2 coagulation

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Story of Band-Aid invention

• By Earle Dickson in 1920.

• He worked for a company that manufactured gauze and adhesive tape called Johnson & Johnson.

•Earle Dickson was Married to Josephine Dickson

•We will never know the reason, but it is a fact that Josephine Dickson was accident prone.

•During the first week that she was married to Earle Dickson, she cut her self twice with the kitchen knife.



After that, it just went from bad to worse. It seemed that Josephine was always cutting herself.

The dressing made by him would come off easily while she was working

One day her husband had an idea. He sat down with some tape and gauze and a pair of scissors. Then he cut the tape into strips. In the middle of each strip he stuck a little square of gauze.

From then on, whenever Josephine had an accident, ready-made bandages were on hand for her to use quickly and without a lot of fuss.

At Johnson & Johnson, they heard about these new bandages that could be put on in thirty seconds. Soon the company was making them to sell on a small scale.

Four years later, in 1924, the company installed machines for mass producing the new product, and the trade name BAND-AID was adopted



Hemostasis & Blood Coagulation



Contentso Introductiono Definition- Hemostasis - Coagulationo Basic units of Hemostasis and

Coagulation

o Hemostasis- Primary Hemostasis - Secondary Hemostasiso Coagulation Cascade.o Factors controlling coagulationo Fibrinolytic pathway.o Applied aspectso Investigationso Refferences



Introduction• Coagulation is a complex process by which

blood forms clots. It is an important part of hemostasis

• Human body has amazing protective mechanisms to combat all sorts of injuries to body.

• Bleeding has to be stopped as early as possible to prevent further complication

• Whenever vessel is severed, hemostasis is achieved by

- Vascular spasm - Formation of Platelet plug - Formation of Blood clot - Growth of fibrous tissue into the

clot.


http://en.wikipedia.org/wiki/Blood

http://en.wikipedia.org/wiki/Clot

http://en.wikipedia.org/wiki/Hemostasis


Definitions• Hemostasis : Defined as prevention of blood

loss By

Willium F Ganong

o Blood coagulation the sequential process by which the multiple coagulation factors of blood interact in the coagulation cascade, resulting in formation of an insoluble fibrin clot.

Medical Dictionary


http://medical-dictionary.thefreedictionary.com/cascade


Hemostasis• Primary hemostasis: Vasoconstriction

and platelet plug together produce the immedieate stopping of hemorrhage ( within say few seconds to few minutes ). This phase is called Primary hemostasis.

• Secondary hemostasis. Formation of fibrin clot over platelet plug is designated as secondary hemostasis.



Serial events after blood loss• Constriction of small arterioles. Achieved by

two mechanisms i) Neural- by action of sympathetic

vasoconstrictor nerves. ii) Locally released chemicals – serotonin

and endothelin.

• Adhesion: Platelets adhere to damaged vessel wall and are activated. Ultimately platelet plug is formed. This plug seals the vessel.

• These two events taken togather constitute Primary hemostasis

.• Time between onset of bleeding and

primary hemostasis is called bleeding time.



• Finrin clot develops over platelet plug by a mechanism called Coagulation.

• This fibrin clot bolsters the platelet plug. This event is called as secondary hemostasis and it stabilizes the platelet plug.

• Fibrinolytic mechanism : After few days clot is lysed and recanalization of the vessel again occurs.



Exposure of Collagen Von Willebrand F

Adhesion of Platelets to collagen Activation of Platelets

Injury to blood vessel and damage to endothelium

Secretion of Serotonin Secretion of ADP & Thromboxane A2

Formation of Prothrombin activator

Vasoconstriction

Stage I

Aggregatoin of Platelets

Formation of Platelet plug

Stage II

Blood Clotting

Stage III



Basic units of Hemostasis and Coagulation

• Blood : The fluid that circulates in the heart, arteries, capillaries, and veins of a vertebrate animal carrying nourishment and oxygen to and bringing away waste products from all parts of the body

• Vascular wall :

• Platelets : a minute colorless anucleate disklike body of mammalian blood that is derived from fragments of megakaryocyte cytoplasm, that is released from the bone marrow into the blood, and that assists in blood clotting by adhering to other platelets and to damaged epithelium—called also blood platelet, thrombocyte



Vessel wall or Endothelium• The endothelium is the thin layer of

cells that lines the interior surface of blood vessels,[1] forming an interface between circulating blood in the lumen and the rest of the vessel wall.

• These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart to the smallest capillary.

• The endothelium normally provides a non-thrombogenic surface because it contains heparan sulfate which acts as a cofactor for activating antithrombin III, a protease that cleaves several factors in the coagulation cascade.


http://en.wikipedia.org/wiki/Cell_%28biology%29

http://en.wikipedia.org/wiki/Blood_vessel

http://en.wikipedia.org/wiki/Endothelium#cite_note-0


Platelets• Non- nucleated• During hemostasis inactive platelets

become active.• Normal count : 1.5 to 4 lacs per Micro

liter.• Less than 40,000 is called critical count.• Pools : Red bone merrow, blood and

spleen• Morphology : -Diameter- 2-4 Microns - When inactive- Disc shaped -When active- Become spherical.



Membrone

Inner Lipoprotein

layer.

Glycoproteins. Receptors of membrane are glycoprotiens

Lipid molecules which are phospholipids-Precursors of

TxA2,

Outer glycocalyx



• Cytosol – Granules - Tubules - Contractile elements - Mitochondria - Golgi apparatus

• Granules- Alfa granulae- Dense granules-

• So platelets also called as “Tiny pharmaceutical bags”

Fibronectin, Factor V, VII, PF4, PDGF,

ADP, ATP, 5 HT,

histamine and Ca.



• Tubules- Open and Dense Open- communicate with ECF Dense- donot communicate

with exterior. Contractile clements_ Actin and Myosin-

action of these help in producing pseudopods.

Platelets donot have DNA or RNA.



Functions of Platelets

• Adheison: Platelets have receptors for collagen. So bind to subendothelial collagen at the site of injury. This is reinforced by Von Willebrand factor

• Aggregatoin: Following adhesion platelet get activatec and secrete ADP and Thromboxane A2 which attract other platelet to form a lump of platelets.



Development of Platelet• In RBM from pluripotent stem cells

Committed stem cell CFU

Promegakaryoblast Megakaryoblast

Megakaryocyte

Platelets.



Coagulation factors : I. Fibrinogen II. Prothrombin III. Tissue Thromboplastin IV. Ca V. Proaccelerin or Labile factor VI. Not Present VII. Proconvertin or Stable factor VIII. Antihemophelic factor IX. Christmas facotr or Plasma

thromboplastin component or AHF B X. Staurt facotor XI. Plasma thromboplastin anticedent XII. Hageman factor or glass factor XIII. Fibrin stabilizing factor or Laki Larland

factor.



Coagulation cascade

• Coagulation of blood is secondary hemostasis. Occurs little after platelet plug formation.

• There are procoagulant substances in blood which are proenzymes in nature. Once process of clotting starts these proenzymes become activated one after another in a sequential manner. Final end product is fibrin. Fibrins are thread like structures .

• Large number of fibrin threads crisscross with each other and blood cells are entangled in the fibrin network. Fibrin thread containing blood cells is known as clot.



• Ultimately fibrin must be formed. This is formed from precursor fibrinogen. Thrombin acts on fibrinogen to form fibrin. Thrombin is present as prothrombin which is activated to thrombin by factor Xa.

• Xa is produced by one of the two major pathways. – Intrensic or Extrensic pathway.



• Triggering mechanism for Intrensic pathway- injury to vessels leading to contact of factor XII with the subendothelial tissue of the blood vessel.

• Triggering mehcanism for extrensic

pathway – release of tissue thromboplastin from the injured vascular and other cells.

• Fibrin formed is stabilized by XIIIa.

• Clot formed is soft and friable. After clot retraction yellowish fluid separates out from clot. This fluid is serum.


XII contact with subendothelium

XII XIIa

XI XIa VIIIa,PL,Ca

IX IXa

Release of Tissue thrombopolastin

VII VIIa

Common Pathway

X Xa

Xa, PL, Va, Ca

Prothrombin Thrombin

Fibrinogen Fibrin XIIIa Stable Fibrin

Intrinsic Pathway Extrinsic Pathway


Inhibitors of Coagulation

• Clot formed remains confined to the site of injury. How???

i) Naturally occurring anticoagulants- Antithrombin

- Heparin

- Protein C

- Protein S

ii) TFPI : Tissue factor pathway inhibiors. iii) Thrombomodulin: iv) Fibrinolytic mechanism.


Fibrinolytic Pathway

Plasminogen

Plasminogin is adsorbed on the clot

Local endothelial cells produce plasminogen activator.

Plasminogen Plasmin

Breaksdowns the fibrin threads

Engulfed by the RES

Present in liver and circulating blood

( tPA: tissue plasminogen activator and Urokinase)


Role of Vit K, Liver, vWF,

• Vit K: - Essential for activation of factors II, VII,

IX, X

- Sourses: - Vegetables ( Cabbage) - Intestinal flora

- Deficiency is seen in- Comatose patient - New borns - Obstructive

juandice


Role of Liver

• Synthesizes factors II,VII,IX,X, I, V, XI

• Also synthesize : antithrombin III, heparin, protein C & protein S.

• So in real life liver failure may be associated with excessive bleedign as well as intravascular coagulation


Role of vWF• It is synthesized by Megakaryocyte and

vascular endothelium

Functions-

-Acts a bridge betweenplatelet

and denuded subendothelium

.

-between platelet and platelet.

- Acts as a carrier for factor VIII


Applied aspects


Investigations• Bleeding time: - Ivy method- 7-11mins - Duke’s method-1-4 mins

• Clotting time- Wright cappillary tube method- 1-7 mins

- Lee and white method-5-10 mins

• Prothrombin time ( PT) Normal value- 10-20 seconds ( Quick

method) Defect in extrinsic and common pathway.•


• Activated partial thromboplastin time ( APTT)

Normal value- 40 sec Defect in intrinsic and common

pathway.

• Platelet count : 150,000 to 400,000cells/cu mm

• Clot retraction time : 30-60 mins

• Cappillary fragility test : more than 10 petechiae/ inch


Conclusion• Hemostasis & coagulation are the body’s

best mechanisms to prevent blood loss from the body.

• Many bleeding and clotting disorders manifest mainly in oral cavity.

• Thorough medical history and investigations help in identifying those persons at risk of increased bleeding after surgery.

• Those people at risk must be identified prior to minor or major surgery to prevent further complication

• Thorough understanding of hemostatic and coagulation will help in us to determine the appropriate test and treatment.


Refferences• Arthur C Guyton. Text book of medical

physiology. 8th ed

• Chaudhuri. Text book of Concise medical physiology. 4th ed

• Willium F Ganong. Review of Medical physiology. 12th ed

• K. Sembulingam. Essentials of medical physiology

• www.wikipedia .com

• Google immages


Thank you…

2 coagulation

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