Pediatric hematology

Done by Dr.Mohammad Hamadneh

 ‫اﻟﻨﺒﻴﻴﻦ‪ ،‬وﺣﻔﻆ اﻟﻤﺮﺳﻠﻴﻦ‬
‫ّ‬ ‫ﻓﻬﻢ‬ ‫أﺳﺄﻟﻚ‬ ‫ﻲ‬ ‫ّ‬
‫إﻧ‬ ‫اﻟﻠﻬﻢ‬
‫ّ‬
‫ﺑﻴﻦ‪،‬اﻟﻠﻬﻢ اﺟﻌﻞ أﻟﺴﻨﺘﻨﺎ ﻋﺎﻣﺮة‬
‫ّ‬ ‫اﻟﻤﻘﺮ‬
‫ّ‬ ‫واﻟﻤﻼﺋﻜﺔ‬
‫ﺑﺬﻛﺮك‪ ،‬وﻗﻠﻮﺑﻨﺎ ﺑﺨﺸﻴﺘﻚ‪ ،‬وأﺳﺮارﻧﺎ ﺑﻄﺎﻋﺘﻚ‪ّ ،‬‬
‫إﻧﻚ‬
‫ﺷﻲء ﻗﺪﻳﺮ‪ ،‬وﺣﺴﺒﻲ ا وﻧﻌﻢ اﻟﻮﻛﻴﻞ‬ ‫ٍ‬ ‫ّ‬
‫ﻛﻞ‬ ‫‪».‬ﻋﻠﻰ‬
 Done by :
Dr. Mohammad Ali Hamadneh.
- MD-Azerbaijan medical university graduate.
- Pediatric specialist /MOH: Prince Hamza Hospital.
-Jordanian Board certified in Pediatrics
and neonatology.
-MRCPch part 1 and 2 in pediatrics.
- Approved by the JMA as a teaching member for
junior doctors who are applying for the JMC general
exam in Pediatrics and Neonatology (2020).
- Author of Dr.Hamadneh’s essential of pediatrics
and neonatology book.
 Intrauterine hematopoesis
• Passes into 3 stages :
• Mesoblastic hepatic myeloid

• yolk sac liver bone marrow

• 1-8 GW 8-24GW 24- onwards

 Active bone marrow contain
• Erythroid cells ----- give ----- RBCs .
• Myeloid cells -------- give ----- WBCs .
• Megakaryocytic cells ----- give--- platelets .
 Hemoglobin Hb composition
• Hb molecule is composed of HEME groups ( ferrous iron containing
) attached to 4 polypeptide chains which define the type of
hemoglobin .
• ------------------------------------------------------------------
• Emberyonic Hb Fetal Hb adult Hb
• Gower 1 Hb F Hb A
• Gower 2 Hb A2
• portland
Normal human hemoglobins
• Intrauterine at birth >6months
• Hb F dominant 70% < 0.5%
• Hb A ------ 30% 97%
• Hb A2 -------- trace 2.5%
• ---------------------------------------------------------------------

• At the 3rd-6th month – normal switch from gamma to beta chan

production occurs …
 Complete blood count /CBC
• WBC : NEUTROPHILS % , LYMPHOCYTES % , MONOCYTES , EOSINOPHILS ,
BASOPHILS .
• RBC :
• HB
• HCT : : this is the percent of RBCs in 100 ml blood = 40-60%
• MCV = size
• MCHC= calculation of the amount of HB /unit volume in a single RBCs
• MCH = quantity ( MCV + MCHC )
• RDW ( measures the amount of RBC variation in volume and size )
• PLATETET
• MPV
 AMEMIA
• It is reduction of hemoglobin and/or RBCs count below average
value for age and sex interfering with O2 carrying capacity of the
blood ……

• Symptoms Signs
• Anorexia-weight loss pallor
• Easy fatigability tachycardia
• headache-tinnitus-sweating murmur
• Fainting HF
• Normal” hemoglobin and hematocrit vary with age and
sex race.
 Causes of anemia
1-Decrease production .

2-Increase destruction .

3- Hemorrhagic anemia ( acute or chronic

hemorrhagre ).
 Anemia due to decreased production
1-Decrease erythroid cells in the BM ( BM failure ) :
A-Pure red cell anemia . B- Aplastic anemia .
C-BM infiltration ( leukemia ).
2-Decrease production despite normal RBCs precursors :
Anemia of chronic disease : chronic infection , inflammation or renal
failure .
3-specific factor deficiency :
Iron, folic acid ,B12 or B6 -----
 Anemia due to increase destruction
• 1-Intracorpuscular :

• Membrane defect hemoglobinopathy enzymatic defect

• spherocytosis alph -beta thalassemia G6PD deficiency

• SCD pyruvate kinase def

2-extracorpuscular :
Immunologic non immunologic
Coombs +ve Coombs -ve
• Isoimmune autoimmune MAHA
• HA of the NB active antibodies HUS/DIC/RVT/
ABO intracardiac prosthesis
sepsis
wilson disease
hyperslenism
heavy metals
 Bone marrow failure
• 1-trillineage failure
Congenital : Fanconi anemia .
Acquired : Idiopathic , Secondary .
• 2-one cell line failure:
• 1-Red cell :
• Congenital : Diamond blackfan anemia
• Acquired :idiopathic or secondary :drugs/PB19/infection
• 2-White cells :
1-Schwashman Diamond syndrome .
2-kostman disease .
3-Platelets :
1-TAR syndrome : thrombocytopenia absent radii syndrome .
 Congenital pure red cell anemia
diamond blackfan anemia
AD or AR disorder.
decreased sensitivity of erythroid cells to erythropoitin leading to hypoplasia of
RBC precursors.
• Clinical picture :
• Anemia 2nd – 6th months .
• CHD /abnormal thumb( triphalangeal )/short stature /craniofacial
malformations/GU …
• CBC : macrocytosis / increased Hb F and ADA / reticulopenia / normal
platelets and WBCs .
• TTT : steroid + PRBCs transfusion with deferoxamine . /HSCT …
 Acquired pure red cell anemia
• 1- Auto antibodies against erythroid cells .
• 2-Parovirus B19 .
• 3-Transient erythroblastopenia of childhood :
• -anemia 6 months – 6years .
• -RBCs volume , HbF, ADA are normal for age .
• -no anomalies .
• -No treatment --- recover within 2 months …
 Aplastic anemia
• Decrease or absence of blood forming elements in bone marrow with
peripheral pancytopenia ..
• 1-Congenital : Fanconi anemia .
• 2-Acquired : Idiopathic (70% )
secondary (30%) :
Iraddiation / infection/drugs /
Pathogenesis : altered stem cells proteins in the bone marrow by drugs or
infection Stimulates T lymphocytes secretes interferon gamma
suppress stem cells pancytopenia ….
Clinical picture : Anemia + Thrombocytopenia +Leukopenia
 Fanconi anemia
• AR disorder with new mutations …..
• Pancytopenia from infancy till the age of 12 years .
• Clinical picture : short stature/skin pigmentation- café-au lait spots /skeletal :
absent or hypoplastic thumb –microcephaly
• Labs : pancytopenia/elevated HbF/ reticulocytopenia.
• TTT : steroid and androgens /BMT .
• In Fanconi and Diamon Blackfan anemia there is increase risk of malignancy
specially AML .
 Iron deficiency anemia
• Most of dietary iron is present in ferric state .
• Iron changes to ferrous by combined action of HCL& viatmin C .
• Only 10% of dietary iron is bound to serum transferrin and stored as ferritin .
• Causes :
• Store depletion in term infant at age 6-9 months..
• Diet (cows milk protein, malnutrition) .
• Blood loss .
• Infection with hookworm, Plasmodium, and Helicobacter pylori.
• Growth spurt .
• menstrual blood loss in adolescent girls .
• Signs and symptoms in iron deficiency anemia :
- CNS: fatigue, irritability .
- Cardiac: increased cardiac output, cardiac hypertrophy .
- Dry skin, thin hair, pallor, nail ridges .
- GI: Anorexia, poor weight gain, pica, atrophic glossitis
- LABS :
- HB /MCV/SF/SERUM IRON /RETIC/RBC : decreased .
- RDW/TIBC : increased .
- On blood film : microcytic /hypochromic .
- Treatment : iron therapy / treat the underlying cause .
 Response to iron therapy
• Time after iron Response
administration
• By 1 day
st
increase appetite /low irritability
• By 2nd day erythroid hyperplasia in the BM
• By 3rd day reticulocytosis ( 5-7 d)
• Y 1st month increase Hb
• 1- 3 months repletion of stores
 Anemia of chronic disease
• Anemia of inflammation which occurs in infection,malignancies ,
autoimmunity ,CKI …..
• Why ??: elevated levels of cytokines such as interleukin- 1 that may
increase the macrophages ability to ingest and destroy erythrocytes.

• LABS : normochromic normocytic anemia , reticc normal , low serum

iron , normal tarnsferrin , serum ferritin can be elevated .
• Treat the underlying cause .
 Physiologic Anemia of Infancy
• At term, cord blood hemoglobin is 16.8 g/dL (14-20 g/dL) .
• hemoglobin levels in very-low birthweight (VLBW) infants are 1-2 g/
dL below those in term infants .
• A “physiologic” decrease in hemoglobin content is noticed at 8-12
wk in term infants (hemoglobin, 11 g/dL) and at approximately 6 wk
in premature infants (7-10 g/dL).
• Pathogenesis : intrauterine hypoxia stimulates production of
erythropoietin with subsequent increasing in the HB .
• After birth the baby will get more oxygen leading to decrease
production of erythropoietin leading to decreasing in the HB .
• No treatment .
 Megaloblastic anemai
• Most cases of childhood megaloblastic anemia result from a deficiency of folic
acid B9 or vitamin B12 (cobalamin) .
• Anemia with megaloblasts in the BM and macrocytes in the peripheral blood .
• There is often an associated thrombocytopenia & leukopenia .
• Causes of B9 deficiency : food , phenytoin, valproate , methotrexate , prematures , goat
milk .
• Vitamins B12 ( cobalamin ) :
• Causes of vitamin B12 deficiency :
• Inadequate dietary intake of cobolamin (nutritional, resulting from low
Cbl levels in the breast milk of B12-deficient mothers) .
• Lack of intrinsic factor IF (pernicious anemia ) .
• Impaired intestinal absorption of IF-Cbl (celiac ,IBD, previous surgery,
Pancreatic insufficiency ).
• Absence of vitamin B12 transport protein .
• Infants born to mothers with deficiency will have vitamin B12 deficiency wthin 5
months of life
• CLINICAL MANIFESTATIONS:
• Weakness, lethargy, feeding difficulties, failure to thrive,and irritability.
• Other common findings include pallor, glossitis, vomiting, diarrhea, and
icterus.
• Neurologic symptoms can include paresthesia,sensory deficits ,
hypotonia , seizures developmental delay, developmental regression, and
neuropsychiatric changes.
 Anemia due to increase destruction/G6PD deficiency
• X-linked . Some with new mutations .
• Pathogenesis : G6PD is a key enzyme of Hexose Mono phosphate
(HMP ) which produce reduced glutathione which protects the RBCs
against oxidizing agents oxidation of Hb .
• Oxidizing agents : fava beans ( favism ) /viral or bacterial / sulpha/
chloramphenical/nitrofurantoin/primaquine –anit malarial .
- Favism: Acute life-threating hemolysis caused by ingestion of fava
beans .
• Genetic variants :
• Types A+/ B+ /A-/canton type/mediterranean type .
• Blood film : Heinz bodies .
 Chronic hemolytic anemia
• Chronic hemolytic anemia is characterized by :
• Anemia .
• Jaundice ( indirect hyperbilirubinemia ) .
• Hepatosplenomegaly .
• Skeletal changes ( macrocephaly +prominent maxillae ) – due to
hyperactive bone marrow .
• Gall bladder stones ( calcium bilirubinate stones ) .
• Retic count is always high .
• Coombs test : can be either positive or negative according to the
cause .
 Hereditary spherocytosis
• AD disorder .
• Some with New mutations .
• Due to deficiency of RBCs wall skeleton proteins : alpha –beta spectrin or
Ankyrin-1 or band 3 or protein 4.2 .
• Anemia mild to moderate .

• In erythroblastopenic crisis Hb may drop to 2 – 3g/dl .

• MCV usually decreased, MCHC raised.
• Reticulocytosis .
• Coomb’s test negative .
• Do osmotic fragility test to confirm the diagnosis .
• Indication of splenectomy in HS :
• Severe anemia / frequent crises / poor growth/cardiomegaly .
 Thalassemia
• AR disorder due to defective globin chain production .
• 1- Alpha thalassemia chromosome 16
• A- silent carrier .. < 3 % Barts Hb .
• B- Alpha thalassemia trait . . 3-8% Barts Hb
• c- Hemoglobin H disease . 15-30 % Barts Hb
• D-fetal hydropes . Dominant Barts Hb
2-Beta thalassemia chromosome 11
A- Beta thalassemia trait :
Hb A2 = 3-6% in 90% .
Hb F 1-3% in 50 %
B-Beta thalassemia major :
• B0 : Hb F 98% / Hb A2 2% / HbA =0 .
• B+ : some Hb A .
• Anemia :Starts at the age of 6 months when switch from gamma to
beta chain production normally occur .
• Features of hemosiderosis :
• Skin- bronzed color / heart – cardiomyopathy /pancreas – DM /liver
–cirrhosis / pituitary-hypogonadism and growth failure .
• BF= target cells ….
 Indications of splenectomy
• Hypersplenism suggested by :
• Increasing need for transfusion > 50% than usual for more than 6
months .
• Annual PRBCs > 250 ml/kg/year .
• Severe leucopenia or thrombocytopenia .
• Huge spleen with pain or pressure symptoms.
• Preferably after the 5 year .
th

• Immunize the patient against : H.influenza , pneumococci and

meningococci (encapsulated )
• After splenectomy : penicillin .
 Sickle cell disease
• AR disorder results from single amino acid substitution in the
number 6 position of the beta chains ( valine for glutamic ) resulting
in Hb S .
• Hb S cant withstand hypoxia leading to intravascular sickling with
subsequent :
• 1-aggregation leads to vascular oclusion .
• 2-trapping and hemolysis in the reticuloendothelial system in the
spleen and liver …
• Anemia/aplastic crises /CVA/painful crises/acute chest syndrome /
priapism/retinopathy/gallbladder/renal/cardiomyopathy/infection/
leg ulceration------
 Auto immune hemolytic anemia
• Hemolytic anemia due to circulation antibodies against own RBCs .
• Warm type Cold type
IgG IgM
• Active at T 37 below T37
• Macrophages /spleen kupfer cells/liver
• Causes : idiopathic or secondary to : infection such as : CMV/HBV/
EBV. /SLE/lymphoma/MMR/DPT.
• Paraxysmal cold hemoglobinuria : due to Donath landsteiner
antibody ( IgG ) …
• Splenectomy is effective in the warm type .
 Hemostasis
• 1- vascular factor : via vasoconstriction at the site of bleeding +
damaged endothelium activate F XII .
• 2-Platelets :
• A- adhesion to exposed collagen fibers ( VWF ) .
• B- aggregation ( adenosine diphosphate &thromboxane ) .
• C- release of :
• thromoxane A2 – platelet aggregation .
• Serotinine – vasoconstriction .
• Platelet factor 3 – enhance clotting .
• Thrombasthinine – clot retraction .
• All clotting factors are formed in the liver except F VIII formed by
endothelial cells .
• Vitamin K dependent factors : ( II – VII-IX-X ) 1972 .
• Coagulation inhibitors : antithrombin III / protein C / protein S .
• Factor : VII (extrinsic pathway ) .
• Factors : VIII /IX/ XI /XII ( intrinsic pathway ) .
• Factors : I /II /V /X (common pathway ) .
 Prolonged PT, PTT and Bleeding time
PT PTT BT PT+PTT

VII (extrinsic VWF VWF deficiency DIC

pathway )
Vit K deficiency VIII /IX/ XI /XII ( platelet disorders Vit K deficiency
intrinsic pathway )
warfarin heparin aspirin Heparin + warfarin

I /II /V /X I /II /V /X I /II /V /X

(common pathway
)
liver disease liver disease
 THROMBOCYTOPENIA
• The normal platelet count is 150–450 × 109 per liter.
• Thrombocytopenia refers to a reduction in platelet count to
150–450 × 109 per liter .
• Causes :
• 1- decreased production on either a congenital or an acquired
• 2- sequestration of the platelets within an enlarged spleen or
other organ,
• 3- increased destruction of normally synthesized platelets on
either an immune or a nonimmune basis .
 Autoimmune thrombocytopenic purpura
• 1-4 wk after exposure to a common viral infection, an autoantibody directed against the
platelet surface develops with resultant sudden onset of thrombocytopenia.
• The peak age is 1-4 yr, although the age ranges from early in infancy to the elderly.

• Pathogenesis:
• The exact antigenic target for most such antibodies in most cases of childhood acute ITP
remains undetermined.
• Although in chronic ITP, many patients demonstrate antibodies against the platelet
glycoprotein complexes, αIIb-β3 and GPIb .
• After binding of the antibody to the platelet surface, circulating antibody-coated platelets
are recognized by the Fc receptor on splenic macrophages, ingested, and destroyed.

• Epstein-Barr virus-related ITP is usually of short duration and follows the course of
infectious mononucleosis.
• HIV-associated ITP is usually chronic.
• In some patients ITP appears to arise in children infected with Helicobacter pylori or rarely
following vaccines Such as MMR .
CLINICAL MANIFESTATIONS:
• sudden onset of generalized petechiae and purpura.
• be bleeding from the gums and mucous membranes, particularly with
profound thrombocytopenia (150–450 × 109 per liter).
• Splenomegaly, lymphadenopathy, bone pain, and pallor are rare.
• Classification system characterize the severity of bleeding in ITP on the
basis of symptoms and signs, but not platelet count:
• 1. No symptoms .
• 2. Mild symptoms: bruising and petechiae, occasional minor epistaxis,
very little interference with daily living
• 3. Moderate: more severe skin and mucosal lesions, more troublesome
epistaxis and menorrhagia
• 4. Severe: bleeding episodes—menorrhagia, epistaxis, melena—requiring
transfusion or hospitalization, symptoms interfering seriously with the
quality of life .
• Outcome :
• In 70-80% of children who present with acute ITP, spontaneous
resolution occurs within 6 mo.
• Therapy does not appear to affect the natural history of the illness.
• Fewer than 1% of patients develop an intracranial hemorrhage.
• Approximately 20% of children who present with acute ITP go on to
have chronic ITP.
• The outcome/prognosis may be related more to age, as ITP in
younger children is more likely to resolve whereas the development
of chronic ITP in adolescents approaches 50%.
• LABORATORY FINDINGS :
• normal or increased platelet size .
• In acute ITP, the hemoglobin value, white blood cell (WBC) count,
and differential count should be normal.
• Hemoglobin may be decreased if there have been profuse
nosebleeds or menorrhagia.
• Bone marrow examination shows normal granulocytic and
erythrocytic series, with characteristically normal or increased
numbers of megakaryocytes .
• Treatment :
• platelet transfusion in ITP is usually contraindicated unless life-
threatening bleeding is present.
• 1. No therapy other than education and counseling of the family
and patient for patients with minimal, mild, and moderate symptoms,
as defined earlier.
• 2. A single dose of IVIG [intravenous immunoglobulin] (0.8-1.0 g/kg).
• 3. Prednisone.
• 4. Intravenous anti-D therapy : For Rh-positive patients .
• The role of splenectomy in ITP should be reserved for 1 of 2
circumstances.
• The older child (≥4 yr) with severe ITP that has lasted >1 yr (chronic
ITP) and whose symptoms are not easily controlled with therapy is a
candidate for splenectomy.
• Note : the risk of recurrency after splenectomy in ITP is up to 30 % .
 Platelet Function Disorders
Congenital :
• Glanzmann thrombasthenia .
• Bernard-Soulier syndrome .
-Acquired :
• systemic illnesses : liver disease, kidney disease (uremia).
• drugs : acetylsalicylic acid (aspirin).
• other nonsteroidal antiinflammatory drugs, valproic acid, and
high-dose penicillin.
 Bernard-Soulier syndrome/ Glanzmann thrombasthenia
• Bernard- Soulier syndrome : Deficiency of glycoprotein Ib complex
(VWF receptor).
• Glanzmann thrombasthenia : deficiency of glycoprotein IIb-IIIa (the
fibrinogen receptor).

• Both disorders are inherited as autosomal recessive pattern .

• The platelet count is always normal ( but in Bernard- Soulier
syndrome the platelets can be low And giant in shape ).
• Bleeding time : prolonged .
• The diagnosis is confirmed by flow cytometric analysis of the
patient’s platelet glycoproteins .
 Von Willebrand Disease
• von Willebrand disease (VWD) is the most common inherited bleeding disorder .
• Autosomal dominant .
• VWF serves to tether platelets to injured subendothelium via binding sites for
platelets and for collagen.
• VWF serves as a carrier protein for factor VIII (FVIII) .
• Type 1 VWD is the most common type .
• Type 3 VWD is the most severe type .
• Clinical presentation: mucocutaneous bleeding (excessive bruising, epistaxis, men-
orrhagia, postoperative bleeding)
• Labs : increased bleeding time and PTT .
• Quantitative assay for vWFAg, vWF activity (ristocetin cofactor activity), plasma
factor VIII, determination of vWF structure and platelet count
• Treatment : need to increase the level of vWF and factor VIII .
• Most with type 1 : desmopressin induces release of vWF .
• For types 2 or 3 : need replacement → plasma-derived vWF-containing concentrates
with factor VIII .
 Hemophilia
• Hemophelia A ( classic hemophelia ) 85% = FVIII deficiency .
• F VIII deficiency = F VIII a and F VIII c
• It is deficiency in F VIIIc ….
• Mild moderate severe
• F VIIIc <1% 1-5% 6-3-%
• Hemophelia B ( chrismas disease ) = F IX deficiency .
• Hemophelia C = F XI deficiency .
• Parahemophelia = F V deficiency .
• Vascular hemophelia ( VWD ) : AD
• It is essential for platelet adhesion and it is a carrier of F VIII .
• 2% of neonates with hemophilia sustain intracranial hemorrhages.

• 30% of male infants with hemophilia bleed with circumcision.

• Easy bruising, intramuscular hematomas, and
hemarthroses(induced by minor trauma or occur spontaneously ) .
• LABORATORY FINDINGS :
• 1- prolonged PTT .
• 2- platelet count, bleeding time, prothrombin time, and
thrombin time) are normal.
• 3-The specific assay for factors VIII and IX will confirm the
diagnosis of hemophilia.
• Treatment :
• 1-recombinant factor VIII (FVIII) or recombinant factor IX (FIX) .
 ‫دﻋﺎء ﺑﻌﺪ اﻟﻤﺬاﻛﺮة‬

‫اﻟﻠﻬﻢ إﻧﻲ أﺳﺘﻮدﻋﻚ ﻣﺎ ﻗﺮأت وﻣﺎ ﺣﻔﻈﺖ وﻣﺎ‬

‫ﺗﻌﻠﻤﺖ‪ ،‬ﻓﺮده ﻋﻨﺪ ﺣﺎﺟﺘﻲ إﻟﻴﻪ‪ ،‬إﻧﻚ ﻋﻠﻰ ﻛﻞ ﺷﻲء‬
‫‪.‬ﻗﺪﻳﺮ‪ ،‬ﺣﺴﺒﻨﺎ ا وﻧﻌﻢ اﻟﻮﻛﻴﻞ‬
Done by :
Dr. Mohammad Ali Hamadneh.
- MD-Azerbaijan medical university graduate.
- Pediatric specialist /MOH: Prince Hamza Hospital.
-Jordanian Board certified in Pediatrics
and neonatology.
-MRCPch part 1 and 2 in pediatrics.
- Approved by the JMA as a teaching member for
junior doctors who are applying for the JMC general
exam in Pediatrics and Neonatology (2020).
- Author of Dr.Hamadneh’s essential of pediatrics
and neonatology book.