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Platelet Function and Hemostasis

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Platelet Function and Hemostasis Powered By Docstoc
					Functions of Platelets & Hemostasis
       Hemostasis (haima-blood, stasis- standing)
    mechanism which prevent further blood loss by initiating a
    series of events that leads to the formation of a clot.


    Platelets:-
•   small (2-4 µ), irregularly shaped.
•   no nucleus but mitochondria are present.
•   150,000- 400,000 per cu mm.
•   75% in circulation, 25% in the spleen.
•   Extensive canalicular and microtubular system.
A. Membrane of platelets receptors for collagen, ADP,
   vessel wall von Willebrand factor, and fibrinogen.
B. Cytoplasm Contractile proteins (actin and myosin),
   glycogen, lysosomes, and 2 types of granules.
a) Dense granules:- serotonin, and ADP.
b) α- granules:- clotting factors and PDGF.

Functions of platelets:
• Serotonin released, plays a role in vasoconstriction.
• Aggregate to plug the vascular injury.
• Platelet factor 3 which accelerates clotting
• Clot retraction.
• Repair of the damaged vessel walls.
                       Hemostasis


4 phases
•   Vasoconstriction
•   Platelet plug formation
•   Blood coagulation
•   Fibrinolysis



The phases are not separated but rather manyfold
  interconnected
    Vasoconstriction
•   Transient
•   Direct mechanical stimulation of vascular smooth muscle
•   Stimulation of perivascular nerve
•   Sertonin

    Platelet plug formation
1. Platelet adhesion and von Willebrand Factor (vWF)
2. Platelet activation
•    Shape change
•    Aggregation (primary and secondary)
•    Liberation and oxidation of arachidonic acid
•    Secretion of granular contents
               Adhesion of platelets & vWF
Initial step
    vWF
•   Adhesive protein; synthesized by endothelial cells,
                                     megakaryocytes
•   Arg-Gly-Asp
•   Subendothelial and Plasma vWF; Weibel-Palade body
•   Acute phase protein
•   GPIb receptor (platelet)
•   GPIIb-IIIa complex

  Platelet activation
• Shape change & primary aggregation reversible
• Secondary aggregation & later phase irreversible
  Two primary agonists trigger PA
• Initial thrombin formed at injury site
• Sequences on collagen in the subendothelium
                                          Agonists

     Membrane inositol phospholipids      G- Protein in PL mem

                        phospholipase C

           DAG                IP3

     Protein kinase C         Ca-ionophore (↑cytosolic Ca)
↑cytosolic Ca triggers:- activation of
                                myosin light chain kinase
                                calcium dependent protease
                                Phospholipase A₂

                 Arachidonic Acid
           Lipoxygenase      cyclooxygenase
      12-HPETE                     PGG₂

      12-HETE                       PGH₂
                        platelets          endothelium
                  PGD₂
                    Thromboxane A₂              PGI₂
Platelet shape change
Flattened discs spheres with multiple pseudopods
Actin is polymerized
Microtubules dissolve and reform centrally
Platelet aggregation
Primary phase fibrinogen receptors expressed in GPIIb-IIIa
                 complex on PL surface membrane

Secondary phase After PL secretion
           Thrombospondin (α granule protein)

      fibrinogen        GPIV
         Injury to wall of blood vessel

                                                  Tissue
contraction               collagen              thromboplas
                                                     tin

              Platelet          Activation of
              reactions          coagulation
         Loose platelet          Thrombin
           aggregation

                                                Definitive
Temporary                                        hemostat
  hemostatic                                      ic plug
                             Limiting reactions
                   Blood coagulation
• Alexander Schmidt and Paul Morawitz
They discovered the enzymatic cascade nature of blood
  clotting



1st phase – generation of prothrombin activator
2nd phase -- conversion of prothrombin to thrombin
3rd phase – conversion of fibrinogen to fibrin
Intrinsic system
    HMW Kininogen, Kallikrein
XII   XIIa
                                                             EXTRINSIC
         HMW Kininogen
                                                               SYSTEM
    XI        XIa
                                                                    TPL
         IX                     IXa
                                  PL, Ca²+, VIIIa           VIIa       VII
              VIII

                     X                       Xa
                                  V               PL, Ca²+, Va

                         Prothrombin                  Thrombin

                                               Fibrinogen          Fibrin

                         XIII                XIIIa
Anticlotting mechanisms
1. Vascular endothelium:- smooth surface
2. Thrombomodulin:- affects both intrinsic and extrinsic
                      mechanism.
3. Antithrombin III-Heparan sulphate:-
4. Negative Feedback
5. Anticoagulants:-
• Binds with calcium sodium citrate, potassium
                      oxalate, EDTA
• Coumarin derivatives Vit K antagonist e.g.
                           dicumarol and warfarin
• Heparin naturally occuring
     Endothelial cell
     Thrombomodulin
        Thrombin


Protein C                  Activated protein C (APC)



       VIIIa        Inactive VIIIa                Va         Inactive Va


                        Inactivates inhibitor of t-PA

                 Plasminogen                    Plasmin

                                              Lyses fibrin
Fibrinolysis
LABORATORY EVALUATION
• PLATELET COUNT
• BLEEDING TIME (BT)
• PROTHROMBIN TIME (PT)
• PARTIAL THROMBOPLASTIN TIME
  (PTT)
• THROMBIN TIME (TT)
      BLEEDING TIME

   PROVIDES ASSESSMENT OF
  PLATELET COUNT AND FUNCTION



NORMAL VALUE
 2-8 MINUTES
      PROTHROMBIN TIME
 Measures Effectiveness of the Extrinsic Pathway




NORMAL VALUE
 10-15 SECS
 PARTIAL THROMBOPLASTIN
           TIME
 Measures Effectiveness of the Intrinsic
  Pathway




   NORMAL VALUE
     25-40 SECS
            THROMBIN TIME
 Time for Thrombin To Convert
  Fibrinogen            Fibrin

 A Measure of Fibrinolytic Pathway



 NORMAL VALUE
   9-13 SECS
So What Causes Bleeding
      Disorders?
VESSEL DEFECTS           ?
PLATELET DISORDERS
FACTOR DEFICIENCIES
OTHER DISORDERS
                   ?
  VESSEL DEFECTS

 VITAMIN C DEFICIENCY

 BACTERIAL & VIRAL INFECTIONS

 ACQUIRED
 PLATELET DISORDERS

 THROMBOCYTOPENIA

 THROMBOCYTOPATHY
THROMBOCYTOPENIA

  INADEQUATE NUMBER
     OF PLATELETS
THROMBOCYTOPATHY
 ADEQUATE NUMBER
   BUT ABNORMAL
     FUNCTION
  THROMBOCYTOPENIA
DRUG INDUCED
BONE MARROW FAILURE
HYPERSPLENISM
OTHER CAUSES
  THROMBOCYTOPATHY
 UREMIA
 INHERITED DISORDERS
 MYELOPROLIFERATIVE
 DISORDERS
 DRUG INDUCED
FACTOR DEFICIENCIES
                   (CONGENITAL)

 HEMOPHILIA A

 HEMOPHILIA B

 VON WILLEBRAND’S DISEASE
     OTHER DISORDERS
                        (ACQUIRED)
 ORAL ANTICOAGULANTS
   COUMARIN
   HEPARIN
 LIVER DISEASE
 MALABSORPTION
 BROAD-SPECTRUM ANTIBIOTICS
ANY QUESTIONS?

				
DOCUMENT INFO
Description: Detailed Description on Different types of Blood component,RBC,WBC,Platelates Description on Ageing,Immunity and Growth and Development Leucopoiesis,Erythropoiesis,Platelat Formation,erythrocyte,innate immunity,acquired immunity,moncyte,neutrophil phagocyte system,lymphoid organ growth,clotting cascade,thrombin formation,complement system,extinsic and intrinsic pathway,Blood Transfusion,Blood Group,RBC,