Bleeding

1. Bleeding Disorders
AMJAD FAYYAD

2. Normal Hemostasis
Hemostasis is the process by which bleeding is controlled through a complex network of
prothrombotic and fibrinolytic activity.
Primary hemostasis describes the interaction between platelets, von Willebrand factor (vWF),
and the vessel wall.
Secondary hemostasis refers to the activation of coagulation factors that eventually lead to
fibrin clot formation.

3. ▼PATHOPHYSIOLOGY
Basic Mechanisms of Hemostasis and Their
Interactions
Hemostasis can be divided into four general phases:
• the vascular phase
• the platelet phase
• the coagulation cascade phase
• the fibrinolytic phase.
The coagulation cascade is underway within 10 to 20 seconds
of injury, an initial hemostatic plug is formed in 1 to 3
minutes, and fibrin has been generated and added to stabilize
the clot by 5 to 10 minutes.

4. Hemostasis
BV Injury
Platelet
Aggregation
Platelet
Activation
Blood Vessel
Constriction
Coagulation
Cascade
Stable Hemostatic Plug
Fibrin
formation
Reduced
Blood flow
Tissue Factor
Primary hemostatic plug
Neural

5. NORMAL CLOTTING
Response to vessle injury
1. Vasoconstriction to reduce blood flow
2. Platelet plug formation (von willebrand factor binds
damaged vessle and platelets)
3. Activation of clotting cascade with generation of fibrin
clot formation
4. Fibrinlysis (clot breakdown)

6. Normally the ingredients, called factors, act like a row of
dominoes toppling against each other to create a chain
reaction.
If one of the factors is missing this chain reaction cannot
proceed.
CLOTTING CASCADE

7. VASCULAR PHASE
WHEN A BLOOD VESSEL IS DAMAGED,
VASOCONSTRICTION RESULTS.

8. PLATELET PHASE
PLATELETS ADHERE TO THE DAMAGED
SURFACE AND FORM A TEMPORARY
PLUG.

9. COAGULATION PHASE
THROUGH TWO SEPARATE PATHWAYS
THE CONVERSION OF FIBRINOGEN TO
FIBRIN IS COMPLETE.

10. Coagulation Factors
Factor (Name)
XIII (fibrin-stabilizing factor)
XII (Hageman factor )
XI (plasma thromboplastin antecedent )
X (Stuart factor)
IX (Christmas factor)
VIII (antihemophilic factor)
VII (proconvertin)

11. FIBRINOLYTIC
PHASE
ANTICLOTTING MECHANISMS ARE
ACTIVATED TO ALLOW CLOT
DISINTEGRATION AND REPAIR OF THE
DAMAGED VESSEL.

12. HEMOSTASIS
DEPENDENT UPON:
 Vessel Wall Integrity
 Adequate Numbers of Platelets
 Proper Functioning Platelets
 Adequate Levels of Clotting Factors
 Proper Function of Fibrinolytic Pathway

13. Evaluation of Patients with Suspected
Bleeding Disorders
Patients with bleeding disorders present with symptoms of
◦ easy bruising
◦ bleeding gums
◦ Menorrhagia
◦ gastrointestinal bleeding
◦ postoperative bleeding.
The clinical history provides guidance regarding how to proceed in the evaluation, with attention
paid to history of tooth extraction, menstrual bleeding, minor and major surgical procedures, and
family history of bleeding.
Medication use and exposure to alcohol or recreational drugs must be documented.
The physical examination focuses on finding evidence of petechiae, ecchymoses, deep tissue
hematomas, or joint effusions.

14. Clinical Features of Bleeding Disorders
Platelet Coagulation
disorders factor disorders
Site of bleeding Skin Deep in soft tissues
Mucous membranes (joints, muscles)
(epistaxis, gum,
vaginal, GI tract)
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

15. Evaluation of Patients with Suspected
Bleeding Disorders
Laboratory tests used to measure hemostasis are the prothrombin time (PT) and the activated
partial thromboplastin time (aPTT).
◦ The PT, expressed as the INR, is more sensitive to the effects of the vitamin K-dependent factors (II, VII,
and X)
◦ whereas the aPTT is a more sensitive measurement of factors VIII, IX, XI, and XII.
The thrombin time measures fibrinogen convergence to fibrin clot, and the Platelet Function
Analyzer-100 (PFA-100 '') measures platelet function.
Specialized tests include mixing studies to evaluate inhibitors, specific factor level assays, and
tests for fibrin degradation products and D-dimers.

16. LABORATORY EVALUATION
PLATELET COUNT
BLEEDING TIME (BT)
PROTHROMBIN TIME (PT)
PARTIAL THROMBOPLASTIN TIME (PTT)
THROMBIN TIME (TT)

17. PLATELET COUNT
 NORMAL 100,000 - 400,000 CELLS/MM3
< 100,000 Thrombocytopenia
50,000 - 100,000 Mild Thrombocytopenia
< 50,000 Sev Thrombocytopenia

18. BLEEDING TIME
PROVIDES ASSESSMENT OF PLATELET COUNT AND FUNCTION
NORMAL VALUE
2-8 MINUTES

19. PROTHROMBIN TIME
Measures Effectiveness of the Extrinsic
Pathway
NORMAL VALUE
10-15 SECS

20. PARTIAL THROMBOPLASTIN TIME
 Measures Effectiveness of the Intrinsic
Pathway
Mnemonic - PITT
NORMAL VALUE
25-40 SECS

21. THROMBIN TIME
 Time for Thrombin To Convert
Fibrinogen Fibrin
 A Measure of Fibrinolytic Pathway
NORMAL VALUE
9-13 SECS

23. So What Causes Bleeding Disorders?
VESSEL DEFECTS
PLATELET DISORDERS
FACTOR DEFICIENCIES
OTHER DISORDERS
?
?

24. VESSEL DEFECTS
 VITAMIN C DEFICIENCY
 BACTERIAL & VIRAL INFECTIONS
 Infectious and hypersensitivity vasculitides
- Rickettsial and meningococcal infections
- Henoch-Schonlein purpura (immune)
 ACQUIRED & HEREDITARY CONDITIONS

25. PLATELET DISORDERS
 THROMBOCYTOPENIA
 THROMBOCYTOPATHY

26. THROMBOCYTOPENIA
INADEQUATE NUMBER
OF PLATELETS

27. THROMBOCYTOPENIA
DRUG INDUCED
BONE MARROW FAILURE
HYPERSPLENISM
OTHER CAUSES
Lymphoma
HIV Virus
Idiopathic Thrombocytopenia Purpura (ITP)

28. THROMBOCYTOPATHY
ADEQUATE NUMBER BUT
ABNORMAL FUNCTION

29. THROMBOCYTOPATHY
 UREMIA
 INHERITED DISORDERS
 MYELOPROLIFERATIVE DISORDERS
 DRUG INDUCED

31. Qualitative Platelet Disorders
Acquired Platelet Dysfunction
Patients presenting with mucocutaneous bleeding
After platelet dysfunction is identified, treatment depends on the clinical situation.
Acute bleeding can be managed with platelet transfusions, but complete reversal of antiplatelet
agent effects may be detrimental if the therapy is lifesaving (for example, patients with recent
cardiac stents).
Minor dental procedures or menorrhagia can be managed with antifibrinolytic agents
(tranexamic acid or e-aminocaproic acid).

32. Platelet Coagulation
Petechiae, Purpura Hematoma, Joint bl.

33. Petechiae
Do not blanch with pressure
(cf. angiomas)
Not palpable
(cf. vasculitis)
(typical of platelet disorders)

34. Hemarthrosis

35. Hematoma

36. Petechiae

37. Purpura

38. Ecchymosis

39. Senile Purpura

40. Petechiae in patient
with Rocky Mountain
Spotted Fever

41. Henoch-Schonlein purpura

42. Ecchymoses
(typical of coagulation
factor disorders)

43. Coagulation factor disorders
Inherited bleeding disorders
◦ Hemophilia A and B
◦ vonWillebrands disease
◦ Other factor deficiencies
Acquired bleeding disorders
◦ Liver disease
◦ Vitamin K deficiency/warfarin overdose
◦ DIC

44. Hemophilia A and B
Hemophilia A and B (deficiency of factors VIII and IX, respectively) are X-linked hereditary
Hemophilia A is more common than hemophilia B, but both are rare.
The hemophilia's are classified as mild, moderate, or severe according to the circulating factor
levels (mild, 5%-40%; moderate, 1%-5%; severe, <1% .
Patients with mild disease may not present until adulthood

45. Hemophilia
Clinical manifestations (hemophilia A & B are indistinguishable)
Hemarthrosis (most common)
Fixed joints
Soft tissue hematomas (e.g., muscle)
Muscle atrophy
Shortened tendons
Other sites of bleeding
Urinary tract
CNS, neck (may be life-threatening)
Prolonged bleeding after surgery or dental extractions

46. Hemophilia A and B
Diagnosis requires a prolonged aPTT (that corrects in mixing studies) and a normal PT and
complete blood count.
Assay of individual factors (VIII and IX) confirms the diagnosis.
Arthropathy of the knees, ankles, and elbows occurs as a late sequela in 50% of patients as a
result of recurrent hemarthroses.
Inhibitors to infused factors develop in up to 25% of patients with hemophilia A, and 3% to 5%
of patients with hemophilia B

47. Mixing study :
 Mixing studies are tests performed on blood
plasma used to distinguish factor deficiencies
from factor inhibitors, such as lupus
anticoagulant .
Mixing studies take advantage of the fact that
factor levels that are 50 percent of normal
should give a normal Prothrombin time (PT) or
Partial Thromboplastins time

48. Hemophilia A and B and Other Factor
Deficiencies
Managing bleeding in hemophilia A and B requires using virally inactivated factor concentrates.
Patients with mild hemophilia A can be treated with desmopressin, which stimulates the release
of preformed factor VIII from endothelial cells.
Antifibrinolytic agents (such as e-aminocaproic acid and tranexamic acid) are useful in
controlling bleeding from dental procedures

49. Hemophilia A and B and Other Factor
Deficiencies
Factor XI deficiency (also known as hemophilia C) is a rare autosomal hereditary disorder seen
predominantly in persons of Ashkenazi Jewish heritage.
Bleeding symptoms are variable and cannot be predicted by the level of factor XI alone.
Asymptomatic patients do not require intervention (for example, before surgery); symptomatic
patients require plasma infusions for bleeding episodes and surgical procedures.

50. Hemophilia A and B
Hemophilia A
Hemophilia B
Coagulation factor deficiency Factor VIII Factor IX
Inheritance X-linked X-linked
recessive recessive
Incidence 1/10,000 males 1/50,000
males
Severity Related to factor level
<1% - Severe - spontaneous
bleeding
1-5% - Moderate - bleeding
with mild injury

51. Von Willebrand Disease
Von Willebrand disease (vWD), the most common hereditary bleeding disorder, is caused by
either deficiency or ineffectiveness of vWF.
vWF promotes platelet adhesion and functions as a protective carrier protein for factor VIII, so a
mild secondary decrease in factor VIII levels occurs. vWF deficiency leads to mucocutaneous
bleeding symptoms that mimic thrombocytopenia
Hereditary vWD is subclassified into three broad groups (Table), with type 1 being the most
common.
Patients become symptomatic when vWF levels decrease to less than 30%.

52. Von Willebrand Disease
Although the aPTT may be prolonged or normal, a prolonged closure time on the PFA-100"
would suggest vWD, making this a useful initial evaluation tool.
The diagnosis is confirmed by finding a reduction in von Willebrand antigen (quantitative
analysis) and reduced vWF ristocetin cofactor activity (a measurement of the functional affect)
(see Table ).

54. Von Willebrand Disease
Desmopressin is effective in type 1 vWD, releasing preformed vWF and factor VIII from
endothelial cells.
Patients with rare type 2B vWD should not receive desmopressin because it induces platelet
aggregation, which can cause secondary thrombocytopenia In these patients.
Desmopressin is ineffective in patients with type 3 vWD.
vWF concentrates are the preferred treatment for these two subgroups; cryoprecipitate is no
longer used because virally inactivated vWF concentrates are safer and more effective.
Antifibrinolytic therapy (e-aminocaproic acid and tranexamic acid) is useful after surgical
procedures to protect against delayed bleeding and can be used to treat menorrhagia.

55. Vitamin K deficiency
Source of vitamin K Green vegetables Synthesized by intestinal flora
Required for synthesis Factors II, VII, IX ,X Protein C and S
Causes of deficiency Malnutrition Biliary obstruction Malabsorption
Antibiotic therapy
Treatment Vitamin K Fresh frozen plasma

56. Disseminated Intravascular Coagulation (DIC)
Mechanism
Systemic activation
of coagulation
Intravascular
deposition of fibrin
Depletion of platelets
and coagulation factors
Bleeding
Thrombosis of small
and midsize vessels
with organ failure

57. Disseminated Intravascular Coagulation
Classic laboratory findings of disseminated intravascular coagulation include thrombocytopenia,
prolonged activated partial thromboplastin and prothrombin times, elevated INR,
hypofibrinogenemia, and elevated D-dimer levels.

58. Acquired Bleeding Disorders
Coagulopathy of Liver Disease
The liver is the site of production for procoagulant and fibrinolytic factors.
Liver disease is associated with bleeding and thrombosis
Liver disease can result in factor deficiency, hyperfibrinolysis, and mild to moderate
thrombocytopenia, leading to PT prolongation, INR elevation, and aPTT prolongation.
Distinguishing between liver disease and disseminated intravascular coagulation may be
challenging.

59. Acquired Bleeding Disorders
Coagulopathy of Liver Disease
Asymptomatic patients do not require treatment, but vitamin K supplementation should be
considered if the INR is elevated.
Patients experiencing bleeding may require blood product replacement, with
◦ cryoprecipitate
◦ platelet transfusions
◦ Fresh frozen plasma
◦ Prothrombin complex concentrates
◦ Antifibrinolytic agents

60. Acquired von Willebrand Disease
Acquired vWD occurs in conditions of high circulatory shear stress (valvular heart disease,
hypertrophic cardiomyopathy, circulatory assist devices, and extracorporeal membrane
oxygenation systems) caused by excessive degradation of high molecular-weight von Willebrand
multimers by the proteolytic enzyme ADAMTS13.
Affected patients develop bleeding conditions similar to those in hereditary vWD.
Desmopressin and vWF concentrates have been used in management.

61. Acquired Hemophilia
Acquired hemophilia results from an autoantibody directed against factor VIII.
Patients present with bleeding symptoms that mimic hereditary hemophilia A.
Approximately half of all cases are associated with pregnancy and the postpartum state,
malignancy, and other autoimmune disorders, as well as with medications.
Laboratory evaluation shows a normal platelet count and PT with a prolonged aPTT: Mixing
studies do not correct the aPTT Factor analysis shows a low factor VIII level
Factor VIII concentrates do not correct the problem.
Management of acute bleeding requires activated
◦ prothrombin complex concentrates or activated factor VII to overcome the inhibitor.
◦ Immunosuppression, using corticosteroids and cyclophosphamide, is required to decrease the formation
of inhibitors.

62. Dental Management
Dental management required for patients with bleeding disorders depends
on both the type and invasiveness of the
Dental procedure and the type and severity of the bleeding disorder.
When significant bleeding is expected, the goal of management is to
preoperatively restore the hemostatic system to an acceptable
range, while supporting coagulation with adjunctive and/or
local measures. For reversible coagulopathies, (eg, coumadin
anticoagulation), it may be best to remove the causative agent
or treat the primary illness or defect in order to allow the
patient to return to a manageable bleeding risk for the dental
treatment period. For irreversible coagulopathies, the missing
or defective element may need to be replaced from an exogenous
source to allow control of bleeding (eg, coagulation factor
concentrate therapy for hemophilia). Assessment of the
coagulopathy and delivery of appropriate therapy prior to
dental procedures is best accomplished in consultation with
a hematologist.

63. Patients on Anticoagulants
Management of the dental patient on anticoagulant therapy
involves consideration of the degree of anticoagulation
achieved. It is generally held that nonsurgical dental
treatment can be successfully accomplished
without alteration of the anticoagulant regimen, provided
the PT/INR is not grossly above the therapeutic range and
trauma is minimized. Greater controversy exists over
the management of anticoagulated patients for oral surgical
procedures. Preparation of the anticoagulated patient
for surgical procedures depends on the extent of bleeding
expected.

64. For surgical procedures, physician consultation is advised
in order to determine the patient’s most recent PT/INR level
and the best treatment approach based on the patient’s
relative thromboembolic and hemorrhagic risks
Antifibrinolytic mouthwash has proven effective in control of
oral surgical bleeding. Use of antifibrinolytics may have value
in control of oral wound bleeding, thereby alleviating the need
to reduce the oral anticoagulant dose.