Hematology Ch 12-17

Microbial agents associated with anemia of inflammation:

-Bacterial (M. tuberculosis) -Fungal (C. neoformans) -Viral (HIV, Cytomegalovirus)

Iatrogenic Agents

-Benzene and benzene derivatives -Trinitrotoluene -Insecticides and weed killers -Inorganic arsenic -Antimetabolites -Antibiotics

Signs and symptoms of aplastic anemia depend on the degree of the deficiencies and include the following:

-Bleeding from thrombocytopenia (low platelets) -Infection from neutropenia (low wbc's) -Signs and symptoms of anemia -Splenomegaly and lymphadenopathy are absent

Fanconi's Anemia

-Congenital for of aplastic anemia; condition is produced due to one or more mutations in the FAC gene -Diagnosis is usually made in children 5 to 10 years of age

Laboratory assays that suggest inflammation or infection include the following:

-Elevated platelet counts -Elevated total leukocyte counts -Evidence of acute-phase reactants

Chronic blood loss is frequently associated with disorders such as

-GI Tract -Heavy menstruation in women -Urinary Tract abnormalities

Hereditary Hemochromatosis

-Genetic error of metabolism that produces inappropriately increased GI absorption of iron due to hepcidin deficiency -Typically not seen in females

Laboratory characteristics of AOI/ACD

-Hematocrit fixed in the 28% to 32% range -In some cases hemoglobin may be as low as 5 g/dL

Laboratory Characteristics SA

-Hypercellular marrow with normal reticulocyte count -Mature, nonnucleated RBC's are generally hypochromic with normocytic and/or microcytic

Acute Blood Loss Anemia Laboratory Findings

-Increased WBC and platelets -Normal reticulocytes -Normal HCT -No iron deficiency

Chronic Blood Loss Adaptation

-Increased erythropoietin production -Increased 2,3 DPG production -Decreased hemoglobin-oxygen affinity

Acute Blood Loss Adaptations

-Increased respiratory rate -Increased heart rate and cardiac output -Redirected blood flow from the periphery of the body to the vital body core i.e heart and brain

Anemia results in illnesses as diverse as

-Inflammation -Infection =Malignancy -Various systematic diseases

Iron overload can result from

-Inherited alterations in factors that control iron uptake and retention -Chronic disorders like sideroblastic anemia -Iron therapy or transfusion -Hemolytic anemias -Hereditary hemochromatosis

Idiopathic aplastic anemia

-Major form of aplastic anemia, occurs in patients with no established history of chemical or drug exposure or viral infection -Most occur due to immune process

Porphyrias: clinical presentation

-Neurological symptons -Skin problems

Chronic Blood Loss Anemia Laboratory Findings

-Normal WBC and platelets - Normal or slightly increased reticulocytes -Decreased HCT -Iron deficiency

C-Reactive Protein (CRP)

-Number 1 blood test used to diagnose inflammation in the body; increases before anything else goes up; quicker, faster, more accurate than ESR -May or may not correlate with hepcidin levels

Aplastic Anemia

-One of a group of disorders known as hypoproliferative disorders, that are characterized by reduced growth or production of red blood cells -Bone marrow failure

The cause of IDA is

-nutritional deficiency -faulty iron absorption -excessive loss of iron

Iron deficiency is still common in

-toddlers -adolescent girls -women of childbearing age

Diagnosis of aplastic anemia is made when at least __ of the three PB values fall below critical levels

2

In acute blood loss, the return of the red cell profile to previous values takes longer than __ weeks.

2

Acute blood loss occurs within

24- 48 hours

It can be ___ to ___ hours after the hemorrhage until the full extent of the red cell loss is apparent.

48 to 72

Shock

A condition where severe hemorrhage or rapid blood loss amounts to more than 20% of the circulating blood volume reduces and individuals total blood volume

Hepcidin

A small plasma protein that is a key molecule in controlling iron absorption and recycling

Is a hypoproliferative defect not related to any nutritional deficiency

AOI/ACD

Clinical signs and symptoms of Fanconi's Anemia

About 50% of patients show clinical abnormalities such as short stature, microcephaly, malformed thumbs, strabismus, and mental retardation

The systemic diseases that produce AOI are accompanied by the release of __________________ in the blood.

Acute Phase Reactants: --Elevated C-Reactive Protein --Fibrinogen --Haptoglobin --Ceruloplasmin

Anemias can be caused by

Acute or Chronic Blood Loss

Pancytopenia

All cell lines show a decrease

Cytopenia with a hypocellular marrow can impact:

All three cell lines, resulting in a pancytopenia as in constitutional aplastic anemia

In acute blood loss, the body itself adjusts to the situation by expanding the circulatory volume, which produces the subsequent ___________________.

Anemia

ACD

Anemia of Chronic Disease

AOI

Anemia of Inflammation

Acute Loss of Blood

Associated with traumatic conditions such as an accident or severe injury; may occur during or after surgery

Hypoproliferative

Bone marrow not making enough cells

IDA Indice progression

MCV-normocytic to microcytic MCHC-normochromic to hypochromic Retic count- normal or low

Iron Deficiency with Severe Anemia (Iron Study)

Marrow iron stores- 0 Serum Iron Level- Decreased Fe binding capacity- Increased Hemoglobin- Decreased Microcytic/Hypochromic- 4+ Ferritin- Decreased Free RBC protoporphyrin level- Decreased

AOI/ACD cases can be caused by:

Neoplasms Rheumatoid Arthritis Rheumatic Fever Systemic lupus erythemotosus (SLE) Uremia Chronic liver disease

Sequential phases of iron deficiency:

Prelatent-Decrease in storage iron (ferritin) Latent-Decrease in functional and circulating iron for erythropoiesis (decreased serum iron and increased TIBC/UIBC) Anemia-Decrease in circulating red blood cell parameters (RBC/H&H); decrease in oxygen delivery to peripheral tissues

The cytochemical stain that can demonstrate iron, hemosiderin, and ferritin is

Prussian Blue

Absolute Iron Deficiency

Represents a decrease in total body iron caused by blood loss, decreased intake of iron, or increased utilization of iron

Functional Iron Deficiency

Represents inadequate utilization of iron stores; such as iron sequestration syndromes like ACD/AOI

ACD/AOI Iron Levels

Serum Iron-- Decreased TIBC-- Normal or decreased Serum Ferritin--Normal to increased Transferrin Saturation--Decreased RBC morphology-- Normocytic or microcytic, hypochromic

IDA Iron Levels

Serum Iron-- Significant decrease TIBC-- Increased Serum Ferritin-- Decreased Transferrin Saturation--Decreased RBC morphology--microcytic/hypochromic

In this type of anemia, the body has a sufficient amount of iron but unable to incorporate into hemoglobin

Sideroblastic Anemia

ACD/AOI Treatment

Treatment of the underlying cause of anemia is the most direct approach

Hemogloblin and hematocrit do not fall immediately during acute blood loss.

True; but fall as tissue fluids move into the blood circulation

Constitutional Aplastic Anemia

Designates a congenital or genetic predisposition to bone marrow failure

iatrogenic

Drug related

Increased platelets can be observed in

acute blood loss

Increased iron utilization can be the result of

adolescent growth spurt

The sudden appearance of aplastic anemia or pure red cell aplasia is often caused by

an immune process

The chronic and continual loss of small volumes of blood does not disrupt the

blood volume

True aplastic anemia is characterized as a

bone marrow failure and results in inadequate production of hemopoietic cells

Faulty iron absorption can result from

celiac disease

Disorders of the GI system or heavy menstruation can cause

chronic blood loss

Results in an iron deficiency and hypochromic RBC morphology on a peripheral blood smear

chronic blood loss

The blood volume is not disrupted in

chronic blood loss

Retic count increase in

chronic blood loss situation

Cytopenia

deficiency of cells

If only one cell line is involved it is usually the

erythrocytic cells

In acute blood loss anemia, an increased number of reticulocytes reach the circulating blood because of increased____________________. This phenomenon takes place beginning approximately __ to __ days after the blood loss and reaches a maximum approximately 10 days late

erythropoiesis; 3-5

Anemia caused by chronic blood loss is characterized by

hypochromic, microcytic erythrocytes

In chronic blood loss anemia, platelets are______________ and only later in severe iron deficiency the are likely to be ________________.

increased; decreased

Gradually chronic bleeding results in ______________________ and the newly formed cells are morphologically ________________ and ______________________.

iron deficiency; hypochromic and microcytic

Long term survivors of acquired aplastic anemia may be at high risk for _________________, both leukemic and solid tumors, years after remission.

malignancy

Serum Iron

measures circulating iron bound to transferrin

Transferrin Saturation

measures percentage of transferrin occupied by iron

Serum Ferritin

measures storage iron

The peripheral blood smear demonstrates______________ red blood cells in IDA

microcytic/hypochromic

Abnormal bone marrow has

more fat and less cells

In acute blood loss, it takes about 2 weeks for the ________________________to disappear.

morphological picture

In acute blood loss, it takes 2 to 4 days after the blood loss for the total blood cell count to return to

normal

In chronic blood loss anemia, white blood cell count is

normal or slightly decreased

The RBC morphology associated with smears in an otherwise healthy individual caused by acute blood loss is usually

normochromic

In acute blood loss anemia the peripheral blood smear film at 24 hours should be

normochromic and normocytic with normal RBC indices (MCV/MCH.MCHC)

In aplastic anemia RBCs are usually

normochromic with varying degrees of anisocytosis and poikilocytosis with normal RDW in most cases.

They typical blood film of a patient with AOI typically reveals _____________ erythrocytes.

normocytic/normochromic

Chronic blood loss occurs over

periods of months to years

Decreased iron intake can result from

red meat deficient diet

Iron deficiency anemia is a progressive disease so

results may shift as disease progresses

A common feature of sideroblastic anemia is

ringed sideroblasts

In chronic blood loss regeneration of red blood cells occur at a ______________ rate.

slower

In chronic anemias, blood loss of _______ amounts occurs over an extended period, usually months.

small

A noticeable anemia does not usually develop until after______________ iron is depleted

storage (ferritin)

White count and platelet increase when body is

stressed (acute situation)

Approximately half of AOI/ACD cases are caused by

subacute or chronic infections

A characteristic of Fanconi's anemia is

the best described congenital form of aplastic anemia

After acute blood loss, blood smears may not initially look anemic due to

the body releasing plasma to expand blood that is already there

Prussian Blue

this stain reveals the excess iron as blue deposits circling the nucleus like a pearl necklace

Acquired aplastic anemia may be caused by

-benzene/ benzene derivatives -ionizing radiation and vitamin B12 -purine/pyrimidine analogues

Sideroblastic anemia can be caused by

-congenital defects -drugs -associated with malignant disorders

If a patient with aplastic anemia is referred to as exhibiting pancytopenia, which cell lines are affected?

-erythrocytes -leukocytes -thrombocytes

Anemias of inflammation/chronic diseases can be caused by

-inflammation and infection -increased hepcidin production -malignancy

Acute blood loss does not produce an

Immediate Anemia

Sideroblastic Anemia

Inherited or acquired disorder characterized by ringed sideroblasts in the bone marrow

IDA

Iron Deficiency Anemia; can be caused by an absolute or functional iron deficiency