1. Principles of Hematology in Relation to Dental Management Dr. Saleh Al-Bazie, BDS, OMFS (USA), D.Sc.D, Consultant, OMFS, KSU, SHMC

2. Goals provide an overview of the coagulation system provide an overview of the coagulation system concepts rather than details of hemostasis concepts rather than details of hemostasis if time, discussion of some cases if time, discussion of some cases

3. OVERVIEW What is Hemostasis ? What is Hemostasis ? Mechanism of Normal Control of Bleeding. Mechanism of Normal Control of Bleeding. Classification and Etiology of Bleeding Disorders. Classification and Etiology of Bleeding Disorders. Identification of Bleeding Problems. Identification of Bleeding Problems. Management in a Dental Office. Management in a Dental Office.

4. What is Hemostasis ? It is simply the arrest of Bleeding ! It is simply the arrest of Bleeding ! Physiological Hemostasis depends of normal functioning of Physiological Hemostasis depends of normal functioning of 1.Vascular Endothelium 2.Blood Flow Dynamic 3.Platelets 4.Coagulation Cascade 5.Anticlotting Mechanisms 6.Fibrinolytic System

5. Vascular integrity Platelet reaction Coagulation cascade Clot lysis Hemostasis

6. Conditions which can cause Bleeding Disorders ScurvyAutoimmune disease InfectionsvON Willibrand’s disease ChemicalsUremia AllergyRadiation Genetic DefectsLeukemia AspirinHemophilia NSAIDsChristmas Disease AlcoholLiver Disease PenicillinVitamin deficiency DICAnticoagulants

7. Platelet Disorders Normal 150,000-400,000/ml. Normal 150,000-400,000/ml. 50,000/ml.Hemorrhage Platelet Antibodies 50,000/ml.Hemorrhage Platelet Antibodies 10,000/ml. Immune diseases. Cytotoxic drugs. Bone marrow failure. 10,000/ml. Immune diseases. Cytotoxic drugs. Bone marrow failure. Elective surgery below 50,000/ml. is contraindicated. Elective surgery below 50,000/ml. is contraindicated. If count < 100,000, increased bleeding tendency If count < 100,000, increased bleeding tendency If count < 20,000, spontaneous bleeding If count < 20,000, spontaneous bleeding

9. PATIENT IDENTIFICATION Is your patient a “BLEEDER” ? Is your patient a “BLEEDER” ? A Good History : A Good History : 1.Physical Examination. 2.Screening Clinical lab tests. 3.Observation of excessive bleeding following a surgical procedure.

10. WHAT TESTS TO ORDER ? TESTS NORMALABNORMAL 1.PT11-15 sec.Defective Vitamin K (Extrinsic /dependent, factors, Liver Common Pathways)disease, Oral Anticoagulant 2. PTT.30-45 sec.Hemophilia, vWD, (Intrinsic / Heparin Common Pathways) 3. BT1-6 min.Platelet Disfunction (Platelet / vWD,Thrombocytopenia Vascular phases) 4.Platelet Count150,000 to ( Platelet Phase)400,000/ml.

11. HEMOPHILIA - A sex linked disorder sex linked disorder 1in 5,000 to 1 in 10,000 male births 1in 5,000 to 1 in 10,000 male births Factor VIII deficient Factor VIII deficient 80% reduction in or absence of Factor VIII leads to a bleeding disorder 80% reduction in or absence of Factor VIII leads to a bleeding disorder Hemophilia-AFactor VIII level 1.mild5-25% of normal 2.moderate1-4% of normal 3.severe< 1% of normal

12. SCREENING TESTS PT, Platelet count ======>Normal PT, Platelet count ======>Normal APTT======>Prolonged APTT======>Prolonged Specific Factor Assays Specific Factor Assays Factor VIII inhibitors Factor VIII inhibitors

13. DENTAL MANAGEMENT Detection and Referral Detection and Referral Consultation with Hematologist Consultation with Hematologist Hospitalization for surgical procedures Hospitalization for surgical procedures Use of good surgical techniques Use of good surgical techniques Use of local measures, microfibrillar Collagen, Gelfoam with Thrombin, packed Collagen, Surgicel and sutures Use of local measures, microfibrillar Collagen, Gelfoam with Thrombin, packed Collagen, Surgicel and sutures Prophylactic Antibiotics Prophylactic Antibiotics Avoid Aspirin Avoid Aspirin

14. REPLACEMENT THERAPY Heat Activated and Recombinant Factor VIII / Cryoprecipitate for mild Hemophilia Heat Activated and Recombinant Factor VIII / Cryoprecipitate for mild Hemophilia Fresh Frozen Plasma Fresh Frozen Plasma Fresh Whole Blood Fresh Whole Blood Epsilon - aminocaproic acid Epsilon - aminocaproic acid Local therapy with ice packs Local therapy with ice packs

15. HEMOPHILIA - B / CHRISTMAS DISEASE Factor IX deficiency (Vitamin K dependent) Factor IX deficiency (Vitamin K dependent) X-linked, Hereditary X-linked, Hereditary Affects 1 in 30,000 male births Affects 1 in 30,000 male births Mild (5-25%), moderate (1-4%), severe(<1%) Mild (5-25%), moderate (1-4%), severe(<1%) Clinically similar to Hemophilia A Clinically similar to Hemophilia A

16. Screening Tests Specific Factor Assays Specific Factor Assays PTT - Prolonged (corrected by normal serum but not by Barium - adsorbed Plasma) PTT - Prolonged (corrected by normal serum but not by Barium - adsorbed Plasma) PT-Normal PT-Normal BT-Normal BT-Normal

17. Replacement Therapy Fresh Frozen Plasma or Prothrombin complex concentrates Fresh Frozen Plasma or Prothrombin complex concentrates Lyophilized Factor IX concentrate Lyophilized Factor IX concentrate

18. VON-WILLEBRAND’S DISEASE Most common bleeding disorder Most common bleeding disorder Males and Females equally affected Males and Females equally affected Abnormal Platelet function Abnormal Platelet function Prolonged BT Prolonged BT May be a decrease in factor VIII leading to a prolonged APTT May be a decrease in factor VIII leading to a prolonged APTT Mild Mucosal Bleeding Mild Mucosal Bleeding Factor VIII Deficiency Factor VIII Deficiency

19. VON-WILLEBRAND’S DISEASE (continued.) Nose bleeds, heavy menses, bleeding gingiva, easy bruising Nose bleeds, heavy menses, bleeding gingiva, easy bruising Bleeding following surgery or trauma can be severe Bleeding following surgery or trauma can be severe

20. vWD type I, II & III vWd type I : vWd type I : 1.most common. 2.Decrease in overall concentration of vWF. vWD type II : vWD type II : 1.Abnormality in vWF. 2.Mild symptoms vWD type III vWD type III 1.Most severe form 2.vWF absent 3.Factor VIII very low 4.Prolonged BT, and APTT 5.Bleeding into muscles and joints.

21. Dental Management vWF Type I and Type II vWF Type I and Type II Surgical procedures by using DDAVP (Desmopressin) and EACA vWF Type III vWF Type III Fresh Frozen Plasma Cryoprecipitate replacement Factor VIII concentrates ineffective (contain low level of vWF).

22. Liver Disease History of Jaundice / Alcoholism ? History of Jaundice / Alcoholism ? Most coagulation factors produced in liver Most coagulation factors produced in liver Defect in Coagulation or Platelets ? Defect in Coagulation or Platelets ? Screening Tests : Screening Tests : 1.PT for Coagulation defect 2.BT for Platelet defect 3.If PT and BT are normal, surgery possible. Management : Management : 1. Vitamin K for factor deficiency 2. Fresh frozen Plasma for Thrombocytopenia, deficiency of fibrinogen, plasminogen.

23. Dental Management of Patients on Anti Coagulation Therapy 2 main groups of Anticoagulants 2 main groups of Anticoagulants 1.Heparin 2.Coumadins

24. Heparin Inactivates Thrombin Inactivates Thrombin Inhibits activation of factors IX, X, XI &XII Inhibits activation of factors IX, X, XI &XII Inhibits aggregation of Platelets Inhibits aggregation of Platelets Immediate effect, given intravenously Immediate effect, given intravenously Good Anticoagulation level is kept at 2-3 times the control (Clotting time) 20-25 min., < 40 min.) Good Anticoagulation level is kept at 2-3 times the control (Clotting time) 20-25 min., < 40 min.) Length of effect 2 - 4 hrs. Length of effect 2 - 4 hrs. Overdose may cause internal bleeding Overdose may cause internal bleeding Action reversed by Protamine-Sulfate Action reversed by Protamine-Sulfate

25. Coumadin Inhibit in Liver Vitamin K - dependent clotting factors - II, VII, IX, & X Inhibit in Liver Vitamin K - dependent clotting factors - II, VII, IX, & X Optimum effect achieved in 36-48 hr.. Optimum effect achieved in 36-48 hr.. Therapy kept within 25-35 sec. (PT) Therapy kept within 25-35 sec. (PT) Given orally, slow onset Given orally, slow onset Length of effect 48 hrs. Length of effect 48 hrs. INR INR

26. Considerations Potential bleeders Potential bleeders Surgery safe when PTT 1.5 - 2 times normal Surgery safe when PTT 1.5 - 2 times normal (20 -25 sec.) Handle tissues gently, use local measures Handle tissues gently, use local measures Always consult physician before operating Always consult physician before operating PTT always needed at least 24 hr.. pre-op. PTT always needed at least 24 hr.. pre-op. If anticoagulation level too high, withhold drug 1-2 days pre-op. If anticoagulation level too high, withhold drug 1-2 days pre-op.

27. Considerations (continued.) Effect reversed by Vitamin K1 (25-50 mgs.), given slowly @ 5 mg/min. I/V. Effect reversed by Vitamin K1 (25-50 mgs.), given slowly @ 5 mg/min. I/V. Recall Recall

28. Drugs which inhibit Anticoagulants Antacids Antacids Barbiturates Barbiturates Oral Contraceptives Oral Contraceptives Vitamin C Vitamin C

29. Drugs which Potentiate Anticoagulants Aspirin Aspirin Broad Spectrum Antibiotics Broad Spectrum Antibiotics Methyl Dopa Methyl Dopa

30. Drugs with No Interaction Tylenol Tylenol Librium Librium DO NOT USE ASPIRIN. DO NOT USE ASPIRIN.

31. CONCLUSION Encourage patients to maintain good oral health Encourage patients to maintain good oral health Dental treatment often requires hospitalization. Dental treatment often requires hospitalization. Patients in terminal phase secondary to other diseases should be offered conservative dental treatment. Patients in terminal phase secondary to other diseases should be offered conservative dental treatment. With proper understanding and preparation, most indicated dental treatment can be provided With proper understanding and preparation, most indicated dental treatment can be provided

32. CLINICAL CLUES CLINICAL SIGNDISORDER Lifelong history of easy bruising or Factor deficiency bleeding.VWD Family history in Males onlyHemophilia A or B Family history in both sexesFactor XI deficiency, VWD Excess bleeding at surgeryMild Factor deficiency VWD, Thrombocytopenia Acquired bruising tendencyAspirin / other drug Thrombocytopenia Delayed BleedingFactor XIII deficiency Bruising / Bleeding starting duringDrugs, Thrombocytopenia, another illnessAcquired anticoagulant.

33. COAGULATION CASCADE INTRINSIC PATHWAY XII XIIaEXTRINSIC PATHWAY XI XIa Tissue Factor Tissue Damage IXIXa VIIa VII XXa V Prothrombin Thrombin FibrinogenFibrin XIIIa XIII XIIIa XIII COMMON PATHWAY Stabalized fibrin Stabalized fibrin

34. PATIENTS ON ASPIRIN THERAPY Irreversibly inhibits Cyclooxygenase Irreversibly inhibits Cyclooxygenase Aspirin inhibits Platelet aggregation Aspirin inhibits Platelet aggregation Bleeding time moderately prolonged Bleeding time moderately prolonged One dose may inhibit Platelet function for a week One dose may inhibit Platelet function for a week Thrombin induced Platelet Activation unaffected Thrombin induced Platelet Activation unaffected Never give with another Anticoagulant Never give with another Anticoagulant Antidote - Platelet transfusion Antidote - Platelet transfusion

35. What are the three phases of hemostasis? VascularPlatelets Coagulation phases

36. Thrombocytopenia that less than 50,000/mm 3 is absulote contraindication for elective surgery Thrombocytopenia that less than 50,000/mm 3 is absulote contraindication for elective surgery 50,000-100,000/mm 3 is save to perform surgery provided normal platelets function 50,000-100,000/mm 3 is save to perform surgery provided normal platelets function Bleeding time is used to test platelets function Bleeding time is used to test platelets function

37. Which blood tests used to monitor warfarin (coumadin), ASA, and Heparin?

38. How dose heparin, ASA, Coumadin affect clotting?

39. PT -  APTT, TT, PLC - N PT TT PTT XII XI IX VIII VII X V II I Coumadin Affects extrinsic pathway, interferes with hepatic synthesis of vit K dependent clotting factors.

40. APTT -  PT, TT, PLC - N PT TT APTT HMWK XII PK XI IX VIII VII X V II I Heparin Heparin: affects intrinsic pathways, prevents formation of prothrombine activator Heparin: affects intrinsic pathways, prevents formation of prothrombine activator

41. APTT -  PT, TT, PLC - N * Factor deficiency * vWD * Inhibitors * Heparin therapy PT TT APTT HMWK XII PK XI IX VIII VII X V II I Heparin

42. PT TT APTT PT, APTT -  TT, PLC - N HMWK XII XI IX VIII VII X V II I * Common Pathway Factor deficiency * Vitamin K deficiency * Oral anticoagulant therapy * Liver disease Liver Disease

43. ASA: Alter cyclooxygenase activity, which control the release of the adhesive protein from platelets. ASA: Alter cyclooxygenase activity, which control the release of the adhesive protein from platelets.

44. What are the diseases caused by deficiency of factors VIII, IX?

45. VIII: VIII: Hemophilia A IX: IX: Hemophilia B

46. Which blood clotting factors are vit K dependent?

47. II, VII, IX, X II, VII, IX, X

48. What are the normal values for each of PT, PTT, platelets count, WBC count, Bleeding time (BT)?

49. PT: PT: 12-14 sec PTT: PTT:35-45min Platelets Platelets150-400k WBC: WBC:5-11k BT: BT: 7-11 min

50. What are the reversal agents (if any) for each of ASA, Warfarin, and Heparin?

51. ASA: ASA: Time, platelets transfusion Warfarin: Warfarin: Vit K Heparin: Heparin: Protamine sulfate

52. How long you should wait after stopping each of ASA, Warfarin, and Heparin?

53. ASA: ASA:

54. ASA: 5 days ASA: 5 days

55. Warfarin: Warfarin:

56. ASA: 5 days ASA: 5 days Warfarin: 2-3 days Warfarin: 2-3 days

57. ASA: 5 days ASA: 5 days Warfarin: 2-3 days Warfarin: 2-3 days Heparin: Heparin:

58. ASA: 5 days ASA: 5 days Warfarin: 2-3 days Warfarin: 2-3 days Heparin: 4 hrs Heparin: 4 hrs

59. When it is safe to re-start each of ASA, Warfarin, and Heparin after a surgical procedure?

60. ASA ASA

61. ASA Same day ASA Same day Warfarin Warfarin Heparin: Heparin:

62. ASA Same day ASA Same day Warfarin Same day Warfarin Same day Heparin: Heparin:

63. ASA ?: Same day ASA ?: Same day Warfarin ?: Same day Warfarin ?: Same day Heparin ?: After one hr Heparin ?: After one hr

64. Case #1 44 yo male healthy presented for extraction of tooth 44 yo male healthy presented for extraction of tooth Taking 2 tabs of Asprin in the last few days Pain management Taking 2 tabs of Asprin in the last few days Pain management Stop Aspirin for 5 days Stop Aspirin for 5 days Do extraction as normal parient Do extraction as normal parient

66. Case #2 39 yo female w/fever + RLQ pain 39 yo female w/fever + RLQ pain hx excessive bleeding s/p tonsilectomy and dental extractions hx excessive bleeding s/p tonsilectomy and dental extractions Hct 39% plat = 190,000/ mm3 PT, aPTT slightly prolonged Bleeding time = 18 mins Cryoprecipitate, FFP

67. Case #3 48 yo f w/exercise intolerance s/p MVR for regurgitation 48 yo f w/exercise intolerance s/p MVR for regurgitation large liver, jvd large liver, jvd no hx bleeding no hx bleeding continued oozing in OR continued oozing in OR post op: Hct 28% aPTT sl prolonged PT prolonged TT normal BT nl fibrinogen 225 mg% Tx = FFP; Vitamin K of little value in this instance

68. Case #4 78 yo male s/p TURP 78 yo male s/p TURP excessive bleeding from bladder excessive bleeding from bladder oozing from IV site oozing from IV site moderately hypotensive moderately hypotensive Hct 30% platelets normal prolonged PT, aPTT, and TT (twice normal) RT normal FSP present fibrinolytic state exists

69. If BT, aPTT, PT are all normal: One or more of the following must be true: Surgical problem - suture deficiency Surgical problem - suture deficiency Patient is hypothermic - ACT, aPTT, PT run in vitro at 37 0 C Patient is hypothermic - ACT, aPTT, PT run in vitro at 37 0 C lab tests are in error lab tests are in error