L:4
Platelets
Platelet Structure:
A)Bilipid membrane and membrane proteins(outer membrane has 2 layers of lipid):
1)Bilipid membrane:
On it glycoproteins that function as surface receptors.(2 types of glycopt.)
a)glycoprotein Ib(GPIb): Binding site for von Willebrand factor(vWf) → imp. in plat. adhesion.
b)glycoprotein IIb, IIIa(GPIIb-IIIa): Function as fibrinogen receptor → imp. in plat. aggregation.
2)Bilipid membrane is the site of some of the complexes:
Coagulation activities of platelets.
B)Microtubules and microfilaments(inside plat.):
●Microtubules:
cytoskeletal support of plat.
●Microfilaments:
contain actin and participate in platelet pseudopod formation.
C)Dense tubular system:
*calcium reservoir(Ca imp. in plat. function).
*Is the site of plat cyclooxygenase and of prostaglandin synthesis.
D)Granules:
●Dense granules → contain [ADP((Adenosine Tri Phosphate))]s and Ca, also serotonin (all) → enhance AGGREGATION.
●α granules → contain PF4(plat. Factor 4), β-thromboglobulin, PDGF(plat. derived growth factor), Fibrongen, Factor V, and vWf (all) → imp. for ADHESION.
E)Canaliculi: = vacules.
●↑surface area.
●site of releasing granules contents.
Platelet Kinetics:
*Production:
CFU-Meg (stem cell in B.M.) →
↓ Meg-CSF(
Megakaryoblast
↓ proliferation
Megakaryocyte
↓
Platelets TP
●Thrombopoietin (TP):
-stimulate CFU-Meg.
-Meg. Maturation.
-plat. production and shed from the most mature Meg.
*Meg. is most great largest cell in B.M. (20-50μm) in diameter.
*Defect of production → Thrombocytopenia(decrease no. of plat.).
*Distribution:
1)peripheral blood and spleen:
⅔ of plat. are in P.B. ⅓ in splenic pool of plat.
2)B.M.:
also site pf plat. pooling, but to a much lesser extent.
*Life span:
NL = 8-14 days.
*Shortened life span → Thrombocytopenia.
Platelet Function:
●Sequence of events → formation of plat. plug and stable fibrin clot(to close injury) at site of vessel interruption(cut, injury, bleeding, etc.)
A-*Adhesion:
Normally plat. do not adhere to intact(not injured, not interrupted) vascular endothelium due to action of prostacyclin [(prostaglandin I2) (PI2)] which is produced by endothelial cell and is potent plat. function inhibitor.
*Constituents required for plat. Adhesion:
-Collagen: present in blood vessels, interstitium, and basement membrane. Also stimulate aggregation.
-GPIb.
-vWf: bind GPIb.
-Other: fibronectin, thrombospondin, and calcium.
B-*Aggregation:
-aggregation is induced by exposure to a variety of stimuli such as ADP, thrombin, or epinephrine, and in vivo it appears to be stimulated by adhesion.
1ry curve
-Agg.
2ry curve
(in vitro to test plat.)with application of ADP, collagen and ristocetin.
*Absent 1ry agg.(curve) = Thrombasthenia.
*Absent 2ry agg.(curve) = ITP and storage pool diss.
C*Interaction with coagulation system:
1)Coagulation factors: included:
-Fibrongen.
-vWf.
-Factor V.
-Factor XIII.
-HMWK(High Molecular Weight Kininogen).
2)Coagulation cascade:
*-ve charged surface → facilitate activation of F.XII by kallikrein and HMWK.
*Bind F.Xa → ↑prothrombin action(activation).
*vWf → associate with F.VIII complex.
*Test for plat. function → B.T.(bleeding time).
Disorders of platelets number :
N.B. NL count=150,000-450,000/μl
*Thrombocytopenia:
1)Decreased production:
a)Congenital:
1)TAR: ((Thrombocytopenia with Absent Radii))(radii=radius bones).
-↓or absent Meg.
-absent radii.
-serious bleeding.
treatment: plat. transfusion.
2)Other:
-Fanconi's anemia.
-May-Hegglin anomaly(defect in Meg. maturation but no. is normal): autosomal dominant with bizarre gaint plat. + basophilic inclusions in granulocytes(Döhle bodies).
b)Acquired:
-A plastic anemia.
-Neoplasms.
-Vit B12.
-Alcohol.
-Chemotherapy.
-Radiation.
2)Increased destruction:
a)Congenital:
1)NAIT:
Neonatal alloimmune thrombocytopenia.
2)Structural disorders
e.g. Wiskott-Aldrish syndrome:
-Thrombocytopenia.
-Eczema.
-Immunological disorders.
b)Acquired:
1)ITP (Idiopathic Thrombocytopenic Purpura).
2)TTP(Thrombotic Thrombocytopenic Purpura).
3)Drugs.
4)DIC (Disseminated Intravascular Coagulation).
*Thrombocytosis:
1)Resulting from Myeloproliferation:
-CML (Chronic Myeloid Leukemia).
-Essential thrombocytosis.
-Polycythemia Vera.
2)Secondary:
-Iron deficiency (>million/μl).
-Postsplenctomy(as we said before that ⅓ of plat. inter splenic pool, so, after removing of spleen these plat. will present in blood cause increase no. of plat.)
-Others:
●Chronic inflammatory conditions.
●Haemolytic anemia.
●Hemorrhage.
●Malignancy.
*Idiopathic (immune) thrombocytopenic Purpura (ITP):
-Is the most common cause of isolated thrombocytopenia(U/M we see thrombocytopenia while other cells are normal = isolated thrombocytopenia).
-2 forms : ●Acute : self limited. Children.
●Chronic: seen in adults. Most common women(20-40 yrs).
*Pathophysiology:
-Autoimmune disorders thrombocytopenia result from action of antiplatelet antibodies shortened life span of platelets.
-In sever cases antibodies may also affect Meg. causing ineffective platelets production.
*Clinical features:
The pt usually presents with petechiae, mucous membrane bleeding, or menorrhagia.
*Diagnosis:
-B.M. examination reveals normal or increased number of Meg.
-Antiplatelet antibodies demonstrated in serum.
*Therapy:
-In children: acute form-self limited.
-In adults: corticosteroids.
*ITP-Like syndrome:
-Associated with HIV.
-SLE.
Disorders of platelets function:
*Congenital:
a)Disorders of membrane receptors:
1)GPIB deficiency → Bernard-Soulier syndrome.
2)GPIIb-IIIa deficiency → Glanzmann's thromboasthenia.
b)Disorders of platelet secretion abnormal in plat. granules storage pool diss.:
-Dense granules(δ storage pool diss.).
-α granules (gray plat. syndrome) (α-storage pool diss.).
*Acquired:
1)Myeloproliferative disorders:
-CML.
-Essential thrombocytopenia.
-Polycythemia Vera.
-Myelodysplastic syndrome(MDS).
2)with immunologic mechanisms:
-ITP.
-Multiple Myeloma(Hyper viscosity syndrome).
3)With non hematologic conditions:
-Uremia.
-Liver diss.
4)Drugs:
-Aspirin.
-Penicillin.
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Dr. Ashwag B. ALshareif http://medicineunitedgroup.tripod.com