1. The bleeding child diagnostic approach
By rafat mosalli

2. 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 sum total of specialized function within the circulating blood & its vessels designed to stop hemorrhage.

3. HEMOSTASIS:
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 (thrombin and fibrinogen-mediated effects). Upon activation, platelets release ADP and TXA2 (which activate additional platelets).

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.

5. The bleeding child diagnostic approach
Vascular Phase
Platelet Phase
Coagulation Phase
Fibrinolytic Phase

6. Vascular Phase Vasoconstriction
Exposure to tissues activate Tissue factor and initiate coagulation
Tissue Factor

7. Platelet phase Non-nucleated - arise from magakaryocytes
blood vessel wall (endothelial cells) prevent platelet adhesion and aggregation
platelets contain receptors for fibrinogen and von Willebrand factor
after vessel injury Platelets adhere and aggregate.
Release permeability increasing factors (e.g. vascular permeability factor, VPF)
Loose their membrane and form a viscous plug

8. Platelets and Thrombo embolism
Arteries : White Thrombus
Platelets adhere
Release ADP
More adhesion/ aggregation
Reduced blood flow (stasis)
Fibrin clot
Veins low pressure : Red thrombus is formed
Especially in valve pockets
Contains a long tail of fibrin
Can detach and form emboli

9. Coagulation Phase Two major pathways Both converge at a common point
Intrinsic pathway
Extrinsic pathway
Both converge at a common point
13 soluble factors are involved in clotting
Biosynthesis of these factors are dependent on Vitamin K1 and K2
Most of these factors are proteases
Normally inactive and sequentially activated
Hereditary lack of clotting factors lead to hemophilia -A

10. Intrinsic cascade: initiated when contact is made between blood and exposed endothelial cell surfaces.
Extrinsic pathway: initiated upon vascular injury which leads to exposure
of tissue factor (TF), a sub endothelial cell-surface glycoprotein that
binds phospholipids.

11. Intrinsic Pathway
All clotting factors are within the blood vessels
Clotting slower
Activated partial thromboplastin test (aPTT)
Extrinsic Pathway
Initiating factor is outside the blood vessels - tissue factor
Clotting - faster - in Seconds
Prothrombin test (PT)

12. Bleeding time
It is the primary ,oldest test for the primary hemostasis( vascular &platelets phase).
Measure interval time required for hemostasis following standard superficial incision 1-2mm deep & up to 5mm length in the skin of forearm with venous pressure maintained at 40mmHg.
Gives information immediately
Ideally done with help of template and related to age usually in children 4-7 minutes.

13. When performed with the standard methods I t depend on the following: platelet no., vascular factors, temperature& hormones.
Could be affected when Aspirin and other drugs ingested within 7d.
Prolongation doesnot correlate with bleeding risk.

14. Prothrombin time (PT) Tissue Thromboplastin factor III
Mix with phospholipids extract
Add calcium and blood sample
Determine clotting time
Generally seconds
Used to detect defects in extrinsic &common pathway.
i.e. 7, 10, 5, 2,1

15. Activated partial thromboplastin time (APTT)
Blood sample + EDTA or Citrate
No clot ( recalcification will result in clot in about min)
Add calcium
Mix with negatively charged phospholipids
Kaoline (aluminum silicate)
Determine clotting time
Generally clotting occurs in 26 to 33 seconds
Used to detect defects in the intrinsic pathway I.e. 12,11,9,8,10,5,2,1

16. Diagnosis of coagulation defects
Prolonged APTT Defective in intrinsic
No change in PT
No change in APTT Defective in Extrinsic
Prolonged PT
Prolonged APTT Defective in common Prolonged PT

17. NB : the bleeding disorders might not be associated with any abnormalities in the screening tests:
Mild factors deficiency
Factors 13 deficiency.
HSP.
Ehler danlos syndrome .
Scurvy.
Hereditary hemorrhagic telengectasia.

18. Intrinsic Pathway Extrinsic Pathway Blood Vessel Injury Tissue Injury
Tissue Factor
XII
XIIa
Thromboplastin XI
XIa IX
IXa
VIIa
VII X Xa X
Prothrombin
Thrombin
Factors affected
By Heparin
Fibrinogen
Fribrin monomer
Fibrin polymer
Vit. K dependent Factors
Affected by Oral Anticoagulants
XIII

19. Activation
XIIa
Inactive XI
Active XIa +

20. Thrombosis Arterial Thrombosis : Venous Thrombosis :
Adherence of platelets to arterial walls - White in color - Often associated with MI, stroke and ischemia
Venous Thrombosis :
Develops in areas of stagnated blood flow (deep vein thrombosis), Red in color- Associated with Congestive Heart Failure, Cancer, Surgery.

21. Fibrinolysis Enhance degradation of clots
Activation of endogenous protease
Plasminogen (inactive form) is converted to Plasmin (active form)
Plasmin breaks down fibrin clots

22. Bleeding child diagnostic approach
The bleeding child my present as:
1-an increase in severity or frequency of bleeding from one site e.g.; nose.
2-asc bleeding from unusual sites such as joints or internal organs.
3- As excessive bleeding for the degree of the trauma experienced.

23. Bleeding child diagnostic approach
Abnormal bleeding can be the result of an acquired or congenital disorders of coagulants, platelets, or the vessel wall.
It is necessary to decide whether the bleeding is –Nature of bleeding?
-Significant or not?
-Generalized or localized?.
-Acquired or hereditary?
Consider child abuse with unusual bruising

24. Bleeding child diagnostic approach
Nature of bleeding; is the bleeding due to vascular, platelet, coagulation or a combination of this?
It is not always possible to categorize Vascular and platelet dysfunction usually present with :
Spontaneous subcutaneous or mucus membrane bleeding eg; purpura, petechiae, epistaxis
Usually precipitate by injury.
Continue for hours.
Often controlled by pressure, once controlled doesn't recur easily

25. Bleeding child diagnostic approach
Coagulation factors deficiency:
Usually occur deep into joins, muscles,retroperotineal space.
Post traumatic bleed are often delayed (sometimes hours).
May recur& bleeding my not get controlled by direct pressure.

26. Diagnostic approach Phase one:
-Thorough history& physical examination as well as standard screening laboratory test.
Phase two:
If the initial screening test is negative then test for VWD, platelets dysfunction, factor 13 and or dysfibrongenemia.
Phase three:
Interprets the abnormal result&&try to define the specific disorders.

27. Bleeding child diagnostic approach
History:
Spontaneous bleeding?
Bleeding in unusual site without significant trauma?
Bruising and bleeding disproportionate to injury? large or palpable bruising?
Poorly controlled epistaxis?is it unilateral
Excessive bleeding with tooth extraction?
Abnormal bleeding at or after circumcision or surgical procedure?

28. Bleeding child diagnostic approach
Excessive bleeding following fracture or minor cuts?
Time of the presentation & detailed Family history of bleeding disorders?
1- sex linked recessive (hemophilia A,B,WAS)
2-autosomal recessives disease( clotting factors defeciency2,5,7,10,11,13.
3- autosomal dominant( VWF, qualitative platelet disorders, dysfibronogenimia.)

29. Bleeding child diagnostic approach
-Questions that help target the defective components of hemostasis:
-mucosal bleeding(gum, nose)?
-Petechiae?
-Menorrhagia?
Recent medications?
-Presence of chronic disease e.g.; renal or liver disease?
-Nutritional status?
significance: scurvy, decreased hepatic synthesis

30. Bleeding child diagnostic approach
Physical examination:
General stability, vitals signs, evidence of chronic disease, evidence of malignancy.
Skin stigmata :
petechiae
purpura
ecchymosis
hematoma

31. Bleeding child diagnostic approach
Delayed wound healing? Factor 13 deficiency, dysfibrinogemia
Musculoskeletal examination for bleeding and extensibility.

32. Bleeding child diagnostic approach
Laboratory aids:
Phase one;
Initial laboratory screening .
platelet count,PT,PTT, bleeding time.
Phase two; special confirmatory tests
- If qualitative platelets defect suspected
platelet aggregation studies with restocetin, collagen, thrombin,and ADP.
VWF analysis for VWF disease .
Thrombin time or fibrinogen for dys fibronegenimia..

33. Bleeding child diagnostic approach
phase three : discriminating laboratory studies for abnormal phase one tests:
1-when thrombocytopenia is present: -inspection of blood film (for bone marrow disease) Mean platelet volume(elevated in destruction,low in WAS) Bone marrow aspiration .

34. Bleeding child diagnostic approach
Prolonged PTT Inhibitor screen (50:50 mixing study of patients and normal plasma) if PTT fully corrected  factors assay in the following order:8,9,11, partial or no correction after mixing inhibitor present ,check for lupus anticoagulant .
Prolonged PT inhibitor screen factors 7,10,5,2,1.
Prolonged PTT, PT:
Test for DIC, liver disease, sever vitamin K deficiency.factor 10, 2.

35. Indications for referral
If the history and physical examination or the screening tests strongly suggest the presence of a bleeding disease.
If the VWF disease is suspected, to determine the exact type and treatment.
Patient with hemophilia for regular visit follow up and coordination of care.
Prior to invasive procedure, surgery, dental work.

36. summary When you face a child with bleeding problem what should I do?
Careful history including past and family history.
Detailed clinical examination.
Few screening test then appropriate specialized tests
Appropriate referral
This will help in proper diagnosis and hence better management of bleeding child.