Hemolytic Anemias

Defined as those anemias result from an increased in the rate of red cell destruction.

The red cell destruction is usually removed extravascular by macrophages of reticuloendothelial system (RE) [BM, liver & spleen].

Acute destruction or chronic destruction Extravascular or Intravascular hemolysis Hereditary or Acquired hemolytic anemia

SJAOUNI, KAU

SJAOUNI, KAU

Classification of hemolytic anemiasHereditary Acquired

Membrane

Hereditary spherocytosis, hereditary elliptocytosis

Immune

Autoimmune Warm antibody type

Metabolism Cold antibody type

G6PD deficiency, pyruvate kinase deficiency

Alloimmune

Hemolytic transfusion reactions

Hemoglobin

Thalassemia disorders Hemolytic disease of the newborn Allografts, especially marrow transplantation

Abnormal (Hb S, Hb C, unstable); Drug associated

Red cell fragmentation syndromes

Arterial grafts, cardiac valves

SJAOUNI, KAU

cont. of Classification of hemolytic anemias

Hereditary Acquired

Microangiopathic

Thrombotic thrombocytopenic purpura Hemolytic uraemic syndrome Meningococcal sepsis Pre-eclampsia Disseminated intravascular coagulation

March hemoglobinuria

Infections

Malaria, clostridia

Chemical and physical agents

Especially drugs, industrial/domestic substances, burns

Secondary

Liver and renal disease

Paroxysmal nocturnal hemoglobinuriaG6PD, glucose-6-phosphate dehydrogenase; Hb, hemoglobin.

Diagnosis

History Clinical features Laboratory findings

CBC (Hb & MCV), Plt, (WBC & diff) Retic Blood film Specific tests

SJAOUNI, KAU

CBC

WBC 8.3 10^3/L

NE % 64.5 %

LY % 27.6 %

MO % 5.1 %

EO % 2.6 %

BA % 0.2 %

NRBC %0.0 %

NE # 5.3 10^3/L

LY # 2.3 10^3/L

MO # 0.4 10^3/L

EO # 0.2 10^3/L

BA # 0.0 10^3/L

NRBC #0.0 10^3/L

RBC 4.94 10^6/L

HGB 14.3 g / dL

HCT 40.8 %

MCV 82.6 fL

MCH 28.9 pg

MCHC 35.0 g / dL

RDW 12.8 %

PLT 268 10^3/L

MPV 7.5 fL

RET %

RET #

IRF

MRV SJAOUNI, KAU

Laboratory findings in Hemolytic Anemia1. Features of increased red cell destruction:

S. bilirubin, urine urobilinogen breakdown, fecal stercobilinogen, s. haptoglobins absent.

2. Feature of red cell productions Reticulocytosis BM erythroid hyperplasia

3. Damaged red cell Morphology Osmotic fragility & autohemolysis Red cell survival

SJAOUNI, KAU

Autoimmune Hemolytic Anemia (AIHAs)

Caused by antibody production by the body against its own red cells.

Characterized by a positive direct antiglobulin test (DAT) called Coombs test

Divided into warm and cold according Abs react at 37oC or 4oC.

SJAOUNI, KAU

SJAOUNI, KAU

Autoimmune Hemolytic AnemiaWarm Type Cold Type

Idiopathic Idiopathic

Secondary: Systemic lupus erythematosus, other connective tissue disorders

chronic lymphocytic leukaemia

malignant lymphoma

ulcerative colitis

ovarian teratoma

drugs, e.g. methyldopa

Secondary: Mycoplasma pneumonia

infectious mononucleosis

malignant lymphoma

paroxysmal cold hemoglobinuria: rare; may be primary or associated with infection

Cold Autoimmune Hemolytic AnemiaIn these syndromes the antibodies whether: Monoclonal: Idiopathic cold agglutination

lymphomas. Polyclonal as infection: Infectious

mononucleosis, Mycoplasma pneumonia Patient may have a chronic hemolytic anemia

aggravated by cold. Sometimes associated with intravascular hemolysis.

Laboratory: Similar like warm AIHA Less spherocyte, more red cell agglutination DAT reveals complement (C3d)

SJAOUNI, KAU

SJAOUNI, KAU

Causes of intravascular hemolysis

Mismatched blood transfusion (usually ABO)

G6PD deficiency with oxidant stress

Red cell fragmentation syndromes

Some autoimmune hemolytic anemias

Some drug- and infection-induced hemolytic anemias

Paroxysmal nocturnal hemoglobinuria

March hemoglobinuria

Unstable hemoglobin

G6PD, glucose-6-phosphate dehydrogenase.

Causes of hereditary hemolytic anemia.

SJAOUNI, KAU

Hereditary Hemolytic Anemia

Membrane defects Metabolic defects Hemoglobin defects

hereditary deficiency of: defective synthesis,

spherocytosis e.g. thalassemia

pyruvate kinase ( or )

hereditary

elliptocytosis triose phosphate abnormal variants,

isomerase e.g. Hb S, Hb C,

hereditary unstable

stomatocytosis pyrimidine-5-

nucleotidase

etc. glucose-6-phosphate

dehydrogenase

glutathione synthetase

etc.

INHERITANCE

■ AUTOSOMAL

■ SEX-LINKED

SJAOUNI, KAU

SJAOUNI, KAU

Sex-linked Inheritance

Glucose-6-Phosphate Dehydrogenase (G6PD)Deficiency

Sex-linked hereditary hemolytic anemia Acute intravascular hemolysis due to oxidant stress. Episodes of acute hemolytic anemia

Most patients are asymptomatic 4 Clinical syndromes:

1. oxidative stress-induced hemolysis by certain drugs, infection and other illness.

2. Favism (fresh and uncooked beans are more dangerous than dried cooked ones.

3. Neonatal jaundice4. Chronic hemolytic anemia

SJAOUNI, KAU