Anemia Flashcards
Define Anemia
A decrease in the circulating RBC mass, with a reduction in one or more of the major RBC measurements:
• RBC count
• Hemoglobin (Hb) concentration
• Hematocrit (Hct): % RBC
Normal ranges for Hb and Hct
Varies but usually Hb:Hct is 1:3
For Males:
Hb 14-18 g/dL
Hct 40-50%
For Females:
Hb 12-16 g/dL
Hct 35-45%
Anemia is defined as Hb<14 in men, <12 in women
Populations for which the normal ranges of Hb/Hct don’t usually apply
Athletes People living at high altitude Smokers African-Americans Chronic disease Older adults
What are reticulocytes and what does the reticulocyte count tell us?
Immature RBCs —> mature RBCs
• spend about 3 days in bone marrow, 1 day in peripheral blood
RBC life-span ~120 days - old RBCs are primarily removed by the spleen
Reticulocyte count (“retic”) can detect abnormalities with bone marrow (should be elevated following blood loss)
Normal retic count = 0.5-2%
Recognizing reticulocytes on a peripheral smear
“Lots of blue means lots of new” - polychromasia (lots of different colors)
Reticulocytes are larger than mature RBCs, lack central pallor (because not yet concave)
Causes of anemia
Decreased RBC production
• Nutritional deficiencies (Iron deficiency, B12/folate deficiency), chronic disease, ineffective erythropoiesis
Increased RBC destruction
• Hemolysis (hemolytic Anemia, malaria)
Blood loss
• Menstrual, GI, trauma
Mean Corpuscular Volume (MCV)
Calculated value to determine average volume (size) of RBCs
Microcytic —> MCV < 80fL
Normocytic —> MCV 80-100fL***
Macrocytic —> MCV >100fL
Mean Corpuscular Hemoglobin (MCH) and Mean Corpuscular Hemoglobin Concentration (MCHC)
Reflect the amount of hemoglobin in RBCs
MCH = avg hemoglobin content MCHC = avg hemoglobin concentration
Low MCH = hypochromic (pale on smear b/c low Hb)
High MCH = hyperchromic
MCH/MCHC usually “follow” MCV
• “Microcytic hypochromic” anemia
Red Cell Distribution Width (RDW)
A measure of the variation in RBC size (normal = 11-15%
Measured by machine
“Anisocytosis” = variation in size of RBCs
Helpful in DDx
Signs and Symptoms of Anemia
Fatigue/weakness Headache Dizziness, Dyspnea, Palpitations (due to cardiac compromise) Pallor Heme+ stool Orthostatic changes Tachycardia
Acute, abrupt onset - may have Sx with relatively mild anemia
Chronic, insidious onset - Sx may not appear until Hb <7-8 g/dL
Three main categories of Anemia
Microcytic hypochromic
• Iron deficiency, thalassemia, sideroblastic anemia
Normocytic, normochromic
• Hypothyroidism, liver disease, chronic disease
Macrocytic (megaloblastic)
• Folate deficiency and vitamin B12 deficiency
Iron Deficiency Anemia
Most common microcytic anemia
Major causes:
• Blood loss (most common cause of iron def in adults in resource rich countries)
• Decreased dietary intake
• Decreased iron absorption (celiac disease, bariatric surgery, H. pylori infection)
Dx study results for iron deficiency anemia
Low RBC, H/H
Microcytic, hypochromic
-MCV sometimes normal in early IDA b/c we deplete our iron stores first before we take it out of circulation
Iron studies:
• Low ferritin (stored iron)
• Low serum Fe
• High TIBC (total iron binding capacity) - we have less so we have more capacity to take it up
Increased RDW (variations in cell size)
Retic count may be low or inappropriately normal
Other clinical manifestations of iron deficiency anemia (besides blood counts etc)
Gloss it is, angular ceilings, koilonychia (spoon nails)
Pica (craving for ice, clay, dust)
Dysphasia (esophageal webs) - Plummer-Vinson syndrome
Restless legs syndrome
Why is it important to identify the underlying cause of iron deficiency anemia?
To rule out occult malignancy
Consider referral for endoscopic and/or radio graphic testing, esp if not woman of child-bearing age
Treatment for iron deficiency anemia
Treat underlying cause
Replace iron stores
• Orally: ferrous sulfate 325 mg BID-TID (must take on an acidic stomach); appropriate response = Hct 1/2 way to normal in 3 weeks, full return in 2 months; continue for 3-6 months after anemia has corrected to replenish stores
• Parenteral iron for select patients (chronic kidney disease - problem of absorption)
Blood transfusions (select patients - not recommended for iron replacement)
Define thalassemia
Inherited hemoglobinopathy —> reduction in the synthesis of globin chains (alpha or beta)
Highest prevalence in parts of Africa, Asia, and the Mediterranean
Leads to ineffective erythropoiesis and hemolysis
Result: variable degrees of anemia and extramedullary hematopoiesis
Can cause bone changes, impaired growth, and iron overload
Different types of Alpha Thalassema
Selection of one or more of the four alpha-globin chains
1 Deletion —> Silent carrier (aa/a-) no symptoms
2 Deletions —> Alpha-thalassemia minor (aa/- -), mild Microcytic anemia
3 Deletions —> Hemoglobin H disease (a-/- -), moderate microcytic anemia (chronic hemolytic anemia)
4 Deletions —> Hydrops fetalis (- -/- -) usually fatal in utero
Different types of Beta-Thalassemia
Due to reduced or absent beta-globin chain synthesis, usually a point mutation rather than gene deletion
Thalassemia Minor (Trait) • Dysfunction of one ß-globin chain • Asymptomatic or mild microcytic anemia (abnormal labs but no Sx)
Thalassemia Intermedia
• Less severe phenotype than Thalassemia Major
• Non-transfusion dependent
• Chronic hemolytic anemia
Thalassemia Major • Dysfunction of BOTH ß-globin chains • Transfusion-dependent • Severe hemolytic anemia • If untreated, 85% of children will die w/in the first 5 years
Lab evaluation for Dx of Thalassemias
Normal to increased RBC MCV is strikingly low (<75 fL) RDW is NORMAL Retic count variably increased Normal to increased ferritin and iron (can have overload) Normal to decreased TIBC
***Hemoglobin Electrophoresis - helps with Dx, detects the type of hemoglobin present
Tx of Thalassemia
Tailored to severity of disease
Folic acid supplementation (b/c needed for erythropoiesis in chronic hemolysis)
AVOID IRON SUPPLEMENTS!
Regular transfusion schedule if severe
May also require iron chelation therapy or splenectomy
Hematopoietic cell transplantation for severe beta thalassemia
Genetic counseling
Sideroblastic Anemia
Hereditary or acquired RBC disorder
Abnormal RBC iron metabolism —> dismissed heme synthesis —> iron accumulation in cells
Hallmark sign of sideroblastic anemia
Ring sideroblasts in bone marrow aspirate (blue-stained iron rings around cells)
May also see siderocytes with Pappenheimer bodies on peripheral smear (reflection of iron accumulation
Causes of sideroblastic anemia
In adults, acquired is more common
Often a variant of myelodysplastic syndrome (MDS)
Other causes:
• Chronic alcoholism
• Medications
• Copper deficiency
Diagnostic Studies for Sideroblastic Anemia
Bone marrow aspirate (***Ring sideroblasts)
MCV - low, normal, or slightly increased (varies)
Elevated RDW
Normal to low retic count
Normal or elevated ferritin
SYSTEMIC IRON OVERLOAD (b/c increased absorption from gut)
• May be indistinguishable from hereditary hemochromatosis
• May lead to irreversible organ damage
Treatment for Sideroblastic Anemia
Pt Ed and referral to hematology Treat underlying cause Discontinue offending drugs Removal of toxic agents Pyridoxine (vitamin B6) - contributes to hemoglobin synthesis Transfusion/management of iron overload
Anemia of Chronic Disease (ACD)
Second most common cause of anemia worldwide (after iron deficiency)
Common chronic systemic diseases • Inflammatory diseases • Rheumatologic disorders •Malignancy • Chronic infection • Organ failure • Anemia of older adults
Pathogenesis for Anemia of Chronic Disease
Hepcidin-induced alterations in iron metabolism
Hepcidin = key regulator of the entry of iron into circulation (traps iron); high levels seen with inflammation —> iron trapping within macrophages and decreased gut iron absorption
Inability to increase erythropoiesis (esp in older populations)
Impaired EPO production (kidney disease)
Sx and Tx for Anemia of Chronic Disease
Sx
• Often mild anemia (Hb of 10-11 g/dL)
• MCV usually normal (normocytic, normochromic)
• Reticulocyte count may be low (particularly if EPO is low)
• Normal or increased serum ferritin
• Serum Fe and TIBC both low in the setting of inflammation
Tx
• Treat underlying disease
• EPO may be of benefit (difficult with comorbidities)
Causes of Macrocytic anemia
Reticulocytosis (hemorrhage/hemolysis)
• “Lots of blue means lots of new”
• Occurs when bone marrow responds as it should to blood loss
Megaloblastic anemias
• Defective DNA synthesis —> disordered RBC maturation, accumulation of cytoplasmic RNA, reduced cell division in BM, and larger RBCs
Other causes:
• Liver disease/alcoholism
• Hypothyroidism
• Gastric bypass surgery
Drug induced megaloblastic anemia
Less common than folate/b12 deficiencies
Caused by meds that interfere with purine or pyramidine metabolism
• Hydroxyurea, chemotherapies, and antiretrovirals are most common
Folate deficiency causes
Folate found in diet (vitamin B9) in beef liver, fresh leafy vegetables, fruits, fortified cereals, rice
Don’t see as much in the US because we have fortified foods
Recommended daily allowance is 400mcg in adults, 600mcg if pregnant, 500mcg if lactating
4-5 months of deprivation can result in macrocytic anemia, with same blood and bone marrow findings as in B12 deficiency
Common causes of nutritional folate deficiency:
Poor nutritional intake (anorexia)
Alcohol abuse
Towards the end of pregnancy (body using more of it)
*Anticonvulsant therapy (enzyme inhibition reduces folate absorption)
Malabsorption syndromes (rare)
Hemolytic anemia
On dialysis (give supplements)
Clinical manifestations of folate deficiency
Symptoms related to anemia
**Glossitis: pain, swelling, tenderness, loss of papillae on the tongue
Vague GI symptoms
*Absence of neurological symptoms (as compared to B12
Folate deficiency in pregnancy can lead to _____________
Neural tube defects
Lab findings for folate deficiency
Low folate level
Normal B12
**High homocysteine level with normal methylmalonic acid (both would be elevated in B12)
Treatment of Folate Deficiency anemia
Treat underlying cause
• Can usually stop supplementation once levels normalize if underlying cause is correctable
Replacement therapy with folic acid (synthetic form of folate)
• ***1 mg PO daily
• Better absorbed with food
Be sure to rule out coexisting B12 deficiency
Vitamin B12 (cobalamin) is available only from _______________.
Dietary consumption of animal products
Daily B12 requirement
1.0 - 2.0 µg
B12 deficiency typically develops over the course of years (not acutely in a few months like folate) — body has large stores of B12
How is B12 absorbed?
Vitamin B12 is bound to intrinsic factor (IF) in the stomach (IF produced by gastric parietal cells)
Vitamin B12 is released from the cobalamin-IF complex in the ileum where it is absorbed
Etiology of Vitamin B12 deficiency
Pernicious anemia • Autoimmune, ***most common cause Vegan diet Malabsorption (elderly) Gastric surgery, gastritis • Partial or complete gastrectomy prevents IF secretion and therefore B12 absorption Ileal disease or resection, bacterial overgrowth or intestinal parasites, and pancreatic insufficiency all prevent B12 absorption Medications • Metformin, H2 antagonists and PPIs
Pernicious Anemia is a deficiency of _____ leading to _____________.
IF deficiency —> B12 malabsorption and megaloblastic anemia
Autoantibodies against the gastric parietal cells impair IF secretion
Sx: • Typical anemia Sx • Glossitis, jaundice, splenomegaly may be present • Neurologically findings*** - decreased vibratory/position sense - ataxia - ***stocking-glove parathesias (hands and feet only) - confusion/dementia
Reversible if treated within six months
Lab findings consistent with pernicious anemia
Macrocytosis (Increased MCV)
Peripheral smear
• Hypersegmented neutrophils (≥ 5 nuclear lobes)
• Anisocytosis, poikilocytosis
• “Macro-ovalocytes” large oval RBCs
Low B12 level
(+) Shilling test or antibodies to IF
High methylmalonic acid AND homocysteine levels
Treatment for Pernicious Anemia
Parenteral Vitamin B12
• Daily IM/SQ injections of 1000mcg for 1 week
• Then weekly injections for 1 month
• Then monthly injections for life
Must do IM/SQ because won’t absorb PO
Treat reversible causes (ie-malabsorption, diet)
What happens if you treat pernicious anemia with folate replacement?
The abnormal blood findings will be corrected but if B12 is not also replaced, the patient may develop serious, possibly irreversible neurological damage —> “subacute combined degeneration of the spinal cord”
***Always test for B12 too before treating folate deficiency
Define hemolytic anemia
Hemolysis = destruction of RBCs
Decreased RBC survival time (normal = 120 days)
RBC survival between 20-100 days can be compensated for by increased production
Marrow cannot compensate for RBC survival < 20 days —> Acute Hemolytic Anemia
Common symptoms of hemolytic anemia
General anemia symptoms
Jaundice
Gallstones (usually bilirubin stones)
Dark urine (product of hemoglobin in urine)
Lab findings for hemolytic anemia
Increased reticulocyte count
Immature RBCs, uncleared RBCs and possibly schistocytes on peripheral smear
Increased unconjugated bilirubin (why you get jaundice, gallstones)
Increased lactate dehydrogenase (LDH)
Decreased hemoglobin
Hemoglobinuria/urine hemosiderin
Decreased haptoglobin in intravascular hemolysis
Direct anti globulin (Coombs) Test (DAT)
Classification of hemolytic anemia is based on __________________.
Site of RBC destruction
Intravascular = within the blood stream
Extravascular = in the reticuloendothelial system (esp the spleen or liver)
It’s possible to have components of both intravascular and extravascular hemolysis!
Examples of causes of intravascular hemolysis
Shear stress (mechanical heart valve) Lysis from bacterial toxins (C. diff sepsis, malaria) Thrombotic microangiopathies (TTP, HUS) Red cell enzyme defects (G6PD deficiency) Paroxysmal nocturnal hemoglobinuria Paroxysmal cold hemoglobinuria Transfusion reactions Severe infection Snake bites
- **Foot strike hemolysis
- **March hemoglobinuria (bongo drummers)
- **Runners’ macrocytosis (marathoners)
Examples of causes of extravascular hemolysis
Hereditary spherocytosis Sickle-cell anemia Thalassemias Red cell enzyme defects (G6PD deficiency - Heinz bodies) Autoimmune hemolytic anemia Liver disease/hypersplenism Certain infections Oxidant agents, IV immune globulin (IV IG)
What is G6PD Deficiency?
X-linked recessive disorder
G6PD is an enzyme essential for ensuring the normal lifespan of an RBC and is involved in the oxidizing process
Deficiency of G6PD or unstable hemoglobin leads to oxidative damage and precipitation of hemoglobin
Oxidative drugs and infections cause episodic hemolysis (episodic pt are usually health, no splenomegaly)
Severe deficiency may cause chronic hemolysis
Female carriers are rarely affected (more common with African Am./Mediterranean descent)
Lab findings for G6PD deficiency
During hemolytic episodes, reticulocytes and serum indirect biliirubin are increased
Peripheral smear:
• Bite cells
• Heinz bodies (denatured hemoglobin)
G6PD levels will be low
Tx - episodes are self-limited as RBCs replaced; avoid oxidative drugs
Hereditary Spherocytosis is a ____________________ disorder characterized by ____________________.
Autosomal dominant disorder; mild hemolytic anemia
RBCs maintain a normal MCV but a smaller surface area —> dense, globular appearance and lack central pallor
RBCs are poorly deformable, get trapped in the splenic sinusoids, and are phagocytized by splenic macrophages
RBC life span is reduced in patients with a spleen, and normal in pots with splenectomy
Clinical features of hereditary spherocytosis
Often asymptomatic, well adapted
May have mild jaundice/sclera icterus
Splenomegaly
Lab finding - Osmotic Fragility Test***
• RBCs demonstrate increased hemolysis on exposure to hypotonic flue due to RBC membrane defect
Treatment for hereditary spherocytosis
***Splenectomy is tx of choice
• Restores RBC life span to normal and removes risk of future bilirubin gallstones
Splenectomy increases the risk of infections from encapsulated organisms (ie Pneumococcus) therefore administer appropriate vaccinations and delay splenectomy until adulthood if possible
Sickle Cell Anemia is a hereditary hemoglobinopathy due to ________________
Autosomal recessive gene
Homozygous HbSS —> sickle cell disease and Sx
Heterozygous HbS/HbA —> asymptomatic carrier
Occurs primarily in those of African-American descent
• 8-10 % carriers, 1/500 have disease
• for those with HbS/HbA, 1/4 chance their offspring will have disease
Males and females equally affected
RBCs become sickle shaped when deoxygenated, causing painful symptoms
Clinical findings in sickle cell anemia
Usually develops in childhood (after HbF replaced)
Vaso-occlusive ischemic tissue injuries —> Pain crises —> avascular osteonecrosis of the femoral and humeral heads, CVA, MI, Splenic infarcts, leg ulcers
Sx precipitated by: • Dehydration • Hypoxia • High altitude • Intense exercise
Lab findings in sickle cell anemia
RBCs are normochromic, normocytic Thrombocytosis may be present Increased reticulocyte count (10-20%) Peripheral smear shows: • Sickled RBCs • Nucleated RBCs • Target cells • Howell-Jolly bodies*** classic sign
Hemoglobin electrophoresis reveals HbS in RBCs ** to confirm Dx
Treatment for Sickle Cell Disease
Avoid precipitating factors
RBC transfusions as needed
Analgesics, fluids, and oxygen during pain crisis
Vaccinations and folate supplementation
Hydroxyurea (chemo) to decrease incidence of painful crises
• Suppresses BM function of all cell lines though
Bone marrow transplant may also help
Life expectancy. = 40-50 years
Autoimmune Hemolytic Anemia (AIHA)
Primary: No underlying systemic disorder
Secondary: identifiable underlying systemic illness
Immunologic destruction of RBCs mediated by autoantibodies directed against antigens on the patient’s RBCs
Clinical manifestations depend on the type of antibody that is produced
• IgM = “cold” agglutinins
• IgG = “warm” agglutinins
Major causes/associations for AIHA
SLE (up to 10%) and other autoimmune or connective tissue diseases
Hematologists malignancies
Preceding viral infection (children)
Immune deficiency diseases
HIV
Prior blood transfusion, stem cell transplant, or solid organ transplant
Drugs
**Note - at risk for VTE
Clinical findings for AIHA
Typical symptoms of hemolytic anemia
Pallor, jaundice, splenomegaly
Fevers
Lymphadenopathy (look for underlying condition)
Hemoglobinuria (dark urine)
***Acrocyanosis (dark purple to gray discoloration of fingertips, toes, nose when exposed to cold
Labs for AIHA
Typical labs for hemolytic anemia
Direct antiglobulin (Coombs) test
Tx of AIHA
Depends on “warm” or “cold” disease and age
• “Cold” AIHA does not need to be treated in most children (mild and self-limited)
***Corticosteroids are first line
Rituximab: antibody that targets B cell lymphocytes
Cytotoxic agents
Splenectomy
FIRST stabilize the patient and search for underlying causes
Hemolytic Transfusion Reactions occur during or within __________ of transfusion
4 hours (though less severe rxn can occur up to 4 weeks later)
Fever Hemoglobinuria Severe hypotension Severe flank pain Pain at infusion site Chest tightness DIC (oozing from IV site) N/V/D
Severity correlates with the amount of blood transfused
When suspected, act immediately!
Treatment for hemolytic transfusion reaction
Stop the transfusion!
Treat with IVF and blood pressure support
Submit a transfusion reaction work up (tests donor blood for problem)
Aplastic Anemia is …
An immune injury of hematopoietic stem cells that may be life-threatening
It may be total or selective for RBCs, WBCs or platelets (or all three)
> 50% of cases are idiopathic
Other causes: Drug or chemical exposure (benzene, chloramphenicol, chemo)** Viral illness (EBV, CMV, Hepatitis)** Ionizing radiation Genetic
Clinical features of aplastic anemia
Sx related to pancytopenia
• Weakness and fatigue due to progressive anemia
• Recurrent infections due to neutropenia
• Bleeding or hemorrhage due to thrombocytopenia
Lab findings for aplastic anemia
***Pancytopenia is the hallmark (all lines down)
• Anemia (and reticulocytopenia)
• Leukopenia
•Thrombocytopenia
Bone marrow shows absence of precursors of those cells (normoblasts, granulocytes, megakaryocytes)
Tx for aplastic anemia
Identify cause and if possible, treat
Differentiate from other serious illness that may require different Tx: Acute leukemia, myelodysplasia, granulomatous infection involving marrow (TB)
Hematology referral
***Bone marrow transplant = preferred Tx (immunosuppressive therapy if no BM transplant)
