Hemostastis Pada Anak

Hemostasis DiseaseIn Children

dr. Bertha

• Vascular response• Plateletadhesion• Platelet aggregation• Clot formation• Clot stabilization• Limitation of clotting (antitrombil III, Protein C,

Protein S, TFP1)• Re-establishment of vascular potency

Fibrinolusis & vascular healing

Hemostatic Mechanism

History

• Site, severity,duration of bleeding• Age of the symtomp onset• Spontaneous or after trauma• Previous history or family historyof bleeding• Does bruising (memar) occur spontaneously?• IS there has been previous surgery or dental

procedure?• Menstrual history

• Symptoms primarily associated with mucous or skin (mucocutaneous bleeding) defects in platelet or blood vessel wall interaction (vWF disease)

• Or muscle & joints bleeding (deep bleeding) clotting factor deficiency

• Presence of petechiae, ecchymoses, hematomas, hemarthroses, or mucous bleeding

Physical examination

-Platelet count-Bleeding time

-PT / aPTT

Normal

Ab Normal

Trombin time vWF

Specific work-up

• Bleeding time (BT)– Assesses platelet function & their interaction with vascular wall– Platelet < 100.000/µL prolonged BT– Disproportionate BT qualitative platelet defects or vWF

disease

• aPTT– Measures the initiation of clotting (intrinsic pathway)– doesn’t measure factor VII, XIII or anticoagulant

• PT– Measures extrinsic pathway– Normal in defiencies offactor VIII, IX, XI or XIII

Laboratory

• TT– Measures final step of the clotting cascade– Prolonged reduced fibrinogen levels

• Dysfunctional fibrinogen (hypo/afibrinogenemia)• Substances that interfere with fibrin polymerization (heparin or fibrin

split products) reptilase time

• Mixing studies– if there is unexplained prolongation of PT, PTT or TT– Normal plasma + patient’s plasma repeat lab exam

• Correction of PT/PTT by mixing clootting factor deficiencie• Not corrected + bleeding inhibitor• Not corrected, no bleeding lupus-like-anticoagulant

• Clotting factor assays

Laboratory

Hemophilia

• Hemophilia A Factor VIII deficiencies (85%)

• Hemophilia B Factor IX deficiencies ( 10-15%)

• Most common & serious congenital coagulation factor deficiencies

• Prevalence 1:5000 males• No racial predilection• Clinical finding same

Hemophilia

• Classification– Severe deficiency <1% factor activity

• Spontaneous bleeding

– Moderate deficiency 1-5% factor activity• Mild trauma to induce bleeding

– Mild deficiency >5% factor activity• May be asymptomatic, took years to diagnose

Hemophilia

• Clot formation is delayed & fragile• When bleeding occurs in the closed space

tamponade• Open wound profuse bleeding• Bleeding symptoms may be present in utero• Neonates intracranial bleeding• Easy bruising, IM hematomas, hemarthroses• Bleeding from minor trauma of the mouth

persist for days

Hemophilia

• Iliposoas bleeding life threatening– Inability to extend the hip– Confirmed by UTZ or CT scan– Aggresive therapy

• Life threathening bleeding– CNS, Upper airways bleeding– External bleeding– GI bleeding

Hemophilia

• Prolonged PTT

• Factor assay:– Severe def.– Moderate def.– Mild def.

• Inhibitor assay

Treatment

• Prevention of trauma• Phychosocial• Avoid aspirin & NSAID• Replacement therapy

– Recombinant fact. VIII/IX– Cryoprecipitate/ cryosupernate

• Joint bleeding:– Ice pack– Elevate the limb– Immobilization of the limb

• Supportive therapy• multidiciplinary

Chronic Complication

• Chronic joint destruction

• Risk of transfusions associated disease

• Development of inhibitor

Disseminated Intravascular Coagulation (DIC)

• Consumptive coagulopathy

• Consumption of clotting factors, platelets & anticoagulant protein

• Widespread intavascular deposition of fibrin tissue ischemic & necrosis, generalized hemorrhagic state, hemolytic anemia

DIC

• Trigger factors:– Hypoxia– Acidosis– Tissue becrosis– Shock– Endothelial damage– Septic shock– Incompatible blood transfusion– Snake bite

DIC

• Manifestations:– Bleeding from surgical incision/venipuncture

(pungsi vena)petechiae, ecchymoses– Organ damage– Anemia microangiopathic hemolytic anemia

DIC

• Labs:– Prolonged PT, PTT & TT– Thrombocytopenia– Hemolytic process on blood smear– FDP, d-dimer appear in blood

DIC

• Treatment:– Treat the cause– Restore normal homeostasis

• Correct shock, acidosis, hypoxia

– Blood component transfusions• Platelet concentrate, cryoprecipitate, FFP

– Heparin infusions• For acute promyelocytic leukemia• Not indicated for septic shock, snack bite, massive

head injury, incompatible transfusions

Platelet

• Size: 1-4 µm (younger platelets are larger)• Mean platelet volume (MPV) : 8,9 ± 1.5 µm3

• Number : 150.000 – 400.000 / mm• Distribution : 1/3 in the spleen, 2/3 in blood

stream• Life span : 7-10 days

Bleeding may occur because :• Reduce in number (thrombsytopenia)• Defective in function

The characteristic of platelets

Macrothrombocytes (MPV ↑)• ITP or condition with increased

platelet turnover (eg. DIC)

• Bernard-Soulier Syndrome

• May Heggin anomaly and other MYH-9-Related disease

• Swiss Cheese platelet syndrome

• Montreal platelet syndrome

• Gray platelet syndorme

• Various mucopolysaccharisoses

Microthrombocytes (MPV ↓)• Wiskott –Aldrich syndrome

• TAR syndrome

• Some storage pool diseases

• Iron def. Anemia

Normal size (MPV normal)• Disease with hypocellular marrow

or infiltrated with malignant disease

Thrombocytopeni based on pletelet sized

Clasification of Trombocytopenia

Incrase platelet destruction

Disorder of platelet distribution or

pooling

Decrased platelet production

Pseudothrombocytopenia

Thrombocytopenia


Disorder of platelets

distribution or pooling

Hypersplenism(Portal hypertension,

Gaucher disease,cyanitic congenital, heart disease,

neoplasm, infection)

Hypothermia


Decrase plateletproduction

Hyperplasia or suppresion of megakaryocyte

MarrowInfiltrativeProcess

Drugs:Chlorothiazide, ethanol

Constitusional:Rubella,…

Ineffective Thrombopoeisis:……..

Disorder of control mechanism:

Trombopoetin deficiency

Acquired myelositic disorder:

Drugs

Benign:Osteoporosis

Malignancy


Pseudo-thrombocytopenia

Platelet inactivationduring bloofcollection

Undercounting ofmegathrombocytes

In vitro agglutinationof platelets to EDTA


Increase plateletdestruction

Non-immuneThrombocytopenia

ImmuneThrombocytopenia

Idiopathic (ITP)

Secondary:Infection, drugs,

SLE, etc

Neonatal:Autoimune, Erito-blastosis fetalis

Platelet consumption

Platelet destruction:

drugs

Immune Thrombocytopenia

The most frequent cause of thrombocytopenia is immune mediated platelet destruction due to:

1. autoantibodies

2. drug-dependent antibodies

3. alloantibodies

A syndrome characterized by thrombocytopenia :

1. Shortened platelet survival

2. Presence of antiplatelet antibody in the plasma

3. Increase megakaryocytes in the bone marrow

Immune (Idiopathic) Thrombocytopenic Pupura

ITP

• The syndrome can be:– Acute

• Platelet count return to normal within 6 month & relaps does not occur

• Most in children– Chronic

• Platelet count remain low beyond 6 month• More common in adult

– Recurrent• Platelet count decrease after having returned to

normal

Predisposing Factor

• 50-80% : infection (usually viral) prior to thrombocytopenia

• About 20% : a specific infection can be identified, eg. Rubella, measel, varicella, pertussis, mumps, infectious mononucleosis, CMV, parvovirus or bacterial

• Measel or smallpox vaccination

Clinical Manifestation

• Skin: Ecchymosess/purpira usually on the anterior surface of lower extremities and body prominences (ribs, scapula, shoulders, legs, pubic)

• Mucous membranes: subconjunctival, buccal mucosa, soft palate

• Menorrhagia• Hematemesis & melena infrequent• Others: nose, gum, G.I, Kidnets (usually at the

onset of the disease

Clinical manifestation

• Intracranial bleeding:– Usually preceded by:

• Headache, dizziness, acute bleeding at other place

• Retinal hemorrage

• Middle ear hearing impairment

• Deep muscle hematoma and hemarthrosis• Rare, seen after i.m injection or significant trauma• Characteristic of plasma coagulation

Laboratory Findings

• Low platelet count– Always <150.000 /mm3

– Often <20.000 /mm3 in patients with severe generalized hemorrhagic manifestations

– MPV ( N : 8.9 + 1.5 um3)• Blood smear

– Thormbocytopenia must be confirmed by peripheral blood examination to exclude the diagnosis pseudothrombocytopenia, the presence of megathrombocytes and other hematologic manifestation

– Blood semar normal apart from thrombicytopenia• Anemia present in proportion to amount of blood loss

Bone Marrow Aspiration

• Indication– Atypical presentation– Poor respone to therapy– To exclude other hematologic disorder sucg as

leukemia

• Characteristic – ↑ ,megakaryocytes, immature and asence of budding– Nomlar erythroid and myeloid cells– Occasionally eosinophilia– Erythroid hyperplasia if significant blood loss

Intracranial Hemorrhage

• Incidence : 0,1 – 0,5 %• Age: 13 month – 16 years• Platelet count :

– < 10.000 /mm3 in 73% cases– 10-20.000 /mm3 in 25% of cases– >20.000 /mm3 in 2% of cases

• Interval between diagnosis of ITP and ICH:– <4 wekks in 51% of cases– 4 weeks – 9 years in 49%of cases (mean 27 weeks)

Intracranial Hemorrhage

• Risk Factors in 45 % cases of ICH include:– Head injury (29%)– Aspirin treatment (5%)– AV malformation (17%)– Mucocutaneous hemorrhage (49%)

• Site of ICH:– Intra cerebral (77%)– Subdural hematoma (23%)

• 50 % had prior tretament with steroid and / or IVIG

• 54% survival, most without permanent damage

Supportive Treatment

• No treatment is required when platelet count >20.000 /mm3 , asymptomatic or has mild bruising but no evidence of mucous membrane bleeding

• Competitive sport should be avoided• Depoprovera or any other long-acting

progesteron in suspending menstruation for several month

• Aspirin, Nonsteroidal antiinflammatory agents and any other drug the interfere with platelet function should not be given

Farmacological Treatment

• Treatment choice : Steroid, IVIG, and anti–D

• Indication– Platelet count <20.000 /mm3 and significant

mucous membrane bleeding– Platelet <10.000 /mm3 and minor purpura

Steroid Therapy• Mechanisms:

– Inhibits phagocytosis of antibody coated platelet in the spleen prolongs platelet survival

– Improves capillary resistance and thereby improve platelet economy

• Dose and Duration:– Dose : 2mg/kg/day (max. 60/mg/day) in divided dose. Tap

off in 5-7 day interval and stopped at the end of 21-28 days, regardless of the response

– In severe cases methylprednisolone 30mg/kg/day (max 1 g/day) for 3 days

• Prolonged case of steroid in undesirable:– Worsen the thrombocytopenia and depress platelet

[rpduction– Side effect : weight gain, caushingoid facies, fluid retention,

acne, hyperglycemia, hypertension, mood swings, pseudotumor cerebri, cataracts, growth retradation , avascular necrosis

IVIG

• Mechanism of action– Reticuloendothelial Fc-receptor blockade– Activation of inhibitor pathways– Decrease autoantibody synthesis

• Indication– Neonatal Symptomatic Immune Thrombocytopenia

Infant less than 2 y.o are generally more refractory to steroid treatment

– Alternative therapy to corticosteroid therapy

• Much more expensive and has significant side effects

Anti –D Therapy

• Plasma derived gamma immune globulin of anti –Rh antigen

• Mechanism action :– Blockade of Fc receptor of reticuloendothelial cell

• Platelet is increase after 48 hours, therefore the therapy is not appropriate for emergency treatment

• Patients who have not undergone splenectomy and Rh positive are more likely to respond to IV Anti-D

Splenectomy

• Indication– Severe acute ITP with acute life-threatening bleeding

and not responsive to medical treatment– Chronic ITP with bleeding symptom or platelet count

persistently below 30.000 /mm3 an not responsive to medical treatment for several years

– In very active patient subject to frequent trauma, early splenectomy may be indicated

• Because the hazard of overwhelming postsplenectomy infection (OPSI) the procedure should be performed after clear indication

Splenectomy

• Indication for splenectomy are rare because of judicious use if steroid and IVIG

• It is rarely necessary to perform splenectomy before 2 years adter diagnosis

• Laparoscopic splenectomy is preferable to open splenectomy

• Up to 70% have complete and long-lasting recovery

• 40% wuth persistent thrombocytopenia after splenectomy have acsseory spleen

Treatment Algorithm

Yang skema itu.. Gak keliatan di foto.. Maaf ya kawan..

Live Threatening Hemorrahage

• Platelet transfusion

• Methylprednisolone 500 mg/m2 IV per day for 3 days

• IVIG 2 /kg for 12 hours infusion

• Emergency splenecomy

Prognosis• Excellent, 50 % recover within 1 month % 70-80% within 6

month

• Spontaneous remission after 1 year in uncommon, but may occur even after several years

• When demonstration underlying cause, the prognosis is related to the cause

• Age older than 10 years, insidious onset, female are associated with chronic ITP

• 50-60 % chronic ITP………….. without any other therapy and without splenectomy

Hemostastis Pada Anak

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