1. Seminar Presantation on;
Bleeding Disorders In Pediatrics Patient
By C- I Med. Students ; Siraj Shiferaw,
.
1
Ambo University
Collage Of Medicine & Health Sceince
Department Of Medicine
Feb,25/2014

2. PRESANTATION OUTLINE
1. Over view of homeostasis and the blood clotting process.
2.Approach to a child with bleeding disorder.
3.Lab investigations.
4.Bleeding disorde in pediatrics patient .
-Hereditary coagulation disorders
-Acquired coagulation disorders
-Platelate disorders .
-Vascular disorders.
2

3. 1.Over view of homeostasis and the blood clotting
process.
HEMOSTASIS:
The ability of the body to control the flow of blood following vascular injury
is paramount to continued survival. The process of blood clotting and then the
subsequent dissolution of the clot, following repair of the injured tissue.
is composed of 4 major events that occur in a set order following the loss of
vascular integrity:
- Vascular constriction -limits the flow of blood to the area of injury.
- Platelet aggregation –Blood platelets clump when binding to collagen that
becomes exposed following rupture of the endothelial lining of vessels.
-Blood platelets become activated and aggregate at the site of injury .
-Upon activation, platelets release ADP and TXA2 (which activate
additional platelets).
3

4. • Clot formation -to insure stability of the
initially loose platelet plug, a fibrin mesh
(also called the clot) forms and entraps the
plug.
• Fibrinolysis -the clot must be dissolved in
order for normal blood flow to resume
following tissue repair. The dissolution of the
clot occurs through the action of plasmin
4

5. 1.Over view of homeostasis and the blood clotting process.
5

6. 1.Over view of homeostasis and the blood clotting
process.
6

7. 2.Approach to a child with bleeding disorder
HISTORY
The history should determine;
• The site or sites of bleeding,the severity and duration of
hemorrhage, and the age at onset.
• Was the bleeding spontaneous, or did it occur after trauma?
• Was there a previous personal or family history of similar
problems?
• If a child or adolescent has had surgery that affects the
mucosal surfaces, such as a tonsillectomy or major dental
extractions, the absence of bleeding usually rules out a
hereditary bleeding disorder
7

8. 2.Approach to a child with bleeding disorder
PHYSICAL EXAMINATION
• The P/E should focus on whether bleeding symptoms are associated primarily
with the mucous membranes or skin (mucocutaneous bleeding) or with the
muscles and joints(deep bleeding).
• The examination should determine the presence of
petechiae, ecchymoses, hematomas, hemarthroses, or mucous membrane
bleeding.
• Patients with defects in platelet-blood vessel wall interaction (VWD or platelet
function defects) usually have mucocutaneous bleeding.
• Individuals with a clotting factor deficiency of factor VIII or IX (hemophilia A
or B) have symptoms of deep bleeding into muscles and joints.
• Individuals with disorders of the collagen matrix and vessel wall may have
loose joints and lax skin associated with easy bruising (Ehlers-Danlos
syndrome).
8

9. 3.Laboratory investigations
• Blood count and film
– show the number and morphology of platelets and
any blood disorder such as leukaemia or lymphoma.
– The normal range for the platelet count is 150- 400
109/L
• Bleeding time
– measures platelet plug formation in vivo
– normally between 3 and 10 minutes
– Prolonged bleeding times are found in patients with
platelet function defects
9

10. 3.Laboratory investigations
• Bleeding time
– Time taken for a standardized skin puncture to stop
bleeding
– Measures platelet plug formation in vivo (assessment
of platelet response to limited vascular injury)
– Normally between 3 and 10 minutes
– Prolonged bleeding times are found in patients with
platelet function defects
10

11. 3.Laboratory investigations
• Coagulation tests
– Performed using blood collected into citrate, which
neutralizes calcium ions and prevents clotting.
– The prothrombin time (PT)
– The partial thromboplastin time (PTT)
– The thrombin time (TT)
– Correction tests
– Factor assays
– Special tests of coagulation
11

12. 3.Laboratory investigations
• Coagulation tests
– The prothrombin time (PT)
• Time needed for the plasma to clot in the presence of tissue
thromboplastin and calcium
• Evaluates the ability of blood to clot properly
• Normal time for clotting is 10-14s
• Prolong PT results from def of:
– Factor V
– Factor VII
– Factor X
– Prothrombin
– Fibrinogen
12

13. 3.Laboratory investigations
• Coagulation tests
– The partial thromboblastin time (PTT)
• Time needed for the plasma to clot in the presence of a
surface activator (kaolin), cephalin and calcium.
• Normal time of clotting is 30-40s
• Prolong PPT results from def of:
– Factor V
– Factor VIII
– Factor IX
– Factor X
– Factor X1
– Prothrombin
– Fibrinogen
13

14. 3.Laboratory investigations
• Coagulation tests
– The thrombin time (TT)
• Measures clotting time of plasma after adding thrombin
• Normal clotting time is 14-16s
• Prolong TT results from:
– Deficiency of fibrinogen
– Dysfibrinogenaemia
14

15. 4. BLEEDING DISORDERS IN PEDIATRICS
15

16. 4. Bleeding Disorders In Pediatrics
A. Hereditary coagulation disorders
– Hemophilia A
– Hemophilia B
– Von Will brand's disease
B.Acquired coagulation disorders
– Vitamin K deficiency
– Liver disease
– DIC
– Coagulation disorders caused by antibodies
– Massive transfusion syndrome
16

17. 4. Bleeding Disorders In Pediatrics
C.Platelet disorders
-Thrombocytopinic (dereased number of platelates)
-Idiopathic thrombocytopenic purpura (ITP).
-Thrombotic thrombocytopenic purpura (TTP).
-Drug induced thrombocytopenic purpura .
-Platelate function disorder
- Congenital
- Acquired
D. Vascular disordes
-Congenital
-Acquired
17

18. A. Hereditary coagulation disorders
– Uncommon
– Usually involve deficiency of one factor only
– Deficiencies of all factors have been described, but
most common are:
• Hemophilia A – factor VIII deficiency
• Hemophilia B – factor XI deficiency
• Von Will brand’s syndrome
• Others are rare
18

19. 19

20. Hemophilia A
(classic hemophilia)
• The most common of hereditary clotting factor
deficiencies
• Due by factor VIII deficiency
• The prevalence about 1 in 5000 of the male
population
• Inherited as X-linked disorder
– But up to 30 % have no family history and results
from spontaneous mutation
20

21. Hemophilia A
21

22. Hemophilia A: X-linked
• The
22

23. Hemophilia A
• Clinical features
– Atypical profuse bleeding at circumcision
– Bruising at neonatal vaccines
– Joints and soft tissue bleeds and excessive bleeding when they
start to be active
– Prolonged bleeding after teeth extraction
– Recurrent painful hemarthrosis
– Muscle haemoatomas
– Spontaneous haematouria
– GIT hemorrhage
– Spontaneous intracranial hemorrhage (rare)
23

24. Hemophilia A
• Clinical features
– The clinical severity depend on the level of factor
VIII:C = severity of condition
– Severe = factor level < 1%
– Moderate = factor level 1 – 5%
– Mild = factor level > 5 %
24

25. Hemophilia A
• Clinical features
– Severe disease – factor level < 1%
• Frequent spontaneous bleeding from early life
• Haemarthroses are common and may lead to joint
deformity
• Bleeding into muscles is also common
– Moderate disease – factor level 1 – 5 %
• Post traumatic Bleeding
• Occasional apparently spontaneous episodes
25

26. Hemophilia A
• Clinical features
– Mild disease – factor level > 5 %
• Usually with bleeding only after injury or surgery
• Diagnosis in this group is often delayed until quite late in
life
26

27. Hemophilia A
• Clinical features
Massive haemorrhage in the
area of right buttock
Gross swelling from acute
haemarthroses of the knee joints 27

28. Hemophilia A
• Laboratory finding – investigations
– Coagulation testing
• Prolonged activated partial thromboplastin time (APTT)
• Normal prothrombin time (PT)
• Normal bleeding time (BT)
• Factor assay (reduced level of factor VIII)
28

29. Hemophilia A
• Treatment = factor replacement
– Bleeding is treated by administration of factor VIII
concentrate by intravenous infusion.
– Minor bleeding: the factor VIII:C level should be
raised to 20-30%
– Severe bleeding: the factor VIII:C should be raised to
at least 50%
– Major surgery: the factor VIII:C should be raised to
100% preoperatively and maintained above 50% until
healing has occurred.
29

30. Hemophilia A
• Treatment
– Synthetic vasopressin (Desmopressin)
• An analogue of vasopressin
• Intravenous, subcutaneous or intranasal
• Produces a rise in factor VIII:C in mild hemophilia
• It avoids the complications associated with blood products
• It is ineffective in severe haemophilia
30

31. Hemophilia A
• Supportive treatment
– For treating haemarthrosis and haematomas
– Resting of affected part
– Avoid other trauma
– Social and psychological support
31

32. Hemophilia B
• Also known as Christmas disease
• Caused by a deficiency of factor IX
• The inheritance and clinical features are identical
to hemophilia A
• Only can be distinguished by specific
coagulation factor assays
• The incidence is only about 1 in 30 000 males
• Hemophilia B is treated with factor IX
concentrates
32

33. Von Willbrand’s disease
• Hereditary coagulation abnormality caused by
either:
– Reduced level of vWF
– Abnormality in vWF
Due to
Point mutation
or
Major deletion
33

34. Von Willbrand’s disease
34

35. Von Willbrand’s disease
• vWF is a protein that has two roles
– It promote adhesion of platelets to the endothelium
– It is a carrier molecule for factor VIII, protecting it
from premature destruction
• So in vWD there is:
– Defective platelet function
– Factor VIII:C deficiency
35

36. Von Willbrand’s disease
• vWD has been classified into three types:
– Type 1 vWD
• Characterized by a mild reduction in vWF and is usually
inherited as an autosomal dominant
– Type 2 vWD
• Loss of high-molecular-weight multimers, and it too is
usually inherited as an autosomal dominant
– Type 3 vWD
• Characterized by severe reduction in vWF and usually
inhereted as autosomal recessive
36

37. Von Willbrand’s disease
• Clinical features
– Typically there is mucus membrane bleeding
(epistaxis, menorrhage...)
– The severity of symptoms are variable with types
• Type 1, 2 usually mild symptoms
• Type 3 severe symptoms
37

38. Von Willbrand’s disease
• Laboratory finding
– The bleeding time is prolonged
– APTT is prolonged
– Factor VIII is low
– vWF is usually low (type 1,2)
– Platelets count is normal
38

39. Von Willbrand’s disease
• Treatment
– Depends on the severity of the condition
– May be similar to that of mild haemophilia, including
the use of Desmopressin where possible
– Factor VIII or von Willebrand factor concentrates
should be used to treat bleeding or to cover surgery in
patients who require replacement therapy
39

40. Haemostasis tests in hereditary coagulation disorders
Haemophilia A Haemophilia B VW disease
Bleeding time Normal Normal Prolonged
Prothrombin
time
Normal Normal Normal
APTT Prolonged Prolonged Prolonged
Factor VIII Low Normal Low or normal
Factor IX Normal Low Normal
VWF Normal Normal Low
40

41. Other coagulation factors
• Factor XI deficiency
– Rare
– Seen mainly in Ashkenazi Jews
– Caused bleeding only after trauma
– Treated by factor XI
• Factor XII deficiency
– Usually cause no bleeding
41

42. B. Acquired coagulation disorders
• Acquired coagulation disorders
– More common than inherited disorders
– Usually multiple clotting factors
– Includes
• Vitamin K deficiency
• Liver disease
• DIC
• Coagulation disorders caused by antibodies
• Massive transfusion syndrome
42

43. Vitamin K deficiency
-Vitamin K is a fat soluble vitamin
– Obtained from green vegetables and bacterial
synthesis in the gut
– Important on coagulation factors II, VII, IX and X
and on proteins C and S.
– Without it, these factors cannot bind calcium.
43

44. Vitamin K deficiency
– haemorrhagic disease of the newborn
– Biliary obstruction
– Malabsorption of vitamin K
– Vitamin K antagonist drugs
44

45. Liver disease
– Biliary obstruction results in malabsorption of
vitamin K and therefore decresed synthesis of factors
II, VII, IX and X
– Also there are decreased in factor V and fibrinogen
– Dysfibrinogenemia
– Thrombocytopenia.
– Functional abnormalities of platelets
– Hypersplenism associated with portal hypertension
– DIC
45

46. Disseminated coagulation disorders (DIC)
– There is widespread deposition of fibrin within blood
vessels with consumption of coagulation factors and
platelets occurs as a consequence of many disorders
which release procoagulant material into the
circulation or diffuse endothelial damage or
generalized platelet aggregation.
46

47. DIC: causes
• Infections
– Gram neg septicaemia
– Septic abortion
• malignancy
– Widespread mucin
secreting adeno-
carcinoma
– Acute promyelocytic
leukaemia
• Hypersensitivity reactions
– Anaphylaxis
– Incompatible blood
transfusion
• Obstetric complications
– Amniotic fluid embolism
– Eclampsia, retained
placenta
• Widespread tissue damage
– Following surgery/trauma
– After severe burns
• Miscellaneous
– Liver failure
– Severe burns
– Hypothermia
– Snake venoms
– Acute hypoxia
47

48. DIC: pathogenesis
1. DIC may triggered by the entry of procoagulant
material into circulation:
– Amniotic fluid embolism
– APML
– Premature separation of placenta
2. Initiated by widespread endothelial damage and
collagen exposure:
– Septicemia
– Severe burns
3. Widespread intravascular platelet aggregation
– Some bacteria, viruses and immune complexes may have
direct effect on platelets.
48

49. DIC
• F
Changes in clotting factors, platelets and fibrin degradation
products (FDP) that occur in DIVC
49

50. DIC
50

51. DIC
• Clinical features
– Bleeding, particularly from venepuncture
– Purpura
– Generalized bleeding in
GIT, oropharynx, lungs, urogenital tract, vaginal
bleeding
– Less frequently, microthrombi may cause skin
lesions, renal failure, gangrene of fengures
51

52. DIC
52

53. DIC
• Laboratory finding
– The platelet count is low
– Fibrinogen low
– Thrombin time is prolonged
– High level of fibrin degradation products (FDP)
– PT and APTT are prolonged in acute syndromes
• Blood film
– Fragmentation of red cells
53

54. DIC
• Treatment
– Treat underlying cause
– Supportive therapy with fresh frozen plasma (FFP)
and platletes concentrates
– Cryoprecipitate may also required
54

55. C. PLATELETS DISORDERS
55

56. C.Platelet disorders
Abnormal bleeding due to;
-Thrombocytopinic (dereased number of platelates)
-Idiopathic thrombocytopenic purpura (ITP).
-Thrombotic thrombocytopenic purpura (TTP).
-Drug induced thrombocytopenic purpura .
-Platelate function disorder
- Congenital eg.
- Acquired eg.
56

57. C.Platelet disorders
• Characterized by petechae, purpura and bleeding
from mucous membranes
• Bleeding is uncommon with platelet counts
above 50 109/L, and severe spontaneous
bleeding is unusual with platelet counts above 20
109/L
57

58. Thrombocytopenia
– Reduced platelet production in the bone marrow
• The most common cause of thrombocytopenia
– Excessive peripheral destruction of platelets
– Abnormal distribution of platelets
• Splenomegally
– Dilutional loss
• Massive transfusion of stored blood
58

59. Thrombocytopenia
Impaired production Increase consumption
Bone marrow failure Immune
Autoimmune (idiopathic)
Associated with SLE, CLL
Infections
Drug-induced
Post-transfusion purpura
Feto-maternal alloimmune
Megaloblastic anaemia
Aplastic anemia
Myelofibrosis
Multiple myeloma
MDS
HIV infection DIC
Marrow infiltration TTP
Leukaemia 59

60. PLATELET DISORDERS
• Increased destruction of platelets
60

61. Idiopathic thrombocytopenic purpura (ITP)
• Thrombocytopenia is due to immune destruction of
platelets.
• The antibody-coated platelets are removed following
binding to Fc receptors on macrophages.
• Both acute and chronic forms of ITP exists
– Acute ITP more commonly seen in pediatric population
– Chronic form is more common in adults
61

62. Idiopathic thrombocytopenic purpura
• Acute ITP
– Common in children
– Usually following vaccination or infection
– Spontaneous remission is common
– 10% the disease become chronic (lasting > 6 months)
– The diagnosis is one of exclusion
62

63. ITP
• Chronic ITP
– Relatively common disorder
– Occur mainly in women between 15 – 50 years old
– This is the most common cause of thrombocytopenia
without anemia and neutropenia
– Usually idiopathic but can be seen in associated with
other disorders as SLE, HIV, CLL.
63

64. ITP
• Chronic ITP: pathogenesis
– The platelets are sensitized with autoantibodies
(IgG), this results in their premature removal from
the circulation by the macrophages of
RES, especially in the spleen.
– Normal lifespan for normal platelets is about 7
days, but in ITP this is reduced to a few hours
64

65. ITP: pathogenesis
65

66. Chronic ITP
• Clinical pictures
– Petechial haemorrhage
– Purpura
– Easy brusing
– Menorrhagea in women
– Epistaxis
– Gum bleeding
– Major haemorrhage is rare
– Intracranial bleeding – very rare
66

67. Petechia
•
67

68. Purpura
•
68

69. Purpura
•
69

70. Chronic ITP
• Diagnosis
– CBC
• The only blood count abnormality is thrombocytopenia
• The haemoglobin concentration and WBCs count are
typically normal.
– Blood film
• Decreases number of platelets
• Those present are large
70

71. Chronic ITP
• Diagnosis
– Bone marrow
• The BM shows normal or increased number of
megakaryocytes
– The detection of platelet autoantibodies is not
essential for confirmation of the diagnosis
71

72. Chronic ITP
• Treatment
– The aim of treatment is to maintain platelets count
above the level at which spontaneous bruising or
bleeding occur with minimal intervention
– In general, platelets count above 50 x 109/L dose not
required treatment.
72

73. Chronic ITP
• Treatment
– Corticosteroids
• 1mg/kg/day – is the usual initial therapy
• Dose gradually reduced after 14 days
– Splenectomy
• If platelets <30 x 109/L after 3 months of steroid therapy
– High dose intravenous immunoglubulin therapy
• Rapid raise of platelets
• 400mg/Kg/day for 5 days or 1g/Kg/day for 2 days
73

74. Chronic ITP
• Treatment
– Immunosuppressive therapy
• Vincristin, cyclophosphamide, cyclosporine, azathioprine
– Platelets transfusion
• In acute life-threatening bleeding
74

75. D.VASCULAR BLEEDING DISORDERS
75

76. D.Vascular bleeding disorders
• A group of disorders characterized by easy
bruising and spontaneous bleeding from small
blood vessels.
– Bleeding mainly occur in the skin causing
petechiae, ecchymoses or both
• Caused by
– Abnormality in the blood vessel themselves
– Abnormality in the perivascular connective tissues
• Can be congenital or acquired
76

77. D.Vascular bleeding disorders
• Congenital
– Hereditary haemorrhagic telangiectasia (HHT)
• Uncommon, AD disorder
• Dilated microvascular swellings
• These telangiectasia develop in the skin, mucous
membranes and internal organs (recurrent GIT
haemorrhage)
– Connective tissue disorders (Ehlers-Danlos
syndrome, osteogenesis imperfecta, pseudoxanthoma
elasticum, Marfan's syndrome)
77

78. D.Vascular bleeding disorders
78

79. D.Vascular bleeding disorders
• Acquired
– Severe infections
• Septicaemia, meningococcal infections, measles, typhoid
– Allergic
• Henoch-Schönlein purpura
– Drugs
• Steroids, Sulphonamides
– Others
• Senile purpura, Easy bruising syndrome, Scurvy, Factitious
purpura
79

80. D.Vascular bleeding disorders
• Senile purpura
– Atrophy of the
supporting tissues of
cutaneous blood vessels
– Dorsal aspects of the
forearm and hand
80

81. REFERENCE
• Nelson textbook of pediatrix ,19th edition
• Current diagnosis and treatment in pediatrics,20th edition
• Pediatrics and child health lecture note for health sceince
students ,jimma university
81

82. 82