PLATELETSPLATELETS
Prepared By : Zahid AliPrepared By : Zahid AliBaqai medical unniverstyBaqai medical unniversty
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, 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.
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
• GlanzmanGlanzman’’s diseases disease
• Bernard SoluierBernard Soluier’’ss• 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!
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