Platelets and Blood coagulation Flashcards
thrombopoiesis
- avg platelet count range - 150,000 to 400,000 / mm3
- lifespan - 10 days
- avg adult produces 10^11 platelets per day
- formed by megakaryoblasts which is a precursor cell to a promegakaryocyte which inturn becomes a megakaryocyte during thrombopoiesis.
- the megakaryoblast is formed by CFU-Mg which in turn is formed from CFU-S
- primary regulator - thrombopoietin produced primarily in the liver, kidney and bone marrow.
- following stimulation by thrombopoietin, platelet granule formation begins along with demarcation of the cytoplasm into regions destined to fragment into mature platelets which are released.
- a chemokine stromal cell derived factor 1 (SDF-1) has been shown to influence thrombopoiesis independent of thrombopoietin
hemostasis events
hemostasis - the process of arrest of bleeding while maintaining blood in a fluid state within the vascular system.
Mechanics leading to hemostasis are:
1. vascular constriction
2. Platelet plug formation: in which platelets adhere to each other forming a plug which seals the opening in
blood vessel.
3. formation of blood clot as a result of blood Coagulation.
4. Growth of fibrous tissue into clot.
vascular constriction
- three ways
a) local myogenic spasm
b) local autocoid factors from traumatized tissues and platelets
c) nervous reflexes - the nervous reflexes are initiated by pain nerve reflexes
- even more vasoconstriction results from local myogenic contraction
- platelets release vasoconstrictor substance thromboxane A2, which causes constriction in smaller vessels.
formation of platelet plug
- if cut in bv is very small
- the cut will be sealed often by the platelet plug rather than a blood clot
• mechanism
- when platelets come in contact with damaged vascular surface, especially collagen fibers they rapidly change their own characteristics—begin to swell, assume irregular forms with numerous irradiating pseudopods protruding from their surfaces
- their contractile proteins contract forcefully causing the release of granules that contain multiple active factors, they become sticky so that they can adhere to collagen in the tissues and to a protein called van willebrand factor that leaks into the traumatized tissue from the plasma
- the adp and thromboxane A2 (released by platelets in combat) in turn act on nearby platelets to activate them and cause them to adhere to original platelets
-this forms the platelet plug and subsequently fibrin thread js also formed
blood clot
- clot begins to develop in 15-20 secs if the trauma has been severe and in 1-2 min if it is minor.
- within 3-6 minutes the opening is filled with the clot
- after 20 min - 1 hour - clot retracts which closes the vessel still further
- platelets play an imp role in this clot retraction
fibrous organisation/ dissolution of blood clot
- once a blood clot is formed it can follow two courses
- it can become invaded by fibroblast which will form connective tissue all through the clot
- it can dissolve
blood coagulation
COAGULATION:
Definition : It is the process in which fluid blood is converted into a semisolid jelly like mass called clot. It is the
property of plasma.
Coagulation occurs in 3 stages:
I) Formation of Prothrombin activator:
Can occur via 2 pathways :
a) Extrinsic pathway :
begins with trauma to the vessel wall and surrounding tissues
• release of tissue factor: It is initiated by tissue damage which results in release of complex substances called tissue thromboplastin. They include lipoproteins and membrane phospholipids.
• activation of factor X - role of factor vii and tissue factor: The lipoprotein part combines with Factor VII and this along with tissue phospholipids acts on factor X in presence of Calcium ions to
form activated factor X.
• effect of Xa to form prothrombin activator- Activated factor X then combines with tissue phospholipids and
with factor V in presence of Ca ions and forms a complex substance called Prothrombin activator. Here factor V is activated by thrombin.
b) Intrinsic Pathway:
trauma to the blood
Contact of blood with exposed collagen fibers brings about activation of factor XII and also of platelets which release
lipoprotein (Platelet factor III) and
phospholipids.
• Activation of Factor XI: Activated factor XII acts as proteolytic enzyme and converts factors XI into activated factor XIa. facilitated by high molecular weight kinninogen and accelerated by pre kallikrein
• Activation of factor IX by activated factor XI
• Activation of Factor X: Activated factor IX then forms a complex with factor VIII, phospholipids and platelet factor III and in presence of calcium ions converts factor X to activated factor Xa,
• Action of activated factor X to form prothrombin activator: activated factor X combines with factor V and
phospholipids in presence of calcium ions and forms prothrombin activator.
II) Conversion of prothrombin to
thrombin: Prothrombin is an alpha 2
globulin present in plasma (15 mg per
100ml). It is synthesized in the liver and Vit. K
is essential for its synthesis.
Prothrombin activator acts as proteolytic enzyme and in the presence of Ca ions, splits prothrombin into smaller unit called thrombin.
III) Conversion of fibrinogen into fibrin: Thrombin is also proteolytic enzyme. It acts on soluble plasma protein fibrinogen and splits 4 small peptides from each fibrinogen molecule to form insoluble fibrin monomers, which then polymerize spontaneously forming long fibrin threads. The network of fibrin threads along with trapped plasma, RBCs, WBCs and platelets forms the clot that effectively seals the opening in the vessel wall and stops bleeding.
Stabilization of clot: Is brought about by factor XIII (fibrin stabilizing factor) present in the plasma which forms
cross linkages between adjacent Fibrin threads.
Thus whole process of coagulation involves sequential activation of (cascade) coagulation factors in plasma
ultimately forming fibrin threads and is complete in 3 to 6 minutes.
Clot retraction is a process in which the clot becomes smaller and more firm and exudes serum. It occurs in 30
to 60 minutes and is due to platelets.
Applied Physiology:
Hemophilia a clinical condition that results from deficiency of factors VIII,IX and XI of genetic origin and is
characterized by bleeding in joints and prolonged coagulation time.
properties and functions of platelets
- temporary hemostasis : prevent bleeding
- blood coagulation : contribute by releasing platelet factor 4 and synthesizing clotting factors V and XI
- clot retraction
- thrombolysis : platelets control fibrinolysis
- phagocytosis:
- storage and transport: synthesize, secrete and transport many chemical substances
- vascular growth: help in growth/repair of vascular endothelium by secreting platelet derived growth factor pdgf.
thrombocytopenia
- platelet count less than 150,000
- bleeding occurs when fall below 50,000
- levels as low as 10,000 are frequently lethal
- occurs in idiopathic thrombocytopenic purpura, aplastic anemia, hypersplenism, acute leukemia etc.
- splenectomy is often helpful, sometimes effecting almost complete cure.
fibrinolysis
it is a process that involves breakdown and dissolution of blood clot inside the blood vessel
- requires plasmin or fibrinolysin
anticlotting mechanisms
important factors for preventing clotting
1) smooth surface of endothelium of blood vessels
2) glycocaylx layer on the inner surface of endothelium repels clotting factors and platelets
3) continuous flow of blood
4) presence of natural anticoagulant
- heparin (produced by liver and basophilic mast cells)
- protein c
1.Heparin:-
It is a strongly negatively charged conjugated polysaccharide.
Production:- In the body, it is produced by mast cells in liver and lungs and also by basophils in blood.
Actions:- 1.It combines with Antithrombin III and forms a powerful Heparin Antithrombin III cofactor. This
factor blocks the effect of thrombin on fibrinogen. It also inactivates thrombin that is bound to fibrin threads.
2.It removes other activated coagulation factors like IX, X, XI & XIII. 3.It also prevents formation of thrombin by
opposing the action of activated factor X.
Clinical:-Heparin is given by injection because it is destroyed in G.I.T .when given orally. It’s anticoagulant
effect is seen immediately.
2.Oral Anticoagulants :-These are coumarin derivatives e.g. Warfarin or Dicoumarol. These drugs can be
given orally because they are not destroyed in G.I. tract.
Mechanism of action:- These drugs are naphthoguinone derivatives having structure similar to vitamin K.
Therefore they compete with Vit. K for receptor sites on liver cells and reduce the synthesis of clotting factors
like prothrombin, factors VII, IX and X(Competitive inhibition). Decreased synthesis of these factors retards the
process of coagulation.
These drugs have longer latent period of action because they reduce synthesis of clotting factors and do not
have direct action on coagulation process .Prothrombin time and clotting time should be monitored in patients
receiving anticoagulants.
Clinical uses of Anticoagulants:-
- In treatment of thromboembolic conditions like
(a) Thrombophlebitis.
(b) Pulmonary embolism.
(c) Disseminated intravascular coagulation. - To prevent occurrence of coronary thrombosis.
haemophilia
It is a condition characterized by prolongation of clotting time.
There are 2 types of hemophilia-
1.Hemophilia A(classical):-forms 85% of hemophilia cases and is due to deficiency of coagulation factor VIII,
i.e. Anti Hemophilic Globulin.
Function of factor VIII:-In the intrinsic pathway of coagulation,factor VIII is essential along with factor IX,
calcium ions and platelet phospholipids for activation of X which then forms prothrombin activator.
Factor VIII is made up of 2 components a smaller component(mol wt 270,000)whose deficiency causes
hemophilia and a larger component called Von Willebrand factor whose deficiency produces Von Willebrand
disease.
2. Hemophilia B (Christmas disease):-Forms 15% of hemophilia cases and is due to deficiency of factor
IX(Christmas factor or PTA)which is also essential for activation of factor X. It is a hereditary disorder due to
presence of a defective gene on X chromosome which fails to cause synthesis of factor VIII or IX. Therefore the
disease is seen in males while females act as carriers.
Clinical Features: This condition is characterized by extensive and prolonged bleeding even after a mild
trauma. Knee joint and elbow joint may be suffused with blood. Prolonged uncontrollable hemorrhage may
cause death. Bleeding time is normal and clotting time is increased.
Treatment:-Administration of purified factor VIII or IX prepared from fresh human plasma (cryoprecipitate) or
plasma transfusio
