Blood and Clotting Mechanism

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BLOOD AND

CLOTTING
MECHANISM
BY DR RAHUL PANDEY
MDS IST YEAR
DEPARTMENT OF PEDODONTICS AND PREVENTIVE DENTISTRY

SEEMA DENTAL COLLEGE AND HOSPITAL RISHIKESH.


CONTENTS:

• Introduction
• Functions of blood
• Composition of blood
• Hemostasis
• Coagulation mechanism
• Anticoagulants
• Applied physiology
• References
INTRODUCTION:

• Blood is a connective tissue in fluid form.


• Fluid of life
• Color: Scarlet red – Arterial blood
Purple red – Venous blood
• Volume: Avg Adult volume – 5L
Newborn baby – 450mL
• pH: Normal Conditions – 7.4

K sembulingam, Prema Sembulingam. Essentials of physiology for dental students,2 nd Edition,Jaypee Publications, New
Delhi; Chapter 6:39-91
Functions of blood:

• Nutrient function
• Respiratory function
• Excretory function
• Transport of Hormones & Enzymes
• Regulation of water balance
• Regulation of acid-base balance
• Regulation of body temperature
• Storage function
• Defensive function
K sembulingam, Prema Sembulingam. Essentials of physiology for dental students,2 nd Edition,Jaypee Publications, New
Delhi; Chapter 6:39-91
Composition of blood:

• Blood cells – Red Blood cells


White Blood cells
Platelets/Thrombocytes
• Plasma
• Serum

K sembulingam, Prema Sembulingam. Essentials of physiology for dental students,2 nd Edition,Jaypee Publications, New
Delhi; Chapter 6:39-91
Red blood cells aka Erythrocytes:
• They are the non-nucleated formed
elements in the blood.
• The red color of the RBC is due to
the presence of hemoglobin.
• In adult males, it is 5 millions/cu
mm and in adult females it is 4.5
millions/cu mm.
• The normal RBC range
for children is 4.0 to 5.5 million
mcL.
K sembulingam, Prema Sembulingam. Essentials of physiology for dental students,2 nd Edition,Jaypee Publications, New
Delhi; Chapter 6:39-91
Hemoglobin:

• Hemoglobin (Hb) is the iron-containing coloring pigment of red blood cell (RBC).
It forms 95% of dry weight of RBC and 30 to 34% of wet weight.

K sembulingam, Prema Sembulingam. Essentials of physiology for dental students,2 nd Edition,Jaypee Publications, New
Delhi; Chapter 6:39-91
Structure of Hemoglobin:

• Hb is a conjugated protein.
• Consists of a protein – globin
• Iron-containing pigment - heme.
• 2 types of hemoglobin: 1. Adult hemoglobin
• 2. Fetal hemoglobin

Cantu I, Philipsen Sjaak. Flicking the switch: adult hemoglobin expression in erythroid cells derived from cord blood and
human induced pluripotent cells, Haematologica 2014;99(11):1647-1650.
Cantu I, Philipsen Sjaak. Flicking the switch: adult hemoglobin expression in erythroid cells derived from cord blood and
human induced pluripotent cells, Haematologica 2014;99(11):1647-1650.
White Blood Cells: (Leukocytes)

• Defence mechanism of body.


• 2 types: Granulocytes and Agranulocytes

Neutrophils Lymphocytes
Basophils
Eosinophils Monocytes

K sembulingam, Prema Sembulingam. Essentials of physiology for dental students,2 nd Edition,Jaypee Publications, New
Delhi; Chapter 6:39-91
Platelets: (Thrombocytes)

• Functions:
• Blood clotting
• Clot retraction
• Haemostasis
• Repair of ruptured blood vessel
• Defence mechanism

K sembulingam, Prema Sembulingam. Essentials of physiology for dental students,2 nd Edition,Jaypee Publications, New
Delhi; Chapter 6:39-91
Hemostasis:

• Hemostasis is defined as arrest or stoppage of bleeding.


• Stages:
1. Vasoconstriction
2. Platelet plug formation
3. Coagulation of blood

K sembulingam, Prema Sembulingam. Essentials of physiology for dental students,2 nd Edition,Jaypee Publications, New
Delhi; Chapter 6:39-91
Coagulation of blood:
• Coagulation or clotting is defined as the
process in which blood loses its fluidity
and becomes a jelly-like mass few
minutes after it is shed out or collected
in a container.

K sembulingam, Prema Sembulingam. Essentials of physiology for dental students,2 nd Edition,Jaypee Publications, New
Delhi; Chapter 6:39-91
Sequence of Clotting
Mechanism
ENZYME CASCADE THEORY:
Enzyme cascade theory:
Fibrinolysis:

• Removal of clot from blood vessels.


• Plasmin or Fibrinolysin.

Liver Plasminogen
t-PA, lysosomal enzymes, thrombin

Lysis of clot Plasmin


Anticlotting mechanism of the body:

• Under physiological conditions, clotting does not occur.


1. Physical factors: - continuous flow of blood & smooth endothelial
lining of blood vessels
2. Chemical factors:
Heparin produced by Liver
Thrombomodulin

K sembulingam, Prema Sembulingam. Essentials of physiology for dental students,2 nd Edition,Jaypee Publications, New
Delhi; Chapter 6:39-91
Anticoagulants:

• The substances, which prevent or postpone coagulation of blood are


called anticoagulants.
• 2 types:
1. In vivo
2. In vitro

K sembulingam, Prema Sembulingam. Essentials of physiology for dental students,2 nd Edition,Jaypee Publications, New
Delhi; Chapter 6:39-91
Heparin:

• Produced by mast cells present in lungs and liver.


• Basophils also produce heparin
• Commercially prepared from animal liver.
• Available in liquid and dry forms.
• As salts of sodium, calcium, ammonium, lithium

K sembulingam, Prema Sembulingam. Essentials of physiology for dental students,2 nd Edition,Jaypee Publications, New
Delhi; Chapter 6:39-91
Mechanism of Heparin:
Clinical use:

• To prevent intravascular blood clotting during surgery.


• Dialysis
• Cardiac surgery
• Preserve blood before transfusion
• Sample collection

K sembulingam, Prema Sembulingam. Essentials of physiology for dental students,2 nd Edition,Jaypee Publications, New
Delhi; Chapter 6:39-91
Dicoumarol and Warfarin:

• Inhibit vitamin K.
• Vitamin K is essential for formation of clotting factors like
II,VII,IX,X.
• Uses: Commonly used as oral anticoagulants.

K sembulingam, Prema Sembulingam. Essentials of physiology for dental students,2 nd Edition,Jaypee Publications, New
Delhi; Chapter 6:39-91
EDTA:

• 2 forms: a. Disodium salt (Na2EDTA)


b. Tripotassium salt (K3EDTA)
• Acts by removing calcium from blood
• Uses:
a. I.V in lead poisoning
b. In laboratory settings

K sembulingam, Prema Sembulingam. Essentials of physiology for dental students,2 nd Edition,Jaypee Publications, New
Delhi; Chapter 6:39-91
Other substances:

• Peptones
• Proteins form venom of copper head snake
• Hirudin from leech.

K sembulingam, Prema Sembulingam. Essentials of physiology for dental students,2 nd Edition,Jaypee Publications, New
Delhi; Chapter 6:39-91
Procoagulants:

• Thrombin
• Snake venom
• Extracts of lungs and thymus
• Sodium and calcium alginate
• Oxidized cellulose

K sembulingam, Prema Sembulingam. Essentials of physiology for dental students,2 nd Edition,Jaypee Publications, New
Delhi; Chapter 6:39-91
Tripodi A, Lippi G, Plebani M. How to report results of prothrombin and activated partialthromboplastin times. Clin
Chem Lab Med. 2016;54(2):215-222.
Tripodi A, Lippi G, Plebani M. How to report results of prothrombin and activated partialthromboplastin times. Clin
Chem Lab Med. 2016;54(2):215-222.
Applied physiology:
Bleeding disorders:

1. Hemophila
2. Purpura
3. Von Willebrand Disease
Hemophilia:

• Results from deficiency of procoagulants.


• Inherited bleeding disorder
• Prevalence: 1 in 7500 males.
• 2 types: Hemophilia A
Hemophilia B

McDonald R, Avery D, Dean J. Dentistry for the child and adolescent, 8 th Edition, Mosby Elsevier Publishers, USA, 2004; Ch
24, Management of medically compromised patient:557-579
Classification of Hemophilia A & B:

• Based on levels of procoagulants present:


a. Severe deficiency- levels less than 1%
b. Moderate deficiency – levels between 1% to 5%
c. Mild deficiency – Levels greater than or equal to 5%

McDonald R, Avery D, Dean J. Dentistry for the child and adolescent, 8 th Edition, Mosby Elsevier Publishers, USA, 2004; Ch
24, Management of medically compromised patient:557-579
Complications:

• Serve cases – bleeding episodes 2-4 times a month.


• Common sites – joints, muscles, skin
• Hemarthrosis – pain, stiffness, limited motion
• Pseudotumors – Hemorrhagic pseudocysts
site – jaws
management – curettage.

McDonald R, Avery D, Dean J. Dentistry for the child and adolescent, 8 th Edition, Mosby Elsevier Publishers, USA, 2004; Ch
24, Management of medically compromised patient:557-579
Complications:

• Moderate cases – 4-6 bleeding episodes per year.


• Mild cases – bleeding only during injury or surgery.

• Mouth ulcerations common in children with hemophilia.

McDonald R, Avery D, Dean J. Dentistry for the child and adolescent, 8 th Edition, Mosby Elsevier Publishers, USA, 2004; Ch
24, Management of medically compromised patient:557-579
Hemiphilia A:

• Deficiency of factor VIII (antihemophilic factor)


• X-linked recessive trait
• Males affected, females carriers.
• No male-male transmission

McDonald R, Avery D, Dean J. Dentistry for the child and adolescent, 8 th Edition, Mosby Elsevier Publishers, USA, 2004; Ch
24, Management of medically compromised patient:557-579
Hemophilia B:

• Christmas disease.
• Deficiency of factor IX.
• One-fourth as prevalent as factor VIII deficiency.

McDonald R, Avery D, Dean J. Dentistry for the child and adolescent, 8 th Edition, Mosby Elsevier Publishers, USA, 2004; Ch
24, Management of medically compromised patient:557-579
Treatment:

• Replacement of deficient procoagulant.


• Hemophilia A –
• Factor VIII concentrate: 1U
• DDAVP (1-diamino-8-D-ariginine vasopressin)
• Intra nasal desmopressin
• Hemophilia B -
• Factor IX concentrate – Prothrombin complex conc.(PCC)

McDonald R, Avery D, Dean J. Dentistry for the child and adolescent, 8 th Edition, Mosby Elsevier Publishers, USA, 2004; Ch
24, Management of medically compromised patient:557-579
Von Willebrand disease:

• Deficiency of von Willebrand factor.


• Reduced platelet adhesion to subendothelium
• Impaired platelet plug formation.
• Bleeding from skin, mucosa, bruising, epistaxis, prolonged bleeding
during surgical procedures, menorrhagia.

McDonald R, Avery D, Dean J. Dentistry for the child and adolescent, 8 th Edition, Mosby Elsevier Publishers, USA, 2004; Ch
24, Management of medically compromised patient:557-579
von Willebrand Disease:
Treatment:

• DDAVP
• Antifibrinolytics:
• ε-aminocaproic acid (Amicar) – (Tab & Syp)
100-200mg/kg loading dose before procedure
50-100mg/kg per dose 6th hourly for 5-7 days.
• Tranexamic acid (Cyklokapron) –
25mg/kg before procedure
same dose continued 6th hourly for 5-7 days

McDonald R, Avery D, Dean J. Dentistry for the child and adolescent, 8 th Edition, Mosby Elsevier Publishers, USA, 2004; Ch
24, Management of medically compromised patient:557-579
Analgesics:

• DO NOT USE Aspirin & Ibuprofen


• Acetominphen (Tylenol, Tempra)
• Propoxyphene hydrochloride (Davron)
• Narcotic analgesics for severe pain.

McDonald R, Avery D, Dean J. Dentistry for the child and adolescent, 8 th Edition, Mosby Elsevier Publishers, USA, 2004; Ch
24, Management of medically compromised patient:557-579
Anesthesia:

• PDL injections recommended in absence of factor replacement.


• Cautious administration for PSA nerve blocks to avoid Hematoma.

McDonald R, Avery D, Dean J. Dentistry for the child and adolescent, 8 th Edition, Mosby Elsevier Publishers, USA, 2004; Ch
24, Management of medically compromised patient:557-579
Purpura:
Treatment:
Thrombosis:

• Causes:
I. Injury to blood vessels
II. Roughened endothelial lining
III. Sluggish blood flow
IV. Agglutination of RBC’s
V. Snake venom, mercury, arsenic compounds
VI. Congenital absence of vitamin C.
Complications of thrombosis:

1. Thrombus
2. Embolism and Embolus
3. Ischemia
4. Necrosis and Infarction

K sembulingam, Prema Sembulingam. Essentials of physiology for dental students,2 nd Edition,Jaypee Publications, New
Delhi; Chapter 6:39-91
Thrombus:
Disseminated Intravascular Coagulation:

• DIC is a syndrome characterized


by the systemic activation of
blood coagulation.
• Generates intravascular thrombin
and fibrin.
• Resulting in the thrombosis of
small- to medium sized vessels
and ultimately organ dysfunction
and severe bleeding.
Wada H, Matsumoto T, Yamashita Y. Diagnosis and treatment of disseminated intravascular coagulation (DIC) according to
four DIC guidelines, Journal of intensive care 2014;2:15-22.
Treatment:

• Treatment of underlying disease


• Blood transfusion
• Heparin
• Protease inhibitors
• Antifibrinolytic treatment

Wada H, Matsumoto T, Yamashita Y. Diagnosis and treatment of disseminated intravascular coagulation (DIC) according to
four DIC guidelines, Journal of intensive care 2014;2:15-22.
References:

• Cantu I, Philipsen Sjaak. Flicking the switch: adult hemoglobin expression in erythroid cells
derived from cord blood and human induced pluripotent cells, Haematologica 2014;99(11):1647-
1650.
• K sembulingam, Prema Sembulingam. Essentials of physiology for dental students,2nd
Edition,Jaypee Publications, New Delhi; Chapter 6:39-91
• Wada H, Matsumoto T, Yamashita Y. Diagnosis and treatment of disseminated intravascular
coagulation (DIC) according to four DIC guidelines, Journal of intensive care 2014;2:15-22.
• McDonald R, Avery D, Dean J. Dentistry for the child and adolescent, 8th Edition, Mosby
Elsevier Publishers, USA, 2004; Ch 24, Management of medically compromised patient:557-579.
• Tripodi A, Lippi G, Plebani M. How to report results of prothrombin and activated
partialthromboplastin times. Clin Chem Lab Med. 2016;54(2):215-222.
Questions:
Ozer S, Kazanci N O et al. A rare seen hemorrhage disorder: Factor XI deficiency Hemophilia C, Meandros Med Dent
J,2018;19:75-8.
Totipotent Pluripotent Multipotent

Relative potency High Medium Low

Cell types capable of Differentiate into any Differentiate into cells Differentiate into a
generating cell type from any of the three limited range of cell
germ layers types

Terminology Toti = Whole Pluri = Many Multi = Several


Examples Zygote, early morula Embryonic stem cells, Haematopoietic stem
Induced pluripotent cells, neural stem cells,
stem cells mesenchymal stem
cells

Found Early cells of fertilised Inner mass cells of the In many tissues
egg blastocyst
THANK YOU

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