background image

1

 

 

L1                                                Pediatric                                       D. Ali  

Sickle cell anemia 

Definition

: formation of abnormal globin chain (abnormal B chain) 

Incidence:

 common in black race 

 Genetics:

 

Defect in B chain gene show mutation that result in replacement of amino acid number 6 in the 
chain (glutamic by valine) 

  Heterozygous : sickle cell trait : only 20-40 % Hb S. only it present with vaso - 

occlusive crisis with severe hypoxia and resistant to infection with falciparum malaria  

  Homozygous ( Hb SS ) : sickle cell anemia 

Pathogenesis: 

A single amino acid substitution in beta chain result in different Hemoglobin ( Hb S ) which is 
less soluble than Hb A . with hypoxia , deoxygenated Hb S polymerize inside RBCs , distortion 
of shape ( sickle shaped ) result in easy destruction & occlusion of blood vessels 

  

Clinical picture 

Onset:

 by the2nd half of the 1st year. The course is less severe than thalassemia  

Complication

: no Hypersplenism but Autosplenectomy usually develop 

Investigation

 Prove anemia & Hemolysis 

Blood film:

 sickling characteristic sickle RBCs in blood film under low O2 tensions  

  Hb electrophoresis : Hb S is present ( > 90% ) no Hb A 
  Genetic study of the affected gene Parents : Hb S 20-40% Hb A 60-80% 

 


background image

2

 

 

Crisis in chronic Hemolytic anemia 

Sequestration crisis 

  Cause : for unknown cause , large amount of blood become acutely pooled in spleen 
  Clinical picture : shock , marked enlargement of spleen and liver & acute anemia 
  Treatment : I .V fluids - packed RBCs transfusion - Splenectomy for recurrent cases 

Hyper- hemolytic crisis 

  Cause : patient with sickle cell anemia who have in addition G6PD deficiency 
  Clinical picture : acute anemia , Hemoglobinuria ( dark urine ) 
  Investigation : reticulocytosis - enzyme assay later on 
  Treatment : packed RBCs transfusion 

Aplastic crisis 

  Cause : infection with parvovirus B19 result in failure of erythroid serious 
  Clinical picture : severe anemia that last for 3-4 weeks 
  Investigation : reticulocytopenia 
  Treatment : packed RBCs transfusion once in twice over 4 weeks 

Vaso - occlusive crisis 

Definition

: painful crisis peculiar to sickle cell anemia. It may be the only presentation in sickle 

cell trait 

Causes: 

  Hypoxia - infections - dehydration - acidosis all deoxygenate Hb S 
  HbS polymerizes within red blood cells result in sickling 
  Erythrocytes express a number of adhesion molecules and adhere to the vascular 

endothelium resulting in obstruct blood vessels 

Clinical picture : 

  Bony pains : hand - foot syndrome which may be the 1

st

 presentation of SCA with 

severe pain & swelling ( ischemia of the metacarpal and metatarsal bones ) 

  recurrent strokes : neurological defect and poor school performance 
  acute chest syndrome : acute chest pain & fever due to pulmonary infarction 
  GIT ischemia : acute abdominal pain - ischemic nephropathy , priapism : fibrosis and 

impotence . spleen : splenic infarctions            ( Autosplenectomy ) : so spleen is 
enlarged early then regress gradually . 

Infection crisis 

In patients S.C.A due to Autosplenectomy infection mainly by capsulated organisms  


background image

3

 

 

Treatment of sickle cell anemia: as thalassemia 

  Supportive 
  Blood transfusion and chelation. ( less frequent ) 
  No need for Splenectomy 
  Treatment of VOC : 

 

Oxygen IV and fluid - antibiotics for infection - analgesics for pain. Bicarbonate for acidosis. 
Blood transfusion if ( Hb is < 6 g/dl ) 

Complete rest in bed. Exchange transfusion (acute chest syndrome - stroke - priapism) . 

Hereditary spherocytosis 

Genetics

: autosomal dominant form of chronic hemolytic anemia (25% new mutation) 

Incidence:

 more common in Europe 

Pathogenesis:

 A defect in spectrin or Ankyrin of the RBC membrane increases Na permeability. 

This increases water influx so that RBCs become spherical shape, less deformable with premature 
destruction in the spleen. 

Clinical features: 

•  Onset : may present with neonatal jaundice and anemia 
•  May present later in infancy or childhood 
•  Less incidence of complications 

 

Acute Hemolytic Anemia 

Definition: It is anemia caused by acute ( sudden ) and rapid destruction of the RBCs in 
peripheral blood and in the spleen . 

Investigation 

:  

  Evidence that cause is spherocytosis 

  Blood smear : spherocytosis 
  Osmotic fragility test : increased 

  Cryohemolysis : increased 

Treatment 

:   

   Blood transfusion & chelation are required less frequent  

  Choleceystomy if gall bladder stones are present  
  Splenectomy is very beneficial ( considered curative ) only in severe cases 


background image

4

 

 

Glucose - 6 - phosphate dehydrogenase deficiency  

Incidence: 

  The most common cause of Hemolysis 
  Geography: in middle east and middle Africa - far east 
  It is commonest RBC enzymopathy 

Etiology: 

  X linked recessive ( more common in males ) 
  Heterozygous female : 50% of enzymatic activity ( appear normal ) 
  Female may be affected ( If homozygous or with lionization ) 

Pathogenesis: 

  G 6PD is the rate limiting enzyme in synthesis of NADPH & reduced glutathione. 
  NADPH & glutathione provide H + protect Hemoglobin against oxidation 
  G6PD deficiency result in deficiency in NADPH & glutathione 
  If exposure to oxidants , Hemoglobin become oxidized to met - Hemoglobin and 

precipitate as Heinz bodies leading to Hemolysis ( mainly intravascular ) 

Clinical picture: 

  History of neonatal jaundice . ( mild to very severe ) 
  History of exposure to oxident . infection or drugs and chemicals : analgesics : aspirin in 

high dose - novalgin , antibiotics : chloramphenicol - sulphonamides - quinolones 

o  Antimalarial : primaquine - chloroquine - quinine . naphthalene . naphthalene  

  Acute pallor with palpitation - dyspnea - irritability or drowsiness 

  Acute jaundice 

  Acute dark urine ( hemoglobinuria ) indicating high rate of Hemolysis 

Complications: acute heart failure  

Investigation: 

  CBC : anemia ( normocytic normochromic ) 
  Reticulocytosis in blood film ( Hemolysis ) 
  Chemistry : unconjugated hyperilirubinemia - hemoglobinemia - Hemoglobin in urine 
  Blood film show fragmented & Heinz bodies 
  Estimation of enzyme activity after 2 weeks of hemolytic attack , because immediately 

after Hemolysis , bone marrow release new RBCs and reticulocytes with normal 
enzyme level giving misleading normal result . 

Treatment : 

•  Urgent packed red cell transfusion ( 10 ml/kg ) is life saving in very severe Hemolysis 
•  Prevention of subsequent attacks : a list containing oxidants materials must be offered 

to parents 


background image

5

 

 

DD of the cause of acute Hemolysis 

 

Aplastic Anemia 

Definition

: A plasia of blood precursors in the bone marrow that result in pancytopenia in the 

peripheral blood.  

Clinical picture: 

•  Anemia 
•  Purpura 
•  Fever : persistent fever resistant to treatment - persistent oral fungal infection 
•  specific picture of the cause  

Investigation: 

•  Blood picture : pancytopenia 
•  Bone marrow examination : hypocellular bone marrow 

Causes: 

A.  Congenital : 
•  Fanconi anemia : most common 
•  Dyskeratosis congenital : with dysgenesis in skin & nails  
B.  Acquired : 
1.  Idiopathic : the most common ( 70% ) 
2.  Secondary to : 

  Chemicals : like benzene 
  Chemotherapy 
  Infection ( EBV - HBV ) 
  Exposure to radiation 
  Exposure to toxins 
  Drugs : chloramphenicol - sulfa 

D.D. of aplastic anemia:

 Leukemia - ITP 

Fanconi Anemia 

  Autosomal Recessive 
  Onset of bone marrow failure : after the age of 3 years ( average 6-8 years ) 
  Skeletal association in 50% of cases 


background image

6

 

 

  Skeletal anomalies : microcephaly , short stature absent thumb , absent radius 
  Mental retardation 
  Skin pigmentation , renal malformation , and micro-ophthalmia. 

Investigations: 

  Karyotyping : increased chromosomal breaks  
  Skeletal survey - abdominal U/S 

Acquired aplastic anemia 

Clinical features:

 onset: at any ago ( acute onset ) after certain event or idiopathic  

Treatment of aplastic anemia: 

Supportive therapy : ( controlling anemia - infection - bleeding ) 

Fanconi anemia : 

  Prolong survival by androgen and corticosteroid therapy  
  Bone marrow transplantation ( BNT ) is the treatment of choice  

Acquired : 

  Mild cases : anti - thymocyte globulin ( ATG ) or cyclosporine 
  Severe cases : bone marrow transplantation ( BNT ) is the treatment of choice from HLA 

matched sib . 

  If not available immunosuppressive therapy  

Platelets 

Megakaryocytes of the bone marrow , release platelet by budding ( fragmentation ) of the 
cytoplasm of mature Megakaryocytes Platelet are non-nucleated cell fragments ( short half-life 7-
10days ) 

Function of Platelets 

  Adhere and aggregate to seal points bleeding 
  Platelet plays a role in initiation of coagulation and in clot retraction . 

 

Purpura 

Definition: minute bleeding due to platelet or vascular defect characterized by purple petechie 
and ecchymosis 


background image

7

 

 

Thrombocytopenic Purpura: (low platelets ) 

A- Increased Platelet destruction ( normal megakaryocytes )

 

  Immune : 

-    Idiopathic thrombocytopenia 

1.  Neonatal 

   Isoimmune thrombocytopenia   

  Maternal ITP 

-    Systemic Lupus Erythematosus. 

  Non immune : 

-  DIC 
-  Hemolytic uremic syndrome 
-  Hypersplenism 
-  Drug induced 

B- Decreased Platelet Production (Low Megakaryocytes)

 

   Congenital : 

-  Thrombocytopenia with absent radius ( TAR syndrome ) 
-  Constitutional pancytopenia ( Fanconi anemia ) 
-  Thrombopoietin deficiency 

•  Acquired : 

-  Megakaryocytic aplasia ( idiopathic or 2ry to drugs ) 
-  Aplastic anemia ( idiopathic - drugs - toxin - irradiation ) 
-  Marrow infiltration ( leukemia - lymphoma - metabolic disorders ) 

Non - thrombocytopenic Purpura: (normal platelets) 

A- Platelet dysfunction:

 

-  Drugs as aspirin 
-  Uremia 
-  Inherited abnormal Platelets e.g. giant Platelet syndrome 

B- Vascular Purpura:

 

  Infections as meningococcemia 
  Vitamin C deficiency ( Scurvy ) 
  In hearted : Ehlar Danlos syndrome - marfan syndrome 
  Immune vasculities ( HSP) 


background image

8

 

 

Immune Thrombocytopenic Purpura 

Definition

: acquired generalized hemorrhagic state due to destruction of circulating platelets due 

to autoantibodies 

Incidence

: the most common cause of Purpura 

Acute: 85 - 90 % usually by nonspecific viral illness or rubella 

It is characterized with autoantibodies 

Chronic: 10-15% persistence of clinical and laboratory findings > 12months . it is related to 
autoimmune disease . hereditary factors may be present . 

Intravenous immunoglobulin (IVIG) : dose 0.8.1mg /kg/day for 2 days . duration for 2 days 
action it causes rapid rise of platelet count . ( block the phagocytic activity ) 

C- In Severe Cases : ( severe muco-cutaneous hemorrhage or intra-cranial hemorrhage ) 

  I.V. methyl prednisolone 20mg/kg/day--,5days 
  Platelet transfusion +/- fresh whole blood is needed 
  IVIG. 
  Plasmapheresis : ( transient effect ) ( only when others fail) 
  Emergency Splenectomy : final solution  

D- In chronic cases ( > 12 month ) : 

  Careful evaluation for associated disorders 

  ( E.g. SLE: frequent of screening of autoantibodies ) 

  Prednisone & IVIG 
  Splenectomy (75% curative )  
  Immunosuppressive therapy ( e.g. azathioprine - cyclosporine ). 

Prognosis:

 acute serious hemorrhage occur in the acute phase (1-2weeks). 75 % of cases recover 

in < 3 month 

 


background image

9

 

 

PHASE I : 

thromboplastin is formed through successive activation of coagulation factors in the 

presence of phospholipids . 

Assessed by partial thromboplastin time ( normal value = 25-40 seconds ) 

It measure clotting factors ( XII,XI.IX and VIII ) 

PHASE II :

 Thrombin is Formed by factor II ( prothrombin ) in the presence of thromboplastin 

complex . 

This phase can be assessed by prothrombin time ( normal value 11-14 sec ) 

It evaluate factors II, V, VII and X 

PHASE III :

 fibrin is formed by splitting of fibrinogen ( factor I ) in the presence of thrombin  

assessed by thrombin time ( normal value = 15-20 seconds ) it assess the fibrinogen level 

Coagulation defects  

1.  Hemophilia A  ( Classic Hemophilia ) 

Genetics

: X linked recessive disease with reduced factor  VIII cone . ( more in male )  

Incidence:

 1/14000 male – 80% 0f cases of hemophilia . 

Clinical features:

  bleeding in the neonatal period [ circumcision bleeding – prolonged bleeding 

from heal stick or venipuncture from umbilical stump . 

Extensive bruising. Hematoma and bleeding with minor trauma on ambulation 

 hemoarthrosis 

  The hallmark of hemophilia  
  With trauma or spontaneous  
  If repeated : degenerative joint changes and fibrosis ( ANKYLOSIS ) with unstable 

fixed joint  

  Spontaneous bleeding from orifices : epistaxis or hematuria in severe cases 
  Internal organs : intracranial hemorrhage . intramuscular hemorrhage ( e.g. psoas 

hemorrhage ) 

Complications: 

  Intracranial hemorrhage 
  Psoas hemorrhage may be fatal 
  Complication of treatment 

o  Blood born infection ( HBV - HCV - HIV - CMV ) 
o  Development of antibodies against transfused factor 8 ( 5-20% ) 

This result in resistance & effect of treatment 
The condition required higher dose of plasma or bypassing agent ( a f VII ) 

o  Complication of vascular access [ difficult cannulation - thrombosis or infection ] 

Investigation : 


background image

10

 

 

1-  Phase I coagulation defect ( prolonged PTT ) 
2-  Specific factor VIII assay ( reduced below normal ) 

  Normal > 60 % 
  Carrier 30-60% ( female ) 
  5-30% : mild hemophilia ( bleeding with trauma or surgery ) 
  1-5% : moderate ( bleeding with minor trauma ) 
  >1% : severe ( spontaneous joint bleeding ) 

Prevention: 

Avoid trauma - aspirin - give HBV - physiotherapy prevent ankylosis power  

Treatment : 

  Cold compress minimize bleeding in mild cases 
  Replacement ( essential severe cases ) 

I.V. infection of cryoprecipitate ( plasma concentrate Of factor VIII ) ( dose : 25 - 50 unit / kg 
every 12 hours ) . I.V infusion of purified factor VIII concentrate 

Recombinant factor 8. prophylactic F VIII in severe hemophilia ( 2times per week ) 

  Desmopressin : in mild hemophilia A it increase endogenous release of FVIII ( ineffective 

in hemophilia B ) 

  Physiotherapy : Specially after immobilization to prevent muscle wasting and joint 

contracture 

2. 

Hemophilia B ( Christmas disease ) factor IX deficiency

 

 

Genetics

: X linked recessive -15% of all hemophilia due to factor IX deficiency 

 

Clinical features:

 like hemophilia a but with ( delayed onset ) - milder bleeding 

 Treatment

: fresh frozen plasma or factor IX concentrate ( once or every 24 hours ) 

Von willebrand disease ( vascular hemophilia ) 

Genetics

: autosomal dominant defect in the production of VW protein  

Pathogenesis

  Von- willebrand protein play 2 roles 

-  Facilitate platelet adhesion and 
-  Protect factor VIII from breakdown ( act as carrier protein ) 
-  If reduced , it reduced factor activity & defective platelet adhesion 

Clinical features

  Mild bleeding tendency : mainly epistaxis , bleeding gums bruising , menorrhagia & 

bleeding with surgery  

  Spontaneous hemorrhage is extremely rare 


background image

11

 

 

Investigation: 

1-  Normal platelet count  but defective platelet adhesion ( prolonged bleeding time ) 
2-  Prolonged PTT 
3-  Reduced level of vw protein & factor 8. 

Treatment: 

  I.V Infusion Of Fresh Frozen Plasma , cryoprecipitate or vw factor 
  Desmopressin can help in mild cases  

Differential diagnosis of hemophilia in general: 

  Acquired coagulation defects as liver failure 
  Disseminated intravascular coagulation (DIC) 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Mubark A. Wilkins 




رفعت المحاضرة من قبل: Mubark Wilkins
المشاهدات: لقد قام 7 أعضاء و 181 زائراً بقراءة هذه المحاضرة








تسجيل دخول

أو
عبر الحساب الاعتيادي
الرجاء كتابة البريد الالكتروني بشكل صحيح
الرجاء كتابة كلمة المرور
لست عضواً في موقع محاضراتي؟
اضغط هنا للتسجيل