Chief complaint : 2

Case 2 . .

HistoryPresent illness :

4 . vaccine DPT-HB

2 . 4 . CBC Plt. 7,000 ..

General appearance : A Thai infant , active crying with tear vital signs : BT 36.5 C , PR 84 bpm , RR 22 bpm , BP 90/60 mmHg HEENT : AF 1x1 cm. , no bulging , not pale , no jaundice , no petechial in oral mucosa

Abdomen : no distention ,normoactive BS, soft , not tender, no guarding , liver and spleen cant be palpable.

Ext : Petechiae at both legs , hand , face , no ecchymosis , no edema all extremities.

.

Lab ( ..)CBC :Hb 9.5 Hct 29% , WBC 9580 /mm3 ,platelet 7,000 /mm3 ,PMN 9 % , Lymphocyte 81 %, MCV 75.4 , MCH 24.9

Past History

- - (

)- -

HistoryFamily history :

-

Personal history :

- C/S due to PIHApgar score 9,10 2,755

- - 5.5 . , 65 .-

Physical examinationVital signs : BT 37.0 C, PR 156 bpm,full RR 44 /min BP 76/50 mmHg ,

Body weight 5.5 kg,Height 65 cmGeneral appearance : A Thai infant, good consciousness, no

drowsinessHEENT : AF 2x1 cm. ,not pale conjunctivae,anicteric sclerae, pharynx

and tonsils were not injected, CLN & SCLN were impalpableLungs : equal breath sound, no retraction, no adventitious sound Heart : normal S1S2, no murmurAbdomen : soft, not tender, active bowel sound, liver and spleen

were impalpable, kidneys were impalpableExtremities : Petechial both legs, hand, face, no ecchymosis, no edema,

no deformitiesNS : Active , Pupil 2mm RTLBE , Moro+ , Tonic neck+ ,Sucking and rooting +

Problem lists

1. History of Vaccination (DPT-HB 4 days PTA)2. Generalized Petechial hemorrhage (2 days PTA)3. Nausea and vomiting 2 days PTA4. Thrombocytopenia with Lymphocyte predominate

with anemia

Provisional diagnosis- ITP

DDx

- Microangiopathic Hemolytic anemia (MAHA)- Von Willebrand disease - Collagen vascular disease- Vitamin C def.

Investigation

CBC ( 25/07/57)Hb 9 g/dl Hct 26.6 %

Hypochromia 1+ Anisocytosis few Microcytosis few

platelet count 8,000/mm3 ,platelet smear : decrease

WBC 7,920 /mm3

PMN 15%, L 77 %, M 2%, E 2%, B 0%, Blast cell 4

MCV 75.1 fl, MCH 25.4 pg

Chest X-ray

Normal bony structure, No pleural effusion, No lung infiltration, No cardiomegaly

Impression :Immune thrombocytopenic purpura

ManagementAdmitSpecific treatment Hydrocortisone

30 mg. iv. q 6 hr. CBC tomorrow

Supportive treatment Observe clinical (Observe bleeding and neuro sign) Regular diet

26/7/57

S:

O: BT 36.5 PR 136/min full RR 36/minAbdomen : soft, not tenderExt: generalized petechiaeA: ITP

Clinical and vital sign stable , no active bleedingP: Cont. hydrocortisone

CBC ( 26/07/57)Hb 9 g/dl Hct 27.4 %

Hypochromia 1+ Anisocytosis few Microcytosis

few Polychromasia 1+

platelet count 71,000/mm3 ,platelet smear :

decrease

WBC 11,500 /mm3

PMN 61%, L37 %, M 2%, E0 %, B 0%

MCV 75.1 fl, MCH 24.7 pg

27/7/57S:

O: BT 36.5 PR 140/min full RR 36/minAbd: Normoactive bowel sound, distend abdomen, soft, not tenderExt: generalized petechiae

A: ITPClinical and vital sign stable , no active bleeding

P: CBC , if platelet 80,000 D/C F/U 2 weeks with CBC

CBC ( 27/07/57)Hb 9.4 g/dl Hct 29 %

Spherocyte 1+ Schistocyte few Polychromasia 1+

platelet count 262,000/mm3

WBC 11,700 /mm3

PMN 57%, L40 %, M 3%, E0 %, B 0%

MCV 74.8 fl, MCH 24.7 pg

Discharge 27/7/57 F/U 2weeks with CBC

Home medicationPrednisolone (1MKD) X 20 tabs

1x1 po pcSimethicone x I

0.3 ml po tid ac

Hemostasis

Primary hemostasis

Platelet adhesion platelet exposed subendothelial

layerPlatelet activation

resting activated platelet

Platelet aggregation platelet

Secondary hemostasis

Tertiary hemostasis

Approach to bleeding disorder

Local or Systemic bleeding Primary or Secondary Hemostatic defect Congenital or acquired Initial investigation Diagnosis and treatment

1. Local or Systemic bleeding (local bleeding)

(systemic bleeding) systemic bleeding

(massive bleeding) (prolong bleeding) (unrelated to injury) (multiple site bleeding) (spontaneous bleeding) (delay bleeding) (uncommon site bleeding)

(hemathrosis) (intracerebral hemorrhage)

2.Primary or Secondary Hemostatic defect

Platelet Coagulation disorders factor disorders

Site of bleeding Skin Deep in soft tissuesMucous membranes (joints, muscles)

(epistaxis, gum,vaginal, GI tract)

Petechiae Yes No Ecchymoses (bruises) Small, superficial Large, deep Hemarthrosis / muscle bleeding Extremely rare Common Bleeding after cuts & scratches Yes No Bleeding after surgery or trauma Immediate, Delayed (1-2 days),

usually mild often severe27

3.Congenital or acquired ( ) : Aspirin :

Hemophilia A, B >>> X-linked recessive

Hemophilia C >>> Autosomal recessiveVon Willebrand disease >>> Autosomal dominantBernard Soulier >>> Autosomal recessive Glanzmann thrombasthenia >>> Autosomal recessive

Initial investigation primary hemostasis (thrombocytopenia)

(platelet dysfunction) CBC peripheral blood smear

thrombocytopenia

bleeding time platelet aggregation test

secondary hemostasis coagulogram PT aPTT

CBC, platelet aggregation test, PT aPTT

Mild bleeding disorders mild von Willebranddisease (vWD)

Factor XIII deficiency Hyperfibrinolysis Vascular disease Ehler Danlos syndrome,

Osler Weber Rendu syndrome, Marfansyndrome, Scurvy

Initial investigation (cont.)

Approach to thrombocytopenia

aplasia infiltration ineffective megakaryopoiesis

eg. MDS selective impairment of platelet production

Causes of splenomegaly infection inflammation congestion maligancy red cell disorders storage diseases

immuneauto-immune (ITP, SLEdrugsinfectionsallo-immune

non-immunesepsisDIC, TTP, HUShypertensive disorders of pregnancy

look for splenomegaly

bone marrow investigationreview meds

look for underlying disordersreview meds

THROMBOCYTOPENIA

rule out pseudothrombocytopenia

SEQUESTRATION PRODUCTION DESTRUCTION

Immune thrombocytopenic

purpura (ITP)

ITP

An autoimmune Ab affecting platelets. Platelet counts 100,000 cell/mm3

Newly diagnosed ITP Persistent ITP Chronic ITP Refractory ITP

34

ITP - EtiologyMost common occur in the young

70% 1-10 yrs. 20 % 10-16 yrs. 10 % 3-12 months

Most pediatric cases appear to be related to

sensitization by viral infection 1-4 wk before the onset

of thrombocytopenia .

Infections include a non-specific URI, Rubella,

Varicella, Measles , Pertussis, Mumps, EBV, CMV,

HIV and bacteria or MMR vaccine

ITP - PATHOGENESIS

Infection >>> IgG antibodies directed against specific platelet antigens or antigen-antibody complexes (viral antigen-antiviral antibody complex on the platelet surface)

Platelet Ab Macrophage Fc receptors

Platelet Ab to megakaryocyte

36

ITP: Clinical features The classic presentation of ITP is a previously healthy

1-4 yr old

child who has sudden onset of generalized petechiae

and purpura.

typically in children and young female

viral infection

37

signs and symptoms (insidious onset)

: superficial ecchymosis , petechiae.

Epistaxis 25 % of case but not severe.

Hepatosplenomegaly was uncommon.

Severity depend on platelet count.

ICH 0.1-0.5 %

ITP

ClinicalMucocutaneous bleeding

100%Epistaxis 25%GI bleeding 2-8%

Hematuria 1-10%CNS bleeding 0-3%

39

Diagnosis

Age : 1-10 yrsAcute onset of bleeding No feverNo hepatosplenomegalyNo lymphadenopathyCBC : Platelet count < 100,000 / mm3

ITP

Investigation ITP IS A DIAGNOSIS OF EXCLUSION CBC : Low plt. Count ( blood smear : giant plt.) Coagulogram (PT, aPTT, TCT) : normal Bleeding time : prolong (plt

ITP

42

Management

Restrict activityAvoid aspirin, non-steroidal anti-inflammatory drugs, antihistamines

Observe clinical 6-12

43

2011 Clinical Practice Guideline on the Evaluation and

Management of Immune Thrombocytopenia (ITP)

Initial Management of ITP1. Assessment of Disease Status: What bleeding is the patient experiencing?

Determine the timing, location, and severity of

bleeding symptoms. Does this patient have any additional risk factors for bleeding such as use of antithrombotic agents orhigh-risk occupation? Is a surgical procedure anticipated?

Is this patient likely to comply with recommended treatments?

Is the bleeding experienced by this patient interfering with his or her daily activities or causing significant anxiety?

2.General Considerations for Initial Management: The majority of patients with no bleeding or mild bleeding (defined here as skin manifestations only, such as petechiae and bruising) can be treated with observation alone regardless of platelet count. First-line treatment includes observation, corticosteroids, IVIg, or anti-D immunoglobulin (anti-D). Anti-D should be used with caution given recent FDA warnings of severe hemolysis. It is therefore not advised in patients with bleeding causing a decline in hemoglobin, or those with evidence of autoimmune hemolysis.

Indication to treatment

Platelet count (mm3)

Bleeding Treatment

>30,000 No bleeding No treatment

1.

1.

2. 20,00 cell/mm3

3.

*** 20,000 cell/mm3

ITP IVIG, Steroid, anti-D

Platelet count < 20,000 cell/mm3 with mucosal bleeding

Platelet count < 10,000 cell/mm3 with no clinical of bleeding

50

Children: A single dose of IVIg (0.8-1.0 g/kg) or a short course of corticosteroids should be used as first-line treatment. IVIg should be used instead of corticosteroids if a more rapid increase in platelet count is required.

There is no evidence to support using corticosteroids for longer

courses compared to very brief courses.

Anti-D may be considered for first-line therapy in Rh+non-splenectomized children with recognition of the risksnoutlined above.

ITP: Corticosteroid

FunctionsDecrease Ab synthesisDecrease function of phagocytosis reticuloendocthelial system

Vascular integrityIncrease platelet production

52

ITP: Corticosteroid

Prednisolone 1-2 mg/kg/day (Max 60 mg/day) per oral X 2-3 wks

Or Prednisolone 4mg/kg/day per oral X 4 days no tape

off Methylprednisolone 30mg/kg/day i.v. X3 days

ITP INTRAVENOUS IMMUNOGLOBULIN G (IVIG)

Functions Blockade of Fc receptors leading to decreased uptake

by the RES Antibody specific clearance of viral infection Decreased autoantibody production due to antibody

specific feedback on antibody synthesis Dose : IVIG 800 mg/kg /day OD

or 1g/kg/day bid S/E : headache, fever, neutropenia, hemolytic anemia

ITP Intravenous anti D

Patient must be Rh (D) positive Antibody to D binds to Antigen D on red blood cells Antibody tagged RBCs bind to Fc receptors in the RES,

which allows antibody tagged platelets to survive longer in circulation

Dose : 75 microgram/kg i.v. OD S/E : fever with chill, N/V, hemolytic anemia

55

II. Subsequent Management of ITP1. Assessment of Disease Status: What bleeding is the patient experiencing? Determine the timing, location, and severity of bleeding symptoms. Does this patient have a change in history or physical examination that requires evaluation for another diagnosis that could be causing thrombocytopenia? Does this patient have any contraindications to splenectomy? How is the diagnosis of ITP affecting the patients ability to work, go to school, or participate in activities?

Does the patient respond intermittently to his or her current drug therapy? Is the patient experiencing side effects from chronic medication use? How is the patient coping psychologically with having a low platelet count?

2. General Considerations for Subsequent Management: Adults who have a platelet count > 30 x 109/L and areasymptomatic following splenectomy do not require further therapy. In children, splenectomy or other interventions with potentially serious complications should be delayed for at least 12 months, unless warranted by severe disease unresponsive to other measures or due to quality of life considerations. If previous treatment with corticosteroids, IVIg, or anti-Dhas been successful, these options may be used as needed to prevent bleeding. If previous treatment with corticosteroids, IVIg, or anti-Dhas been unsuccessful, subsequent treatment may includesplenectomy, rituximab, thrombopoietin receptor agonists,or more potent immunosuppression.

Chronic ITP 20-25 % ITP Platelet count 30,000-100,000 cell/mm3 so, no need to treatTreatment

IF platelet count 20,000 cell/mm3 with clinical of bleeding.1. Prednisolone per oral 4mg/kg x 4days (Max 180

mg/day)2. IVIG 0.8-1 g/kg single dose or3. Anti-D i.v. 75 g/kg single dose

Emergency

ITP

Methylprednisolone 30 mg/kg (Max dose 1 g i.v.)Drip in 20-30 mins + Platelet transfusion

IVIG 1g/kg X 1-2days Splenectomy

Splenectomy

Chronic ITP with clinical bleeding 70% of Primary ITP >>> good result

Hemophillus influenza Pneumoccus antibiotic penicillin 1

antibiotic overwhelming post-splenectomy infection

Section 1: ITP in childrenCase 1: newly diagnosed ITP in childrenDiagnosis of ITP 1.1.A. We recommend: Bone marrow examination is unnecessary in children and adolescents with the typical features of ITP (grade 1B).Bone marrow examination is not necessary in children who fail IVIg therapy (grade 1B). 1.1.B. We suggest: Bone marrow examination is also not necessary in similar patients prior to initiation of treatment with corticosteroids or before splenectomy (grade 2C).Testing for antinuclear antibodies is not necessary in the evaluation of children and adolescents with suspected ITP (grade 2C)Initial management of ITP 1.2.A. We recommend: Children with no bleeding or mild bleeding (defined as skin manifestations only, such as bruising and petechiae) be managed with observation alone regardless of platelet count (grade 1B).Initial pharmacologic management of pediatric ITP 1.3.A. We recommend: For pediatric patients requiring treatment, a single dose of IVIg (0.8-1 g/kg) or a short course of corticosteroids be used as first-line treatment (grade 1B).IVIg can be used if a more rapid increase in the platelet count is desired (grade 1B).Anti-D therapy is not advised in children with a hemoglobin concentration that is decreased due to bleeding, or with evidence of autoimmune hemolysis (grade 1C). 1.3.B. We suggest: A single dose of anti-D can be used as first-line treatment in Rh-positive, nonsplenectomized children requiring treatment (grade 2B).

Case 2: children who are treatment nonresponders

Appropriate second-line treatments for pediatric ITP

2.1.A. We suggest:Rituximab be considered for children or adolescents with ITP who have significant ongoing bleeding despite treatment with IVIg, anti-D, or conventional doses of corticosteroids (grade 2C).Rituximab may also be considered as an alternative to splenectomy in children and adolescents with chronic ITP or in patients who do not respond favorably to splenectomy (grade 2C).High-dose dexamethasone may be considered for children or adolescents with ITP who have significant ongoing bleeding despite treatment with IVIg, anti-D, or conventional doses of corticosteroids (grade 2C).High-dose dexamethasone may also be considered as an alternative to splenectomy in children and adolescents with chronic ITP or in patients who do not respond favorably to splenectomy (grade 2C).

Splenectomy for persistent or chronic ITP or ITP unresponsive to initial measures

2.2.A. We recommend:Splenectomy for children and adolescents with chronic or persistent ITP who have significant or persistent bleeding, and lack of responsiveness or intolerance of other therapies such as corticosteroids, IVIg, and anti-D, and/or who have a need for improved quality of life (grade 1B).

2.2.B. We suggest:Splenectomy or other interventions with potentially serious complications be delayed for at least 12 months, unless accompanied by severe disease defined by the International Working Group as unresponsive to other measures or other quality of life considerations (grade 2C).

H pylori testing in children with persistent or chronic ITP

2.3.A. We recommend:Against routine testing for H pylori in children with chronic ITP (grade 1B).

Case 3: management of MMR-associated ITP

3.1.A. We recommend:Children with a history of ITP who are unimmunized receive their scheduled first MMR vaccine (grade 1B).In children with either nonvaccine or vaccine-related ITP who have already received their first dose of MMR vaccine, vaccine titers can be checked. If the child displays full immunity (90%-95% of children), then no further MMR vaccine should be given. If the child does not have adequate immunity, then the child should be re-immunized with MMR vaccine at the recommended age (grade 1B).

TreatmentAvoid traumaImmunosuppressive drugs

- IVIG, corticosteroids- Blood Tx (plt. Tx) in life threatening bleeding

Splnectomy in chronic case

65

American Society of Hematology 2011 Guidelines for Immune Thrombocytopenic Purpura

Slide Number 1HistorySlide Number 3Slide Number 4Past HistoryHistoryPhysical examinationSlide Number 9InvestigationSlide Number 11Slide Number 12Management26/7/57Slide Number 1527/7/57Slide Number 17Discharge 27/7/57 F/U 2weeks with CBCHemostasisSlide Number 20Primary hemostasisSlide Number 22Secondary hemostasisTertiary hemostasisApproach to bleeding disorder1. Local or Systemic bleeding 2.Primary or Secondary Hemostatic defect Slide Number 283.Congenital or acquired Initial investigationInitial investigation (cont.)Approach to thrombocytopeniaImmune thrombocytopenic purpura(ITP)ITPITP - EtiologyITP - PATHOGENESISITP: Clinical featuressigns and symptomsITPDiagnosisITPITPManagementSlide Number 44Initial Management of ITPSlide Number 46Indication to treatment1. Slide Number 49ITP IVIG, Steroid, anti-DSlide Number 51ITP: CorticosteroidITP: CorticosteroidITP INTRAVENOUS IMMUNOGLOBULIN G (IVIG)ITP Intravenous anti D II. Subsequent Management of ITPSlide Number 57Chronic ITPEmergencySplenectomySlide Number 61Slide Number 62Slide Number 63Slide Number 64Slide Number 66