Hemostasis Disease In Children

dr. Bertha

Hemostatic Mechanism
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

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

Physical examination
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

Trombin time vWF

-Platelet count -Bleeding time -PT / aPTT

Specific work-up

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

aPTT
Measures the initiation of clotting (intrinsic pathway) doesnt 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 + patients 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

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

The characteristic of platelets

Size: 1-4 m (younger platelets are larger) Mean platelet volume (MPV) : 8,9 1.5 m3 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

Thrombocytopeni based on pletelet sized

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 Some storage pool diseases Microthrombocytes (MPV ) Wiskott Aldrich syndrome TAR syndrome

Iron def. Anemia

Normal size (MPV normal) Disease with hypocellular marrow or infiltrated with malignant disease

Clasification of Trombocytopenia
Incrase platelet destruction Disorder of platelet distribution or pooling

Thrombocyto penia

Decrased platelet production

Pseudothrombocyto penia

Clasification of Trombocytopenia
Hypersplenism (Portal hypertension, Gaucher disease,cyanitic congenital, heart disease, neoplasm, infection)

Disorder of platelets distribution or pooling

Hypothermia

Clasification of Trombocytopenia
Hyperplasia or suppresion of megakaryocyte

Drugs: Chlorothiazide, ethanol Constitusional: Rubella, Ineffective Thrombopoeisis: .. Disorder of control mechanism: Trombopoetin deficiency Acquired myelositic disorder: Drugs

Decrase platelet production

Marrow Infiltrative Process

Benign: Osteoporosis Malignancy

Clasification of Trombocytopenia
Platelet inactivation during bloof collection Pseudothrombocytopenia Undercounting of megathrombocytes In vitro agglutination of platelets to EDTA

Clasification of Trombocytopenia
Immune Thrombocytopenia

Idiopathic (ITP) Secondary: Infection, drugs, SLE, etc Neonatal: Autoimune, Eritoblastosis fetalis Platelet consumption

Increase platelet destruction

Non-immune Thrombocytopenia

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

Immune (Idiopathic) Thrombocytopenic Pupura

A syndrome characterized by thrombocytopenia : 1. Shortened platelet survival 2. Presence of antiplatelet antibody in the plasma 3. Increase megakaryocytes in the bone marrow

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 antiD Indication
Platelet count <20.000 /mm3 and significant mucous membrane bleeding Platelet <10.000 /mm3 and minor purpura

 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

Steroid Therapy

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