Hemolytic anemia

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objectives

Hemolytic anemia general principles

SICKLE CELL DISEASE

AUTOIMMUNE, COLD AGGLUTININ, AND DRUG-INDUCED HEMOLYTIC ANEMIA

HEREDITARY SPHEROCYTOSIS

PAROXYSMAL NOCTURNAL HEMOGLOBINURIA

GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY

General principles

Hemolytic anemias are caused by decreased RBC survival from increased destruction of the cells.

Chronic vs. acute

Extravascular vs. Intravascular

Clinical Presentation : - The usual symptoms of anemia (Fatigue and weakness occur with mild disease , Dyspnea and later confusion )

- Usually the onset is sudden . “simple blood loss excluded”

- Associated with jaundice and dark urine - Fever, chills, chest pain, tachycardia, and backache may occur if the intravascular hemolysis is particularly rapid.

Diagnosis: Normal MCV , The reticulocyte count is elevated (10–20%

range), The LDH and indirect bilirubin are elevated . peripheral smear abnormalities

haptoglobin maybe low with intravascular hemolysis

Hemoglobin and Hemosiderin , Hemosiderin may be present

in the urine

There should not be bilirubin in the urine

Treatment. Transfusion is needed as in all forms of anemia when the hematocrit becomes low. Hydration is, in general, useful to help prevent toxicity to the kidney tubule from the free hemoglobin

SICKLE CELL DISEASE

Pathology : Autosomal recessive hereditary disease

Hemoglobin S is due to a substitution of a valine for glutamic acid as the sixth amino acid of the beta globin chain .

Heterozygous form vs. Homorozygous form

A sickle cell acute painful crisis may be precipitated by hypoxia, dehydration, acidosis, infection, and fever.

Sickle cell crisis is usually not associated with an increase in hemolysis or drop in hematocrit.

Cont.

Clinical Presentation : chronic : renal concentrating Defects, hematuria, bilirubin,

Gallstones, osteomyelitis, retinopathy, recurrent infections from Pneumococcus or Haemophilus , splenomegaly (autosplenectomy)

Acute painful crisis : PAIN, life-threatening manifestations of sickling : 1) acute chest syndrome : (severe chest pain, fever, leukocytosis, hypoxia, and infiltrates on the chest x-ray. )

2) Stroke and TIA 3) Priapism 4) Blindness , myocardial infarction and cardiomyopathy

5) spontaneous abortion and low birth weight

Sickle trait gives normal hematologic picture with no anemia and a normal MCV.

The only significant manifestation of trait is the renal concentrating defect presenting with isosthenuria and microscopic hematuria

Increase risk for UTIs .

Diagnosis:

mild to moderate anemia.

The hemoglobin electrophoresis is the most specific test.

The peripheral smear shows sickled cells.

The sickle prep

The white blood cell count is often elevated in the 10,000–20,000 range.

Treatment: An acute sickle cell pain crisis is treated with fluids,

analgesics, and oxygen. Antibiotics(Ceftriaxone) are given with infection or even to

patients with fever and leukocytosis. In life threatening conditions : are managed with red blood

cell transfusions if the hematocrit is low, and exchange transfusion if the hematocrit is high

Chronic management: folic acid replacement and vaccinations Hydroxyurea Bone marrow transplantation

AUTOIMMUNE, COLD AGGLUTININ, AND DRUG-INDUCED HEMOLYTIC ANEMIA

can result from the production of IgG, IgM, or activation of complement C3 against the red cell membrane

Cold ass. With IgM Vs. Warm ass. With IgG

Cause usually idopathic

Chronic deseases/drugs could induce it

The most common drugs are the penicillins, cephalosporins, sulfa drugs, quinidine, alphamethyldopa, procainamide, rifampin, and thiazides.

Clinical Presentation :

The onset may be very sudden resulting in fever, syncope, congestive failure, and hemoglobinuria

Mild splenomegaly ( long duration )

Cold agglutinin disease : cyanosis of the ears, nose, fingers, and toes.

Diagnosis :

The Coombs test is the specific test that diagnoses autoimmune

Spherocytes are often present on the smear

Cont,

Treatment:

Mild disease often occurs, which needs no treatment. In cases of drug-induced hemolysis, stop the offending drug

More severe autoimmune hemolysis is treated with steroids first. Splenectomy is done for those unresponsive to steroids.

Cold agglutinin disease is primarily managed by

avoiding the cold

Rituximab

HEREDITARY SPHEROCYTOSIS

Pathology : autosomal dominant disorder where the loss of spectrin in the red cell membrane

Clinical Presentation :

A chronic disorder with mild to moderate symptoms of anemia.

there is often splenomegaly and jaundice.

Cont,

Diagnosis:

osmotic fragility test.

The mean corpuscular hemoglobin concentration (MCHC) is elevated.

a negative Coombs test.

Treatment:

Most patients require no treatment beyond folate replacement chronically.

more severe anemia : spleen removal

PAROXYSMAL NOCTURNAL HEMOGLOBINURIA

Pathology : A red cell membrane defect in phosphatidyl-inositol glycan A (PIGA) allows increased binding of complement to the red cell, leading to increased intravascular hemolysis.

Clinical Presentation:

Thrombosis of major venous structures, particularly the hepatic vein is a common cause of death in these patients

Diagnosis : The gold standard test is flow cytometry for CD55 and CD59 on white and red cells. In PNH, levels are low or absent.

Treatment.

Some patients with few or no symptoms require only folic acid and possible iron supplementation.

The disease may progress : prednisone is often given to slow the rate of red blood cell

destruction. In the patient with acute thrombosis, thrombolytic therapy

(streptokinase) Antiplatelet agents and avoid medication that increase the

risk for thrombosis (OCPs) Allogeneic bone marrow transplantation has been the

mainstay of curative therapy for PNH

Eculizumab treat the symptoms

GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY

Pathology : X-linked recessive , G6PD defect leads to increase RBCs susceptibility to oxidative stress .

The most common type of oxidant stress is actually from infections, not drugs.

The most commonly implicated drugs are sulfa drugs, primaquine, dapsone, quinidine, and nitrofurantoin.

Clinical Presentation :

A sudden, severe, intravascular hemolysis, jaundice, dark urine, weakness, and tachycardia.

The main clue : history of recent drug ingestion

Diagnosis:

Heinz bodies, Bite cells are seen on smear.

The definitive test is the G6PD level, which can be falsely normal immediately after an episode of hemolysis. Hence, the level is best tested about 1 week after the event.

Treatment:

There is no specific therapy beyond hydration and transfusion if the hemolysis is severe.

The main therapy is to avoid oxidant stress in the future.