Common Haematological Problems In Children -...
Transcript of Common Haematological Problems In Children -...
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