Cytopenias (PEARLS) (Smarty PANCE): Anemia and Leukopenia

Normal or ↓ MCV, ↓ TIBC, ↑ Ferritin (high iron stores), ↓ serum erythropoietin

Anemia of chronic disease

The only anemia where all three cell lines are decreased (pancytopenia) ↓ WBC, ↓ RBC, ↓ Platelets - will have normal MCV and ↓ Retic count

Aplastic anemia

↓ Folate, ↑ MCV (macrocytic anemia). looks like B12 deficienxy but no neurologic symptoms. Common in alcoholics

Folate deficiency

After infection or medication in an African American male + *Heinz Bodies and Bite Cells on smear*. Flare triggers: Fava beans, antimalarials, sulfonamides

G6PD deficiency

History of jaundice, transfusion, new medication or infection (+) direct coombs test

Autoimmune Hemolytic anemia

↓ MCV (microcytic), ↑ TIBC, ↓ Ferritin (low iron stores) ↓ MCH (hypochromic). Associated with *pica* and nail spooning, target cells

Iron deficiency

African American, pain, family history of blood disorder. Hemoglobin electrophoresis: Hemoglobin S, Blood smear: Sickled RBCs, howell-Jolly bodies, target cells

Sickle cell anemia

Microcytic hypochromic, elevated iron. Most severe, Mediterranean descent, failure to thrive. Hemoglobin electrophoresis: Hemoglobin A2 and F.

Beta thalassemia major

Microcytic hypochromic, elevated iron. Mild anemia, often misdiagnosed as iron deficient. Hemoglobin electrophoresis: Hemoglobin A2

Beta thalassemia trait

Chinese and southeast Asians. Hemoglobin electrophoresis: Hemoglobin H (H disease), Hemoglobin Bart's (hydrops fetalis), Hemoglobin A (trait)

Alpha thalassemia

↑ MCV (macrocytic anemia), Hypersegmented Neutrophils and normal folate, decreased vibratory and position sense

Vitamin B12 deficiency

Less than 10% radiolabeled vitamin B12 in urine. Normal results when repeated with administration of intrinsic factor

Schilling test for the diagnosis of pernicious anemia (antibody to intrinsic factor) (test is no longer used in the USA)

What type of anemia are cephalosporins, PCN, NSAIDs, and methyldopa associated with?

Immune hemolytic anemia

Erythropoietin analogs should only be initiated if the hemoglobin is < ____?

10 mg/dl

Erythropoietin analogs should be suspended once the hemoglobin is >_____?

11 mg/dl

What two types of anemia have macroovalocytes?

B12 and folate deficiency

Which anemia has a decreased MCV, decreased MCH (hypochromic) yet normal TIBC and ferritin?

Thalassemia

Acute chest syndrome occurs during the acute phase of which anemia?

Hemolytic sickle cell crisis

What are some common oxidative events which may trigger hemolysis in G6PD deficiency?

Antimalarials - Sulfa drugs - Aspirin - Febrile Illness - Acidosis - Fava beans

What type of anemia does a (+) osmotic fragility test indicate?

Hereditary Spherocytosis

What does an increased LDH, decreased haptoglobin, and increased indirect bilirubin represent?

Hemolysis

What type of anemia does a + direct coombs indicate?

Autoimmune hemolytic anemia

Which type of anemia is most likely associated with leukopenia and thrombocytopenia?

Aplastic anemia

How would you expect TIBC and ferritin to present in anemia of chronic disease?

Decreased TIBC - Normal/increased Ferritin

Anemia of renal failure is defined by decreased levels of which hormone?

Erythropoietin

Can oral B12 be used as an initial treatment in a B12-deficient patient?

Yes - Oral B12 is considered initial therapy - Other routes if oral fails or pernicious anemia is diagnosed

Which route is best for administering B12 to a deficient patient?

Sublingual IM or deep subcutaneous

Increased MCV with smooth tongue, loss of proprioception and vibratory sense is likely which type of anemia?

B12 deficiency

List 5 common causes of folate deficiency

EtOH abuse - Advancing age - Gastric bypass - Pregnancy - Methotrexate

What symptom differentiates B12 from folate deficiency ?

Neuropathy occurs with B12 deficiency but not with folate deficiency

Slowly decreasing MCV in an elderly patient?

Occult GI blood loss

Pica is a specific symptom of which type of anemia?

Iron deficiency anemia

Decreased Ferritin and Increased TIBC?

Iron deficiency anemia

What surgery can induce B12 deficiency?

Gastric bypass

Anemia due to renal failure may be confirmed by which test?

Decreased serum erythropoietin levels

What type of megaloblastic anemia causes neurologic deficits?

Vitamin B12 deficiency

What type of anemia can occur in hypothyroidism?

Macrocytic non-megaloblastic anemia

What factor is produced in the stomach and required for Vitamin B12 absorption?

Intrinsic factor

What test confirms the diagnosis of pernicious anemia?

Antibodies to intrinsic factor and parietal cells

Which anemia is associated with bilirubin cholelithiasis?

Hereditary spherocytosis

What is the Dx? Very low MCV, normal/high RBC, normal RDW and high/normal serum iron normal TIBC.

Thalassemia

What is the Dx? Low MCV, low RBC, high RDW, low serum iron, high TIBC.

Iron deficiency anemia

What is the Dx? Microcytic hypochromic anemia, low serum iron and low TIBC. Unresponsive to iron therapy.

Anemia of chronic disease

Basophilic stippling of RBCs?

Lead poisoning (May also occur in thalassemia and chronic EtOH abuse)

Type of anemia in which serum iron is decreased and TIBC is increased?

Iron deficiency anemia

What is the Dx? Teenage African American with severe bone and joint pain severe anemia.

Sickle cell disease

What is the etiology of pernicious anemia?

Antibodies to gastric parietal cells and intrinsic factor

Which anemia is most commonly associated with EtOH abuse?

Folate deficiency

List three medications which may trigger autoimmune anemia

Cephalosporins - Penicillins - NSAIDs

Priapism may occur in which acute anemia?

Sickle cell crisis

What test is diagnostic for sickle cell disease?

Hemoglobin electrophoresis

Which test is more sensitive than B12 levels for B12 deficiency in early disease?

Increased Methylmalonic acid levels occur in early B12 loss and may precede decreased serum B12 levels

What are the two medications available for treatment of anemia due to renal failure?

Epoetin alfa and darbepoetin alfa

Which test is most specific for hemolysis?

Haptoglobin is decreased in both extra and intravascular hemolysis

List three medications which may cause aplastic anemia.

ACE inhibitors - Sulfonamides - Phenytoin

What heritage is associated with an increased chance of thalassemia?

Mediterranean descent

A 31 year old Mediterranean female has a hemoglobin of 10.3 gm/dl, MCV of 54, TIBC and Ferritin are normal. What is the most likely etiology of her anemia?

Thalassemia minor

Measurement of which laboratory value is the best indicator of whether or not a sickle cell crisis is resolving?

Reticulocyte count - Decreasing reticulocyte counts are the best indicator that a crisis is resolving

What medications related to travel can be an oxidative trigger for a patient with G6PD?

Anti-malarial medications

A 42 year-old black female with SLE has an increased bilirubin and a mild anemia. Which test is most definitive to evaluate this patient's anemia?

Direct coombs in patient with autoimmune anemia

A patient who recently started lisinopril has a hemoglobin 7.4, WBC 1.1, platelets 55. What is the most likely disorder?

Aplastic Anemia

A dialysis patient has been on darbepoetin alfa for 3 months. His most recent hemoglobin is 11.3 gm/dl. Should he continue to use this medication?

No. erythropoetin analogs must be stopped when the hemoglobin is greater than 11 gm/dL

A 36 year old black male s/p gastric bypass surgery has peripheral neuropathy. Oral B12 has not improved his symptoms. What is the next step?

Sublingual or IM B12

What antibody test would confirm a diagnosis of pernicious anemia?

Intrinsic factor and parietal cell antibodies

A 74 year old white male with a history of chronic ETOH abuse has an MCV of 102. Physical exam finds no neurological deficit. What is the most likely diagnosis?

Folate deficiency

A 23 year old white female has weakness, fatigue and has developed a habit of chewing ice. What are the expected findings in regard to TIBC and Ferritin?

Increased TIBC and decreased Ferritin in patient with iron deficiency anemia

A 74-year-old female with long-standing rheumatoid arthritis that has been difficult to control is seen in the office. She is noting fatigue and exertional intolerance. What laboratory findings do you anticipate and secondary diagnosis?

Laboratory findings: Normal or ↓ MCV, ↓ TIBC, ↑ Ferritin (high iron stores), ↓ serum erythropoietin

● Secondary diagnosis: Anemia of chronic disease

What is anemia of chronic disease?

Anemia of chronic disease is also called anemia of inflammation, which refers to a low red blood cell that may be associated with many chronic disease states like infections, malignancy, diabetes, or autoimmune disorders

What is the disease mechanism of anemia of chronic disease?

The disease mechanism is a two-fold process:

● Shortened RBC lifespan results from direct cellular destruction via toxins from cancer cells, viruses, or bacterial infections.

● Decreased RBC production involves several mechanisms.

What are the symptoms associated with anemia of chronic disease?

Symptoms of anemia of chronic disease are usually mild, including fatigue, pallor, and shortness of breath - and the latter is usually associated with physical activity, like walking up 3 flights of stairs. Anemia of chronic disease is usually discovered incidentally, during the workup for the chronic disease process

Is anemia of chronic disease normocytic, microcytic, or macrocytic?

Initially, the anemia is normocytic, which means that RBCs have a normal size, but eventually it can become microcytic, meaning RBCs get smaller

How is serum iron affected in anemia of chronic disease?

Serum iron is decreased in anemia of chronic disease

How is the total iron binding capacity affected in anemia of chronic disease?

Total iron binding capacity is decreased in anemia of chronic disease

How are ferritin levels affected in anemia of chronic disease?

Ferritin levels are increased in anemia of chronic disease

Summarize the iron studies found in anemia of chronic disease?

low serum iron levels, normal to low TIBC, and normal or increased serum ferritin levels

What are the lab findings in iron deficiency anemia?

There's low serum iron, high TIBC, and low ferritin

What is the treatment of anemia of chronic disease?

Treatment involves correcting the underlying condition, or, in severe cases, RBC transfusions or erythropoietin injections

What medication can be used to treat anemia of chronic disease associated with chronic renal failure?

Erythropoietin can be used to treat anemia of chronic disease associated with chronic renal failure.

Anemia of chronic disease is a nonhemolytic normocytic anemia due to chronic inflammation/disease that can become microcytic/macrocytic in its later stages?

Anemia of chronic disease is a nonhemolytic normocytic anemia due to chronic inflammation/disease that can become microcytic in its later stages

Summarize the lab findings in anemia of chronic disease

Normal or ↓ MCV, ↓ TIBC, ↑ Ferritin (high iron stores), ↓ serum erythropoietin

What is aplastic anemia?

Pancytopenia due to bone marrow hematopoietic failure

What is the most common cause of aplastic anemia?

Aplastic anemia is a type of anemia resulting from bone marrow destruction/failure that can result from radiation exposure, Fanconi anemia, drugs, chemicals, viruses, autoimmune disorders, genetic predisposition, or idiopathic causes.

What is Fanconi anemia?

Aplastic anemia caused by an inherited defect in DNA repair, often associated with congenital anomalies

Pure RBC aplasia (normal WBC/platelets) may be caused by what infectious agent?

Parvovirus B19, typically in patients with underlying hemolytic anemia

What are some substances and drugs that can cause aplastic anemia?

Benzene, chloramphenicol, alkylating agents, and antimetabolites are substances and drugs that can cause aplastic anemia.

What additional viruses are associated with aplastic anemia?

Epstein-Barr virus, hepatitis viruses, and HIV are viruses associated with aplastic anemia.

What is the most accurate diagnostic study for aplastic anemia?

Bone marrow biopsy demonstrating:

- Normal cell morphology

- Hypocellular bone marrow with fatty infiltration

Reticulocyte count in aplastic anemia?

Aplastic anemia is associated with a decreased reticulocyte count

Erythropoietin levels in aplastic anemia?

Aplastic anemia is associated with increased erythropoietin levels

What is the treatment for aplastic anemia?

RBC transfusion, leukoreduced, platelet transfusion.

● Curative: bone marrow transplant for healthy patients under 50.

● Immunosuppressive agents for over 50 or those with comorbidities: anti-thymocyte globulin plus cyclosporine.

● Hematopoietic growth factors: G-CSF (filgastrim) and GM-CSF.

What is folate deficiency?

Folate deficiency is when your blood lacks the amount of vitamin B9 (folate) it needs to function properly.

Is folate deficiency anemia macrocytic or microcytic?

Macrocytic

What are the two megaloblastic forms of macrocytic anemia?

Megaloblastic macrocytic anemia is due to impaired DNA synthesis from

1. Folate deficiency

2. Vitamin B12 deficiency

How does folate deficiency differ in its presentation from vitamin B12 deficiency?

Unlike ↓ vitamin B12, patients with folate deficiency have no neurological symptoms

Abuse of what substance can commonly cause folate deficiency.

Alcohol abuse can commonly cause folate deficiency.

Who is at risk for developing folate deficiency?

Generally, people who get folate deficiency are either pregnant or have had an extremely restricted diet for longer than six weeks. Besides this, excessive alcohol consumption and medications like phenytoin, trimethoprim, sulfasalazine, and methotrexate often interfere with folic acid absorption from the jejunum.

Why are pregnant women at risk for folate deficiency?

Normally, we have up to 2 to 3 months supply of folate in the body, but this can get used up even quicker during pregnancy due to the increased need for it resulting in folate deficiency

Maternal deficiency of folate increases the risk of what?

Maternal deficiency of folate increases the risk of neural tube birth defects

Signs and symptoms of folate deficiency anemia?

Folate deficiency most commonly causes signs and symptoms of anemia like shortness of breath, pallor, and easy fatigability, as well as soreness of the tongue due to glossitis.

Diagnosis of folate deficiency?

Diagnosis of folate deficiency can be made by doing a peripheral blood smear, measuring the MCV and serum levels of vitamin folate and B12, as well as serum homocysteine levels. If serum folate is < 3 deficiency is likely. After confirming that there is folate deficiency, the cause should be found.