The bleeding child diagnostic approach By rafat mosalli

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.

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).

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.

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

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

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

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

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

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.

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)

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.

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.

Prothrombin time (PT) Tissue Thromboplastin factor III Mix with phospholipids extract Add calcium and blood sample Determine clotting time Generally 12 - 14 seconds Used to detect defects in extrinsic &common pathway. i.e. 7, 10, 5, 2,1

Activated partial thromboplastin time (APTT) Blood sample + EDTA or Citrate No clot ( recalcification will result in clot in about 2 - 4 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

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

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.

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

Activation XIIa Inactive XI Active XIa +

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.

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

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.

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

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

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.

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.

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?

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.)

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

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

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

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..

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 .

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:8,9,11,10 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.

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.

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.