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Flashcards in Haematology Deck (47):
1

What is the management for sickle cell disease?

1. Early aggressive treatment for infections with prophylactic antibiotics and appropriate vaccinations
2. Folate supplement
3. Hydroxyurea: to increase HbF concentration
4. Long-term follow-up
     >> Transcranial doppler: stroke risk assessement
     >> Starting at 10 years of age: Annual fundoscopy
     >> Biannual screening for pulmonary hypertension
     >> Biannual urinalysis
5. Chronic transfusion

2

What are the 3 underlying pathophysiological causes of physiological anemia of infancy?

1. HbF has 2/3rd of the half-life of HbA
2. Increased oxygen outside the uterus and the increased oxygen affinity of HbF render less RBCs/Hb necessary after birth
3. Rapid expansion of plasma volume in a newborn

>> Hb 18g/dL at birth of a term infant
>> Hb 8-11g/dL at 2 months of a term infant
>> Reticulocyte count at birth: 5%
     Reticulocyte count at 1 week of life: 1%

3

What are the complications of Hemophilia A?

- Anti-FVIII antibodies: "inhibitors" -- present in 5-20% of patients
- Transfusion-related complications
   >> Line infection
   >> Symptoms of iron overload
         :: Liver cirrhosis
         :: Diabetes (pancreatic deposition)
         :: Cardiomyopathy
         :: Arthritis
         :: Testicular failure
         :: Slate grey discoloration of the skin
- Problems with vascular access for transfusion

4

What is the treatment for B-thalassemia major?

- Life-long regular transfusion with Fe chelation +/- folate supplements
   >> Signs of iron overload
         :: Liver cirrhosis
         :: Cardiac myopathy
         :: Diabetes mellitus from pancreatic deposition
         :: Infertility (testicular failure) and delayed growth from pituitary deposition
         :: Hyperpigmentation of the skin
         :: Arthritis
   >> Chelating agents
         :: Deferoxamine (SC infusion)
         :: Deferasirox (PO)
         :: Deferiprone
- Hydroxyurea (in thalassemia intermedia): to increase HbF levels
- Splenectomy
- Bone Marrow Transplant

5

What are the long-term complications of sickle cell disease?

- Growth delay
- Bone abnormalities, eg. AVN
- Gallstones
- Retinopathy
- Restrictive lung diseases
- Cardiomyopathy with pulmonary hypertension

6

What can DDAVP be used to treat?

- Central diabetes insipidus
- Nocturnal enuresis
- Hemophilia A
- vWF disease

- Uremic platelet dysfunction

>> DDAVP helps release vWF and thus factor VIII

7

What are the reference numbers of anemia in childhood?

Newborn: ~18g/dL
3 months: ~8-10g/dL
Adult female: ~12-16g/dL
Adule male: ~14-18g/dL

8

What are the CBC reference ranges for neonates?

Hb: 14-21g/dL
WBC: 10-25 x 10^9/L
PLT: 150-400 x 10^9/L

Therefore, Hb and WBC levels are elevated in normal neonates, while the PLT levels should be similar to those of normal adults.

9

What is the typical age at presentation of iron deficiency?

6 months - 3 years

>> Iron stores last ~6 months in term infants
>> Iron stores last ~2-3 months in preterm infants

10

What is usually the first sign of vaso-occlusive crisis in sickle cell disease?

Dactylitis

11

What are the features of lead poisoning?

L: Lead lines on gingivae and epiphyses of big long bones on X-ray
E: Encephalopathy; Erythrocyte basophilic stippling
A: Anemia (microcytic); Abdominal colic
D: Drops of the wrist and foot

12

What is the Mentzer index?

= MCV/RBC count

- Thalassemia: <13
- Iron-deficiency anemia: >13

13

What are the three types of crises in sickle cell disease?

- Vaso-occlusive crisis
- Aplastic crisis
- Acute splenic sequestration

14

What are the possible causes of bleeding tendencies in children?

Platelet problem
- Quantitative
   >> Increased consumption
        :: DIC
        :: Giant hemangioma
        :: Hypersplenism
   >> Increased destruction
        :: ITP
        :: TTP/HUS
        :: HIT
   >> Decreased production
        :: Aplastic anemia
        :: Marrow infiltration
        :: Leukemia/lymphoma
        :: Drugs
- Qualitative
   >> Congenital
        :: Bernard-Soulier
        :: Glanzmann's thromboasthenia
   >> Acquired
        :: Drugs (ASA, NSAIDs, alcohol)
        :: Uremia

von Willebrand disease

Coagulation pathway problem
- Congenital
   >> Hemophila A
   >> Hemophilia B
- Acquired
   >> Vit K deficiency -- hemorrhagic disease of newborn
   >> Liver disease
   >> DIC Vascular problem
- Congenital
   >> Connective tissue disorders
         :: Ehlers-Danlos syndrome
         :: Marfan syndrome
   >> Osler-Weber-Rendu syndrome
- Acquired
   >> Henoch-Schonlein Purpura
   >> Cushing's syndrome
   >> Infections
   >> Drugs
   >> Purpura simplex

15

What are the drugs to avoid in a G6PD patient?

Hemolysis IS PAIN.

I: Isoniazid
S: Sulfonamides
P: Primaquine
A: Aspirin
I: Ibuprofen
N: Nitrofurantoin

16

What is the peak age of onset for immune thrombocytopnic purpura (ITP)?

2-6 years (2-10 years)

17

What is the most common cause of thrombocytopenia in childhood?

Immune thrombocytopenic purpura

18

What are the presenting features of ITP?

Usually 1-3 weeks after viral illnesses (URTI, chickenpox)

- Sudden onset of petechiae, purpura and epistaxis
- Otherwise well
- No lymphadenopathy
- No hepatosplenomegaly

CBC
- PLT low
- Hb normal
- WBC normal

19

What are the possible complications of ITP?

- GI bleeding
- Intracranial hemorrhage (<10 PLT) --- Chance: <0.5%

20

What are the indications for a bone marrow aspirate in ITP?

- >1 cell line abnormal
- Hepatosplenomegaly present
- Before steroid treatment

>> Steroid treatment can mask the features of ALL and thus further delay diagnosis and treatment

21

What is the management for ITP?

1. Conservative
    - Spontaneous recovery in >70% within 3 months
    - Avoid contact sports and NSAIDs
2. Medical: usually gum bleeding/PLT <20
    - IVIG
    - IV prednisone
    - Anti-D antibodies
3. Surgical: for life-threatening bleeding
    - Additional platelet transfusion
    - Emergency splenectomy

22

What is the definition of chronic ITP?

PLT remains low 6 months after diagnosis

Management for persistent bleeding affecting daily life:
- Rituximab
- TPO factors
- Screening for SLE
- Splenectomy

23

How do we classify hemophilia severity?

Mild: 5-40% of normal factor VIII levels

Moderate: 1-5% of normal factor VIII levels

Severe: <1% of normal factor VIII levels

24

What is the mode of inheritance of hemophilia A/B?

X-linked recessive

25

What is the management of hemophilia A?

Active bleeding
- Recombinant FVIII concentrate
   >> Aim for 30% in minor bleeds
   >> Aim for 100% for major OT or life-threatening bleeds
         :: Maintain at 30-50% for 2 weeks
         :: Regular infusion of factor concentrate (8-12 hourly)

Prophylaxis for severe hemophilia
- Aim for baseline >2%
- Regular recombinant factor concentrate infusion
- 2-3 times per week, starting at 2-3 years of age

Mild hemophilia
- DDAVP: promotes release of VIII-Ag

26

How can we manage inhibitors to FVIII concentrates in Hemophila A patients?

- Very high doses of FVIII recombinant concentrates
- Activated FVII recombinant concentrate

27

What are the causes of anemia in children?

Decreased production
- Red cell aplasia
   >> Congenital
         :: Aplastic anemia
         :: Diamond-Blackfan syndrome
         :: Fanconi's anemia
   >> Acquired
         :: Parvovirus B19 infection
         :: Acquired aplastic aenmia
         :: Leukemia
         :: Transient erythroblastosis of childhood
- Ineffective erythropoiesis
   >> Iron deficiency
   >> B9/B12 deficiency
   >> Chronic inflammation: JIA, IBD
   >> Chronic renal failure
   >> Myelodysplasia
   >> Lead poisoning

Increased destruction
- RBC enzyme defect: G6PD deficiency
- RBC membrane defect: hereditary spherocytosis/elliptocytosis
- Hemoglobulinopathy: thalassemia, sickle-cell disease

Blood loss
- Fetomaternal bleeding
- Chronic GI blood loss
- Inherited coagulopathies
   >> vWF disease
   >> PLT dysfunction
   >> Coagulation dysfunction
   >> Vasculitis

28

How does one approach anemia in children?

By MORPHOLOGY

Microcytic
- Iron deficiency
- Thalassemia
- Anemia of chronic disease
- Sideroblastic anemia
- Lead poisoning

Normocytic
- High reticulocyte count (destruction problem)
   >> Bleeding
   >> Hemolysis
        :: Enzyme defect: G6PD deficiency
        :: Membrane defect: spherocytosis
        :: Other hemogloblinopathies: sickle cell
        :: Immune causes
            ~ Drugs
            ~ Infection: B19, malaria
        :: Microangiopathic anemia
            ~ DIC
            ~ HUS/TTP

- Low reticulocyte count (production problem)
   >> Pancytopenia
        :: Aplastic anemia
        :: Myelodysplastic syndromes
        :: Leukemia
        :: Amyloidosis/sarcoidosis
        :: TB
        :: Bone marrow-suppressive drugs: chemotherapy
   >> Isolated anemia
        :: Anemia of chronic disease
        :: Renal disease (decreased EPO production)
        :: Liver disease

Macrocytic
- Megaloblastic
   >> B12 deficiency
   >> Folate deficiency
   >> Drug-induced
        :: Methotrexate
        :: Sulfonamides
        :: Chemotherapy
- Non-megaloblastic
   >> Liver disease
   >> Hypothyroidism
   >> Reticulocytosis

29

What is the chronological order of response to iron supplement in iron-deficiency anemia?

- Increased reticulocyte count in 2-3 days
- Increased hemoglobin levels in 4-30 days
- Iron store repletion in 1-3 months

30

What are the complications of iron deficiency?

- Developmental delay if untreated
- Angular cheilitis
- Glossitis
- Koilonychia

31

Which inflammatory mediator is involved in anemia of chronic disease?

IL-6 with increased hepcidin

32

What are the causes of sideroblastic anemia?

Congenital
- X-linked hereditary
- Treat with high-dose vitamin B6

Acquired
- Idiopathic: preleukemic phenomenon (10% to AML)
- Reversible
   >> Drugs
        :: Isoniazid
        :: Chloramphenicol

   >> Alcohol
   >> Lead
   >> Zinc
   >> Hypothryoidism

33

What are the causes of basophilic stippling in RBCs on a peripheral blood smear?

TAIL

T: Thalassemia
A: Anemia of chronic disease
I: Iron deficiency
L: Lead poisoning

34

What are the causes for target cells on a peripheral blood smear?

HALT

H: HbC disease, sickle cell disease
A: Asplenia
L: Liver disease
T: Thalassemia

35

What are the causes for aplastic anemia in children?

Congenital
- Fanconi's anemia
- Schwachman-Diamond syndrome

Acquired
- Idiopathic
- Post-viral infection
   >> Parvovirus B19
   >> EBV
   >> HBV, HDV, HEV
   >> HHV-6
   >> HIV
- Drugs
   >> Chloramphenicol
   >> Phenylbutazone
   >> Chemotherapy
- Toxins
- Ionizing radiation
- Autoimmune
   >> SLE
   >> Graft-versus-host disease

36

What are the laboratory findings in hemolytic anemia?

- Increased reticulocyte count
- Decreased haptoglobin
- Increased unconjugated bilirubin
- Increased LDH
- Increased urobilinogen

37

What are the clinical features of B-thalassemia major?

Onset at 6-12 months >> HbF to HbA at 3-6 months

- Severe anemia and jaundice
- Maxillary overgrowth
- Frontal bossing
- Gross hepatosplenomegaly
- Skull X-ray: hair-on-end/crew-cut appearance
- Pathological fractures common
- Pigmented gallstones

38

What is the mode of inheritance of thalassemia?

Autosomal recessive

39

What are the complications of iron overload?

- Cardiac failure
- Liver failure/cirrhosis
- Diabetes
- Infertility
- Growth failure
- Arthritis
- Skin pigmentation

40

How many b-chain genes do we have?

2 on chromosome 11

41

How many a-chain genes do we have?

4 on chromosome 16

42

What are the different types of a-thalassemia?

1 defective gene: clinically silent (trait)

2 defective genes: normal Hb, decreased MCV (trait)

3 defective genes: HbH (b4) disease

4 defective genes: Hb Barts (gamma4) disease - hydrops fetalis;
incompatible with life

43

What is a specific investigation for vW disease?

Ristocetin-induced platelet aggregation test: decreased in von Willebrand disease

44

What is the mode of inheritance of von Willebrand disease?

Mostly autosomal dominant

45

What is the management for von Willebrand disease?

- Desmopressin
- Tranexamic acid

- High-purity FVIII concentrate
- Conjugated estrogens to increase vWF levels

46

What are the common presenting features of hemophilia A?

Five Hs

- Head hemorrhage
- Hematochezia
- Hematuria
- Hemarthosis
- Hematomas

47

What are the types of vW disease?

Type I: mild quantitative disease (~75%)
Type II: qualitative disease (~20-25%)
Type III: severe quantitative disease (rare)