen and thrombin activate prostaglandin synthesis.

Thromboxane A2: Potentiase aggregation

and vasoconstrictor.

Aggregation: Release ADP+thromboxane

A2 aggregation. This is followed by more secration secondary aggregation.

platelet mass or plug.

Membrane Phospholipid Arachidonic acid

Cyclo-oxygenase

Thromboxane synthetase Thromboxane A2

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• TAR syndromeTAR syndrome

• Wiscott Aldrich syndrome Wiscott Aldrich syndrome

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 children, self limiting Usually in children, self limiting

preceeded by infection usually viral. preceeded 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 children.In children. 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 ImmunothrombocytopeniaPathogenesis: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.• Insidious onset.Insidious onset.• Chronic: last months or years.Chronic: last months or years.• No precipitating causes.No precipitating causes.• Shows fluctuating (cyclical) course with periods in which Shows fluctuating (cyclical) course with periods in which

platelets number return to normal.platelets number return to normal.

Manifestations Manifestations

• Skin purpura, superfacial bruising, Skin purpura, superfacial bruising, epistaxis, menorrhagia.epistaxis, menorrhagia.

• Mucossal hemorrhage is seen in Mucossal hemorrhage is seen in severe cases and intra-cranial severe cases and intra-cranial hemorrhage is rare.hemorrhage is rare.

• Splenomegaly: 10% of cases. Splenomegaly: 10% of cases.

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 +.• . .

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, Gaucher’s, e.g., thalassemia, portal hypertension, Gaucher’s, malaria, Kalaazar, lymphomas, etc.malaria, Kalaazar, lymphomas, etc.

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

InfectionsInfections• Decreased platelets can be seen with many Decreased platelets can be seen with many

infections, e.g., intra-uterine infections: best infections, e.g., intra-uterine infections: best examples are congenital syphilis, toxoplasmosis, examples are congenital syphilis, toxoplasmosis, rubella, cytomegalo virus (CMV), herpes. Also seen rubella, cytomegalo virus (CMV), herpes. Also seen with other infections e.g., influenza, chicken pox, with other infections e.g., influenza, chicken pox, rubella, infectious mononucleosis. rubella, 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 immune mediated or due to DIC in fulminant infections. 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

• Glanzman’s diseaseGlanzman’s disease

• Bernard Soluier’sBernard Soluier’s• Storage granules defectStorage granules defect

AcquiredAcquired

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

Glanzman’s Disease (Thrombasthenia)Glanzman’s Disease (Thrombasthenia)

• Autosomal recessive inheritance.Autosomal recessive inheritance.• Normal platelets count and appearance.Normal platelets count and appearance.• No clumps are seen on peripheral blood film (I.e., no No clumps are seen on peripheral blood film (I.e., no

platelets clumps).platelets clumps).• Due to decreased surface membrane glycoproteins Due to decreased surface membrane glycoproteins

11b + 111a failure of primary aggregation.11b + 111a failure of primary aggregation.• Platelets do not aggregate with all aggregating Platelets do not aggregate with all aggregating

agents but they aggregate with ristocetin.agents but they aggregate with ristocetin.• Bleeding time is prolonged. Bleeding time is prolonged.

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

• Presents as elevated bleeding time but purpura is Presents as elevated bleeding time but purpura is unusual. unusual.

Thank You For Your Thank You For Your Attention!Attention!