aproach to bleeding disorder in pediatrics

Seminar Presentation on;

Approach to Bleeding Disorders In

Pediatrics Patient

By

Alemu A, Amdu T & Aregahegn T

Ambo University

Collage Of Medicine & Health Sceince

Department Of Medicine

Sep,10/2014

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

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

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

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

Cont’d

Cont’d

Cont’d

Cont’d

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.

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

Cont’d

2. A functional excess in anticoagulant

mechanisms.

a. Anticoagulant drugs

b. Natural anticoagulants

3. A functional excess in the fibrinolytic

mechanism.

CAUSES OF BLEEDING

Vessel wall disorders

Platelet disorders: quantitative or

functional.

Coagulation factor: deficiency or inhibitors.

Combination of these.

VASCULAR DISORDERS

ACQUIRED CONGENITAL

•Senile purpura

•Vascular purpura

•Henoch schonleinpurpura

•Hereditary hemorrhagic telengiectasia

•Ehlers danlossyndrome

telengiectasia

Senile purpura

PLATELET ABNORMALITIES

QUALITATIVE QUANTITATIVE

•THROMBASTHENIA

•BERNARD-SOULIER SYNDROME

•DRUGS(ASPIRIN,IND-OMATHACIN

•THROMBOCYTOPENIA

•THROMBOCYTHEMIA

Petechia

•

Purpura

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

Hemophilia A

Massive hemorrhage in the

area of right buttock

Hemophilia A

Gross swelling from acute

haemarthroses of the

knee joints

DIC

Classification of Disorders of Hemostasis

Major Types Disorders Examples

Acquired Thrombocytopenia's

Autoimmune and alloimmune, drug-induced, hypersplenism, hypoplastic (primary, myelosuppressivetherapy, 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

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, thromboembolicPalpable-purpura -Henoch-Schönlein, vasculitis

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

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.

DIAGNOSIS OF BLEEDING DISORDERS

• HISTORY

• CLINICAL EXAMINATION

• LABORATORY INVESTIGATIONS

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?

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

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

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

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, Valsalvamaneuver, blood pressure measurement

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

Cont’d

36

Cont’d

37

Cont’d

38

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.

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

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

Cont’d

Interpretation

Causes of prolonged BT

• Thrombocytopenia

• VWD

• Platelet function disorder

• Disorder of blood vessels.

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)

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

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.

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.

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.

Cont’d

Interpretation

Causes of prolonged TT

1. Disorders of fibrinogen-

Afibrinogenaemia.

Hypofibrinogenaemia

Dysfibrinogenaemia.

2. Liver disease.

3. heparin therapy

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.

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.)

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

Summary of Interpretation of lab. tests & clinical

• Intrinsic

Interpretation cont’d

• Extrinsic

Interpretation cont’d• Common

Reference

Nelson textbook of pediatrics ,19th edition

Current diagnosis and treatment inpediatrics,20th edition

Pediatrics and child health lecture note forhealth sceince students ,jimma university