preda

1. Ambo University
Collage Of Medicine & Health Sceince
Department Of Medicine
Seminar Presentation on;
Approach to Bleeding Disorders In
Pediatrics Patient
By
Alemu A, Amdu T & Aregahegn T
Sep,10/2014

2. Outline
 Over view of homeostasis and the blood
clotting process.
Over view of some bleeding disorders in
pediatrics patient
Approach to a child with bleeding disorder.
Lab investigations
Interpretation of lab. tests & clinical

3. Introduction
Normal hemostasis
 Mechanism by which bleeding from an injured vessel is arrested by
formation of a thrombus.
• Functions
 To maintain the blood in fluid state
 To prevent clots in intact vessels
 To arrest bleeding in injured vessels
• Components
 Blood vessels
 Platelets
 Plasma coagulation factors
 Fibrinolytic system

4. STAGES OF HEMOSTASIS
INJURY
VESSEL WALL+PLATELET
FORMATION OF PLT PLUG
ACTIVATION OF PLASMA COAGULATION
FACTORS
FORMATION OF STABLE FIBRIN CLOT
DISSOLUTION OF FIBRIN CLOT BY FIBRINOLYSIS
PRIMARY
SECONDARY

5. Cont’d
PRIMARY
 Platelet & vessel wall
mediated
 Occurs within seconds of
injury
 Forms Platelet plug
 Prevent blood loss from
capillary , arterioles and
venules
SECONDARY
 Coagulation factors mediated
 Takes several minutes for
completion
 Forms stable fibrin plug
 Prevents blood loss from large
vessels

6. Cont’d

7. Cont’d

8. Cont’d

9. Cont’d

10. Bleeding
 Bleeding or hemorrhaging, is the escape of blood from the circulatory
system.
 Bleeding can occur
– internally, where blood leaks from blood vessels inside the body, or
– externally, either through a natural opening such as the mouth, nose,
ear, urethra, vagina or anus, or through a break in the skin.
 It is then inferred that the bleeding is due to a
functional impairment of the normal hemostatic
process.

11. Cont’d
This impairment may be due to
1. A functional deficiency in the procoagulant
mechanism. This may involve
a. The platelets
b. The procoagulant plasma components

12. Cont’d
2. A functional excess in anticoagulant
mechanisms.
a. Anticoagulant drugs
b. Natural anticoagulants
3. A functional excess in the fibrinolytic
mechanism.

13. CAUSES OF BLEEDING
Vessel wall disorders
Platelet disorders: quantitative or
functional.
Coagulation factor: deficiency or inhibitors.
Combination of these.

14. VASCULAR DISORDERS
ACQUIRED CONGENITAL
•Senile purpura
•Vascular purpura
•Henoch schonlein
purpura
•Hereditary
hemorrhagic
telengiectasia
•Ehlers danlos
syndrome

15. telengiectasia

16. Senile purpura

17. PLATELET ABNORMALITIES
QUALITATIVE QUANTITATIVE
•THROMBASTHENIA
•BERNARD-SOULIER
SYNDROME
•DRUGS(ASPIRIN,IND-OMATHACIN
•THROMBOCYTOPENIA
•THROMBOCYTHEMIA

18. Petechia
•

19. Purpura

20. DISORDERS OF COAGULATION F
Hereditary
 haemophilia A (factor VIII deficiency)
 haemophilia B (factor IX deficiency)
 von will brand disease
 Disorders of fibrinogen-
Hereditary afibrinogenaemia
hypofibrinogenaemia
Dysfibrinogenaemia
Acquired
 Disseminated intravascular coagulation(DIC)
 Liver disease
 Vit k deficiency
 Massive transfusion of stored blood
 Acquired inhibitors of coagulation
 Heparin or oral anticoagulant therapy
 Renal disease

21. Hemophilia A
Massive hemorrhage in the
area of right buttock

22. Hemophilia A
Gross swelling from acute
haemarthroses of the
knee joints

23. DIC

24. Classification of Disorders of Hemostasis
Major Types Disorders Examples
Acquired Thrombocytop
enia's
Autoimmune and alloimmune, drug-induced,
hypersplenism, hypoplastic (primary, myelosuppressive
therapy, myelophthisic marrow infiltration),
disseminated intravascular coagulation (DIC),
thrombotic thrombocytopenic purpura, hemolytic-uremic
syndrome
Liver diseases Cirrhosis, acute hepatic failure, liver transplantation ,
Vitamin K
deficiency
Malabsorption syndrome, hemorrhagic disease of the
newborn, prolonged antibiotic therapy, malnutrition,
prolonged biliary obstruction
Hematologic
disorders
Acute leukemia's , myelodysplasias, monoclonal
gammopathies, essential thrombocythemia

25. Major Types Disorders Examples
Acquired Acquired
antibodies
against
coagulation
factors
Neutralizing antibodies against factors V, VIII, and XIII,
accelerated clearance of antibody-factor complexes,
e.g., acquired von Willebrand disease,
hypoprothrombinemia associated with
antiphospholipid antibodies
DIC Acute (sepsis, trauma, obstetric complications) and
chronic (malignancies, giant hemangiomas, retained
products of conception)
Drugs Antiplatelet agents, anticoagulants, antithrombins, and
thrombolytic, hepatotoxic, and nephrotoxic agents
Vascular Non-palpable purpura ("senile," solar, and factitious
purpura), use of corticosteroids, vitamin C deficiency,
thromboembolic
Palpable-purpura -Henoch-Schönlein, vasculitis

27. Clinical features
• Epistaxis-symptoms of platelet disorders & vWD
• Gingival hemorrhage- platelet disorders & vWD
• Oral mucous membrane bleeding- severe
thrombocytopenia
• Skin hemorrhage ( petechiae and ecchymoses)-
common manifestations of hemostatic & non-hemostatic
disorders
• Hemarthroses- hallmark abnormality in the
hemophilia’s, severe factor VII deficiency and type 3
von Willebrand disease

28. Cont’d
• Easy bruising- Ehlers-Danlos syndrome
• Excessive bleeding in response to razor nicks =platelet
disorders or von Will brand disease.
• Hemoptysis- haemostatic disorders in URT.
• Hematemesis- haemostatic disorders in upper GI
• Hematuria- hemophilia's & haemostatic disorders
• Rectal bleeding -in normal-hemorrhoids- von
Willebrand disease and platelet disorders
• Melena
• Postpartum hemorrhage -DIC
• Habitual spontaneous abortions- quantitative or
qualitative abnormality of fibrinogen.

29. DIAGNOSIS OF BLEEDING DISORDERS
• HISTORY
• CLINICAL EXAMINATION
• LABORATORY INVESTIGATIONS

30. History taking
On Hx
– Site or sites of bleeding,
– The severity and duration of hemorrhage, and
– The age at symptom onset.
– Spontaneous or after trauma?
– Does bruising occur spontaneously?
– Previous personal or family history of similar
problems?
– Recent transfusion?

31. Cont’d
– A history of anemia and/or previous treatment
with iron
– Joint pain, swelling or limitation of movement
– Bleeding from umbilical stump
– Previous surgery or significant dental procedures,
was there any increased bleeding?
– Delayed or slow healing of superficial injuries
suggest a hereditary bleeding disorder

32. Cont’d
– Menstrual history (in post pubertal females)
– Medications ( NSAIDs, anticonvulsant , anti TB,
antihistamin, or herbal medications
cause thrombocytopenia
– Nutritional Hx to assess the likelihood of vt k & C
deficiency and general malnutrition and/or
malabsorption

33. Physical Examination
On PH/E
• We can look for the presence of
– Petechiae , ecchymoses , hematomas,
hemarthroses, or mucous membrane bleeding.
 defects in platelet/blood vessel wall interaction
– fixed drug eruption, erythema nodosum, viral
exanthem and mosquito bites

34. Cont’d
• Look for hepatosplenomegaly
• Do a rectal exam for evidence of GI bleeding
• Look for physical signs and symptoms of diseases
related to capillary fragility:
– Petechiae secondary to coughing, sneezing, Valsalva
maneuver, blood pressure measurement

35. Cont’d
• If there is bleeding is it localized or
generalized?
– Localized- single site
– Generalized
• Is it platelet type or coagulation type of bleeding?
• Is it congenital/hereditary or acquired disorder?
• Symptoms of a longer duration are indicative of a congenital
disorder such as von Will brand Disease (vWD) or
coagulation-factor deficiencies

36. Cont’d
36

37. Cont’d
37

38. Cont’d
38

39. Cont’d
NB.
– Petechiae are pathognomonic of platelet-related
bleeding
– Deep tissue and intramuscular bleeds should
prompt the diagnosis of a coagulation factor
deficiency
– Patient with a clotting factor VIII or factor IX
deficiency have deep bleeding into muscles and
joints with much more extensive ecchymoses and
hematoma formation.

41. Laboratory Evaluation
1st line investigation
– Test for platelets
• Platelet count
• Bleeding Time(BT)
– Test for coagulation factors
• Prothrombin Time(PT)
• Activated Partial Thromboplastin Time(aPTT)
• Thrombin Time(TT)
• Fibrinogen assay

42. Lab. exam
Bleeding Time (BT)
Significance
• Assess primary haemostatic defect
– vessel wall or platelet interaction.
• Dependent on adequate functioning of
– Platelets
– Blood Vessels.
Range
• 4-8 min

43. Cont’d
Interpretation
Causes of prolonged BT
• Thrombocytopenia
• VWD
• Platelet function disorder
• Disorder of blood vessels.

44. Cont’d
Prothrombin Time(PT)
Significance
• Reflects overall activity of the Extrinsic Pathway.
• Most sensitive to changes in Factor V,VII,X.
• Lesser to Factor I & II.
Principle
• Platelet poor plasma + Tissue Thromboplastin + Calcium
• In Presence of F VII Extrinsic pathway is activated & clot
formed
Normal Range
• 10-12 seconds (with human thromboplastin)

45. Cont’d
Interpretation
 Causes of prolonged PT
1. Deficiency of Factor VII,X,V,II,I
2. Vit K deficiency
3. Liver disease
4. Oral anticoagulants

46. Cont’d
Activated Partial Thromboplastin Time (aPTT)
Significance
• Reflects efficiency of Intrinsic Pathway.
• Sensitive to changes in Factor VIII,IX,XI,XII.
• Also sensitive to heparin & circulating anticoagulants.
 The test measures the clotting time of plasma after the
activation of contact .
 So it indicates the overall efficiency of the Intrinsic
pathway
Normal range
26 to 40 seconds.

47. Cont’d
Interpretation
 Causes of prolonged aPTT
1. Deficiency of Factor VIII (Haemophilia A).
2. Deficiency of Factor IX (Haemophilia B).
3. Heparin therapy.
4. Circulating anticoagulants.
5. Liver disease.

48. Cont’d
Thrombin Time(TT)
Significance
• Asses the final step of coagulation, i.e. conversion of fibrinogen to
fibrin in presence of thrombin.
• Bypasses Extrinsic & Intrinsic pathway.
Principle
• Thrombin is added to plasma and the clotting time is
measured.
• TT is affected by the concentration and reaction
of fibrinogen and by the presence of inhibitory substances.
Normal range
• 15–19 sec, Times of 20 s and longer are definitely abnormal.

49. Cont’d
Interpretation
 Causes of prolonged TT
1. Disorders of fibrinogen-
Afibrinogenaemia.
Hypofibrinogenaemia
Dysfibrinogenaemia.
2. Liver disease.
3. heparin therapy

50. Cont’d
2nd line investigations
Carried out with each of the patterns of
abnormalities in first line tests
1. Mixing test.
2. Factor VII assay.
3. Liver function test.

51. Cont’d
Mixing test
– If prolong. PT, PTT, or TT
 Normal plasma + patient's plasma, and the PT or PTT
is repeated.
• Correction of PT or PTT => def. of a clotting factor,
(because a 50% level of individual clotting proteins is
sufficient to produce normal PT or PTT.)

52. Cont’d
• If the clotting time is not corrected or only partially
corrected, an inhibitor
– chemical similar to heparin that delays coagulation or
– an antibody directed against a specific clotting
factor.(MC- VIII, IX, or XI, may be present) or
– the phospholipids used in clotting tests is usually
present

53. Summary of Interpretation of lab. tests &
clinical
• Intrinsic

54. Interpretation cont’d
• Extrinsic

55. Interpretation cont’d
• Common

56. Reference
Nelson textbook of pediatrics ,19th edition
Current diagnosis and treatment in
pediatrics,20th edition
Pediatrics and child health lecture note for
health sceince students ,jimma university