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