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Chapter: Medicine Study Notes : Haematology and Immunology

Platelets and Platelet disorders

Reactive: infection, inflammation, bleeding, malignancy, splenectomy, Fe deficiency, haemorrhage. Treat underlying disorder. Not usually necessary to treat platelets, but if so then aspirin

Platelets and Platelet disorders

 

Platelets

 

·        No nucleus: contain granular cytoplasm

·        Normal count: 150 – 400 * 10E9/L

·        Normal size: 2 – 3 um 

·        From megakaryocyte in bone marrow (from pluripotential stem cell under the influence of thrombopoietin)

·        Lifespan 10 days – destroyed mainly in spleen.  20 – 30% of total body platelets are pooled in spleen

·        Function – form haemostatic plug:

o   Adherence: via Ia, indirectly via Ib &VWF

o   Shape change

o   Release reaction

o   Aggregation: glycoprotein IIb/IIIa via fibrinogen

 

·        Bleeding time: time taken for a standardised skin incision to stop bleeding at venous pressure of 40 mmHg. Normal is 1 – 7 minutes. Depends on platelet numbers, platelet function, vascular factors (e.g. connective tissue disorders)

 

·        Disorders:

o   Thrombocytosis: too many

o   Thrombocytopenia: too few

o   Functional disorders

 

Thrombocytosis

 

·        = > 400 *10E9/l

·        Causes: 

o   Reactive: infection, inflammation, bleeding, malignancy, splenectomy, Fe deficiency, haemorrhage. Treat underlying disorder. Not usually necessary to treat platelets, but if so then aspirin 

o   Myeloproliferative: primary or essential thrombocythaemia – largely diagnosis by exclusion

·        Increased risk of venous and arterial thromboses


Thrombocytopenia

 

·        = <150*10E9/L 

·        Symptoms: bleeding in skin & mucosal surfaces, petechiae (<1 mm), purpura (1-5 mm), ecchymoses (>5mm), menorrhagia. Bad bleeding (e.g. in stools) usually only becomes significant below platelet count of 10 

·        Causes:

o  Artefact (e.g. clot in sample – usually due to using EDTA tube not citrate)

o  Dilutional thrombocytopenia: splenomegaly, massive blood transfusion

o  Marrow production failure (low platelet count & reduced/absent megakaryocytes):

§  Component of pancytopenia

§  Isolated thrombocytopenia: alcohol, chlorthiazides, rare megakaryocytic hypoplasias 

o  Peripheral consumption (more common – low platelet count, but normal/increased megakaryocytes):

§  Immune:

·        Idiopathic thrombocytopenic purpura 

·        Secondary to drugs (e.g. quinine, heparin), autoimmune disease (SLE), CLL, virus (e.g. HIV) 

§  Non-immune:

·        DIC

·        Haemolytic uraemic syndrome

 

Immune Thrombocytopenia (ITP)

 

·        Autoantibodies or immune complexes bind to platelets and cause premature destruction in spleen – lifespan reduced to 1 – 2 days

·        ITP does not cause splenomegaly

·        Acute IPT:

o  Immune complex mediated

o  Majority of childhood ITPs

o  Often follows viral infection

o  90% resolve spontaneously within one month

o  Rarely requires treatment

·        Chronic ITP:

o  Autoantibody to platelet glycoprotein

o  Majority of adult ITP

o  Usually no preceding illness 

o  10% resolve spontaneously: need to treat, although if platelets at around 30 – 50 may not need treatment – may dip during a viral illness. Need to review pre-surgery. 

·        Treatment (if any needed):

o  Steroids (1 mg/kg prednisone per day).  30% don‟t respond 

o  Intravenous immunoglobulins (swamp Fc receptors in spleen so platelets not destroyed – temporary). 30% don‟t respond

o  Splenectomy

o  Review if every pregnant: antiplatelet IgG may cross the placenta

 

Heparin-Induced Thrombocytopenia

 

·        1% of patients develop a drug-dependent antiplatelet antibody

·        3% of these immune complexes bind platelet Fc receptors & induce aggregation

·        Presentation is thrombocytopenia followed by thrombosis

·        Can be fatal

·        Management: stop heparin

 

Platelet Function Disorders

 

·        Congenital: rare

·        Acquired: common: 

o  Aspirin (inhibits cyclo-oxygenase ® ¯TXA2 ® ¯aggregation)

o  Uraemia (i.e. renal failure)

o  Cardiac bypass

o  Myelodysplasia


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