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Contents
Haemostasis
Vascular Phase
Platelet Phase
Clot formation
Clot retraction
Fibrinolysis
Bleeding Disorders
Diagnosis of bleeding disorders
Clinical implication in periodontology
Haemostasis
Haima + Stasis




                 Prevent blood
                     loss
Maintains blood flow




Prevents bleeding
• Stages of Hemostasis
Vascular Phase
PLATELET Phase
Platelets
• Thrombocyte = “ thrombos” + “ Kytos”




                                   •1,50,000 to 400,000 per cu mm
                                     Lifespan is 9 – 12 days
• Membrane
• Outer glycocalyx layer—
  glycoproteins
• Inner lipoprotein layer—
  phospholipid
Platelet PLUG
Blood coagulation
Role of thrombin
Fibrin formation
SEM of clot
• Release of fibrin stabilizing factor
• Contractile protein of platelets
• Activated and accelerated by thrombin
  and Ca ions.
ROLE OF ENDOTHILIUM
Approach to the diagnosis of bleeding
disorder
             Clinical Evaluation
                    History
                    Physical Examination
                    Family history




            Laboratory Evaluation
                  Screening test
                  Specific test
Clinical Features of Bleeding Disorders
                                    Platelet disorders Coagulation
                                                       disorders
 Site of bleeding                   Skin                 Deep in soft
 tissues
                                    (epistaxis, gum,     Mucous
                                    vaginal, GI tract)   membranes,
                                                         joints, muscles)

 Petechiae                          Yes                  No
 Ecchymoses (“bruises”)             Small, superficial   Large, deep
 Hemarthrosis / muscle bleeding     Extremely rare       Common
 Bleeding after cuts & scratches    Yes                  No
 Bleeding after surgery or trauma   Immediate,           Delayed (1-2
 days),
                                    usually mild           often severe
Platelet          Coagulation




Petechiae, Purpura   Hematoma, Joint bl.
Tests for Primary Hemostasis
• Bleeding time          platelet & vascular phases

• PFA – 100 system       Platelet function

• Platelet count         Quantification of platelets

• Blood smear            Quantitative & morphological
                         abnormalities of platelets ,
                         Detection of underlying
                         haemotological disorder
Tests for Secondary hemostasis
• Clotting factor        Crude test of coagulation phase

• Prothrombin factor     Extrensic & common pathway

• Activated partial
 thromboplastin time     Intrensic & common pathway
PLATELET COUNT


 NORMAL        150,000 - 400,000 CELLS/MM3

 < 100,000           Thrombocytopenia


 50,000 - 100,000    Mild Thrombocytopenia

 < 50,000            Sev Thrombocytopenia
BLEEDING TIME

  PROVIDES ASSESSMENT OF PLATELET COUNT
               AND FUNCTION



NORMAL VALUE
 2-8 MINUTES
PROTHROMBIN TIME
 Measures Effectiveness of the Extrinsic Pathway
 Measures the activity of V, VII, X, II , I



NORMAL VALUE
 11-16 SECS
Prothrombin time prolongs..

Extrinsic pathway factor deficiencies
(FII, V, VII, X)
– Inherited or acquired
– Consumption (DIC)
– oral anticoagulant therapy
INR
INR: International normalized ratio

-was established by the WHO and the International Committee on Thrombosis
and Hemostasis for reporting the results of prothrombin tests

-All PT results are standardized by this calculation:

INR= ( Patient PT / Control PT)              ISI




ISI= International sensitivity index

- Given by the manufacturer for each particular thromboplastin reagent and
instrument combination
ACTIVATED THROMBOPLASTIN
                     TIME

 Measures Effectiveness of the Intrinsic
  Pathway & common pathway




       NORMAL VALUE
         25-40 SECS
APTT prolongs..
1. Intrinsic pathway factor deficiencies
   (FXII, XI,VIII, IX, HMWK, prekallikrein )

- Inherited or acquired
- Consumption (DIC)
- PIVKA factors in cumarin therapy

2. Specific inhibitors against FXII, XI, VIII, IX, HMWK, prekallikrein

3. Lupus anticoagulant

4. Non-fractionated heparin therapy
THROMBIN TIME
 Time for Thrombin To Convert
  Fibrinogen                    Fibrin
 A Measure of Fibrinolytic Pathway




  NORMAL VALUE
    9-13 SECS
TT Prolongs..

1. Hypo- afibrinogenaemia
2. Dysfibrinogenaemia
3. Non fractionated heparin
4. Fibrinogen/ fibrin degradation product s
5. Chronic liver disease
SPECIFIC TESTS
Tests for specific Platelet Functions
1. Platelet aggregration test
2. Flow cytometry
3. Test for platelet secretion
4. Clot retraction test
5. Platelet procoagulant activity

Test for Coagulation Phase
1. Quantitative estimation of Fibrinogen
2. Coagulation factor assays
3. F XIII Qualitative assay

Latex agglutination test for Fibrinolysis
Bleeding
Disorders
            Inherited
            •   Vascular
            •   Platelet
            •   coagulation
            •   Fibrinolytic


            Acquired
            • Vascular
            • Platelet
            • coagulation
HEMORRHAGIC DISORDERS
    Hemorrhagic syndromes are characterized by a disorder
    of one or more factors that participate in hemostasis.
    The majority of hemorrhagic syndromes are blood vessel
    disorders, platelet number and function disorders, or
    coagulation factor disorders:

•   vasculopathies
•   thrombocytopenias
•   thrombocytopathies
•   coagulopathies.
Vasculopathies
• Vasculopathies may be inherited or acquired. Inherited
  forms result from blood vessel structure disorders
  (inherited telangiectasia,Rendu-Osler-Weber’s disease)
  while acquired disorders can be a consequence of
  inflammatory or immune processes that damage blood
  vessel walls.

• In clinical practice, acquired disorders are found more
  frequently (secondary purpuras, infections,
  effects of some drugs, allergic purpura, effect of aspirin,
  vitamin C deficiency, etc.).
Thrombocytopenias
• Thrombocytopenia, or reduced circulating platelet
  count, can be inherited or acquired; the acquired form
  being more frequent.
• Thrombocytopenia occurs as a result of:
– decreased platelet formation with normal platelet
  survival time (effects of irradiation, drugs, malignant
  tissue pressure on bone marrow, leukemias, aplastic
  anemias) or
− increased platelet degradation or platelet deposit in
  spleen with decreased platelet survival (DIC, effects
  of drugs, bacterial or viral infections, inherited idiopathic
  thrombocytopenic purpura, chronic leukemias, lupus
  erythematosus,Hodgkin’s disease, massive transfusions
  and liver cirrhosis).
Thrombocytopathies
• Inherited Qualitative Platelet Disorders may be due
   to abnormalities of
1. platelet membrane glycoproteins,
- Glanzmann Thrombastenia, abnormal GPIIb/IIIa
– Bernard-Soulier Syndrome, abnormal GPIb, GPIX and
   GPV
– platelet-type of vWD, abnormal GPIb
2. platelet granules,
• These may occur due to absence of granules in
   platelets, storage pool disorder (characterized by
   disturbed platelet aggregation to collagen, adrenaline
   and thrombin), or disturbed release (absence of T A2).
3. platelet coagulant activity, or

4. signal transduction and secretion.
• defects in arachidonic acid metabolism,
• cyclooxigenase deficiency, platelets unable to produce
    thromboxane; endothelium may not produce
   prostacyclin,
• thromboxane synthesis deficiency, and
• defects in platelet secretion and the second wave of
   platelet aggregation, found in response to epinephrine or
   ATP.
Coagulopathies
ACQUIRED BLOOD CLOTTING
DISORDERS
They occur in:
– vitamin K deficiency,
– liver diseases,
– liver transplantation,
– disseminated intravascular coagulation,
– renal diseases,
– primary pathological fibrinolysis
– during the course of anticoagulant therapy.
•    The extent and severity of periodontal disease
    determines the necessity for a surgical or nonsurgical
    treatment approach in its management.

• The nature and severity of an acquired bleeding
  disorder, and the degree of invasive dental
  procedures, determines the need to modify the treatment
  to be provided.

• Various Illnesses, along with pharmacotherapy,may
  contribute to the tendency for excessive bleeding.
Pre-operative management of patients starts with a medical
history focusing on the previous bleeding history of the
patient and medical conditions associated with bleeding.

Presence of following illness may need a modification in
treatment protocol to minimize the risk of intra-operative
and postoperative bleeding.
•   Chronic renal failure
•   Lack of vitamin K
•   Liver failure
•   Aspirin
•   Antiplatelet medication
•   Anticoagulant therpay
Intra-operative measures include a number of systemic and local
measures administered prior to, or during, the procedure to prevent
unlikely bleeding diathesis.


  Surgeries             • Platelet count should be assessed

                        • Iv infusion 1 hr before
                        • Level should be 50% higher in plasma for
Missing factors           Regional anesthesia

Scaling and root
    planing             • Antifibrinolytic mouthwash   (Lee , Boyle)




        LA               • regional anesthesia should be avoided


                         • Conservative design
      Flap               • Mandibular molar

   Prevention of         • Curettage of extraction socket
     infection           • Granulation tissue
Hemostatic agent         Other means         Hard tissue

• Absorbable        •   Sponge            • Bone burnishing
  gelatin           •   Surgical splint   • Bone wax
• Absorbable        •   Electrocautery
  collagen          •   Laser
• Microfibrillar    •   Moistened or
  collagen              hemostatic
• Oxidised              soaked gauze
  cellulose
• Thrombin
• Tranexamic acid
• Fibrin glue
• PRP
General recommendations is crucial for preventing
bleeding, postoperatively.



Prohibition of    Liquid , high    Antifibrinolytic
  Rinsing         protein diet      mouthwash


                             Pain
          Antibiotics
                           medication
References :-
• Textbook of Medical Physiology ,10th edition,Hall &
  Guyton
• Essentials of hematology , Shirish M Kawthalkar
• Periodontal Medicine, Rose
• Bleeding disorders and periodontology, Philip
  Vassilopoulos & Kent Palcanis , Periodontology
  2000, Vol. 44, 2007, 211–223.
• Coagulation Pathway and Physiology, Jerry B. Lefkowitz
• Hemostasis And Hemorrhagic Disorders, R. Baklaja, M.
  C. Pešic´, J. Czarnecki
• Platelet function analysis,Paul Harisson, Blood Reviews
  (2005) 19, 111–123
Thank You

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Blood coagulation

  • 1.
  • 2. Contents Haemostasis Vascular Phase Platelet Phase Clot formation Clot retraction Fibrinolysis Bleeding Disorders Diagnosis of bleeding disorders Clinical implication in periodontology
  • 4. Haima + Stasis Prevent blood loss
  • 6.
  • 7. • Stages of Hemostasis
  • 8.
  • 10.
  • 11.
  • 13. Platelets • Thrombocyte = “ thrombos” + “ Kytos” •1,50,000 to 400,000 per cu mm Lifespan is 9 – 12 days
  • 14. • Membrane • Outer glycocalyx layer— glycoproteins • Inner lipoprotein layer— phospholipid
  • 16.
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  • 24.
  • 28. • Release of fibrin stabilizing factor • Contractile protein of platelets • Activated and accelerated by thrombin and Ca ions.
  • 29.
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  • 32.
  • 33.
  • 34.
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  • 36.
  • 37. Approach to the diagnosis of bleeding disorder Clinical Evaluation History Physical Examination Family history Laboratory Evaluation Screening test Specific test
  • 38.
  • 39. Clinical Features of Bleeding Disorders Platelet disorders Coagulation disorders Site of bleeding Skin Deep in soft tissues (epistaxis, gum, Mucous vaginal, GI tract) membranes, joints, muscles) Petechiae Yes No Ecchymoses (“bruises”) Small, superficial Large, deep Hemarthrosis / muscle bleeding Extremely rare Common Bleeding after cuts & scratches Yes No Bleeding after surgery or trauma Immediate, Delayed (1-2 days), usually mild often severe
  • 40. Platelet Coagulation Petechiae, Purpura Hematoma, Joint bl.
  • 41.
  • 42. Tests for Primary Hemostasis • Bleeding time platelet & vascular phases • PFA – 100 system Platelet function • Platelet count Quantification of platelets • Blood smear Quantitative & morphological abnormalities of platelets , Detection of underlying haemotological disorder
  • 43. Tests for Secondary hemostasis • Clotting factor Crude test of coagulation phase • Prothrombin factor Extrensic & common pathway • Activated partial thromboplastin time Intrensic & common pathway
  • 44. PLATELET COUNT  NORMAL 150,000 - 400,000 CELLS/MM3 < 100,000 Thrombocytopenia 50,000 - 100,000 Mild Thrombocytopenia < 50,000 Sev Thrombocytopenia
  • 45. BLEEDING TIME  PROVIDES ASSESSMENT OF PLATELET COUNT AND FUNCTION NORMAL VALUE 2-8 MINUTES
  • 46.
  • 47. PROTHROMBIN TIME  Measures Effectiveness of the Extrinsic Pathway  Measures the activity of V, VII, X, II , I NORMAL VALUE 11-16 SECS
  • 48. Prothrombin time prolongs.. Extrinsic pathway factor deficiencies (FII, V, VII, X) – Inherited or acquired – Consumption (DIC) – oral anticoagulant therapy
  • 49. INR INR: International normalized ratio -was established by the WHO and the International Committee on Thrombosis and Hemostasis for reporting the results of prothrombin tests -All PT results are standardized by this calculation: INR= ( Patient PT / Control PT) ISI ISI= International sensitivity index - Given by the manufacturer for each particular thromboplastin reagent and instrument combination
  • 50.
  • 51. ACTIVATED THROMBOPLASTIN TIME  Measures Effectiveness of the Intrinsic Pathway & common pathway NORMAL VALUE 25-40 SECS
  • 52. APTT prolongs.. 1. Intrinsic pathway factor deficiencies (FXII, XI,VIII, IX, HMWK, prekallikrein ) - Inherited or acquired - Consumption (DIC) - PIVKA factors in cumarin therapy 2. Specific inhibitors against FXII, XI, VIII, IX, HMWK, prekallikrein 3. Lupus anticoagulant 4. Non-fractionated heparin therapy
  • 53. THROMBIN TIME  Time for Thrombin To Convert Fibrinogen Fibrin  A Measure of Fibrinolytic Pathway NORMAL VALUE 9-13 SECS
  • 54. TT Prolongs.. 1. Hypo- afibrinogenaemia 2. Dysfibrinogenaemia 3. Non fractionated heparin 4. Fibrinogen/ fibrin degradation product s 5. Chronic liver disease
  • 55. SPECIFIC TESTS Tests for specific Platelet Functions 1. Platelet aggregration test 2. Flow cytometry 3. Test for platelet secretion 4. Clot retraction test 5. Platelet procoagulant activity Test for Coagulation Phase 1. Quantitative estimation of Fibrinogen 2. Coagulation factor assays 3. F XIII Qualitative assay Latex agglutination test for Fibrinolysis
  • 56. Bleeding Disorders Inherited • Vascular • Platelet • coagulation • Fibrinolytic Acquired • Vascular • Platelet • coagulation
  • 57. HEMORRHAGIC DISORDERS Hemorrhagic syndromes are characterized by a disorder of one or more factors that participate in hemostasis. The majority of hemorrhagic syndromes are blood vessel disorders, platelet number and function disorders, or coagulation factor disorders: • vasculopathies • thrombocytopenias • thrombocytopathies • coagulopathies.
  • 58. Vasculopathies • Vasculopathies may be inherited or acquired. Inherited forms result from blood vessel structure disorders (inherited telangiectasia,Rendu-Osler-Weber’s disease) while acquired disorders can be a consequence of inflammatory or immune processes that damage blood vessel walls. • In clinical practice, acquired disorders are found more frequently (secondary purpuras, infections, effects of some drugs, allergic purpura, effect of aspirin, vitamin C deficiency, etc.).
  • 59. Thrombocytopenias • Thrombocytopenia, or reduced circulating platelet count, can be inherited or acquired; the acquired form being more frequent. • Thrombocytopenia occurs as a result of: – decreased platelet formation with normal platelet survival time (effects of irradiation, drugs, malignant tissue pressure on bone marrow, leukemias, aplastic anemias) or − increased platelet degradation or platelet deposit in spleen with decreased platelet survival (DIC, effects of drugs, bacterial or viral infections, inherited idiopathic thrombocytopenic purpura, chronic leukemias, lupus erythematosus,Hodgkin’s disease, massive transfusions and liver cirrhosis).
  • 60. Thrombocytopathies • Inherited Qualitative Platelet Disorders may be due to abnormalities of 1. platelet membrane glycoproteins, - Glanzmann Thrombastenia, abnormal GPIIb/IIIa – Bernard-Soulier Syndrome, abnormal GPIb, GPIX and GPV – platelet-type of vWD, abnormal GPIb 2. platelet granules, • These may occur due to absence of granules in platelets, storage pool disorder (characterized by disturbed platelet aggregation to collagen, adrenaline and thrombin), or disturbed release (absence of T A2).
  • 61. 3. platelet coagulant activity, or 4. signal transduction and secretion. • defects in arachidonic acid metabolism, • cyclooxigenase deficiency, platelets unable to produce thromboxane; endothelium may not produce prostacyclin, • thromboxane synthesis deficiency, and • defects in platelet secretion and the second wave of platelet aggregation, found in response to epinephrine or ATP.
  • 63. ACQUIRED BLOOD CLOTTING DISORDERS They occur in: – vitamin K deficiency, – liver diseases, – liver transplantation, – disseminated intravascular coagulation, – renal diseases, – primary pathological fibrinolysis – during the course of anticoagulant therapy.
  • 64. The extent and severity of periodontal disease determines the necessity for a surgical or nonsurgical treatment approach in its management. • The nature and severity of an acquired bleeding disorder, and the degree of invasive dental procedures, determines the need to modify the treatment to be provided. • Various Illnesses, along with pharmacotherapy,may contribute to the tendency for excessive bleeding.
  • 65. Pre-operative management of patients starts with a medical history focusing on the previous bleeding history of the patient and medical conditions associated with bleeding. Presence of following illness may need a modification in treatment protocol to minimize the risk of intra-operative and postoperative bleeding. • Chronic renal failure • Lack of vitamin K • Liver failure • Aspirin • Antiplatelet medication • Anticoagulant therpay
  • 66. Intra-operative measures include a number of systemic and local measures administered prior to, or during, the procedure to prevent unlikely bleeding diathesis. Surgeries • Platelet count should be assessed • Iv infusion 1 hr before • Level should be 50% higher in plasma for Missing factors Regional anesthesia Scaling and root planing • Antifibrinolytic mouthwash (Lee , Boyle) LA • regional anesthesia should be avoided • Conservative design Flap • Mandibular molar Prevention of • Curettage of extraction socket infection • Granulation tissue
  • 67. Hemostatic agent Other means Hard tissue • Absorbable • Sponge • Bone burnishing gelatin • Surgical splint • Bone wax • Absorbable • Electrocautery collagen • Laser • Microfibrillar • Moistened or collagen hemostatic • Oxidised soaked gauze cellulose • Thrombin • Tranexamic acid • Fibrin glue • PRP
  • 68. General recommendations is crucial for preventing bleeding, postoperatively. Prohibition of Liquid , high Antifibrinolytic Rinsing protein diet mouthwash Pain Antibiotics medication
  • 69. References :- • Textbook of Medical Physiology ,10th edition,Hall & Guyton • Essentials of hematology , Shirish M Kawthalkar • Periodontal Medicine, Rose • Bleeding disorders and periodontology, Philip Vassilopoulos & Kent Palcanis , Periodontology 2000, Vol. 44, 2007, 211–223. • Coagulation Pathway and Physiology, Jerry B. Lefkowitz • Hemostasis And Hemorrhagic Disorders, R. Baklaja, M. C. Pešic´, J. Czarnecki • Platelet function analysis,Paul Harisson, Blood Reviews (2005) 19, 111–123