different bleeding_disorders presentation

Bleeding disorders presentation

1. BLEEDING DISORDERS

2. HEMOSTASIS
1. VASCULAR PHASE
2. PLATELET PHASE
3.COAGULATION PHASE
4.FIBRINOLYTIC PHASE

3. 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
Lab Tests
•CBC-Plt
•BT,(CT)
•PT
•PTT
Plt Study
Morphology
Function
Antibody

4. 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)

5. Normally the ingredients, called factors, act like a row of
dominoes toppling against each other to create a chain
reaction.
If one of thefactorsis missingthis chain reaction cannot
proceed.
CLOTTING CASCADE

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

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

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

9. THE CLOTTING MECHANISM
INTRINSIC EXTRINSIC
PROTHROMBIN THROMBIN
FIBRINOGEN
FIBRIN
(II) (III)
(I)
V
X
Tissue ThromboplastinCollagen
VII
XII
XI
IX
VIII

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

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

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

13. PLATELET COUNT
NORMAL 100,000 -400,000CELLS/MM
3
< 100,000 Thrombocytopenia
50,000 -100,000Mild Thrombocytopenia
< 50,000 Sev Thrombocytopenia

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

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

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

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

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

19. VESSEL DEFECTS
VITAMIN C DEFICIENCY
BACTERIAL & VIRAL INFECTIONS
ACQUIRED &
HEREDITARY CONDITIONS

20. Vascular defect -cont.
Infectious and hypersensitivity vasculitides
-Rickettsial and meningococcal infections
-Henoch-Schonlein purpura (immune)

21. PLATELET DISORDERS
THROMBOCYTOPENIA
THROMBOCYTOPATHY

22. THROMBOCYTOPENIA
INADEQUATE NUMBER
OF PLATELETS

23. THROMBOCYTOPATHY
ADEQUATE NUMBER BUT
ABNORMAL FUNCTION

24. THROMBOCYTOPENIA
DRUG INDUCED
BONE MARROW FAILURE
HYPERSPLENISM
OTHER CAUSES

25. OTHERCAUSES
Lymphoma
HIV Virus
Idiopathic Thrombocytopenia Purpura (ITP)

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

27. FACTOR DEFICIENCIES
(CONGENITAL)
HEMOPHILIA A
HEMOPHILIA B
von WILLEBRAND’S DISEASE

28. FACTOR DEFICIENCIES
HEMOPHILIA A (Classic Hemophilia)
80-85% of all Hemophiliacs
Deficiency of Factor VIII
Lab Results -Prolonged PTT
HEMOPHILIA B (Christmas Disease)
10-15% of all Hemophiliacs
Deficiency of Factor IX
Lab Test -Prolonged PTT

29. FACTOR DEFICIENCIES
VON WILLEBRAND’S DISEASE
Deficiency of VWF & amount of Factor VIII
Lab Results -Prolonged BT, PTT

30. OTHER DISORDERS
(ACQUIRED)
ORAL ANTICOAGULANTS
Warfarin
HEPARIN
LIVER DISEASE
MALABSORPTION
BROAD-SPECTRUM ANTIBIOTICS

31. INHIBITORS
30% of people with haemophilia develop an antibody to the
clotting factor they are receiving for treatment. These
antibodies are known as inhibitors.
These patients are treated with high does of FVIIa for bleeds or
surgery. This overrides defect in FVIII or FIX deficiency.
Longterm management involves attempting to eradicate
inhibitors by administering high dose FVIII (or FIX) in a
process called immune tolerance

32. Bleeding Disorders

33. 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, superficialLarge, deep
Muscle bleeding Extremely rare Common
Bleeding after cuts & scratchesYes No
Bleeding after surgery or traumaImmediate, Delayed (1-2 days),
usually mild often severe

34. Platelet Coagulation
Petechiae, PurpuraHematoma, Joint bl.

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

36. Hemarthrosis

37. Hematoma

38. Petechiae

39. Purpura

40. Ecchymosis

41. Senile Purpura

42. Petechiaein patient
with Rocky Mountain
Spotted Fever

43. Henoch-Schonlein purpura


44. CT scan showing large hematoma
of right psoas muscle

45. Coagulation factor disorders
Inheritedbleeding
disorders
Hemophilia A and B
vonWillebrands disease
Other factor deficiencies
Acquiredbleeding
disorders
Liver disease
Vitamin K
deficiency/warfarin
overdose
DIC

46. 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
5-25% -Mild -bleeding with surgery or trauma
Complications Soft tissue bleeding

47. 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

48. Hemarthrosis (acute)

49. Treatment of hemophilia A
Intermediate purity plasma products
May contain von Willebrand factor
High purity (monoclonal) plasma products
No functional von Willebrand factor
Recombinant factor VIII
Virus free/No apparent risk
Adjunctive therapy
Aminocaproic acid

50. Complications of therapy
Formation of inhibitors (antibodies)
10-15% of severe hemophilia A patients
1-2% of severe hemophilia B patients
Viral infections
Hepatitis B Hepatitis C
Hepatitis A HIV
Other

51. Treatment of hemophilia B
Agent
High purity factor IX
Recombinant human factor IX
Dose
Initial dose: 100U/kg
Subsequent: 50U/kg every 24 hours

52. von Willebrand Disease: Clinical Features
von Willebrand factor
Synthesis in endothelium and megakaryocytes
Forms large multimer
Carrier of factor VIII
Anchors platelets to subendothelium
Bridge between platelets
Inheritance -autosomal dominant
Incidence -1/10,000
Clinical features -mucocutaneous bleeding

53. Laboratory evaluation of
von Willebrand disease
Classification
Type 1 Partial quantitative deficiency
Type 2 Qualitative deficiency
Type 3 Total quantitative deficiency
Diagnostic tests:
vonWillebrand type
Assay 1 2 3
vWF antigen  Normal 
vWF activity   
Multimer analysis Normal Normal Absent

54. Treatment of von Willebrand Disease
Cryoprecipitate
Source of fibrinogen, factor VIII and VWF
Only plasma fraction that consistently contains VWF multimers
DDAVP (deamino-8-arginine vasopressin)
plasma VWF levels by stimulating secretion from endothelium
Duration of response is variable
Not generally used in type 2 disease
Dosage 0.3 µg/kg q 12 hrIV
Factor VIII concentrate (Intermediate purity)

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. Common clinical conditions associated with
Disseminated Intravascular Coagulation
Sepsis
Trauma
Head injury
Fat embolism
Malignancy
Obstetrical complications
Amniotic fluid embolism
Abruptio placentae
Vascular disorders
Reaction to toxin (e.g.
snake venom, drugs)
Immunologic disorders
Severe allergic reaction
Transplant rejection
Activation of both coagulation and fibrinolysis
Triggered by

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

58. Pathogenesis of DIC
Coagulation Fibrinolysis
Fibrinogen
Fibrin
Monomers
Fibrin
Clot
(intravascular)
Fibrin(ogen)
Degradation
Products
Plasmin
Thrombin Plasmin
Release of
thromboplastic
material into
circulation
Consumption of
coagulation factors;
presence of FDPs
aPTT
PT
TT
Fibrinogen
Presence of plasmin
FDP
Intravascular clot
Platelets
Schistocytes

59. Disseminated Intravascular Coagulation
Treatment approaches
Treatment of underlying disorder
Anticoagulation with heparin
Platelet transfusion
Fresh frozen plasma
Coagulation inhibitor concentrate (ATIII)

60. Classification of platelet disorders
Quantitative disorders
Abnormal distribution
Dilution effect
Decreased production
Increased destruction
Qualitative disorders
Inherited disorders (rare)
Acquired disorders
Medications
Chronic renal failure
Cardiopulmonary bypass

61. Thrombocytopenia
Immune-mediated
Idioapthic
Drug-induced
Collagen vascular disease
Lymphoproliferative disease
Sarcoidosis
Non-immune mediated
DIC
Microangiopathic hemolytic anemia

62. Liver Disease and Hemostasis
1.Decreased synthesis of II, VII, IX, X, XI, and
fibrinogen
2.Dietary Vitamin K deficiency (Inadequate
intake or malabsortion)
3.Dysfibrinogenemia
4.Enhanced fibrinolysis (Decreased alpha-2-
antiplasmin)
5.DIC
6.Thrombocytoepnia due to hypersplenism

63. Management of Hemostatic
Defects in Liver Disease
Treatment for prolonged PT/PTT
Vitamin K 10 mg SQ x 3 days -usually
ineffective
Fresh-frozen plasma infusion
25-30% of plasma volume (1200-1500 ml)
immediate but temporary effect
Treatment for low fibrinogen
Cryoprecipitate (1 unit/10kg body weight)
Treatment for DIC (Elevated D-dimer, low factor
VIII, thrombocytopenia
Replacement therapy

64. Vitamin K deficiency due to warfarin overdose
Managing high INR values
Clinical situationGuidelines
INR therapeutic-5 Lower or omit next dose;
Resume therapy when INR is therapeutic
INR 5-9; no bleedingLower or omit next dose;
Resume therapy when INR is therapeutic
Omit dose and give vitamin K (1-2.5 mg po)
Rapid reversal: vitamin K 2-4 mg po (repeat)
INR >9; no bleedingOmit dose; vitamin K 3-5 mg po; repeat as necessary
Resume therapy at lower dose when INR therapeutic
Chest 2001:119;22-38s (supplement)

65. Vitamin K deficiency due to warfarin overdose
Managing high INR values in bleeding patients
Clinical situation Guidelines
INR > 20; serious bleedingOmit warfarin
Vitamin K 10 mg slow IV infusion
FFP or PCC (depending on urgency)
Repeat vitamin K injections every 12 hrs as needed
Any life-threatening bleedingOmit warfarin
Vitamin K 10 mg slow IV infusion
PCC ( or recombinant human factor VIIa)
Repeat vitamin K injections every 12 hrs as needed
Chest 2001:119;22-38s (supplement)

66. Approach to Post-operative bleeding
1.Is the bleeding local or due to a hemostatic failure?
1.Local: Single site of bleeding usually rapid with
minimal coagulation test abnormalities
2.Hemostatic failure: Multiple site or unusual pattern
with abnormal coagulation tests
2.Evaluate for causes of peri-operative hemostatic failure
1.Preexisting abnormality
2.Special cases (e.g. Cardiopulmonmarybypass)
3.Diagnosis of hemostatic failure
1.Review pre-operative testing
2.Obtain updated testing

67. Laboratory Evaluation of Bleeding
Overview
CBC and smear Platelet count Thrombocytopenia
RBC and platelet morphologyTTP, DIC, etc.
Coagulation Prothrombin time Extrinsic/common pathways
Partial thromboplastin timeIntrinsic/common pathways
Coagulation factor assaysSpecific factor deficiencies
50:50 mix Inhibitors (e.g., antibodies)
Fibrinogen assay Decreased fibrinogen
Thrombin time Qualitative/quantitative
fibrinogen defects
FDPs or D-dimer Fibrinolysis (DIC)
Platelet functionvon Willebrand factor vWD
Bleeding time In vivotest (non-specific)
Platelet function analyzer (PFA)Qualitative platelet disorders
and vWD
Platelet function tests Qualitative platelet disorders

68. Laboratory Evaluation of the
Coagulation Pathways
Partial thromboplastin time
(PTT)
Prothrombin time
(PT)
Intrinsic pathway Extrinsic pathway
Common pathwayThrombin time
Thrombin
Surface activating agent
(Ellagic acid, kaolin)
Phospholipid
Calcium
Thromboplastin
Tissue factor
Phospholipid
Calcium
Fibrin clot

69. Coagulation factor deficiencies
Summary
Sex-linked recessive
Factors VIII and IX deficiencies cause bleeding
Prolonged PTT; PT normal
Autosomal recessive (rare)
Factors II, V, VII, X, XI, fibrinogen deficiencies cause bleeding
Prolonged PTand/or PTT
Factor XIII deficiency is associated with bleeding and
impaired wound healing
PT/ PTT normal; clot solubilityabnormal
Factor XII, prekallikrein, HMWK deficiencies
do not cause bleeding

70. Thrombin Time
Bypasses factors II-XII
Measures rate of fibrinogen conversion to fibrin
Procedure:
Add thrombin with patient plasma
Measure time to clot
Variables:
Source and quantity of thrombin

71. Causes of prolonged Thrombin Time
Heparin
Hypofibrinogenemia
Dysfibrinogenemia
Elevated FDPs or paraprotein
Thrombin inhibitors (Hirudin)
Thrombin antibodies

72. Classification of thrombocytopenia
Associated with bleeding
Immune-mediated
thrombocytopenia (ITP)
Most others
Associated with thrombosis
Thrombotic thrombocytopenic
purpura
Heparin-associated
thrombocytopenia
Trousseau’s syndrome
DIC

73. Bleeding time and bleeding
5-10% of patients have a prolonged bleeding time
Most of the prolonged bleeding times are due to
aspirin or drug ingestion
Prolonged bleeding time does not predict excess
surgical blood loss
Not recommended for routine testing in
preoperative patients

74. Drugs and blood products used for
bleeding

75. Treatment Approaches to
the Bleeding Patient
Red blood cells
Platelet transfusions
Fresh frozen plasma
Cryoprecipitate
Amicar
DDAVP
Recombinant Human factor VIIa

76. RBC transfusion therapy
Indications
Improve oxygen carrying capacity of blood
Bleeding
Chronic anemia that is symptomatic
Peri-operative management

77. Red blood cell transfusions
Adverse reactions
Immunologic reactions
Hemolysis RBC incompatibility
Anaphylaxis Usually unknown; rarely against IgA
Febrile reaction Antibody to neutrophils
Urticaria Antibody to donor plasma proteins
Non-cardiogenic Donor antibody to leukocytes
pulmonary edema

78. Red blood cell transfusions
Adverse reactions
Non-immunologic reactions
Congestive heart failureVolume overload
Fever and shock Bacterial contamination
Hypocalcemia Massive transfusion

79. Platelet transfusions
Source
Platelet concentrate (Random donor)
Pheresis platelets (Single donor)
Target level
Bone marrow suppressed patient (>10-20,000/µl)
Bleeding/surgical patient (>50,000/µl)

80. Platelet transfusions -complications
Transfusion reactions
Higher incidence than in RBC transfusions
Related to length of storage/leukocytes/RBC mismatch
Bacterial contamination
Platelet transfusion refractoriness
Alloimmune destruction of platelets (HLA antigens)
Non-immune refractoriness
Microangiopathic hemolytic anemia
Coagulopathy
Splenic sequestration
Fever and infection
Medications (Amphotericin, vancomycin, ATG, Interferons)

81. Fresh frozen plasma
Content -plasma (decreased factor V and VIII)
Indications
Multiple coagulation deficiencies (liver disease, trauma)
DIC
Warfarin reversal
Coagulation deficiency (factor XI or VII)
Note
Viral screened product
ABO compatible

82. Cryoprecipitate
Prepared from FFP
Content
Factor VIII, von Willebrand factor, fibrinogen
Indications
Fibrinogen deficiency
Uremia
von Willebrand disease
Dose (1 unit = 1 bag)
1-2 units/10 kg body weight

83. Hemostatic drugs
Aminocaproic acid
Mechanism
Prevent activation plaminogen-> plasmin
Uses
Primary menorrhagia
Oral bleeding
Bleeding in patients with thrombocytopenia
Blood loss during cardiac surgery
Side effects
GI toxicity
Thrombi formation

84. Hemostatic drugs
Desmopressin
Mechanism
Increased release of VWF from endothelium
Uses
Most patients with von Willebrand disease
Mild hemophilia A
Side effects
Facial flushing and headache
Water retention and hyponatremia

85. Recombinant human factor VIIa (rhVIIa; Novoseven)
Mechanism
Direct activation of common pathway
Use
Factor VIII inhibitors
Bleeding with other clotting disorders
Warfarin overdose with bleeding
CNS bleeding with or without warfarin
Cost (70 kg person) -$1 per µg
~$5,000/dose or $60,000/day