Paediatric Refresher Course 2017Department of Paediatrics

Sibu Hospital8-9th April 2017

Common Haematological Problems In Children

Dr Quah Shiao Wei

15 month-old, well baby girl, admitted for viral feverFull blood count as follow:Hb : 7.3g/dLMCV : 60 flMCH : 17pgWBC : 10.0 X 10 9/LPlatelet : 460 X 10 9/L

What is the cause of hypochromic microcytic anemia?

Iron Protoporphyrin

Heme

(1) Iron Deficiency Anemia- Nutritional- Blood loss (GIT, menses)

(2) Anemia of inflammation

(3) Sideroblastic Anemia

Globin Haemoglobin

(4) Haemoglobinopathy

(5) Rare : Lead Poisoning

• Onset

- Acute- Chronic

- Incidental finding

• Diet history, Pica

• Medications / Toxic Exposure

• Systemic illness

• Family history

- Aneamia- Regular blood transfusion- Splenectomy

- Gall bladder surgery

• Blood loss (hematochezia, malenic stool)

• Hemolysis (Jaundice, dark-coloured urine)

Focus History

• Growth

• Dysmorphic

• Pallor, Jaundice

• Hepatomegaly, splenomegaly

• Features of skeletal

expansion

- maxillary hyperplasia- frontal bossing

Relevant Physical Examinations

• Peripheral Blood Film / Full

Blood picture

• Iron Studies

• Reticulocyte count

• Hb analysis

Investigations

• Specific Test :

- Stool for occult blood / ova & cyst

- hemolysis workout - retic count- Coomb’s test- bilirubin (total & direct)- LDH- urine for inspection

- haemoglobinopathy- alpha gene DNA analysis

Question 1History

• Fully breastfeeding since

birth till now

• weaning started at 6

month-old

• Diet : mainly

breastfeeding

• Well child

Investigations

PBF: Hypochromic, microcytic, poikilocytosis,

anisocytosis

Serum iron : 1.5 μmol/L (9.0-35.4)

Serum ferritin : 7.5 ug/L (22-322)

Hb F : 1.0% (≤ 1.0%)

Hb A2 : 2.0 (1-3.3%)

Physical Examinations

• weight : 9.3kg, height :70cm

• pallor, not jaundice

• no dysmorphic features

• no organomegaly

Diagnosis ?

Nutritional Iron Deficiency Anaemia

Treatment for Iron Deficiency Anaemia

1) Iron Therapy

T. Ferrous Fumarate 200mg (66mg elemental iron)Treatment dose : 6mg/kg elemental iron per day

Syrup Iron (III) Hydroxide Polymaltose Complex / Maltofer50mg/5ml (1ml= 10mg elemental iron)

Intravenous Iron-Hydroxide Sucrose Complex / Venofer 500mg/5ml- Dosing : 0.5 -2mg/kg (max 100mg)- ≥ 2 year-old- Infusion, diluted in 25ml NS- Give every four weeks, total 12 weeks

2) Diet motification

3) Follow up for the response

- Hb > 1g/dL with four week- Continue at least 3-6 month- deworming

Dietary Sources of Iron

Treatment for Iron Deficiency Anaemia

1) Iron Therapy

T. Ferrous Fumarate 200mg (66mg elemental iron)Treatment dose : 6mg/kg elemental iron per day

Syrup Iron (III) Hydroxide Polymaltose Complex / Maltofer50mg/5ml (1ml= 10mg elemental iron)

Intravenous Iron-Hydroxide Sucrose Complex / Venofer 500mg/5ml- Dosing : 0.5 -2mg/kg (max 100mg)- ≥ 2 year-old- Infusion, diluted in 25ml NS- Give every four weeks, total 12 weeks

2) Diet motification

3) Follow up for the response

- Hb > 1g/dL with four week- Continue at least 3-6 month- deworming

10month-old, well baby boy, referred for pallor.O/E: pale, tinge of jaundice. Liver 2cm, spleen 1cm

Hb : 6.0g/dLMCV : 54 flMCH : 16 pgWBC : 10.0 X 10 9/LPlatelet : 360 X 10 9/L

What is the cause of anemia?

PBF : Hypochromic, microcytic anemia

Serum iron : 12 μmol/L (9.0-35.4)

Serum ferritin : 17 ug/L (22-322)

Hb F : 98.2% (≤ 1.0%)

Hb A2 : 2.3% (1-3.3%)

Beta- Thalassemia Major

Haemoglobin in Human Life

Haemoglobin Type

EmbryonicGower 1 PortlandGower 2

Fetus/ Hb F -22

Adult -Hb A -22

Hb A2-22

Changes in haemoglobin composition in Human Life

Hb analysis Globin Chains Normal Thalassemia major

Hb A 22 > 95%

Hb A2 22 1.5 -3.3%

Hb F 22 <1%

Hb analysis Globin Chains Normal Thalassemia trait

Hb A 22 > 95% 80-90%

Hb A2 22 1.5 -3.3% > 4.0%

Hb F 22 <1% 1-7% (variable)

Microcytic Hypochromic Anemia (MCH < 27pg)

Iron Deficiency Anemia (reduced RBC production)

Thalassemia Trait (ineffective erythropoesis)

Iron Deficiency Anemia Thalassemia Trait

Hb Moderate to severe 9-10g/dL

RDW High Low

Red Cell Distribution Width (RDW)– measure red cell variation

(normal 11-15%)

Mentzer Index (MCV/RBC)

>13 <13

Vs

3 year-old boy, referred for pallor.O/E: pale, tinge of jaundice. mild frontal bossing Liver 2cm, spleen 2cm

Hb : 7.2g/dLMCV : 70 flMCH : 16 pgWBC : 7.0 X 10 9/LPlatelet : 250 X 10 9/L

What is the cause of anemia?

PBF : Hypochromic, microcytic anemia

Serum iron : 12 μmol/L (9.0-35.4)

Serum ferritin : 170 ug/L (22-322)

Hb F : 46.0% (≤ 1.0%)

Hb A2 : 48.2% (1-3.3%)

Hb analysis Globin Chains Normal Hb E- Thala Hb E trait

Hb A 22 > 95%

Hb A2 22 1.5 -3.3% > 25% > 25%

Hb F 22 <1% normal

When Hb A2 > 10%, think about structural variant share the mobility as A2 : Hb E, C, O

Hb E point mutation at 26, glutamic acid to lysine

Hb analysis Patient Father Mother Brother

Hb (g/dL) 7.2 12.0 10.5 11.5

MCV (fl) 70 72 70 72

MCH (pg) 16 22 20 22

Hb A2 48.2% 32.0% 4.5% 35.0%

Hb F 46.0% 2.0% 1.0% 2.0%

Family Screening

Hb E-thala

Hb E trait

Hb trait

Hb E trait

5 year-old girl, referred for pallor.O/E: pale, tinge of jaundice. Liver 1cm, spleen 1cm

Hb : 8.4 g/dLMCV : 67 flMCH : 24 pgSerum Iron & ferritin : normalHb A : 95%Hb A2 : 2.5%Hb F : 0.8%

What is the cause of anemia? Incubated with methylene blue

“ Golf ball”- Hb H inclusion

Hb H disease

Hb Analysis

Normal : ( / )

(1) Alpha plus (+) : (_ / )- silent carrier

Hb adana : CD59

Codon 59 : GGC -> GAC

(2) Alpha zero (0) : (_ _ / )- alpha thal carrier, in Asian( _ / _)- alpha thal carrier, in African

(B) Alpha non-deletional (ND

/ )

Hb constant spring : CS

Codon 142 : TAA -> CAA

(A) Alpha deletion

Alpha Thalassaemia

(3) 3 genes affected (_ _ / _ ) - Hb H Disease

(4) 4 genes affected (_ _/_ _)- Hb Barts

- Severe intrauterine anemia- Hepatopslenomegaly- Generalized edema, ascites- Skeletal & CVS malformation

Hb H-Constant Spring(CS / _ _)

Hb Barts Hydrops Fetalis Phenotype- Inactivations of the alpha globin

e.g. : (ND/ ND)(_ _/ ND)

Inactivation of alpha globin

Molecular diagnosis is important

Alpha thalassemia need DNA analysis!

Thalassaemia Screening For General Population

MCH ≤ 27 pgHb ≤ 9g/dL

Treat For IDA for 3 months

Repeat FBC

MCH> 27 pgnormal

MCH ≤ 27 pg

Proceed with Hb analysisLook at Hb A2 (normal 1.5-3.3%)

Hb A2 ≥ 4%

Thalassaemia Carrier

Hb A2 3.4-3.9%

DNA analysis for β mutation

Β mutation detected

(1) General rules: Hb A2 ≥ 4% marker for trait

Thalassaemia Screening For General Population

MCH ≤ 27 pg

Proceed with Hb analysisLook at Hb A2 (normal 1.5-3.3%)

Hb A2 ≥ 4%

Thalassaemia Carrier

Hb A2 3.4-3.9%

DNA analysis for β mutation

Β mutation detected

Hb A2 ≤ 3.3%MCH <25 pg

αThalassaemiaCarrier

Hb E variant present

Ethnic: non-Indian, i.e. Chinese, Malay, Indigeneous, mixed parentage

DNA analysis for α mutation

α mutation detected

Hb E <25

αThalassaemia& Hb E Carrier

Hb E ≥25= Hb E carrier

Pale & Jaundice

8 year-old girl, well, admit for pallor and jaundice for 3 days, no liver, spleen 3cm

Hb : 3.5 g/dLMCV : 115 flWBC : 11.0 X 10 9/LPlatelet : 170 X 10 9/LAbsolute Retic count: 200Total bilirubin : 60

AnemiaReticulocytosisHyperbilirubinemia

3 cardinal signs of hemolysis

Absolute reticulocyte count (X109/L)= retic count % X RBC X 10

< 20 – poor reticulocyte response20-80 – preserved reticulocyte response> 80 – brisk reticulocyte response

- Direct comb’s test / Direct Antiglobulin Test

To test antibody & complement on RBC surface

Approach to haemolytic anaemia

Immune or non-immune hemolysis ?

8 year-old girl, well, admit for pallor and jaundicefor 3 days, no liver, spleen 3cm

Hb : 3.5 g/dLMCV : 115 flWBC : 11.0 X 10 9/LPlatelet : 170 X 10 9/LAbsolute Retic count: 200Total bilirubin : 60Direct Coomb’s Test: Positive, Ig G

Warm Immune Hemolytic Anemia

What is the cause of anemia?

Ig G Complement C3d Ig G- C3d

Positive Direct Coomb’s Test –Immune Hemolytic Anemia

Cold AIHAParoxysmal Cold Haemoglobinuria

Connective Tissue Disease

Classic Warm AIHA

1 year-old girl, noted pallor during immunizationo/e : pallor, tinge of jaundice, liver 2cm, spleen 2cm

Hb : 6.0 g/dLMCV : 115 flWBC : 10.0 X 10 9/LPlatelet : 170 X 10 9/LAbsolute Retic count: 150Total bilirubin : 50Direct’s Coomb’s Test : negative

What is the cause of hemolytic anemia ?

Non-Immune Hemolytic Anemia

RBC membrane disorder RBC enzyme deficiencies

Ineffective erythropoiesis

Hereditary Spherocytosis

Hereditary Elliptocytosis

Pyruvate KinaseG6PD deficiency

Osmotic fragility test

Haemoglobinopathy

1 year-old girl, noted pallor during immunizationo/e : pallor, tinge of jaundice, liver 2cm, spleen 2cm

Hb : 6.0 g/dLMCV : 115 flWBC : 10.0 X 10 9/LPlatelet : 170 X 10 9/LAbsolute Retic count: 150Total bilirubin : 50Direct’s Coomb’s Test : negative

What is the cause of hemolytic anemia ? Hereditary Spherocytosis

Summary – Approach to Pale Child

1) Is the child in shock (poor perfusion) ? Or anemia ?

2) If anemia , micocytic / normochromic or macrocytic anemia ?

3) Focus history, physical examination & investigations

4) Screening for thalassemia

(1) General rules: Hb A2 ≥ 4% marker for trait

(2) If MCH <25 pg, Hb A2 ≤ 3.3%No marker for thala trait- need to do DNA analysis

5) Cardinal sign of hemolytic anemia : ↓Hb + ↑retic + ↑bilirubin- determine immune or non-immune

Bleeding child !!!

Approach to bleeding child

1) Well Vs Unwell (haemodynamic instability)

2) Timing of bleeding

Immediate bleeding

Delayed bleeding

Defect in primary hemostasis Vascular abnormaly

Defect in secondary hemostasis

Hemostasis

Primary hemostasisFormation of platelet plug

Defect in primary hemostasis- Platelet disorders- Von-Willebrand disease- Immediate bleeding- Mucocutaneous bleeding- Internal bleeding

Secondary hemostasisFormation of cross-linked fibrin to stabilize the platelet plug

Defect in secondary hemostasis- Factors deficiency- Type III vWD- Delayed bleeding- Deep muscle and joint bleeding- Internal bleeding

Significant bleeding

1) Epistaxis not stopped by 10 minutes compression or required medical intervention

2) Cutaneous haemorrhage or bruising without apparent trauma

3) Prolonged bleeding (> 15 minutes) for trivial wounds, or in oral cavity, or recurring spontaneously

within 7 days

4) Post-operative bleeding

5) Menorrhagia leading to anemia

Approach to bleeding child

1) Well Vs Unwell (haemodynamic instability)

2) Timing of bleeding

Immediate bleeding

Delayed bleeding

Defect in primary hemostasis Vascular abnormaly

Defect in secondary hemostasis

3) Site of bleeding

- Mucocutaneous bleeding (oromucosal, nasal, subconjunctival, skin, GI)

- Deep soft tissue bleeding (muscle, joints)

- Internal haemorrhage (intracranial haemorrhage)

4) Severity of bleeding

Site of Bleeding

1) Petechiae (<3mm)

2) Ecchymosis (>3mm)

Mucocutaneous bleeding Deep soft tissue bleeding Internal bleeding

Mucosal

Petechiae

Blister / bullae

Epistaxis

Gingival

Subconjunctival haemorrhage

Skin

Epidermis and dermis

hematoma

Subcutaneous tissue

Site of Bleeding

1) Petechiae (<3mm)

2) Ecchymosis (>3mm)

Mucocutaneous bleeding Deep soft tissue bleeding Internal bleeding

Mucosal Joints

Petechiae

Blister / bullae

Epistaxis

Gingival

Subconjunctival

haemorrhage

hematoma Hemarthosis

Intracranial haemorrhage

Skin

Epidermis and dermis

hematoma

Subcutaneous tissue

Muscle and soft tissue

Approach to bleeding child

1) Well Vs Unwell (haemodynamic instability)

2) Timing of bleeding

Immediate bleeding

Delayed bleeding

Defect in primary hemostasis Vascular abnormaly

Defect in secondary hemostasis

3) Site & severity of bleeding

- Mucocutaneous bleeding (oromucosal, nasal, subconjunctival, skin, GI)

- Deep soft tissue bleeding (muscle, joints)

- Internal haemorrhage (intracranial haemorrhage)

4) Important histories

- Family history- Hemostasis history (spontaneous and provoked)- Drug history

Hemostasis history

Physiological

Neonate- Cord dehiscence

Infancy- Ambulation- Eruption of primary teeth

Neonate- Instrumental delivery- Heel prick bleed- Injection bleeds- vaccination

Childhood and adolescents- Exfoliation of primary teeth- Sport injuries- Menorrhagia

Provoked

Infancy- Vaccinations

Childhood and adolescents- Circumcisions- Dental procedures- Adenoidotonsillectomy- Appendicectomy- Hernia repair

2) Normal platelet, abnormal coagulation profile

1)Isolated thrombocytopenia, normal coagulation profile

4)Normal platelet & normal coagulation profile

a) Prolonged PT b) Prolonged APTTc) Prolonged PT & APTT

Case Senario

3) Thrombocytopenia, abnormal coagulation profile

Slide 41

Isolated thrombocytopenia

3 year-old, well, bruising for 1 week pink, no hepatosplenomegaly or lymphadenopathy

Hb : 13.0 g/dLWBC : 7.0 X 10 9/LPlatelet : 5 X 10 9/LPT : 13APTT : 31TT : 14 (13-16s)Fibrinogen : 2.5 (1.5-4.5g/L)

What is the cause of isolated thrombocytopenia?

Thrombocytopenia

1) True thrombocytopenia ?FBP : Pseudothrombocytopenia due to platelet clumping ?

2) Associated abnormaly ? Look at FBP

• Thrombocytopenia + RBC fragment

→Microangiopathic Hemolytic Anemia

• RBC & WBC precursors? → Bone marrow infiltration

• Circulating blasts? → Acute leukemia

• Atypical lymphoid cells → consider viral infections

Thrombocytopenia

1) True thrombocytopenia ?FBP : Pseudothrombocytopenia due to platelet clumping ?

2) Associated abnormaly ? Look at FBP

• Thrombocytopenia + RBC fragment →Microangiopathic Hemolytic Anemia

• RBC & WBC precursors? → Bone marrow infiltration

• Circulating blasts? → Acute leukemia

• Atypical lymphoid cells → consider viral infections

3) Look at the platelet

• Giant platelet → Bernard- Soulier Syndrome

• Small platelet → Wiskott-Aldrich Syndrome

• WBC inclusion, large platelet → MYH9-related platelet disorders

Thrombocytopenia

1) True thrombocytopenia ?FBP : Pseudothrombocytopenia due to platelet clumping ?

2) Associated abnormaly ? Look at FBP

• Thrombocytopenia + RBC fragment →Microangiopathic Hemolytic Anemia

• RBC & WBC precursors? → Bone marrow infiltration

• Circulating blasts? → Acute leukemia

• Atypical lymphoid cells → consider viral infections

3) Look at the platelet

• Giant platelet → Bernard- Soulier Syndrome

• Small platelet → Wiskott-Aldrich Syndrome

• WBC inclusion, large platelet → MYH9-related platelet disorders

4) If non of above, think of Immune Thrombocytopenia

FBP : large platelet with atypical lymphocytes

3 year-old, well, bruising for 1 week pink, no hepatosplenomegaly or lymphadenopathy

Hb : 13.0 g/dLWBC : 7.0 X 10 9/LPlatelet : 5 X 10 9/LPT : 13APTT : 31TT : 14 (13-16s)Fibrinogen : 2.5 (1.5-4.5g/L)

FBP : large platelet, no abnormal cells

Immune thrombocytopenia

Immune Thrombocytopenia (platelet < 100 X 109/L)

- Immune- mediated thrombocytopenia antiplatelet autoantibody

- Diagnosis of exclusion

- Precipitating factors following viral infections MMR vaccinations (1 in 40,000 vaccinated children)

- Age : 2-10 year-old

Phase of Immune Thrombocytopenia

monthsProvan et al, Blood, 2010; 115:168

Diagnosis of Immune Thrombocytopenia

Investigations in Immune Thrombocytopenia

1) FBC

2) FBP3) Autoimmune screening4) Recommended – Immunoglobulin level (prior to IV IG treatment)

Bone marrow aspiration ?

Consider if

1) Prolonged history of bleeding

2) Additional cytopenia

3) Bone pain

4) Lymphadenopathy

5) Failure to response to treatment

Treatment in Immune Thrombocytopenia

1) Platelet elevating therapy - based on the severity

Treat the patient, not the numbers !

Severity

Non- Severe(cutaneous bleed)

Minor (Grade 1)→ limited petechiae→ < 5 bruises

Mild (Grade 2)→ extensive petechiae→ > 5 bruises

Severe(mucosa bleed)(internal bleed)

Moderate (Grade 3)→ active mucosal bleed→ hematoma

Serious (Grade 4) → internal bleeding

Grade Platelet elevating therapy

I Not recommended, observation only

II Treatment in selected cases

III Recommended

IV Necessary

Treatment

1) Platelet elevating therapy a) Steroidb) IV IGc) Steroid + IV IG

Dose of IV IG

Single dose 0.8g/kg Lancet 1994

1g/kg Blood 1993

Multiple doses 0.8g/kg Day 1, then 1g/kg 72h later Hum immunol 2005

1g/kg for 2 days Blood 1986

0.4/kg for 5 days Lancet 1981

Treatment in Immune Thrombocytopenia

1) Platelet elevating therapy a) Steroidb) IV IGc) Steroid + IV IG

2) Remission inducing therapya) splenectomyb) rituximab

3) Supportive therapya) tranexamic acidb) hormone therapy in menorrhagia

2) Normal platelet, abnormal coagulation profile

1)Isolated thrombocytopenia, normal coagulation profile

4)Normal platelet & normal coagulation profile

a) Prolonged PT b) Prolonged APTTc) Prolonged PT & APTT

Bleeding Child

3) Thrombocytopenia, abnormal coagulation profile

2 year-old boy, spontaneous right knee swelling.

Hb : 9.2 g/dLWBC : 8.0 X 10 9/LPlatelet : 300 X 10 9/LPT : 12APTT : 90TT : 14 (13-16s)Fibrinogen : 2.5 (1.5-4.5g/L)

Prolong APTT, next step ?

After performing mixing test, APTT : 35

Diagnosis ? Factor deficiency

F8 : 1% (80-100%)F9 : 110% (70-120%)VWF Ag: 80% (70-1105)riCoF: vWF: 100% (80-120%)

Mixing test

If corrected, factor deficiency

If not corrected, presence of inhibitor

Isolated prolong APTT – intrinsic pathway

Further ix1st line : FIII, FIX, vWF2nd line : FXI

Diagnosis : Haemophilia A

D9 of life baby, bleeding from umbilical stump for 2 days

Hb : 11.0 g/dLPlatelet : 300 X 10 9/LPT : 100APTT : 34TT : 14 (13-16s)Fibrinogen : 2.5 (1.5-4.5g/L)

Isolated prolong PT

• Vitamin K deficient bleed• Warfarin toxicity

• Rare : FVII deficiency

5 weeks-old Indonesia girl, presented with status epilepticusBirth History : Term baby, born at home. Mother main caretakerO/E: Pupils unequal, all the tones and reflex increased, AF bulging

Hb : 7.0 g/dLWBC : 15.0 X 10 9/LPlatelet : 516 X 10 9/LPT : > 200APTT : > 200TT : 16 (13-16s)Fibrinogen : 1.8 (1.5-4.5g/L)

Diagnosis ?

CT brain

vit k deficient bleeding

2) Normal platelet, abnormal coagulation profile

1)Isolated thrombocytopenia, normal coagulation profile

4)Normal platelet & normal coagulation profile

a) Prolonged PT b) Prolonged APTTc) Prolonged PT & APTT

Bleeding Child

3) Thrombocytopenia, abnormal coagulation profile

5 year-old girl, in ICU, ventilated for severe pneumonia with septic shock

Hb : 8.0 g/dLWBC : 3.0 X 10 9/LPlatelet : 35 X 10 9/LPT : 20 (12-14)APTT : 50 (28-35)TT : 23 (13-16s)Fibrinogen : 0.8 (1.5-4.5g/L)

Diagnosis ?

Disseminated Intravascular Coagulopathy

2) Normal platelet, abnormal coagulation profile

1)Isolated thrombocytopenia, normal coagulation profile

4)Normal platelet & normal coagulation profile

a) Prolonged PT b) Prolonged APTTc) Prolonged PT & APTT

Bleeding Child

3) Thrombocytopenia, abnormal coagulation profile

15 year-old girl, having heavy menses. Presented with giddiness

Hb : 7.5 g/dLPlatelet : 350 X 10 9/LPT : 13 (12-14)APTT : 34 (28-35)TT : 14 (13-16s)Fibrinogen : 1.8 (1.5-4.5g/L)

Next Step ?

Von-willebrand disease

F8 : 100% (80-100%)F9 : 110% (70-120%)VWF Ag: 38% (70-1105)riCoF: vWF: 41% (80-120%)Diagnosis ?

Screen for1) von-Willebrand disease2) Platelet function defect3) FXIII deficiency4) Rare : vitamin c deficiency

Summary to approach to bleeding child

1) Well Vs Unwell

2) Timing of bleeding- immediate Vs delayed

3) Site & severity of bleeding

4) Important histories- Family history- Hemostasis history (spontaneous and provoked)- Drug history

5) Platelet and coagulation profile

Pancytopenia

8 year-old girl, previously well, presented with 1 month history of recurrent bruises, gum bleeding, nose bleeding. She was referred by clinic with the following full blood count:-Hb : 4.6 g/dLMCV : 65 flMCH : 22pgWBC : 3.0 X 10 9/LPlatelet: 3 X 10 9/L

She was pale, not jaundice. There were multiple petechiaes over face, both upper and lower limbs. No organomegaly or lymphadenopathy. She was not dysmorphic, no skeletal abnormalities or pigmentation.

Pancytopenia is an emergency

Bone marrow Infiltration

Acute leukaemia

Bone marrow Failure

Aplastic Anaemia

Immune dysregulation

Haemophagocystic

Lymphohistiocytosis

(HLH)

Thrombocytosis

12 months; well baby; admitted for acute bronchiolitisIncidentally finding of pallor; no hepatosplenomegaly; no lymphadenopathy

Hb (g/dL) 7.1

MCV (fL) 56

MCH (pg) 16.0

WBC (× 109/L) 10.3

Platelet (× 109/L) 1014

What is the cause of thrombocytosis ?

On examinations,

• Bilateral injected conjuctiva, watery non-purulent

• Maculopapular rash on trunk, face, limbs. Blanching. Not itchy.

• No periorbital/perioral swelling

• 1 cervical lymph nodes 1cm X 2cm on right anterior neck

• BCG scar not flared

• No perianal redness or excoriation

• Lips slightly swollen

6 months; previously wellFever 1 week , Cough 4/7

Rash 2/7 appeared on trunk, limbs, faceRed eyes 2/7, Reduced oral intake 1/7

Hb 9.8TWBC 32.3 Plt 917

What is the cause of thrombocytosis ?

ThrombocytosisDefinition: Platelet count > 400 × 109/L

Reactive

• Iron deficiency anemia

• Infection

• Inflammation:• Kawasaki disease• Autoimmune disease

Reactive thrombocytosis does not result in thromboembolic or haemorrhagic complications

Does not required anti-platelet therapy except:1. Kawasaki disease2. Additional thrombotic

risk factors exist

ThrombocytosisDefinition: Platelet count > 400 × 109/L

Reactive Myeloproliferative or Myelodysplastic

Disease

Asplenia

• Iron deficiency anemia

• Infection

• Inflammation:• Kawasaki disease• Autoimmune disease

• Essential thrombocythemia• polycythemia vera (PV)• primary myelofibrosis (PMF)• chronic myeloid leukemia (CML)• 5q- syndrome• RARS with thrombocytosis

Post-splenectomy

12 months; well baby; admitted for acute bronchiolitisIncidentally finding of pallor; no hepatosplenomegaly; no lymphadenopathy

Hb (g/dL) 7.1

MCV (fL) 56

MCH (pg) 16.0

WBC (× 109/L) 10.3

Platelet (× 109/L) 1014

What is the cause of thrombocytosis ?

Thrombocytosis 2°to iron deficiency anaemia

PBF microcytic hypochromicanemia

Iron 1.0µmol/L 9.0-30.4

Ferritin 6.7ug/L 22.0-322.0

HbA2 2.0%

HbF 1.0%

On examinations,

• Bilateral injected conjuctiva, watery non-purulent

• Maculopapular rash on trunk, face, limbs. Blanching. Not itchy.

• No periorbital/perioral swelling

• 1 cervical lymph nodes 1cm X 2cm on right anterior neck

• BCG scar not flared

• No perianal redness or excoriation

• Lips slightly swollen

6 months; previously wellFever 1 week , Cough 4/7Rash 2/7 appeared on trunk, limbs, faceRed eyes 2/7, Reduced oral intake 1/7

Hb 9.8TWBC 32.3 Plt 917

What is the cause of thrombocytosis ?

Kawasaki Disease• Ultrasound 20/12/12 No sonographic evidence

of hydrops of gallbladder• ECHO = Giant aneurysm noted over coronary

arteries

Establishing the cause requires clinical featureshaematological parametersbone marrow aspirate, trephine biopsy, morphological featuresPresence or absence of clonal genetic abnormalities

Reactive Myeloproliferative disease

Asplenia

Famillial / idiopathic Thrombocytosis

Negative Negative Negative

Summary - thrombocytosis

Thank you