BLOOD, COAGULATION

OF BLOOD & BLEEDING

DISORDERS
BY
DR. ANTARLEENA SENGUPTA
I YEAR MDS
DEPARTMENT OF PERIODONTOLOGY
MCODS MANGALORE
2019
CONTENTS
• BLOOD
• COMPONENTS
• THROMBUS AND EMBOLI
• COAGULATION OF BLOOD
• APPLIED ASPECTS
• BLEEDING DISORDERS
• CLOTTING DISORDERS
• CONCLUSION
• REFERENCES
2
  Specialized tissue composed of many different kinds

BLOOD
of cellular and matrix components, such as RBCs,
WBCs, platelets and plasma.
 Makes up ̴ 7-8% of body weight
 5 L in adult human

• Functions:
• Transports O2 and nutrients to tissues from pulmonary & digestive
systems
• Transports waste products e.g., CO2 away from the tissues to
pulmonary system.
• Maintains pH of body fluids
• Removal of lactic acids (from muscles), urea, ammonia, etc..
• Maintains thermal equilibrium: facilitates homeostasis
• Medium for transport of hormones from site of production to
action
• Important for maintaining immunity. 3
COMPONENTS OF BLOOD
• Erythrocytes/Red blood cells(RBC)
• Leukocytes/White blood cells(WBC)
• Thrombocytes/Platelets
• Plasma
• Serum

4
ERYTHROCYTES
• Biconcave discs having a mean diameter of 7.8 μm
• Average volume: 90-95 mm3
• Shape of RBCs can change as they squeeze through capillaries.
• RBC count:
• Healthy males: 5,200,000 (±300,000)
• Healthy females: 4,700,000 (±300,000)
• Physiological variations: persons living at high altitudes--
↑hypoxia
• Pathological variations:
• ↑ in polycythaemia
• ↓ in nutritional anaemia
• ↓ in haemolytic anaemia
• Major function: transport HEMOGLOBIN(Hb)
• Also contain large quantities of CARBONIC ANHYDRASE 5
STRUCTURE OF HEMOGLOBIN

6
METABOLISM OF ERYTHROCYTES
• RBCs have ability to concentrate Hb in the cell fluid up
to 34 g/100 mL of cells.
• Metabolic limit of cell’s Hb-forming mechanism.
• Hb carries O2 from lungs to tissues.
• Contains a large quantity of Carbonic anhydrase
• The rapidity of this reactionEnzyme
makesthatit catalyses
possible reversible
for thereaction
between CO2 and H2O to form carbonic
water of the blood to transport
acid, enormous quantities
H2CO3, increasing ofthis
the rate of
CO2 in the form of bicarbonate ionseveral
reaction fromthousand
the tissues
folds. to the
lungs, where it is reconverted to CO2 and expelled into
atmosphere as a body waste product.
• Hb in cells is an excellent acid-base buffer of whole
blood. 7
HEMATOCRIT
• The proportion of blood to RBCs is called the
haematocrit.
• Avg. haematocrit value for adult men= 42; women= 38.
• Determined by centrifuging blood in a haematocrit tube
until the cells become tightly packed in the bottom of the
tube.
 WINTROBE’s METHOD to calculate Erythrocyte
Sedimentation Rate (ESR)
65%
10%
8
ERYTHROPOIESIS

9
Stages of differentiation of RBCs

10
Regulation of RBC production- role of
Erythropoietin
Kidney Hematopoietic stem cells

Proerythroblasts
Erythropoietin

Decreases Red blood cells

Tissue Oxygenation
Decreases

1. Low blood volume

2. Anaemia
3. Low Hb
4. Poor blood flow

11
5. Pulmonary disease
CLINICAL CONSIDERATIONS
Macrocytic Normocytic Microcytic
(MCV > 100) (MCV 80-100) MCV < 80)
Vit B12 deficiency Post-hemorrhagic Iron deficiency
(megaloblastic) • Dietary deficiency
• Dietary deficiency • Inhibitory diet (high
• Pernicious anaemia phytate)
Gastric resection
•• ANEMIA • Hookworm
• Ileal disease • Chronic bleeding
•• POLYCYTHEMIA
Tropical sprue • Infection
• Fish tapeworm
• JAUNDICE
Folate deficiency Endocrine disorder Thalassemia
(megaloblastic) • Hypothyroidism
• Dietary deficiency • Addison’s disease
• Drug induced • Hypopituitarism
• Pregnancy
• Tropical sprue
Hypothyroidism Anaemia of chronic disorders Hemoglobinopathies (S, C, E)
12
Alcoholism Anaemia of chronic disorders,
infection
13
 POLYCYTHEMIA
• POLYCYTHEMIA VERA (Erythemia)
• Pathological condition
• Increased RBC count: 7-8 million/mm3; ↑Haematocrit value (60-
70%)
• Caused by genetic aberration in hemocytoblastic cells. The blast
cells no longer stop producing RBCs when too many cells are
already present.
• Total blood volume also increases
• Capillaries become plugged by the viscosity of the blood.

• SECONDARY POLYCYTHEMIA
14
 JAUNDICE
• Refers to a yellowish tint to the body
tissues, including a yellowness of skin
as well as deep tissues.
• Mechanism: large quantities of
BILIRUBIN in extracellular fluids,
either conjugated or unconjugated.
• Normal plasma concentration: 0.5
mg/dL of plasma. In jaundice, starts
from 1.5 mg/dL- 40 mg/dL
• Cause:
1. Increased destruction of RBCs
(rapid release of bilirubin into
blood)– HEMOLYTIC
JAUNDICE
2. Obstruction of bile ducts/ damage
to liver cells (inability to excrete
bilirubin into GIT)–
OBSTRUCTIVE JAUNDICE
15
LEUKOCYTES
• Also called white blood cells (WBCs)
• Mobile units of the body’s protective system.
• Formed partially in the bone marrow (granulocytes,
monocytes and a few lymphocytes) and partially in the
lymph tissue (lymphocytes and plasma cells)
• Transported specifically to areas of serious infection and
inflammation
• Providing a rapid and potent defence against infectious
agents.

16
GENERAL CHARACTERISTICS OF
LEUKOCYTES
• TYPES OF WHITE BLOOD CELLS
• Polymorphonuclear neutrophils
• Polymorphonuclear eosinophils
• Polymorphonuclear basophils
• Monocytes
• Lymphocytes
• Plasma cells
• Megakaryocyte

17
GENESIS OF WBC

18
NEUTROPHILS & MACROPHAGES
• Attack and destroy invading bacteria, viruses and other
injurious agents.
• Macrophages are immature monocytes which swell once
they enter tissues as great as 60-80 micrometres.
• Squeeze through the pores of blood capillaries by
diapedesis.
• Move through tissue surfaces by amoeboid motion.
• Attracted towards inflamed tissue by chemotaxis.
• Most important function: PHAGOCYTOSIS.
• Depends on: 1. smoothness of surface
2. presence of protective protein coat
3. immune system 19
RETICULOENDOTHELIAL SYSTEM

Network of connective tissue fibres inhabited by

phagocytic cells such as macrophages ready to
attack and ingest microbes.

RES is an essential component of immune

system.

20
EOSINOPHILS
• Constitute about 2% of all the blood leukocytes.
• Eosinophils are weak phagocytes
• Often produced in large numbers in cases of parasitic
infections
• Attach themselves to parasites by special surface
molecules and release substances that kill many of the
parasites.e.g., Schistosomiasis, trichinosis etc..
• Propensity to collect in tissues in which allergic reactions
occur via eosinophil chemotactic factor released by mast
cells & basophils.
21
BASOPHILS
• Basophils in the circulating blood are similar to the large
tissue mast cells located immediately outside capillaries
in the body.
• Liberate heparin into blood.
• Also release histamine, bradykinin and serotonin.
• IgE has special propensity to become attached to
basophils.
• Leads to local vascular and tissue reactions of allergic
manifestations.

22
CLINICAL CONSIDERATIONS
• LEUKOPENIA
• Bone marrow produces very few WBCs
• Leaves the body unprotected against many bacteria and
other agents that might invade the tissues.
• LEUKEMIA
• Uncontrolled
Common effects in production ofdevelopment
leukaemia are WBCs; greatly increased
of infection, WBC
severe
anaemia,
countbleeding tendency
in circulating caused by thrombocytopenia.
blood
• LYMPHOCYTIC and MYELOGENOUS
IMPORTANT EFFECT on the body is excessive use of metabolic
 LYMPHOCYTIC
substrates by the growingLEUKEMIA
cancerous cells. The leukemic tissues
• Caused
reproduce new by cancerous
cells production
so rapidly of lymphoid
that tremendous cellsare made on
demands
• Usually begins in lymph node or other lymphocytic tissue and
the body.
Energyspreads
of the patient
throughis the
greatly depleted.
body.
While leukemic tissues grow, others become debilitated. 23
Metabolic starvation over continued period of time can lead to death.
MYELOGENOUS LEUKEMIA
• Cancerous production of young myelogenous cells in the
bone marrow
• Spreads throughout the body
• WBCs are produced in extra medullary tissues– lymph
nodes, spleen, liver.
• The cancerous process occasionally produces partially
differentiated cells
• Results in neutrophilic leukaemia, eosinophilic
leukaemia, basophilic leukaemia, or monocytic
leukaemia..
• Leukaemia cells are bizarre and undifferentiated; no
resemblance to normal WBCs
24
 PLATELETS
• Also called thrombocyte
• Small, colourless disc-shaped
cell fragment without a nucleus
• 1-3 μm in diameter.
• Platelets are formed from bone
marrow megakaryocytes.
• 1/3rd of circulating platelets
become temporarily
sequestered in the spleen.
• Normal platelet count=
150,000-450,000/uL.
25
EVENTS IN HEMOSTASIS
• Whenever a vessel is severed or ruptured, haemostasis is
achieved by several mechanisms:
1) Vascular constriction
2) Formation of a platelet plug
3) Formation of a blood clot as a result of blood coagulation
4) Eventual growth of fibrous tissue into the blood clot to
close the hole in the vessel permanently.

26
VASCULAR CONSTRICTION
• Immediately after a blood vessel has been cut or ruptured,
the trauma to the vessel wall causes the smooth muscle in
the wall to contract.
• Instantaneous reduction of flow of blood from ruptured
vessel
• The contraction results from
1. Local myogenic spasm
2. Local autacoid factors
3. Nervous reflexes
• More vasoconstriction results from local myogenic
contraction of blood vessels initiated by direct damage to
vascular wall. 27
FORMATION OF PLATELET PLUG

• If the cut in the vessel is very small, it is sealed by a

PLATELET PLUG, rather than by a blood clot.

28
 BLOOD COAGULATION IN RUPTURED
VESSEL
• Third mechanism of
haemostasis is formation
of the blood clot.
• Clot begins to develop in
15-20 sec if trauma is
severe, and in 1-2 mins if
minor trauma
• ACTIVATOR substances
from traumatized
vascular wall, from
platelets, and from blood
proteins adhere to
vascular wall, initiating
the clotting process. 29
 THROMBOCYTOPENIA
• Presence of very low
numbers of platelets in
circulating blood.
• Patients have a tendency to
bleed from small venules or
capillaries.
• Small punctate
haemorrhages occur
throughout all body
tissues.(small, purplish
blotches)→
Thrombocytopenic purpura
30
• Ordinarily bleeding will not occur until the number of
platelets in the blood falls below 50,000/𝜇𝐿 [normal=
1,50,000-3,00,000/𝜇𝐿]
• Most people with thrombocytopenia have the disease
known as idiopathic thrombocytopenia.
• In these people, specific antibodies form and react against
platelets to destroy them.
• Relief from bleeding up to 4 days can be achieved by
FRESH WHOLE BLOOD TRANSFUSIONS (containing
large no. of platelets)
• SPLENECTOMY

31
 THROMBUS & EMBOLI
• An abnormal clot that
develops in a blood vessel
is called a THROMBUS.

• Once the clot has

developed, continued
blood flow past the clot is
likely to break it away
from its attachment and
cause the clot to flow with
the blood, which is called
an EMBOLUS. 32
CAUSES OF THROMBOEMBOLIC
CONDITIONS
1. Any roughened endothelial surface of a vessel– as may
be caused by arteriosclerosis, infection, trauma– is
likely to initiate the clotting process.

2. Blood often clots when it flows very slowly through

blood vessels– where small quantities of thrombin/other
pro-coagulants are always being formed.

33
FEMORAL VENOUS THROMBOSIS & MASSIVE
PULMONARY EMBOLISM
• Immobile patients confined to
bed
• Propping knees with pillows

 Intravascular clotting due to

blood stasis for several hours
 Clot grows in the direction of
slowly moving venous blood
 Can grow the entire length of
leg veins and sometimes even
into common iliac vein and
inferior vena cava
34
35
TREATMENT FOR INTRAVASCULAR
CLOTS

• Use of t-PA
• Genetically engineered tissue plasminogen activator
• Effective in activation of plasminogen → plasmin
• Delivered directly to thrombosed area through catheter

• Embolectomy
Surgical removal of an embolus.

36
PLASMA & SERUM
• PLASMA
• 1/4th of extracellular fluid in body (̴ 3 Litres)
• Non-cellular part of blood
• Exchanges substances continuously with interstitial fluid
through pores in capillary membranes
• Higher protein concentration than interstitial fluids.

• SERUM
• Fluid expressed following retraction of clot
37
 BLOOD COAGULATION
• Basic Theory:
 Substances that promote clotting are called procoagulants.
 Substances that inhibit clotting are called anticoagulants.
 Coagulation of blood depends on the balance of these two.
 In the blood stream, anticoagulants normally predominate, so no
clotting occurs whilst in circulation
 When a vessel is ruptured, procoagulants from area of damage
become activated and override the coagulants to form a clot.

• General mechanism:
1. Response to tissue rupture/damage→ formation of prothrombin
activator
2. Catalysis of conversion of prothrombin→ thrombin
3. Fibrinogen into fibrin fibres → enmesh platelets, blood cells,
plasma to form the clot. 38
GENERAL MECHANISM OF CLOTTING

1) Initiation of coagulation by formation of prothrombin

activator :
a) Extrinsic pathway that begins with trauma to the vascular
wall and surrounding tissues
b) Intrinsic pathway that begins in the blood itself.
2) Conversion of prothrombin to thrombin.
3) Conversion of fibrinogen to fibrin to form the clot.

39
40
EXTRINSIC PATHWAY FOR BLOOD CLOTTING
Tissue trauma
(1)

Tissue factor

(2) VII VIIa

X Activated X (Xa)
Ca2+
Ca2+
V
Prothrombin
(3) activator
Platelet
phospholipids

Prothrombin Thrombin
Ca2+ 41
 INTRINSIC PATHWAY FOR BLOOD CLOTTING
Blood trauma or contact
with collagen

(1) XII Activated XII (XIIa)

HMW kininogen, prekallikrein
(2) XI Activated XI (XIa)
Ca++

IX Activated IX (IXa)
VIII
(3) Thrombin
VIIIa
Ca++

(4) X Activated X (Xa)

(5) Platelet
phospholipids EXTRINSIC
PATHWAY 42
COMPARATIVE SUMMARY:
EXTRINSIC & INTRINSIC PATHWAYS
OF COAGULATION
EXTRINSIC PATHWAY INTRINSIC PATHWAY
INITIATION By tissue factor Contact of factor XII &
platelets with collagen
in vascular wall
SPEED OF Faster Much slower
COMPLETION
CLOTTING TIME 15 seconds 1-6 minutes
 Explosive
43
 PREVENTION OF CLOTTING IN
NORMAL VASCULAR SYSTEM
 INTRAVASCULAR ANTICOAGULANTS
• Endothelial surface factors:
i. Smoothness of endothelial cell surface
ii. Glycocalyx layer on the endothelium
iii. Thrombomodulin

• Antithrombin action of fibrin and antithrombin III:

Remove thrombin from blood—
i. Fibrin fibres formed during clotting
ii. Alpha globulin called antithrombin III or antithrombin-
heparin cofactor 44
• Heparin
• Powerful anticoagulant
• Normally low concentration in blood
• Produced in large quantities by MAST CELLS
• Also released in small quantities by basophil cells into the
plasma
• Used widely as pharmacological anticoagulant drug in
HIGH CONCENTRATIONS to prevent intravascular
clotting
• Combines with antithrombin III to speed up removal of free
thrombin from blood
• Also removes several activated coagulation factors viz.,
Factors XII, XI, X, IX
45
LYSIS OF BLOOD CLOTS
• Plasma proteins contain a euglobulin called
PLASMINOGEN, when activated becomes PLASMIN
• Proteolytic enzyme resembling trypsin
• Digests fibrin fibres, fibrinogen, Factor V, VII, XII, etc.
• Released by injured tissues in the form of tissue
plasminogen activator (t-PA)
• Importance: removes minute clots from tiny peripheral
vessels so that they do not get occluded.

46
Applied aspects
• Bleeding disorders
• Coagulation disorders
• Thrombocytopenic purpuras
• Non thrombocytopenic purpuras

• Clotting disorders

47
BLEEDING DISORDERS
A. COAGULATION DISORDERS
HEMOPHILIA A
- Deficiency of coagulation factor VIII
- Mild haemophilia: 6-30% factor VIII; rarely bleed
spontaneously. May still have hemorrhage after
trauma/during surgery
- Moderate haemophilia: 1-5% factor VIII; less frequent
spontaneous hemorrhage. May still bleed with minimal
trauma.
- Severe haemophilia: 0-1% factor VIII; severe bleeding on
slightest provocation

48
HEMOPHILIA B, or Christmas disease:
- Deficiency of factor IX
- Severity depends on amount of factor IX remaining

von WILLEBRAND’S DISEASE:

- Deficiency of von Willebrand’s factor, which mediates
adhesion of platelets to injured vessel wall, required for
primary haemostasis
- Has 3 major subtypes, depending upon clinical severity
- Usually hard to diagnose
- Bleeding during dental treatment: first sign of underlying
disease
49
CLOTTING DISORDERS
DISSEMINATED INTRAVASCULAR
COAGULATION (DIC)
- Due to excessive activation of clotting mechanism
- Presence of large amounts of traumatized tissue releasing
tissue factor into blood
- Clots are small & numerous– plug a large share of
peripheral vessels
- Seen in patients with widespread septicaemia
- Situation leads to CIRCULATORY SHOCK.
- Patient on occasion begins to bleed.

50
BLOOD COAGULATION TESTS

51
 PLATELET COUNT

LOW NORMAL

THROMBOCYTOPENIA BLEEDING TIME

PROLONGED NORMAL

APTT APTT

PROLONGED NORMAL PROLONGED

PT PT

PROLONGED NORMAL PROLONGED NORMAL

von WILLEBRAND’S DISORDER OF PLATELET LIVER DISEASES HAEMOPHILIAS FACTOR VII FACTOR XII
DISEASE FUNCTION ANTICOAGULANTS FACTOR XI & XII DEFICIENCY DEFICIENCY
DIC DEFICIENCY DRUGS
OTHERS
OTHERS
PERIODONTAL CONSIDERATIONS
• PATIENTS WITH COAGULATION DISORDERS:
• Probing, scaling, oral prophylaxis– can be done without
medical modification
• Local block anaesthesia, root planing, surgery– prior
physical consultation
• Complete wound closure and application of pressure
• Antihemostatic agents viz., oxidized cellulose, purified
bovine collagen may be placed over surgical sites
• AMICAR (𝜀 − aminocaproic acid)– orally/via IV; potent
inhibitor of initial clot dissolution
• Tranexamic acid oral rinse– prevent excessive oral
hemorrhage post-surgery 53
• Physician’s consent
• Patients on Aspirin >325 mg/day– no need to discontinue
before periodontal procedures
• Laboratory evaluations: PT, bleeding time, platelet count,
PTT
• In case of required surgery:
• INR should be less than 2.0. for simple procedures,
INR<2.5 is generally safe
• Platelet count should be more than 80,000/mm3
• Care should be taken before prescribing NSAIDs (e.g.,
Ibuprofen) as it inhibits platelet function.

54
• PATIENTS WITH THROMBOCYTOPENIC PURPURAS:
- Avoid need for aggressive therapy– reduce local inflammation
- Oral hygiene instructions
- Frequent maintenance visits
- Scaling and root planing: SAFE for platelet count ‘til
60,000/mm3
- Platelet transfusion may be necessary before surgery
- Atraumatic surgical technique
- Local haemostatic measures.

55
• PATIENTS WITH NON-THROMBOCYTOPENIC
PURPURAS:
- Local measures of haemostasis: direct pressure applied for 15
minutes
- Surgical therapy to be AVOIDED until platelet count is
normal

• PATIENTS WITH BLOOD DYSCRASIAS:

- Laboratory testing
- Physician referral

56
• PATIENTS WITH AGRANULOCYTOSIS:
- Periodontal Rx should be done during periods of remission
- Conservative treatment approach
- Use of CHLORHEXIDINE mouthwash rinse TWICE daily.
- Scaling and root planing– under antibiotic protection.

57
• PATIENTS WITH LEUKEMIA:
- Refer the patient for medical evaluation & treatment
- Monitor hematologic reports daily: bleeding time, coagulation
time, prothrombin time and platelet count.
- Administer antibiotic coverage before staring treatment
- Extract all hopeless, non-maintainable, potentially infectious
teeth at least 10 days prior
- If allowed, periodontal debridement should be performed
along with thorough oral hygiene instructions
- 2x daily oral rinse with 0.12% CHLORHEXIDINE
GLUCONATE
- Use pressure and topical haemostatic agents as indicated
- In acute leukaemia, ONLY EMERGENCY periodontal care
- Oral ulcerations, mucositis: viscous LIDOCAINE
- Systemic antibiotics to prevent secondary infection
- In oral candidiasis: NYSTATIN suspensions (100,000 U/mL 58
4x daily or CLOTRIMAZOLE vaginal suppositories (10mg
4-5x daily)
- Patients with chronic leukaemia/ remission– scaling &
root planing can be performed.
- Periodontal surgery to be avoided.

59
CONCLUSION

• Patients with history of bleeding problems caused by

disease/drugs should be managed to minimize risks of
haemorrhage
• Identification of health history, clinical examination and
clinical laboratory tests is paramount.

60
REFERENCES
• GUYTON & HALL, Textbook of Medical Physiology, 1st
SE Asia Edn.,
• ROBBINS & COTRAN, Pathologic Basis of Disease,
Vol. 1.,
• CARRANZA’s Clinical Periodontology, 10th edn.
• Images: Wikimedia Commons

61
62