FBy Dr. Fahad Fayyaz Butt HEMOLYTIC DISEASES OF NEWBORN
May 25, 2015
FBy Dr. Fahad Fayyaz Butt
HEMOLYTIC DISEASES OF NEWBORN
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.
Causes:
Rh incompatibility Autoimmune Hemolytic Anemia Hereditary Spherocytosis Sickle Cell Disease G6PD Thalassemia
Rh incompatibility:
Rh incompatibility is a condition which develops when an Rh negative mother conceives a fetus which is Rh positive.
When the mother produces Abs directed against fetus RBC surface Ag.
Isoimmunization:
THE MOST COMMON….
Cause of Maternal Isoimmunization
Feto- maternal Bleed
Risk Factors of Feto-maternal Bleed:
AmniocentesisEctopic pregnancy
RBC Rh Antigen : Rh “ D ’’ Ag
Mother produces: Anti Rh (D) Abs
THE MOST COMMON….
Mother must be Rh -
Dad must be Rh +
Coombs test must be positive
Abs must be
associated with Hemolysis
Ab titer must be above 1:8
Is the baby at risk?
• Anti Lewis Abs
Non-Hemolytic
ABS
•Anti KELL Abs•Anti RH(D) Abs
Hemolytic ABS
Presentation:
Mild jaundice
Erythroblastosis Fetalis Generalized Edema Hepatomegaly Ascites
Management:
Phototherapy for neonate with mild jaundice
Exchange transfusion in Severe cases
To prevent Isoimmuization of yet unimmunized mother give Anti Rh D IgG (Rhogam) IntraMuscular at 28 weeks of gestation.
Prevention:
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 .
Types:
There are two types of AIHA: Warm AIHA: IgG is directed against RBCs Cold AIHA: IgM is directed against RBCs
Presentations:
Acute Onset Weakness, Pallor, Fatigue Dark Urine Splenomegaly Underlying disease HIV/SLE
LABS:
Normocytic Hemoglobinemia and Hemoglobinuria Coombs test is positive
Treatment:
Warm AIHA:Prednisolone IV or IV ImmunoGlobulin
Cold AIHA:Self-limited course Plasma Exchange is effective
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
product leading to early destruction of RBCs
Types:
B-Thalassemia Minor: Reduced production of Beta chain B- Thalassemia Major: Complete absence of Beta chain
Presentation:
Children present with severe Anemia, hepatosplenomegaly at the age of 3-6 months
Jaundice Frontal Bossing, Maxillary prominence
Types of expression:
Thalassemia trait: Patients have mild anemia Thalassemia intermedia: Patients have intermediate anemia Thalassemia Major: Severe symptoms
Diagnosis:
Microcytic RBCs Decreased MCH Increased Nucleated RBCs Increased Serum Ferritin & Transferrin
levels.
HPLC confirms diagnosis of Beta Thalassemia
Labs:
Normal RBCs B- thalassemia
Target cells
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: Hematopoietic stem cell transplatation
Hereditary Spherocytosis:
Presentation:
Newborn present with Anemia, jaundice Chronically splenomegaly and Gall
stones are often present.
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.
SPHEROCYTOSIS
Spherocytes
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
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
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:
G6PD in RBCs
Decreased in Glutathione production
Increased susceptibility to Oxidant stress
ANTI-MALARIAL DRUGS FAVA BEANS
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)
Heinz Bodies And Bite cells
Bite cell
Heinz bodies
Management:
Supportive Care: hydration transfusion if needed and monitoring
Folic Acid supplementation Counseling to avoid Similar Drugs in
future
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
Sickle shaped cells
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
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
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.pneumoniaHydroxyurea – increase HbF
Hemolytic Diseases
WeaknessPallorfatigue
Splenomegaly
Coombstest
Hemoglo-binuria
PBS Diagnosis
HereditarySpherocytosis
+ + - - Spherocytes
Osmotic fragilitytest
Pyruvate Kinase deficiency
+ + - - Normocytic PK assay
G6PD deficiency + + - + Bite cells
Heinz Bodies
G6PD assay
Autoimmune Hemolytic anemia
+ + + + Normocytic IgG and IgM Ab against RBCs
B- Thalassemia +
+ ++
- - Nucleated RBCs,Target cell
Hbelectrophoresis
Sickle Cell disease + - - - Sickle
shaped RBCs Howel-jolly bodies
Hbelectrophoresis
THANK YOU FOR YOUR PATIENCE