Blood coagulation is a complex process involving multiple coagulation factors that work together in a cascade to ultimately convert fibrinogen into fibrin to form a blood clot. There are two pathways (intrinsic and extrinsic) that lead to the formation of thrombin, which then converts fibrinogen into fibrin. Some bleeding disorders result from deficiencies in specific coagulation factors, such as Hemophilia A and B due to Factor VIII and IX deficiencies. Von Willebrand disease is caused by a defect in von Willebrand factor which is involved in platelet function. Coagulation tests evaluate different parts of the coagulation cascade to identify deficiencies.

1. BLOOD COAGULATION
Dr. SUSHMITHA SHANKAR
POST GRADUATE STUDENT
DEPARTMENT OF PERIODONTOLOGY

2. CONTENTS
1. INTRODUCTION
2. HEMOSTASIS
3. FACTORS INVOLVED IN BLOOD COAGULATION
4. THE CLOTTING MECHANISM
5. CLOT RETRACTION
6. FIBRINOLYSIS
7. ANTICOAGULANTS
8. TESTS FOR BLOOD CLOTTING
9. BLEEDING DISORDERS
10. THROMBOSIS
11. MANAGEMENT OF PATIENTS WITH BLEEDING DISORDERS
12. COVID AND BLOOD CLOTTING

3. INTRODUCTION
Fluidity is essential for circulation of blood and Clotting
is required as a defense during blood loss. Blood when
shed, loses its fluidity in few seconds and becomes jelly
like. This phenomenon is called coagulation.
Hemostasis is the process of forming clots in the walls
of damaged blood vessels and preventing blood loss
while maintaining blood in a fluid state within the
vascular system.
Morawitz in 1904 described the basic mechanism of
blood clotting.

4. It occurs in three stages:
1. Vasoconstriction
2. Platelet plug formation
3. Coagulation of blood.
HEMOSTASIS

5. VASOCONSTRICTION

6. PLATELET PLUG FORMATION
 Platelets get adhered to the collagen of ruptured
blood vessel and secrete adenosine diphosphate
(ADP) and Thromboxane A2.
 These two substances attract more and more platelets
and activate them.
 Platelet aggregation is accelerated by platelet
activating factor

7. COAGULATION OF BLOOD
 During this process, the fibrinogen is converted
into fibrin.
 Fibrin threads get attached to the loose platelet
plug, which blocks the ruptured part of
blood vessels and prevents further blood loss
completely

9. The precise and balanced generation of thrombin at sites of vascular injury is the result
of an ordered series of reactions collectively referred to as blood coagulation.

11. FACTOR I :FIBRINOGEN
Source : Liver
Pathway : Both extrinsic and intrinsic
Activator : Thrombin
FACTOR II :PROTHROMBIN
Source : Liver
Pathway : Both Extrinsic and Intrinsic
Activator : Prothrombin activator
FACTOR III:THROMBOPLASTIN /
TISSUE FACTOR
Source : Platelets(Intrinsic) and Damaged
endothelium lining of the blood vessel
(Extrinsic)
Pathway : Both extrinsic and intrinsic
Activator : Injury to blood vessel
FACTOR IV: CALCIUM
Source : Bone and by absorption of food in GIT
(intrinsic) and the blood vessel ( Extrinsic)
Pathway : Both extrinsic and intrinsic

12. FACTOR V :PROACCELERIN/
LABILE FACTOR
Source : Liver and platelets
Pathway : Both extrinsic and intrinsic
Activator : Thrombin
FACTOR VII :PROCONVERTIN /
SERUM PROTHROMBIN
CONVERSION ACCELERATOR /
STABLE FACTOR
Source : Liver
Pathway : Extrinsic
Activator : factor III (Tissue factor)
FACTOR VIII :ANTIHEMOPHILIC
FACTOR
Source : Endothelium lining blood vessel and
platelets (plug)
Pathway : Extrinsic
Activator : Thrombin

13. FACTOR IX :CHRISTMAS FACTOR/
PLASMA THROMBOPLASTIN
COMPONENT
Source : Liver
Activator : Factor XI and Calcium
Deficiency leads to : Hemophilia B
FACTOR X :STUART-PROWER
FACTOR/ANTIHEMOPHILIC
FACTOR B
Source : Liver
Pathway : Intrinsic, Extrinsic
Activator : Factor VII (Extrinsic) / Factor IX +
Factor VIII + Calcium (intrinsic)

14. FACTOR XI :PLASMA
THROMBOPLASTIN ANTECEDENT /
ANTIHEMOPHILIC FACTOR C
Source : Liver
Pathway : Intrinsic
Activator : Factor XII + Prekallikrein and Kininogen
FACTOR XII :HAGEMAN FACTOR
Source : Liver
Pathway : Intrinsic
Activator : Contact with collagen in the torn wall of
blood vessels
FACTOR XIII:FIBRIN
STABILIZING FACTOR
Source : Liver
Activator : Thrombin and calcium

15. THE CLOTTING MECHANISM
 The fundamental reaction is conversion of the soluble
plasma protein fibrinogen to insoluble fibrin.
 How is this fibrin formed?
 And, what does this Fibrin do?

16. In general blood clotting occurs in three stages:
 Formation of prothrombin activator
 Conversion of prothrombin into thrombin
 Conversion of fibrinogen into fibrin
ENZYME CASCADE THEORY

17. FORMATION OF PROTHROMBIN
ACTIVATOR
• Formation of prothrombin activator occurs through two pathways:
i. Intrinsic pathway
ii. Extrinsic pathway.

19. CONVERSION OF PROTHROMBIN INTO THROMBIN
 Prothrombin activator converts prothrombin into thrombin in the presence of calcium ions (factor IV).
 Positive feedback effect

20. CONVERSION OF FIBRINOGEN INTO FIBRIN
 Thrombin converts fibrinogen into
activated fibrinogen which is called
fibrin monomer.
 tight fibrin threads are aggregated to
form a meshwork of stable clot

23. CLOT RETRACTION
• The process involving the contraction of blood clot and oozing of serum is called clot retraction.

24. FIBRINOLYSIS
Lysis of blood clot inside the blood
vessel is called fibrinolysis.

25. Formation of Plasmin :
Plasmin is formed from inactivated
glycoprotein called plasminogen.
Plasminogen is converted into plasmin by
tissue plasminogen activator (t-PA),
lysosomal enzymes and thrombin.
The t-PA and lysosomal enzymes are
released from damaged tissues and damaged
endothelium.
Thrombin is derived from blood.

26. ANTICOAGULANTS:
The substances which prevent or postpone
coagulation of blood are anticoagulants.
Thrombomodulin, heparin in blood, continuous blood flow, smooth endothelium lining,
clotting factors are in inactive state

27. * Heparin
* Coumarin derivatives – warfarin, dicoumoral
* EDTA
* Oxalate compounds
* Citrates
* Other substances which prevent blood clotting –
Peptone, C-type lectin, hirudin
Various anticoagulants commonly used are

28. HEPARIN
Heparin is a naturally produced
anticoagulant in the body.
It is produced by mast cells and
basophils.

29. OTHER SUBSTANCES WHICH PREVENT
BLOOD CLOTTING
Physical methods:
• cold
• collecting blood in a container with smooth
surface
Procoagulants:
• Thrombin
• Snake venom
• Extract from lungs and thymus
• Calcium or sodium alginate
• Oxidized cellulose

30. TESTS FOR BLOOD CLOTTING
1. Bleeding time
2. Clotting time
3. Thrombin time.
4. Prothrombin time
5. Activated partial prothrombin time
6. International normalized ratio

31. BLEEDING TIME
Bleeding time (BT) is the time interval from
oozing of blood after a cut or injury till arrest of
bleeding. Usually, it is determined by Duke
method using blotting paper or filter paper
method. Its normal duration is 3 to 6 minutes.
CLOTTING TIME
Clotting time (CT) is the time interval from oozing of blood after a cut or injury
till the formation of clot. It is usually determined by capillary tube method. Its
normal duration is 3 to 8 minutes.

32. THROMBIN TIME
 Thrombin time (TT) is the time taken for the blood to clot after adding
thrombin to it.
 Normal duration of thrombin time is 12 to 20 seconds.
 It is prolonged in heparin therapy and during dysfibrinogenimia

33. PROTHROMBIN TIME
 Prothrombin time (PT) is the time taken by blood to clot
after adding tissue thromboplastin to it.
 Prothrombin time indicates the total quantity of
prothrombin present in the blood.
 Normal duration of prothrombin time is 10 to 12 seconds.

34. PARTIAL PROTHROMBIN TIME OR
ACTIVATED PARTIAL
PROTHROMBIN TIME
Partial prothrombin time (PPT) is the time taken for the
blood to clot after adding an activator such as
phospholipid, along with calcium to it. It is also called
activated partial prothrombin time (APTT). This test is
useful in monitoring the patients taking anticoagulant
drugs.
Normal duration of partial prothrombin time is 30 to 45
seconds

35. INTERNATIONAL
NORMALIZED RATIO (INR)
International normalized ratio (INR) is the rating of a patient’s
prothrombin time when compared to an average. It measures
extrinsic clotting pathway system.

36. >4.0
• No surgical treatment until the INR is reduced
3.5-4.0
• Emergency minor surgical procedures only
• Avoid block anesthesia injections
3.0-3.4
• Minor surgical procedures like extraction, gingivoplasty
2.5-2.9
• Multiple extraction, single bony impaction, periodontal
flap surgery, SRP
1.5-2.4
• All surgical procedures
INR
VALUE
RECOMMENDATIONS CONCERNING INVASIVE
TREATMENT

37. BLEEDING DISORDERS
1) HEREDITARY COAGULATION DISORDERS
- HEMOPHILIA A
- HEMOPHILIA B
- VON WILLEBRANDS DISEASE
2) ACQUIRED COAGULATION DISORDERS
- VITAMIN K DEFICIENCY
- DISSEMINATED INTRAVASCULAR COAGULATION
DISORDER (DIC )
3) PLATELET DISORDERS
THROMBOCYTOPENIC PURPURA

38. HEMOPHILIA
o Sex linked disorder resulting from a deficiency in clotting factor VIII or factor IX
o Hemophilia occurs due to lack of formation of prothrombin activator
o Characterised by prolonged clotting time.
o Affected males, females are carriers.

39. Types of hemophilia: Depending upon the deficiency of the factor involved,
hemophilia is classified into three types:
Hemophilia A or classic hemophilia
Hemophilia B or Christmas disease
Hemophilia C or factor XI deficiency

40. SYMPTOMS OF HEMOPHILIA
Treatment for hemophilia
• Effective therapy for classical hemophilia involves replacement of
missing clotting factor.
• Prolonged bleeding due to injuries
• Hemorrhage
• Bleeding in joints followed by swelling
and pain
• Appearance of blood in urine.

41. ORAL
MANIFESTATIONS:
• Petechiae
• Ecchymoses
• Spontaneous gingival bleeding
PERIODONTAL CONSIDERATIONS:
• In all but severe hemophiliacs, scaling can be carried out without LA.
• Periodontal surgery requires LA and factor VIII replacement to a level between 50 to 75%

42. HEMOPHILIA- A
• TREATMENT:
- Factor replacement
- Bleeding is treated by administration of factor VIII concentrate by intravenous infusion.
- Major surgery: the factor VIII should be raised to 100% preoperatively and maintained
above 50% until healing has occurred.
HEMOPHILIA B
• Hemophilia B is treated with factor IX concentrates

43. VON WILLEBRAND’S
DISEASE:
• Is a bleeding disorder, characterized by excess bleeding
even with a mild injury.
• Hereditary coagulation abnormality caused by either:
– Reduced level of vWF
– Abnormality in Vwf
• So in VWD there is:
– Defective platelet function
– Factor VIII deficiency

44. Clinical features:
– Typically there is mucus membrane bleeding
– The severity of symptoms are variable with types
• Type 1, 2 usually mild symptoms
• Type 3 severe symptoms
– Type 1 VWD
– Type 2 VWD
– Type 3 VWD
VWD has been classified into three types:

45. ORAL MANIFESTATIONS :
• Gingival bleeding
• Uncontrollable bleeding during dental procedures.
PERIODONTAL
CONSIDERATIONS:
 Gingival haemorrhage
 Even minor gingival manipulation can
lead to uncontrollable bleeding.

46. TREATMENT: –

47. ACQUIRED COAGULATION DISORDERS
1.VITAMIN K DEFICIENCY
ORAL MANIFESTATIONS :
Spontaneous gingival haemorrhages
Gingival bleeding is seen after brushing
- Important for formation of factors II, VII, IX and X and
proteins C.
- Without it, these factors cannot bind to calcium.

48. 2. DISSEMINATED INTRAVASCULAR COAGULATION
DISORDER (DIC)
 There is widespread deposition of fibrin within blood vessels with consumption of coagulation factors
and platelets occurs as a consequence of many disorders which release procoagulant material into the
circulation.

49. TREATMENT
-Treat underlying cause
– Supportive therapy with fresh frozen plasma (FFP) and
platelet concentrates
– Cryoprecipitate can be used
CLINICAL FEATURES:
– Bleeding, particularly from venipuncture
– Purpura
– Generalized bleeding in GIT, oropharynx, lungs, urogenital tract, vaginal bleeding

50. PLATELET DISORDERS :
• Platelet disorders may be the result of alteration in platelet numbers, either
- decreased (thrombocytopenia)
- increased (thrombocythemia)
• Thrombocytopenia has platelet count < 1,50,000
• Platelet disorders may be:
Quantitative- Thrombocytopenic purpura
Qualitative- Disorders of platelet function

51. THROMBOCYTOPENIC PURPURA
• Thrombocytopenia is a bleeding disorder characterized by a platelet count below
the normal range.
• It may be:
- Auto- immune or Idiopathic
- Drug induced

52. IDIOPATHIC THROMBOCYTOPENIC PURPURA
• Also known as auto – immune thrombocytopenic purpura.
• most common
• Can lead to purpura and prolonged bleeding.
DRUG INDUCED THROMBOCYTOPENIC PURPURA
• Reactions of drugs or toxins resulting in a low platelet count and bleeding tendency.
• Common cause are:
• Quinidine
• Sulfonamides
• Heavy alcohol consumption

53. GENERAL FEATURES
• Abrupt appearance of petechial hemorrhages.
• Purpura
• Bruises after trauma

54. THROMBOSIS
● Thrombosis or intravascular blood
clotting refers to coagulation of blood
inside the blood vessels.
● Causes of Thrombosis:
1. Injury to blood vessels
2. Roughened endothelial lining

55. 3. Sluggishness of blood flow
4. Agglutination of RBCs
5. Toxic thrombosis
6. Congenital absence of protein C

56. ● Complications of Thrombosis:
1. Thrombus
2. Embolism and embolus
3. Ischemia
4. Necrosis
5. Infarction

57. MANAGEMENT OF PATIENTS WITH BLEEDING DISORDERS
Consultation with a Hematologist
Prophylactic Factor Replacement Therapy
Medication Review
Platelet Count
Thorough Oral Examination
Patient Education
Bleeding Control Measures
pre-operative precautions

58. Intraoperative precautions
Local Anesthesia
Use of Haemostatic Agents
Avoidance of Trauma
Use of Sutures
Monitoring of Vital Signs

59. Post-operative care
Use of Hemostatic Agents
Avoidance of Trauma
Pain Management
Follow-up Appointments:
Prophylactic Factor Replacement Therapy
Monitoring of Vital Signs
Patient Education:

60. Intraoperative Bleeding During Open Flap Debridement and Regenerative
Periodontal Surgery
Hadar Zigdon,*† Liran Levin,*† Margarita Filatov
Background: The objective of this study was to measure the intraoperative bleeding during periodontal flap
surgery.
Methods: Patients scheduled for periodontal surgery were recruited for this study. Data regarding smoking
habits, general health, and medications were collected. The amount of the local anesthetic that was injected
was then recorded, as well as the number of teeth in the operative field and the duration of the procedure.
During surgery, the liquids from the oral cavity were suctioned and collected into a sterile empty vial. To
calculate the net amount of blood volume in the liquids, colorimetric assay using capillary blood fructosamine
as a reference molecule was used.
Results: Twenty-six patients were included in this study. The amount of blood lost during the procedure
ranged from 6.0 to 145.1 mL, with an overall mean of 59.47 – 38.2 mL. Patients taking aspirin (acetylsalicylic
acid) showed mean blood loss of 43.26 – 31.5 mL, whereas the mean blood loss among patients that did not
use this medication was higher (65.4 – 39.4 mL) but not statistically significant. Local anesthetic amount,
surgical field size, and the operation duration did not relate to blood-loss volume. The mean blood loss among
current smokers was significantly higher (96.47 – 44.2 mL) compared to former (12 – 8.4 mL) or never (54.74
– 30.5 mL, P = 0.011) smokers.
Conclusion: The results of the current study support previous papers and confirm that blood loss during
periodontal surgery is minimal.

61. Blood Loss During Periodontal Flap Surgery
by DAVID A . BAAB, D.D.S., M.S.D.* WILLIAM F . AMMONS, JR., D.D.S., M.S.D.* HERBERT
SELIPSKY, B.D.S., H.D.D., M.S.D.*
Berdon published the first report on hemorrhage during periodontal surgery, he measured blood loss during 50
gingivectomies involving a surgical field of 5 to 14 teeth. He established that approximately 5 ml to 149 ml of blood
was lost. The quantity of hemorrhage from two patients undergoing full-mouth gingivectomies under a general
anesthetic was also measured and found to be 435 ml and 624 ml respectively. Observation and supportive therapy was
recommended for those patients with the "higher volume" of blood loss. No specific guidelines for fluid replacement
were recommended
Mclvor and Wengraf studied blood loss colorimetrically during gingivectomies and isolated periodontal flap procedures
on 14 patients. Three patients had small, one- or two-tooth, mucoperiosteal flaps elevated and osteoplasty performed.
Blood loss for these three patients ranged from 12 ml to 62 ml, while the other patients lost 0.7 ml to 18 ml of blood
during gingivectomies. Based upon this data, they speculated that one could expect a 10-fold increase in blood loss per
tooth during a periodontal flap procedure as compared to a gingivectomy

62. Periodontal flap surgery in the mandible
resulted in an average blood loss of 151 ml
per segment, while the corresponding
procedure in the maxilla resulted in an
average blood loss of 110 ml per segment.
The greatest average blood loss per segment
occurred from the mandibular right posterior
area, while surgery in the maxillary left
posterior area resulted in the least average
blood loss per segment
Sex*
Females 121.7 (±116 )
Males 156.4 (±113 )
Area of surgery
Upper right 121.5 (±103 )
Upper left 109.9 (±147 )
Lower left 136.5 (±129 )
Lower right 160.1 (±149 )
AVERAGE
BLOOD LOSS
Type of surgery
Flap Curettage 171.8 (±126 )
Osseous surgery 140.4 (±141 )

63. COVID AND BLOOD CLOTTING
o Patients with coronavirus disease (COVID-19) have elevated D-dimer levels. Early
reports describe high venous thromboembolism (VTE) and disseminated intravascular
coagulation (DIC) rates, but data are limited.
o In support of this hypothesis are recent autopsy studies of COVID-19 patients
demonstrating the presence of fibrin thrombi within distended small vessels and
capillaries and extensive extracellular fibrin deposition
o COVID-19 was associated with similar rates of thrombosis and bleeding as seen in
hospitalized patients with similar degrees of critical illness. Elevated D-dimer levels at
initial presentation predicted bleeding complications, thrombotic complications, critical
illness, and death. Beyond D-dimer, thrombosis was primarily associated with
inflammatory markers rather than coagulation parameters

64. CONCLUSION

65. REFERENCES
 Essentials of medical physiology – Sembulingam
 Text book of Medical Physiology , Guyton, 12th edition,
 Dental management of patients with inherited bleeding disorders: a multidisciplinary approach
 Guidelines for dental treatment of patients with inherited bleeding disorders Andrew Brewer, Maria Elvira Correa
 A.K Jain Human physiology for BDS – 5th edition
 Intraoperative Bleeding During Open Flap Debridement and Regenerative Periodontal Surgery Hadar Zigdon,*†
Liran Levin,*† Margarita Filatov
 Periodontology 2000 vol44
 Blood Loss During Periodontal Flap Surgery by DAVID A . BAAB, D.D.S., M.S.D.* WILLIAM F . AMMONS,
JR., D.D.S., M.S.D.* HERBERT SELIPSKY, B.D.S., H.D.D., M.S.D.*