HAEMOSTATIS, THE FUNCTION OF PLATELETS

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HEMOSTATSIS, THE FUNCTION OF PLATELETS

• By ORIBA DAN LANGOYA
• MBchB II (2012/2013)

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HAEMOSTASIS

• Refers to the complicated chemical interplay that
  maintains blood viscosity, or thickness.
• Blood disorders occur when haemostasis falls out
  of balance.
• If blood becomes too thin, it loses the ability
  to form the blood clots that stop bleeding.
• When blood becomes too thick, the risk of blood
  clots developing within the blood vessels rises
  creating a potentially life-threatening
  condition.

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Platelet Formation (thrombocytopoiesis)
Myeloid Stem Cells
Megakaryoblasts
Megakaryocytes
fragmentation
Platelets (thrombocytes)
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PLATELETS

• Platelets are produced in bone marrow by a
  process known as thrombopoiesis.
• They are formed in the cytoplasm of the
  megakaryocyte (a very large cell).
• The cytoplasm of the megakaryocyte fragments at
  the edge of the cell.
• This is called platelet budding.
• Megakaryocytes mature in about 10 days, from a
  large stem cell, the megakaryoblast.

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PLATELET NUMBERS

• Among all the formed elements, platelets are
  the smallest.
• They are estimated to be 150,000 450,000 per
  cubic mm.
• Their half life is around 10 days.

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Platelets Formation
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PLATELET FUNCTIONS

• They play a role in-
• Blood coagulation
• Formation of plugs
• Prevention of blood loss

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HEMOSTASIS STOPPING BLOOD LOSS

• Three stages
• Vascular Spasm
• Platelet plug formation
• Clotting (coagulation)
• Vascular spasm
• Muscles in cut vessels constricts
• Blood loss is immediately reduced
• Clotting factors concentrate faster

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Hemostasis

• Platelet plug formation
• Platelet adhesion
• Platelet release reaction
• Platelet aggregation

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VASOCONSTRICTION PLUG FORMATION
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CLOT FORMATION

• Clot consists of a gel of fibrin and trapped
  formed elements
• Clot closes cut vessel
• When clot separates from plasma, remaining fluid
  is serum
• Clotting process called coagulation

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Coagulation Clot Stabilization

• Prothrombin
• Ca
• Fibrinogen
• Fibrin
• Polymerization

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CLOTTING FACTOR IN THE BLOOD

• CLOTTING FACTOR SYNONYMS
• Fibrinogen Factor I
• Prothrombin Factor II
• Tissue factor Factor II, tissue
  thromboplastin
• Calcium Factor IV
• Factor V Proaccelerin, labile
  factor, Ac-globulin (AC-G)
• Factor VII Serum prothrombin
  conversion, accerator (SPLA)
  Proconvertin stable factor

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• Factor VIII Antihaemophilic factor (AHF)
• Antihaemophilic globulin (AHG)
• Factor IX Plasma thromboplastin component
  (PTA) Christmas
• factor, Antihaemophilic factor B
• Factor X Stuart factor, stuart-prower factor
• Factor XI plasma thromboplastin antecedent
  (PTA), Antihaemophilic C
• Factor XII Hageman factor
• Factor XIII Fibrin stabilizing factor
• Prekallikrein Fletcher factor
• High molecular wt. Fitzgerald factor
• Kininogen (HWWK)

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• Blood clotting occurs in three stages
• Stage 1.
• Stage 2.
• Stage 3.

Formation of prothrombinase
Formation of thrombin
Formation of fibrin plug (clot)
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BLOOD CLOTTING DIAGRAM
Several clotting factors released from damaged
tissues, vessel wall and platelets
Ca2
Prothrombinase
Prothrombin
Thrombin
Ca2
Thrombin
Fibrinogen
Fibrin (clot)
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• Vitamin K needed to form four of the clotting
  factors
• Within 30 minutes platelets begin to retract the
  clot by pulling edges of cut vessel together

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FIBRINOLYSIS

• Is the process where a fibrin clot, the product
  of coagulation, is broken down.
• Its main enzyme, plasmin, cuts the fibrin mesh at
  various places, leading to the production of
  circulating fragments that are cleared by other
  proteinases or by the kidney and liver.

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CLOT DISSOLVING

• As repair of a cut or damaged vessel proceeds, a
  series of enzyme catalyzed reactions called
  fibrinolysis slowly dissolves the clot
• An enzyme called tissue plasminogen activator
  catalyzes the conversion of inactive plasminogen
  enzyme to active plasmin
• Active enzyme catalyzes the dissolving of clot

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PLASMIN FIBRINOLYSIS
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CLOT DISSOLVING DIAGRAM
Tissue plasminogen activator
Plasminogen
plasmin
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INTRAVASCULAR CLOT

• Intravascular clot clot within closed vessel
• Damaged vessel lining or slowing of blood flow
• Platelets aggregate and release clotting factors
• Resulting clot called a thrombus
• Moving piece of the clot is an embolus
• Clot moves downstream and blocks smaller vessel
  embolism
• May cut off blood supply to organ

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ANTICOAGULANTS

• Chemicals that decrease or prevent blood clotting
  are called anticoagulants
• Heparin is administered medically and it occurs
  naturally in our bodies. It works by decreasing
  thrombin production
• Coumadin (warfarin) is effective as a long-term
  anticoagulant. It is an antagonist of vitamin K.
  
• EDTA and CPD are used in blood banks to keep the
  donated blood from clotting. They both work by
  tying-up and removing calcium.

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Dissolving the Clot and Anticoagulants
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Coagulation and Disease

• Hemophilia
• Cardiovascular Diseases
• Key problem clots block undamaged blood vessels
• Anticoagulants prevent coagulation
• Keep platelets from adhering
• Prevent fibrin coagulation
• "Clot Busters" Prevent further clotting
• Speed fibrinolysis
• Limit tissue damage (heart, brain)

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BLEEDING DISORDERS

• HEMOPHILIA
• Inherited clotting disorder due to a deficiency
  in a clotting factor.
• Hemophilia is perhaps the best known of the
  bleeding disorders.
• Hemophilia is a genetic disorder caused by
  mutations of genes on the X chromosome.
• Because the mutated gene is recessive, the
  majority of hemophiliacs are male.

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Von Willebrand's Disease

• Von Willebrand's disease is the most common of
  the inherited bleeding disorders, including
  hemophilia.
• Von Willebrand's disease affects up to one
  percent of the population,
• and may be found in both sexes (as opposed to
  hemophilia, which primarily affects males).
• Von Willebrand's factor is a protein that allows
  platelets to form temporary plugs at sites of
  blood vessel injury
• Defects in von Willebrand's factor, impair the
  ability of platelet cells to 'cling' to an injury
  and form a plug.

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THROMBOCYTOPENIA

• Thrombocytopenia occurs when platelet cells fall
  to abnormally low levels, impairing coagulation.
• Leukemia, lymphoma, and some other cancers are
  known to cause thrombocytopenia.
• Cases of thrombocytopenia have also occurred due
  to heparin, a blood thinning medication.

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LIVER DISORDERS

• Liver cirrhosis interferes with the liver's
  ability to produce vital proteins, including
  coagulation factors.
• Low levels of coagulation factors in turn may
  lead to bleeding disorders.

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THE END

• Our greatest glory is not in never failing but
  in rising up every time we fail.
• Ralph Waldo Emerson