it is a comprehensive discussion on hemolytic disease of newborn

1. HEMOLYTIC
DISEASES OF
NEWBORN

2. Hemolytic Disease
 The term hemolytic disease is limited to
conditions in which the rate of RBCs
destruction is accelerated and the ability of
bone marrow to respond is unimpaired.

3. Causes:
 Rh incompatibility
 Autoimmune Hemolytic Anemia
 Hereditary Spherocytosis
 Sickle Cell Disease
 G6PD
 Thalassemia

4. Rh incompatibility:
 Rh incompatibility is a condition which
develops when an Rh negative mother
conceives a fetus which is Rh positive.
Isoimmunization:
 When the mother produces Abs directed
against fetus RBC surface Ag.

5. THE MOST COMMON….
 Cause of Maternal Isoimmunization
 Feto- maternal Bleed
Risk Factors of Feto-maternal
Bleed:
 Amniocentesis
Ectopic pregnancy

6. THE MOST COMMON….
 RBC Rh Antigen :
 Rh “ D ’’ Ag
 Mother produces:
 Anti Rh (D) Abs

7. Is the baby at risk?
Abs must
Mother Coombs be Ab titer
Dad must
must be test must associated must be
be Rh +
Rh - be positive with above 1:8
Hemolysis
Hemolytic • Anti KELL Abs • Anti Lewis Non-Hemolytic
ABS • Anti RH(D) Abs Abs ABS

8. Presentation:
 Mild jaundice
 Erythroblastosis Fetalis
 Generalized Edema
 Hepatomegaly
 Ascites

9. Management:
 Phototherapy for neonate
with mild jaundice
 Exchange transfusion in
Severe cases

10. Prevention:
 To prevent Isoimmuization of yet unimmunized
mother give Anti Rh D IgG (Rhogam)
IntraMuscular at 28 weeks of gestation.

11. AutoImmune Hemolytic Anemia
 This Arises as an autoimmune phenomenon
targeting the RBCs .
 It may arise as an isolated problem or as a
complication of HBV, SLE .

12. Types:
There are two types of AIHA:
 Warm AIHA:
IgG is directed against RBCs
 Cold AIHA:
IgM is directed against RBCs

13. Presentations:
 Acute Onset
 Weakness, Pallor, Fatigue
 Dark Urine
 Splenomegaly
 Underlying disease HIV/SLE

14. LABS:
 Normocytic
 Hemoglobinemia and Hemoglobinuria
 Coombs test is positive

15. Treatment:
 Warm AIHA:
Prednisolone IV or IV ImmunoGlobulin
 Cold AIHA:
Self-limited course
Plasma Exchange is effective

16. B-Thalassemia:
 It is an inherited disorders of hemoglobin
synthesis that result from an alteration in the
rate of Beta globin chain production.
 Pathology:
Abnormality occurs when there is defective
production
of beta chain and an excess of normally
produced
type which accumulates in the cell as an
unstable

17. Types:
 B-Thalassemia Minor:
Reduced production of Beta chain
 B- Thalassemia Major:
Complete absence of Beta chain

18. Presentation:
 Children present with severe
Anemia, hepatosplenomegaly at the age of 3-6
months
 Jaundice
 Frontal Bossing, Maxillary prominence

19. Types of expression:
 Thalassemia trait:
Patients have mild anemia
 Thalassemia intermedia:
Patients have intermediate anemia
 Thalassemia Major:
Severe symptoms

20. Labs:
 Microcytic RBCs
 Decreased MCH
 Increased Nucleated RBCs
 Increased Serum Ferritin & Transferrin levels.
Diagnosis:
 HPLC confirms diagnosis of Beta Thalassemia

21. Normal RBCs B- thalassemia
Target
cells

22. Management:
 Blood transfusions:
 Keep Hb between 9-10mg/dl
 Chelation therapy and Iron
Overload:
 After multiple transfusions patient may develop Iron
Overload
 Leading to DIABETES, THYROID AND PARATHYROID
dysfunction
 To remove excess iron chelation therpay is very effective.
 Deferoxamine IV subcutaneously or alternatively Deferiprone
PO
 Cure:

23. Hereditary Spherocytosis:
Defect in protein of the RBC membrane skeleton
and plasma membrane such as Spectrin, ankyrin
leading to rigid spherical shaped RBCs.
The structural membrane defect predispose it to
destruction when they pass through the splenic
sinusoids.

24. Presentation:
 Newborn present with Anemia, jaundice
 Chronically splenomegaly and Gall stones are
often present.

25. Labs:
 Increased MCHC
 Normal MCV
 Reticulocytosis
 Spherocytes on PBS
Diagnosis:
 Family history (autosomal recessive)
 Osmotic Fragility test confirms the diagnosis.
In this test, the spherocytes will rupture in mildly hypotonic solutions - this is due to increased permeability of the
spherocyte membrane to salt and water.

26. SPHEROCYTOSIS
Spherocyt
es

27. Treatment:
 Folic Acid Supplementation 1-5mg/day
 Splenectomy for >6years , immunize against
S.pneumonia priorly.
Complications:
 Aplastic Crisis due to infection with Parvovirus
B19
Cause transient arrest in RBC production for 4-6 weeks

28. Pyruvate Kinase deficiency :
 Deficieny of the PKenzyme in RBCs
responsible for ATP production resulting in
rigid RBCs predisposing them to splenic
destruction.
Presentation:
 Affected individuals present with Splenomegaly
 Pallor, jaundice and icterus
Diagnosis: Pyruvate Kinase Deficiency
Treatment: Splenectomy
Folic Acid supplementation

29. G6PD:
 Disease charaterized by hemolytic anemia
following Oxidant stress such as :
 Fava beans
 Sulfa Drugs
 Anti-Malarial drugs
 An X-linked disorder expressed in Males and carried in
females
 Pathology:
Decreased in Increased
G6PD in RBCs Glutathione susceptibility to
production Oxidant stress

30. ANTI-MALARIAL DRUGS
FAVA BEANS

31. Presentation:
 Following ingestion of such foods/drugs result in crisis
such as:
 Children present with Jaundice in neonatal period ,pallor and icterus
 Dark Urine
 Chronic patients may have splenomegaly.
 Labs:
 Hemoglobinemia and hemoglobinuria
 Heinz Bodies and Bite cells
 Diagnosis:
 The nature of clinical Presentation
 Family history (only present in males)
 Quantitative G6PD enzyme assay (Confirmatory Diagnosis)

32. Heinz Bodies And Bite cells
Bite cell
Heinz
bodies

33. Management:
 Supportive Care:
 hydration
 transfusion if needed and monitoring
 Folic Acid supplementation
 Counseling to avoid Similar Drugs in future

34. Sickle Cell Disease:
 It results from substitution of valine for
glutamic acid at position 6 of Beta globin
Chain.
 Sickle shaped RBCs are rapidly hemolyzed
and have a life span of 10-20 days

35. Sickle shaped cells

36. Presentation:
 Hemolytic anemia develop after 2-4 months of
age
 Pallor , jaundice develops
 Asplenia due to auto-infarction of spleen , spleen
not palpable, after 6 years
 Labs:
 Anemia , thrombocytosis, reticulocytosis
 Normal MCV
 Bone Marrow hyperplasia On BMA
 Sickle shaped Cells, Howel-Jolly bodies

37. Complications/ Acute painful Crisis
 When the microcirculation is obstructed by sickled RBCs
it results in ischemic injury it may present as:
 Dactylitis - Swollen hands and foot
 Retinopathy- obstruction of ophthalmic artery
 Acute Chest syndrome- involving legs causing
pain, dyspnea, hypoxemia
 Sequestration Crisis- SC block outflow to spleen
 Aplastic Crisis- Bone marrow temporarily stops producing RBCs
 Diagnosis:
 History of trigger preceding the crisis such as dehydration or fever
 Hb electrophoresis confirms the diagnosis

38. Management:
 Hydration PO or IV, analgesics (narcotics)
 Specific therapy:
 Aplastic crisis- Blood transfusion may be necessary
 ACS or CVA – require Oxygen, mechanical ventilation
and may require exchange transfusion
 Preventive Care:
 After 2 y/o/a child is kept on penicillin and amoxicillin
 Folate supplements
 Immunization against S.pneumonia
 Hydroxyurea – increase HbF

39. Hemolytic Weaknes Splenom Coomb Hemoglo PBS Diagnosi
Diseases s egaly s -binuria s
Pallor test
fatigue
Hereditary Spherocytes Osmotic
Spherocytosis + + - - fragility
test
Pyruvate Normocytic PK
Kinase + + - - assay
deficiency
G6PD Bite cells G6PD
deficiency + + - + Heinz Bodies assay
Autoimmune Normocytic IgG and
Hemolytic + + + + IgM Ab
against
anemia
RBCs
B- Nucleated Hb
Thalassemia ++ ++ - - RBCs,
Target cell
electrop
horesis
Sickle Cell Sickle shaped Hb
disease + - - - RBCs Howel- electrop

40. THANK YOU FOR YOUR PATIENCE