Hematology Flashcards
Anemia gen info
- A reduction in the number of circulating red blood cells, as measured by hemoglobin or hematocrit
- When red cell mass decreases, several compensatory mechanisms maintain oxygen
delivery to the tissues, including:
a. Increased cardiac output
b. Increased oxygen extraction ratio
c. Rightward shift of the oxyhemoglobin curve (increased 2,3-diphosphoglycerate [2,3-DPG])
d. Expansion of plasma volume - Symptoms are highly variable, depending on the severity of anemia, the rate at which it developed, and the underlying oxygen demands of the patient. If anemia develops rapidly, symptoms are more likely to be present, because there is little time for
physiologic compensation. If the onset is gradual, compensatory mechanisms are able to
maintain adequate oxygen delivery to tissues, and symptoms may be minimal or absent. - As general rule, blood transfusion is not recommended unless either of the following
is true:
a. Hb <7 g/dL OR
b. Patient requires increased oxygen-carrying capacity (e.g., patients with coronary
artery disease or some other cardiopulmonary disease)
Pseudoanemia or dilutional anemia > decr Hb of Hct secondary to volume infusion or overload
Anemia gen sxs
- Fatigue
- Dyspnea
- Headache
- Palpitations
- Tachycardia
- Pallor– best noted in conjunctiva
- Signs/symptoms of the underlying cause: orthostatic lightheadedness, syncope, or
hypotension if acute bleeding; jaundice if hemolytic anemia; blood in stool if Gl bleeding
Anemia gen dx
- Decreased Hb and Hct
a. Formula for converting Hb to Hct: Hb × 3 = Hct (1 unit of packed RBCs increases Hb level by 1 point and Hct by 3 points)
b. Hb of 7 to 8 provides sufficient oxygen-carrying capacity for most patients– anemia is not tolerated as well in patients with impaired cardiac function - Reticulocyte index
a. Reports the number of reticulocytes present as a percentage of the total number of RBCs
b. The reticulocyte count is an important initial test in evaluating anemia because it
indicates whether effective erythropoiesis is occurring in the bone marrow.
c. Effective erythropoiesis is dependent on adequate raw materials (iron, vitamin B12, folate) in bone marrow, absence of intrinsic bone marrow disease (e.g., aplastic anemia), adequate erythropoietin from the kidney, and survival of reticulocytes (no premature destruction before leaving the bone marrow)
d. Reticulocyte index >2% implies bone marrow is responding to increased RBC requirements
e. Reticulocyte index <2% implies inadequate RBC production by bone marrow - RBC indices
a. MCV > average size of RBCs
b. Mean corpuscular hemoglobin (MCH) > average Hb content of RBCs
c. Mean corpuscular hemoglobin concentration (MCHC) > average Hb concentration in each RBC
d. RDW > variation in RBC size - Peripheral blood smear
Transfusion pearls
PRBCs (contain no platelets or clotting factors)
• Mix with normal saline to infuse faster (not with lactated ringer solution because calcium causes coagulation within IV line)
• One unit raises hematocrit by 3-4 points
• Each unit may be given for over 90-120 minutes
• Always check CBC after the transfusion is completed
FFP
• Contains all of the clotting factors
• Contains no RBCs/WBCs/platelets
• Given for high PT/PTT, coagulopathy, and deficiency of clotting factors– FFP can be given if you cannot
wait for vitamin K to take effect or if patient has liver failure (in which case vitamin K will not work)
• Follow up PT and PTT to assess response
Cryoprecipitate
• Contains factor VIll and fibrinogen
• For hemophilia A, decreased fibrinogen (DIC) and vWD
• Platelet transfusions– 1 unit raises platelet count by 10,000
• Whole blood only for massive blood loss
• Massive blood loss > ideal ratio of platelets: FFP: PRBCs transfused should be 1:1:1. Blood should be warmed to prevent a decrease in core body temperature.
Hemolytic Transfusion Reactions
Intravascular Hemolysis (aka acute hemolytic reactions):
• Very serious and life-threatening > caused by ABO-mismatched blood transfused into patient (usually due to clerical error). For example, if B blood is given to type A patient, anti-B IgM antibodies attach to all of the infused B RBCs, activate the complement pathway, and produce massive intravascular hemolysis as C9 punches holes through RBC membranes.
• Sxs: fever/chills, nausea/vomiting, pain in the flanks/back, chest pain, dyspnea
• Complications: hypovolemic shock (hypotension, tachycardia), DIC, renal failure with hemoglobinuria
• Tx: stop transfusion immediately + aggressively replace fluid to avoid shock and renal failure, epinephrine for anaphylaxis, dopamine/norepinephrine prn to maintain blood pressure
Extravascular hemolysis (also called delayed hemolytic transfusion reaction).
• Extravascular hemolysis is less severe and in most cases is self-limited; may occur within 3-4 weeks after a transfusion
• Caused by one of the minor RBC antigens. For example, if a patient is Kell antigen-negative and has anti-Kell IgG antibodies from a previous exposure to the antigen, re-exposure of her memory B cells to Kell antigen on RBCs will result in synthesis of IgG anti-Kell antibodies. These antibodies coat all of the Kell antigen-positive donor RBCs, which will be removed extravascularly by macrophages in the spleen, liver, bone marrow.
• Sxs: more subtle > fever, jaundice, anemia
• No treatment required- good prognosis
Diagnosing the Cause of Anemia (General Approach)
- For RI <2% indicating an inadequate bone marrow response > examine PBS and RBC indices
a. If microcytic anemia (MCV <80), ddx:
• Iron deficiency anemia– mc
• Anemia of chronic disease– iron present in the body but is not available for hemoglobin synthesis due to iron-trapping in macrophages.
• Thalassemia– defective synthesis of globin chains
• Sideroblastic anemia (includes lead poisoning, pyridoxine deficiency, ETOH toxic effects)– defective synthesis of protoporphyrins leading to iron accumulation in mitochondria
b. If macrocytic anemia (MCV >100), ddx:
• Vitamin B12 or folate deficiency– defective DNA
synthesis leading to nuclear defects in RBCs
• Liver disease (MCV increases up to 115)– abnormal incorporation of plasma lipoproteins into RBC membranes alters RBC shape and increases their volume
• Stimulated erythropoiesis (MCV increases up to 110)– reticulocytes are larger than mature RBCs, resulting in an increase in polychromatophilic RBCs
• Alcoholism
• Hypothyroidism
c. If normocytic anemia (MCV 80-100), ddx:
• Aplastic anemia– bone marrow failure
• Bone marrow fibrosis
• Bone marrow infiltration
• Anemia of chronic disease
• Renal failure– decreased erythropoietin production results in decreased erythropoiesis - RI >2%, indicating an adequate bone marrow response, ddx:
a. Acute blood loss
b. Hemolysis
Iron Deficiency Anemia Causes
Microcytic
1. Chronic blood loss
a. Mc cause of IDA
b. Menstrual blood loss is mc source. In absence of menstrual bleeding > Gl blood loss is most likely
Elderly with IDA > rule out colon cancer.
2. Dietary deficiency/increased iron requirements; seen in the following three age groups:
a. Infants and toddlers- occurs especially if the diet is predominantly human milk, which is low in iron; + also have an increased requirement d/t accelerated growth
b. Adolescents- increased requirement d/t rapid growth; adolescent women esp doubly at risk of IDA
c. Pregnant women- pregnancy increases iron requirements
IDA dx
- Iron studies
a. Decreased serum ferritin
b. Increased TIBC/transferrin levels
c. Decreased transferrin saturation
d. Decreased serum iron - Peripheral blood smear— reveals microcytic, hypochromic RBCs
- Bone marrow biopsy– reveals absence of stainable iron; gold standard but only indicated if lab evidence of IDA present + no source of blood loss is found
- Guaiac stool test or colonoscopy if Gl bleeding is suspected— colon cancer is a common cause of Gl bleeding in elderly
IDA tx
- Oral iron replacement (ferrous sulfate)
a. Trial of iron replacement therapy may be given to young, otherwise healthy, menstruating women without investigating for additional sources of blood loss (men and postmenopausal women > attempt to find source of bleeding first)
b. Side effects include constipation, nausea, dyspepsia - Parenteral iron replacement
a. Iron dextran IV or IM
b. Rarely necessary because most patients respond to oral iron therapy– may be useful if poor gut absorption, require more iron than oral
therapy can provide, cannot tolerate oral ferrous sulfate, or certain heart failure patients - Blood transfusion is not recommended unless anemia is severe or the patient has
cardiopulmonary disease
Thalassemias gen info
- Inherited disorders characterized by reduced production of alpha or beta globin chain of hemoglobin
- B-Thalassemias
a. B-Chain production is decreased, but the synthesis of a-chains is unaffected
b. Excess a-chains bind to and damage RBC membrane
c. Severity depends on the number of alleles mutated and the severity of these mutations
d. MC with Mediterranean, Middle Eastern, and Indian ancestry - a-Thalassemias
a. There is a decrease in a-chains, which are a component of all types of hemoglobins
b. Excess B-globin chains form tetramers, which are abnormal hemoglobins
c. Severity depends on the number of alleles that are deleted/mutated, ranging from an asymptomatic carrier state to fetal death
Beta Thalassemia major (Cooley anemia; homozygous B-chain thalassemia)
a. Clinical features
• Severe anemia beginning in late infancy
• Jaundice and dark urine
• Massive hepatosplenomegaly
• Expansion of marrow space– can cause distortion of bones and result in “crew-cut” appearance on skull X-ray
• Growth retardation and failure to thrive
• If untreated, death occurs within the first few years of life secondary to progressive CHF
b. Diagnosis
• Hemoglobin electrophoresis– reveals elevated Hb F and HbA2
• Peripheral blood smear– reveals microcytic, hypochromic anemia +- target cells
Treatment
• Frequent PRBC transfusions required to sustain life
Beta Thalassemia minor
Heterozygous B-chain thalassemia
a. Characterized by asymptomatic carrier state or mild anemia
b. Diagnosed with hemoglobin electrophoresis
c. Peripheral blood smear reveals microcytic, hypochromic RBCs
d. Treatment usually not necessary (patients are not transfusion-dependent)
Beta Thalassemia intermedia
a. Characterized by anemias of varying severity
b. Diagnosed with hemoglobin electrophoresis
c. Peripheral blood smear reveals microcytic, hypochromic RBCs
d. Most individuals are not transfusion-dependent in childhood, but many will become transfusion-dependent in adulthood
Alpha Thalassemia
- Silent carriers (mutation/deletion of only one a-locus)
a. Asymptomatic
b. Normal Hb and Hct level
C. No treatment necessary - a-Thalassemia trait minor (mutation/deletion of two a-loci)
a. Characterized by mild anemia
b. Peripheral blood smear reveals microcytic, hypochromic RBCs
c. No treatment necessary - Hb H disease (mutation/deletion of three a-loci)
a. Characterized by anemias of varying severity
b. Hemoglobin electrophoresis shows Hb H
c. Peripheral blood smear reveals microcytic, hypochromic RBCs
d. Most individuals are not transfusion-dependent, but many require periodic transfusions during episodes of increased hemolysis (e.g., infection) - Mutation/deletion of all four a-loci
Either fatal at birth (hydrops fetalis) or shortly after birth
Sideroblastic Anemia
MICROCYTIC
Caused by abnormality in RBC iron metabolism leading to pathologic iron deposits in RBC mitochondria.
• Hereditary or acquired– acquired causes include drugs (e.g., chloramphenicol, INH, alcohol), exposure to lead, collagen vascular disease, and neoplastic disease (e.g., myelodysplastic syndromes)
Characterized by ringed sideroblasts in bone marrow, increased serum iron, increased serum ferritin, normal TIBC, and normal/elevated TIBC saturation (which distinguishes it from IDA)
Treatment involves removing offending agents and transfusing as necessary– may also
consider pyridoxine
Anemia of Chronic Disease
NORMOCYTIC
Occurs in the setting of chronic infection (e.g., tuberculosis, lung abscess), malignancy
(e.g., lung, breast, Hodgkin disease), inflammation (e.g., rheumatoid arthritis, SLE, or trauma– the release of inflammatory cytokines has a suppressive effect on erythropoiesis)
Generally mild and well tolerated
May be difficult to differentiate from iron deficiency anemia
Laboratory findings include low serum iron, normal-to-low TIBC/serum transferrin, and increased serum ferritin
PBS– normocytic, normochromic anemia, but may be microcytic and hypochromic as well
No specific treatment is necessary other than treatment of the underlying process- do
not give iron
Aplastic Anemia
NORMOCYTIC
Bone marrow failure leading to pancytopenia (i.e., anemia, neutropenia, thrombocytopenia)
Causes
a. Idiopathic–majority of cases
b. Radiation exposure
c. Medications (e.g., chloramphenicol, sulfonamides, gold, carbamazepine)
d. Viral infection (e.g., human parvovirus, hepatitis C, hepatitis B, EBV, CMV, herpes zoster, varicella, HIV), chemical exposure (e.g., benzene, insecticides)
Clinical Features
a. SXS anemia: fatigue, dyspnea, headache, palpitations, pallor
b. SXS thrombocytopenia: petechiae, easy bruising
c. Increased infections– d/t neutropenia
4. Can transform into acute leukemia
Diagnosis
1. Pancytopenia
2. PBS– normocytic anemia + decreased neutrophils, platelets
3. Bone marrow biopsy (for definitive diagnosis)- hypocellular marrow + absence of progenitors of all three cell lines
D. Treatment
1. Discontinue offending agents or treatment of any known underlying causes
2. Transfusion of PRBCs and platelets as necessary– use judiciously
3. Bone marrow transplantation
Vitamin B12 Deficiency gen info
MACROCYTIC
- Vitamin B12 serves as cofactor in two important reactions required for normal erythropoiesis + CNS functioning:
a. conversion of homocysteine > methionine
b. conversion of methylmalonyl-CoA > succinyl-COA - Main dietary sources of vitamin B12 > meat + fish
- After ingestion, vitamin B12 is bound to intrinsic factor (produced by gastric parietal cells) so it can be absorbed by the terminal ileum
- Vitamin B12 stores in liver are plentiful and can sustain an individual for 3+ years
Vitamin B12 Deficiency causes
a. Most commonly due to impaired absorption (either via lack of intrinsic factor or lack of absorptive ileal surface)
b. Pernicious anemia– lack of intrinsic factor due to autoimmune destruction; mc cause in Western world
c. Gastrectomy– lack of intrinsic factor due to removal of parietal cells
d. Inadequate dietary intake (e.g., strict vegetarianism, alcoholism)
e. Crohn disease or resection of terminal ileum (approximately the last 100 cm)
f. Other organisms competing for vitamin B12 (i.e., Diphyllobothrium latum infestation [fish tapeworm] and blind loop syndrome [bacterial overgrowth])
Vitamin B12 Deficiency sxs
- Sore tongue (stomatitis and glossitis)
- Neuropsychiatric changes/dementia > assess vit B12 deficiency dementia workup.
- Neuropathy and subacute combined degeneration of the spinal cord– distinguishes from folate deficiency
a. Leads to a loss of position/vibratory sensation in lower extremities, ataxia, and
upper motor neuron signs (increased deep tendon reflexes, spasticity, weakness, Babinski sign)
b. +- urinary and fecal incontinence, impotence
Vitamin B12 Deficiency dx
- PBS– reveals megaloblastic (macrocytic) anemia with hypersegmented neutrophils
- Low serum vitamin B12 level
- Elevated serum methylmalonic acid and homocysteine levels– most useful if levels borderline
- Antibodies to intrinsic factor (for the diagnosis of pernicious anemia)
S. Schilling test was historically used to determine if B12 deficiency was d/t pernicious anemia but no longer routinely performed
Vitamin B12 Deficiency tx
- Cyanocobalamin (vitamin B12) IM- parenteral therapy is preferred
Folate Deficiency gen info
MACROCYTIC
- Folate plays important role in DNA synthesis
- Green vegetables + folic acid-supplemented foods are main dietary sources
- Folic acid stores in the body are limited, and inadequate intake over a 3-month period can lead to deficiency
- Causes
a. Inadequate dietary intake (e.g., “tea and toast” diet, alcoholism) mc cause
b. Long-term use of oral antibiotics
c. Increased folate requirements (e.g., pregnancy, chronic hemolysis)
d. Use of folate antagonists (e.g., methotrexate)
e. Anticonvulsant medications (e.g., phenytoin)
f. Malabsorptive syndromes (e.g., celiac disease)
g. Hemodialysis
Folate Deficiency sxs
- Similar to those of vitamin B12 deficiency but NO NEURO symptoms
- SXS anemia: fatigue, dyspnea, headache, palpitations, pallor
- Neuropsychiatric changes/dementia– look for folate deficiency in workup for dementia
Folate Deficiency dx
- PBS– reveals megaloblastic (macrocytic) anemia with hypersegmented neutrophils
- Low serum folate level
- Elevated serum homocysteine level– methylmalonic acid levels are normal!!!
Folate Deficiency tx
daily oral folic acid replacement
Hemolytic Anemia gen info
- Premature destruction of RBCs due to a variety of causes
- Bone marrow typically normal and responds appropriately by increasing erythropoiesis, leading to an elevated reticulocyte count. However, if erythropoiesis cannot keep up with the destruction of RBCs, anemia results!
- Hemolytic anemia can be classified according to cause, site, chronicity, or mechanism of destruction.
- Classified based on cause as follows;
a. Hemolysis d/t abnormality extrinsic to RBC– most cases acquired:
• Immune hemolysis
• Mechanical hemolysis (e.g., prosthetic heart valves, microangiopathic hemolytic anemia)
• Medications, burns, toxins (e.g., snake bite, brown recluse spider bite), infections (e.g., malaria, clostridium)
b. Hemolysis d/t intrinsic RBC defects– most cases inherited:
• Hemoglobin abnormality (e.g., sickle cell anemia, hemoglobin C disease, thalassemias)
• Membrane defects (e.g., hereditary spherocytosis, paroxysmal nocturnal hemo-
globinuria (PNH])
• Enzyme defects (e.g., G6PD deficiency, pyruvate kinase deficiency) - Classified based on predominant site of hemolysis as follows:
a. Intravascular hemolysis > within the circulation
b. Extravascular hemolysis > within the reticuloendothelial system, primarily the spleen
Hemolytic Anemia sxs
- SXS anemia: fatigue, dyspnea, headache, palpitations, pallor
- JAUNDICE
- Dark urine color if intravascular process– due to hemoglobinuria, not bilirubin.
- Hepatosplenomegaly, cholelithiasis, and lymphadenopathy if chronic
- SXS underlying disease (e.g., bone crises in sickle cell disease)
Hemolytic Anemia dx
- Low Hb/Hct-level depends on degree of hemolysis and reticulocytosis
- Elevated reticulocyte count– due to increased RBC production
- Peripheral blood smear
a. Schistocytes suggest intravascular hemolysis (“trauma” or mechanical hemolysis)
b. Spherocytes or helmet cells suggest extravascular hemolysis (depending on the cause)
c. Sickled RBCs if sickle cell anemia
d. Heinz bodies if G6PD deficiency - Low haptoglobin (especially with intravascular hemolysis)– haptoglobin binds to
free hemoglobin, so decreased levels suggest hemoglobin release secondary to RBC destruction - Elevated LDH– released when RBCs are destroyed
- Elevated indirect (unconjugated) bilirubin– due to degradation of heme as RBCs are destroyed
- Positive direct Coombs test if autoimmune hemolytic anemia (AIHA)– detects anti-body or complement on RBC membrane
- Positive osmotic fragility test
Hemolytic Anemia tx
- Treat underlying cause
- Transfusion of PRBCs if severe anemia is present or patient is hemodynamically compromised
- Folate supplementation– folate is depleted in hemolysis
Sickle Cell Disease organ involvement
Almost Every Organ Can Be Involved• Blood- chronic hemolytic anemia, aplastic crises
Heart– high-output CHF due to anemia
CNS– stroke
Gl tract– gallbladder disease (stones), splenic infarctions, abdominal crises
Bones– painful crises, osteomyelitis, avascular necrosis
Lungs– infections, acute chest syndrome
Kidneys– hematuria, papillary necrosis, renal failure
Eyes– proliferative retinopathy, retinal infarcts
Genitalia– priapism
