PPt on bleeding disorders

1. Bleeding Disorders-II
Dr Samiyah Syeed Ahmed

2. What to expect in todays class?
● Types of Bleeding disorders
● Thrombocytopenia- causes
● ITP
● vWD

4. Classification of bleeding disorders
Bleeding disorders:
1. Vascular abnormalities
2. Platelet disorders
Clotting disorders:
1. Congenital: Hemophilia A, Hemophilia B, vWD
2. Acquired: Vitamin K deficiency
3. Fibrinolytic disorders
4. Drug induced

5. Bleeding disorder
due to vessel wall

6. Bleeding disorders due to vessel wall abnormality
HEREDITARY
● Hereditary hemorrhagic
telengiectasia
● Marfan’s syndrome
● Ehler Danlos Syndrome
METABOLIC AND INFLAMMATORY
● Henoch Schonlein purpura
● Scurvy
● Senile purpura
● Steroid purpura
● Rickettsial diseases

7. Bleeding disorder
due to platelets

8. QUANTITATIVE DISORDERS
THROMBOCYTOPENIA
ITP
Thrombotic thrombocytopenic purpura
Wiskott Aldrich Syndrome
Heparin induced TCP
THROMBOCYTOSIS
Benign or reactive process
Myelodysplastic syndrome
QUALITATIVE DISORDERS
HEREDITARY
Glanzmanns thromboasthenia
Bernard Soulier Syndrome
Storage granule abnormalities
ACQUIRed
Anemia
Drug induced: Aspirin, NSAIDs
Systemic diseases: Liver failure, uremia

9. Bleeding due to Thrombocytopenia

10. Bleeding due to Thrombocytopenia
● An important cause of generalized bleeding.
● Count < 1, 50,000 platelets/μL is considered: Thrombocytopenia.
● Platelet counts 20,000 to 50,000 platelets/μL: post traumatic bleeding
● Platelet counts < 20,000 platelets/μL: Spontaneous bleeding.
● When thrombocytopenia is isolated, the PT and PTT are normal

11. Symptoms of bleeding due to thrombocytopenia
● Spontaneous bleeding with thrombocytopenia most often
involves small vessels
● Common sites: Skin and the mucous membranes of gi and
gu tracts.
● Most feared: Intracranial bleeding

12. Causes of thrombocytopenia

13. Decreased production of Platelets:
Drug induced: Alcohol, thiazides, cytotoxic
drugs
Infections: Measles, HIV,
Nutritional deficiency: Vit B12, FA
Aplastic anemia
Leukemia, Disseminated cancer
Myelodysplastic syndromes
Increased destruction of platelets:
Immunologic destruction: ITP
SLE, lymphoid neoplasms,
Post transfusion, neonatal
Drug associated: Heparin, quinidine
Infections: HIV, Dengue,
Non immunologic: DIC, TMA
Sequestration:
Hypersplenism
Dilution:
Transfusion
THROMBOCYTOPENIA

17. Immune thrombocytopenic Purpura

18. ● Idiopathic thrombocytopenic purpura (ITP)
● Caused by autoantibody-mediated destruction of
platelets
● Primary: In the absence of any known risk factors
● Secondary: Presence of predisposing conditions and
exposures

19. Pathogenesis
● Autoantibodies directed against platelet membrane
glycoproteins IIb–IIIa or Ib–IX
● Majority: Ab’s are of IgG
● Antiplatelet Ab’s act as opsonins that are recognized by IgG Fc
receptors expressed on phagocytes
● The thrombocytopenia is usually markedly improved by
splenectomy

21. Clinical Features:
● Self limiting thrombocytopenia
● Usually they have a history of purpura in children
● Spontaneous recovery within 2 - 6 mths
● History of antecedent viral infections- Measles, rubella, EBV
infection
● Common in both boys and girls
● History of bleeding from gums, epistaxis or ecchymoses
ACUTE ITP

22. Clinical features: Chronic ITP
● Lasts for more than 12 months
● Requires therapy
● Insidious onset of mucocutaneous bleeding, epistaxis,
bruising
● Occurs in adults
● Women are affected more than men
● Disease lasts > 6 mths to few years
CHRONIC ITP

23. CLINICAL PRESENTATION

26. Uncommon manifestations
● Menorrhagia
● Hematuria
● GI bleeding
● Subarachnoid hemorrhage
● Excessive bleeding after minor surgeries

27. Lab investigations
Blood picture:
● Hb: Normal, may be low if there's significant bleeding
● Platelets are decreased :
● Acute ITP: 40,000-50,000/dl
● Chronic ITP:10,000 - 50,000/dl

28. Lab investigations
Peripheral smear:
● Acute ITP: Decreased platelets, few megathrombocytes
● Large platelets (giant platelets)
● Mean platelet volume is increased

31. Other Lab investigations
● Bleeding time
● PT, APTT
prolonged
Normal
c
c

32. Bone Marrow
Not diagnostic
● Helps to rule out other causes of thrombocytopenia
● Megakaryocyte hyperplasia
● Large number of immature megakaryocytes

34. Bone Marrow
● Increased number of megakaryocytes
● Immature, with large, non lobulated,
single nuclei.
● Smooth borders, lack budding platelets
● Cytoplasm: Basophilic
● Cytoplasmic vacuolation
● Reflect accelerated thrombopoiesis
● Normoblastic hyperplasia
● Myelopoiesis is normal

35. Pseudothrombocytopenia
● Lab artefact
● Platelets to appear low on counter report
● While actually they are adequate on peripheral smear
● 0.1% normal individuals have EDTA dependent agglutinins
which lead to platelet clumping

36. Evans Syndrome
● Autoimmune hemolytic anemia with immune
thrombocytpenia
● More common in women
● Antibodies against RBCs and platelets are demonstrable.

37. Management
● Platelet count > 60,000 are followed up without treatment
● Platelet count > 50,000 + significant bleeding or count <
20,000/dl need active treatment
● Steroids
● Immunosupressive drugs
● High dose immunoglobulins
● Failure of steroid therapy/ relapse: Splenectomy
● Rituximab: 2nd line therapy

38. Secondary Immune thrombocytopenia
1. Drugs: acetaminophen, Digoxin, Quinine, Quinidine, Gold salts
2. Collagen Vascular disease: SLE
3. Pregnancy
4. Neonatal thrombocytopenia
5. Heparin induced thrombocytopenia

39. Platelet function disorders

40. Classification of platelet function disorders
Inherited
● Defect in platelet membranes
○ Bernard Soulier Syndrome
○ Glanzmann’s Thromboasthenia
● Von Willebrands disease
● Storage organelle deficiency
○ Storage pool deficiency
○ Chediak Higashi syndrome
○ Gray platelet syndrome

41. Acquired
● Dysproteinemias
● Uremia
● Drugs- Aspirin, NSAID,Sulfinpyrazole
● Myeloproliferative disorders
● MDS
● DIC,HUS,TTP

42. Bernard Soulier Syndrome
● Rare autosomal recessive disorder
● Defective adhesion of platelets to subendothelial matrix
● Inherited deficiency of platelet glycoprotein Ib–IX
● This glycoprotein is a receptor for vWF
● Essential for normal platelet adhesion to the subendothelial
extracellular matrix
● Prolonged Bleeding time

45. Glanzmann’s thrombasthenia
● Defective platelet aggregation
● Autosomal recessive
● Deficiency or dysfunction of glycoprotein IIb–IIIa
● Thrombasthenic platelets fail to aggregate in response to
adenosine diphosphate (ADP), collagen, epinephrine, or
thrombin
● Participates in “bridge formation” between platelets by
binding fibrinogen.
● The associated bleeding tendency is often severe

46. ● Bleeding time is prolonged
● Platelet count and morphology is normal
● PT APTT ; Normal
● Platelet aggregation to ADP, Collagen, thrombin, and
Epinephrine: Deficient
● Aggregation to ristocetin in normal

49. Von Willebrands disease
ERIK ADOLF
VON
WILLEBRAND

50. ● Genetic disorder with deficient or defective Von Willebrand factor
● Most common inherited bleeding disorder of humans
● It is carried on Chromosome 12
● Occurs equally in men and women.

51. Functions of Von Willebrand factor
VON WILLEBRAND FACTOR
PRIMARY
HEMOSTASIS
Stabilizes
Factor VIII
Platelet
adhesion and
aggregation
SECONDARY
HEMOSTASIS
Multimers of different sizes
Large multimers are responsible for Platelet adhesion /aggregation

53. Clinical presentation
❑Mild to moderately severe bleeding
✓bruising
✓Epistaxis
✓ prolonged bleeding from minor cuts
✓ menorrhagia
✓Bleeding after trauma /surgery
✓Hemarthroses not typical ( except in Type 3 VwD)

54. Classification
Type of vWf deficiency VWF protein function
Type I Quantitative partial
deficiency
Normal
Type II Qualitative functional
deficiency
Abnormal
Type III Quantitative complete
deficiency
Undetectable

55. Type I
● Mild quantitative defect
● Decreased amount and activity of vWD
● AD disorder
● ~70% of all cases, generally is associated with mild disease.

56. Type II
● Qualitative defects in vWF
● Decreased activity
● Subtypes:
○ II A: Most common type, vWF : normal amounts,impaired multimerization (
multimers)
○ II B: Hyperfunctional platelet binding (vWF Platelets)--> Cleared from circulation
○ II M: Decreased GPIb binding (vWF Platelets)
○ II N : Decreased F VIII binding
Type 2 vWD accounts for 25% of all cases and is associated with mild to moderate bleeding

57. Type II

58. Type III
● AR disorder
● Caused by deletions or frameshift mutations involving both alleles
● Little to no vWF synthesis.
● Severe total quantitative defect
● Reduced FVIII level too

60. Diagnosis of Von Willebrand disease
● History of mucosal bleed
● Family history

61. Lab diagnosis
Screening tests:
1. CBC: Anemia
2. Platelet count
3. APTT: Prolonged
4. Bleeding time: Normal to increased
5. PT: Normal
6. PFA-100: Normal
7. Blood Group: Type O group have lower level of vWF, AB has high level vWF

62. Lab diagnosis: Specific tests

63. Diagnosis
● Decreased level of Antigen and activity: Type I
● vWF activity <0.7 of antigen level: Type IIA, IIB, IIM
● Factor VIII << VWF antigen : Type II N
● No VWF Ag : Type III

64. Diagnosis

65. Treatment

66. Bring on the questions…

67. Thank You