MCPHS MMD II Hemolytic Anemias

Anemias due to increased destruction of red cells

is associated with a release of hemoglobin and lactic acid dehydrogenase (LDH).

Hemolysis may be either?

RBCs lyse in the circulation releasing hemoglobin into the plasma.

Causes include mechanical trauma, complement fixation, and other toxic damage to the RBC.

The fragmented RBCs are called schistocytes.

RBCs are phagocytized by macrophages in the spleen and liver.

Causes include RBC membrane abnormalities such as bound immunoglobulin, or physical abnormalities restricting RBC deformability that prevent egress from the spleen.

This is characterized by spherocytes.

If onset of hemolysis is abrupt:
What are the signs/symptoms?

Patients with underlying cardiovascular disease and severe uncompensated hemolysis
May present with:

What are five main causes of hemolytic anemia?

is an autosomal dominant disease of variable severity

CHARACTERISTICS:
Defective or absent spectrin molecule
Leads to loss of RBC membrane, leading to spherocytosis
Decreased deformability of cell
Increased osmotic fragility
Extravascular hemolysis in spleen

Diagnosed during childhood
Anemia -may or may not be present (BM may compensate)
Severe Anemia:
Folate Deficiency
BM impaired by infection (Parvovirus B19)

Chronic hemolysis causes:
jaundice
Gallstones = cholecystitis
Examination = icterus and a palpable spleen

What are the laboratory findings with hereditary spherocytosis?

How do you TX hereditary spherocytosis?

is the most common disease-producing enzymopathy in humans

Inherited as an X-linked disorder

Affects 400 million people worldwide

The disease is highly polymorphic, with more than 300 reported variants. It confers protection against malaria, which probably accounts for its high gene frequency.

is a housekeeping enzyme critical in the redox metabolism of all aerobic cells.

G6PD regenerates?

leads to hemolysis during oxidative stress.

Causative agents:
Infection
Medications
Fava beans

Oxidative stress leads to Heinz body formation and extravascular hemolysis

The spleen pinches off the Heinz body and the overlying membrane, leaving a “bite cell” or “blister cell”

This is associated with an abrupt fall in the hemoglobin concentration of 3 to 4 g/dL, and the peripheral blood smear reveals cell fragments, microspherocytes, and eccentrocytes or "bite" cells .

The laboratory workup for (G6PD) deficiency includes the following:

a plasma protein whose only known function is to bind free hemoglobin.

The quantity of this is increased in certain chronic diseases and inflammatory disorders and is decreased or absent in hemolytic anemia.

Normal adult findings range from 100 to 150 mg/dL

What imaging studies may be useful in diagnosing G6PD deficiency?

How do you treat G6PD deficiency?

Patients with (G6PD) deficiency should heed the following precautions:

Avoid:

Infants with prolonged neonatal jaundice as a result of (G6PD) deficiency are?

Exchange transfusion may be necessary in cases of ?

One of the most common of the hemoglobinopathies is Hgb S. It is a qualitative hemoglobin disorder.


In this there is a point mutation in the ß-chain resulting in encoding of a valine instead of the normal glutamine.

This results in abnormal ßs chains combining with normal a-chains to form the abnormal hemoglobin 'S'

RBC’s take on sickled-shape when in presence of decreased O² tension

Under low oxygen, Hgb becomes insoluble forming long polymers

This leads to membrane changes (“sickling”) and vasoocclusion

Hemolytic anemia, not iron deficient
RBC distortion, 10-20 day lifespan (significantly shortened)

Deoxygenation of SS erythrocytes leads to intracellular hemoglobin polymerization, loss of deformability and changes in cell morphology.

What can be seen in the clinical presentation of sickle cell anemia?

VOC - is caused by abnormally shaped red blood cells resulting in acute and chronic organ dysfunction
VOC- sickled cells occlude capillaries and small blood vessels
VOC - Obstructs blood flow causing tissue ischemia
VOC - Reduces blood flow causing further tissue hypoxia
VOC - Increased tissue hypoxia increases “sickling”

can occur in any tissue, most commonly affect extremities, lower back and abdomen

Can occur in any tissue or organ
Factors contributing to this include fever, hypoxia, dehydration, hypothermia, emotional stress or nothing

Vaso-occlusive crisis lasting longer than 7days search for other causes of bone pain:

What are three complications associated with sickle cell anemia?

How do you manage a sickle cell crisis?

What is the drug of choice for controlling pain in a sickle cell crisis?

Chronic pain associated with sickle cell anemia is controlled how?

Sudden trapping of blood within the spleen. Usually occurs in infants under 2 years of age.
May be associated with fever, pain, and respiratory symptoms. Circulatory collapse and death can
occur in less than thirty minutes.

This is one of the first complications in sickle cell syndromes with the highest incidence between
ages six months and two years. The sickle red cells cause painful swelling of the hands and feet.
This is treated with fulids and pain medication. It usually will go away in a few days without any
problems.

What are two other problems, apart from splenic sequestion and dactylitis, that are associated
with sickle cell anemia

The risk of this is 400 x greater in SCD than in the general population
#1 cause of death infants and young children

Functional asplenia by age 12 months

Predisposition to infection due to functional Asplenia

Prophylactic penicillin significantly reduces death from overwhelming infections

leading cause of death in children & adults over age 5
Clinical presentation of pneumonia and pulmonary infarct may be indistinguishable
Causes: pulmonary infection S.aureus,
S.pneumoniae, chlamydia, mycoplasma, VOC of pulmonary vessels, fat embolism secondary to marrow infarction, RSV

Characterized by:
Chest pain, fever, pulmonary infiltrates & respiratory distress
Can be rapidly progressing
Antibiotics and oxygen are essentials of therapy
Transfusions beneficial in hypoxemic patients

How do you treat sickle cell disease?

Indications for transfusion in SCD

EPISODIC/ACUTE
Management of Severe Anemia/Sudden Acute Illness:

Indications for transfusion in SCD

CHRONIC/PROPHYLACTIC

Only known cure for SCD

Drug therapies that change the structure of the red blood cell
Reduce sickling
Increase hemoglobin

The only drug currently approved by the FDA for the treatment of SCD is ?

increases the production of Hb F, which retards gelation and sickling.

is a group of disorders characterized by a malfunction of the immune system that produces autoantibodies, which attack red blood cells as if they were substances foreign to the body.

Autoimmune hemolytic anemia may be seen in association with?

The hallmark of this disease is a positive Coomb’s test

react with RBCs best at 37° and typically do not agglutinate red cells

typically react best at <32° and do cause RBC agglutination

Usually IgG antibodies
Fix complement only to level of C3, if at all
Immunoglobulin binding occurs at all temps
Fc receptors/C3b recognized by macrophages
Hemolysis primarily extravascular
70% associated with other illnesses
Responsive to steroids/splenectomy

What are the laboratory features of warm type autoimmune hemolysis?

What are the laboratory results for warm type autoimmune hemolysis?

Looks for immunoglobulin &/or complement on surface of red blood cell (normally neither found on RBC surface)

Coombs reagent - combination of anti-human immunoglobulin & anti-human complement

Mixed with patient’s red cells; if immunoglobulin or complement are on surface, Coombs reagent will link cells together and cause agglutination of RBCs

How do you treat warm type autoimmune hemolysis?

• First line is corticosteroids

• If steroids fail to work, or if patient relapses after steroid taper, splenectomy may be necessary

IVIg (intravenous IgG) can be used as adjunctive therapy

• Immunosuppressives such as cyclophosphamide or azathioprine may be required as third third-line therapy

Rituximab (anti-CD20 monoclonal antibody) has been used successfully

Most commonly IgM mediated
Antibodies bind best at 30º or lower
Fix entire complement cascade
Leads to formation of membrane attack complex, which leads to RBC lysis in vasculature
90% associated with other illnesses
Poorly responsive to steroids, splenectomy; responsive to plasmapheresis

Cold agglutinin disease is associated with?

Laboratory findings in cold agglutinin?

Occurs when certain drugs interact with the red blood cell membrane, causing the cell to become antigenic.
Alpha-Methyl dopa type: levodopa, methyldopa.
Hapten type: Penicillins, cephalosporins.
Quinidine type: quinidine.
Others: mefenamic acid, salicylic acid, sulfonamides, Thiazide diuretics, antazoline, chlorpromazine, isoniazid, streptomycin, ibuprofen

Drug-induced hemolytic anemia is most often associated with

Drug binds to & reacts with red cell surface proteins
Antibodies recognize altered protein, ± drug, as foreign
Antibodies bind to altered protein & initiate process leading to hemolysis

• Arsenic - especially arsine gas
• Lead - produces some shortening of RBC lifespan, but anemia mainly due to defect in heme synthesis.
• Copper - deliberate ingestion, accumulation of toxic amounts from dialysis fluid exposed to copper pipes, and Wilson’s disease.
• Insect, spider (esp brown recluse), snake venoms
• Heat/burns

“The great impersonator”
because of the variety of symptoms observed during the initial manifestation and course

Paroxysmal Nocturnal Hemoglobinuria (PNH)

3 types of symptoms including:

Acquired Clonal cell disorder ( remember Aplastic Anemia?)
Ongoing Intra- & Extravascular hemolysis; classically at night (can occur throughout the day)
Testing
Elevated LDH,
The white blood cell count and platelet count may be decreased.
A decreased leukocyte alkaline phosphatase
Flow cytometric assays may confirm the diagnosis by demonstrating the absence of CD59
(a complement-regulating protein)

PNH may have three components, they are?

How do you treat PNH?