Hematology 1 Flashcards
What are 4 possible mechanisms of developing anemia?
Blood loss (acute or chronic)
Decreased absorption
Deficient erythropoesis
Excessive Hemolysis
What are some risk factors of anemia?
dietary deficiencies, menstruation, gastric ulcer, blood in stool, pregnancy, lactation, hemoglobinopathies, alcoholism, prescription drugs, cancer, rheumatic disorders, chronic inflammatory disease, COPD, CHF, heart disease heart valve, marathon running
What are symptoms of anemia?
most occur only if anemia is severe
Weakness, fatigue, seeing spots, drowsiness, syncope, angina, SOB, DOE. May also see vertigo, HA, tinnitus, pica, restless leg syndrome, amenorrhea or menorrhagia, loss of libido, and GI complaints.
What are important signs in PE to assess for anemia?
Blood pressure - supine, seated and standing (orthostatic)
Inspect conjunctiva, lines of palms, mucus membranes, skin color - pallor
Inspect nails for blueness, ridges, spooning, poor nutrition
Cardiovascular exam - increased heart rate, murmurs,
Splenomegaly
peripheral neuropathy
abdominal distention
petechiae
What are some tests that could be done to assess anemia?
Stool occult blood test
CBC with peripheral smear to help differentiate deficient RBC production from excessive RBC destruction
Iron, ferritin, TIBC if CBC or sxs warrant
TSH, free T4 (fatigue, menstrual complaints)
Serum bilirubin, LDH (elevated in hemolysis); if anemia is present
What is microcytic anemia? Some causes?
MCV <80 fL
Altered heme or globin synthesis from:
Iron deficiency, thalassemia, and Hb-synthesis defects, copper deficiency, zinc poisoning, lead poisoning, alcohol.
MB seen in anemia of chronic disease
What is macrocytic anemia? Causes?
MCV > 95 fL
Impaired DNA synthesis from:
B12, folate deficiencies, chemotherapeutic agents, alcoholism, HIV anti-retroviral agents, myelodysplastic disorders
What could cause normocytic anemia?
deficient EPO, hemorrhage
What do elevated reticulocytes indicate? What about decreased reticulocytes?
elevated = excessive RBC destruction decreased = low RBC production
Why would you see RBC fragments, ovalocytes, or schistocytes in smear?
RBC injury
What is meant by anisocytosis? Poikilocytosis?
Anisocytosis: RBCs of excessive variation in size are present
Poikilocytosis: RBCs of excessive variation in shape are present
What would be some indications for ordering bone marrow aspiration and biopsy?
Unexplained anemias Other cytopenias Unexplained leukocytosis Thrombocytosis Suspected leukemia, multiple myeloma, or myelophthisis
What lab result would indicate deficient erythropoesis? What are examples of anemias caused by deficient erythropoesis?
Seen by decreased reticulocytes (Reticulocytopenia)
Microcytic - iron deficiency anemias - iron-transport deficiency anemias - iron-utilization anemias - thalassemias Normocytic - bone marrow failure Macrocytic - B12, folate deficiencies
What is the most common anemia?
Iron deficient anemia
What are some symptoms of severe iron deficient anemia?
pica, glossitis, cheilosis, concave nails, increased heart rate, dyspnea, restless leg syndrome, glossal pain, reduced salivary flow leading to dry mouth, atrophy of tongue papillae, cheilosis, and occasionally, alopecia
Where is the GI is iron absorbed?
What percentage of iron is absorbed?
What is the daily requirement of iron?
How is non-heme iron absorbed?
Absorbed in stomach, duodenum and upper jejunum
about 1mg of every 15mg is absorbed
daily requirement - 25 mg/day
Absorbed best as heme iron (meat products)
Non-heme iron must be reduced and unbound from other food molecules (gastric secretions)
What helps iron absorption? What hinders iron absorption?
Ascorbic acid increases non-heme iron absorption
Reduced absorption by antacids, plant phytates (wheat, cereals), tannins (black tea), lead and malabsorption disorders such as achlohydria, atrophic gastritis, Helicobacter pylori gastritis, SIBO, gastric bypass, and celiac disease
How is iron stored in the body?
Ferritin – liver, bone marrow, spleen, RBCs, and serum
Hemosiderin – Liver, marrow
What are the causes of iron deficient anemia in men? in women? and in children?
MEN - chronic bleed (colon cancer, colitis, PUD, ASA use)
WOMEN - menstruation, repeated pregnancy
CHILDREN - growth spurts
Also due to chronic vascular hemolysis, post gastrectomy, malabsorption, under nutrition
What are some labs that would help diagnose iron deficient anemia?
- Stool Occult blood (Men, post-menopausal women, women with normal menses)
- Iron absorption test (fasting serum iron level is compared to a second serum iron level obtained one to four hours following oral ingestion of one 325 mg tablet of iron sulfate - Should increase at least 100 microg/dL if absorption is normal
- CBC with peripheral smear - LOW Hb, Hct, RBC, MCV, and HIGH RDW
- serum iron - LOW
- iron-binding capacity - HIGH
- serum ferritin - LOW
What is sideroblastic anemia?
- Inadequate or abnormal utilization of marrow iron, in spite of adequate stores
- Usu part of myelodysplastic syndrome, hereditary or secondary to drugs or other toxins. Reversibly if dt alcoholism, copper deficiency (zinc excess), drugs or hypothermia
- Also may occur in hemoglobinopathies (thalassemia)
How is sideroblastic anemia diagnosed (lab results)?
- CBC - microcytic, high RDW
- serum iron - HIGH
- transferrin - HIGH
- ferritin - HIGH
- peripheral smear - anisocytosis,
- BM biopsy - erythroid hyperplasia
*Check serum lead concentration if cause is unknown
What are some causes of anemia of chronic disease?
infectious inflammatory neoplastic disease severe trauma heart failure diabetes mellitus anemia of the elderly acute/chronic immune activation
What are labs done to diagnose anemia of chronic disease?
CBC - (Hb usually 10-11, normo/microcytic, normo/hypochromic, RDW normal early)
peripheral smear
Iron values are normal unless underlying deficiency
ESR and CRP if underlying cause is unknown
EPO maybe depressed
What is hypoproliferative anemia?
Low marrow activity due to lack of EPO or inability of marrow to respond to it
Associated with renal disease
Also associated with hypo metabolic/endocrine deficiency states: hypothyroidism, hyperthyroidism, panhypopituitarism, and primary or secondary hyperparathyroidism
What are some causes of aplastic anemia?
genetic or acquired
- Chemical exposure: drugs, pesticides, industrial chemicals, benzenes, anti-cancer agents (unknown mechanisms)
- Infections such as Parvo-B19, HIV, hepatitis, EBV
- Genetic inability to clear toxicity via glutathione S-transferase
- Fanconi’s anemia – rare type of inherited aplastic anemia
- Pure red cell aplasia due to infections, thymomas, immune system injury, fertilizer exposure, B2 deficiency, CLL
What would be some SSxs of aplastic anemia?
- Anemia: pallor, tachycardia, fatigue, dizziness
- Thrombocytopenia: petechiae, ecchymosis, bleeding from gums, ocular fundi, other tissues
- Agranulocytosis: life-threatening infections
- Suspect in (particularly young) pts with pancytopenia (WBCs <50,000/µL)
What lab values are associated with aplastic anemia?
Low RBCs Low WBCs Low platelets Low reticulocytes High iron Acellular bone marrow
What is myelophthisic anemia?
Marrow is replaced by a tumor, granuloma, lipid storage diseases, or fibrosis
Causes fatigue, night sweats and bone pain, and possible spenomegaly
What lab values would you see with myelophthisic anemia?
marked anisocytosis and poikilocytosis
nucleated red cells in the blood
Immature myeloid cells in the blood
Bone marrow biopsy is definitive (refer)
What are some causes of macrocytic anemia?
High MCV due to defective DNA synthesis
Caused by alcoholism, B12 deficiency, folate deficiency, cytotoxic drugs, hypothyroid, liver disease
What is megaloblastic anemia?
Term given to anemia due to B12 or folate deficiency - Folate deficiency is much more common than B12 deficiency
What are causes of B12 deficiency?
Gastric abnormalities - pernicious anemia, gastrectomy/bypass surgery, gastritis, autoimmune
SI disease - malabsorption, ileal resection/bypass, Chrohn’s
Pancreatitis - pancreatic insufficiency
Diet - strict vegans, vegetarian during pregnancy
Agents that block absorption - neomycin, biguanides, PPIs, N2O anesthesia
What are some causes of folate deficiency?
Nutritional deficiency - substance abuse, alcohol, poor diet, overcooked foods, depression
Malabsorption - Celiac, IBD, infiltrative bowel disease, short bowel syndrome
Drugs - methotrexate, trimethoprim, EtOH, phenytoin
Increased requirement - pregnancy, chronic hemolysis, exfoliative dermatitis
What are SSxs of macrocytic anemia?
Usually none until severe Neuro signs - neuropathy, dementia Glossitis Diarrhea Muscle wasting
What are labs associated with macrocytic anemia diagnosis?
MCV > 95-100 Anisocytosis (high RDW) Poikilocytosis Howell Jolly bodies Hypersegmented PMNs Neutropenia (late) Vitamin B12 and folate levels to determine cause - inaccurate
What are different causes of intrinsic hemolytic anemia?
Abnormal RBC membranes
RBC metabolic disorders
Hemoglobinopathies
What are extrinsic causes of hemolytic anemia?
Hypersplenism (traps RBCs) Toxic exposures (oxidants) Autoimmune Mechanical injury (prosthetic valves, DIC, TTP) Infections (malaria, C. perferingens)
What are typical SSxs associated with hemolytic anemia?
acute hemolytic crisis presents with fever chills, back/abdominal pain, prostration, shock
severe hemolysis presents with jaundice and splenomegaly, and maybe cholelithiasis
What labs/PE findings would make you suspect hemolytic anemia in a patient?
Anemia Splenomegaly Jaundice Elevated reticulocytes Spherocytosis Elevated Bilirubin Elevated LDH
What is autoimmune hemolytic anemia? What are the different types?
Body makes antibodies to its own RBCs
Can be ‘warm’ or ‘cold’ based on temperature of body that induces Ab formation
What are the difference causes of warm and cold AIHA?
WARM - most common - Abs react at temperatures > 37C - viral infections - immune deficiency - drugs - SLE - lymphoma - CLL - spontaneous/idiopathic COLD - Abs react at temps < 37C - infections (M. pneumonia) - lymphoproliferative states - 50% are idiopathic/chronic **May see acrocyanosis, Raynoaud;s levido reticularis, scleral icterus, splenomegaly
What test is done to diagnosis AIHA?
Coombs - dierect antiglobulin test - Ab patterns determine warm vs cold
What is hereditary spherocytosis?
Intrinsic hemolytic anemia
Autosomal dominant congenital red cell membrane defect leading to hemolysis of spherical RBCs causing anemia
What is hereditary elliptocytosis?
Intrinsic hemolytic anemia
RARE autosomal dominant congenital red cell membrane defect causing oval or elliptical RBCs leading to anemia
What are the SSxs associated with spherocytosis/elliptocytosis?
Anemia Jaundice Hepatomegaly Splenomegaly Cholelithiasis
What labs are associated with the diagnosis of spherocytosis/elliptocytosis?
PB smear - spheroidal or oval RBCs Anisocytosis Normal/low MCV Elevated MCHC (hyperchromic) Elevated reticulocytes Elevated leukocytes Elevated LDH Elevated bilirubin Decreased haptoglobin
What is stomatocytosis?
Rare congenital or acquired (excessive EtOH) RBC membrane disorder causing increased fragility and anemia (splenomegaly/jaundice)
What is hypophosphatiemia?
Low phosphate depletes RBC ATP causing membranes to become rigid and more susceptible to injury resulting in small spherical RBCs
How does G6P deficiency result in hemolytic anemia?
X-linked disorder causes reduction in energy available to maintain RBC membrane
Hemolysis occurs when cells are exposed to oxidants (peroxide, primaquine, salicylates, sulfonamides, nitrofuran, vit K, fava beans)
What populations are at higher risk of carrying this genetic trait of G6P defect?
African American males and mediterraneans
What are the labs associated with G6P deficiency diagnoses?
anemia
increased reticulocytes
Heinz bodies
What is the cause of sickle cell anemia?
Homozygous hemoglobin S gene (or heterozygous sickle cell trait) occurring in Africans
What are the SSxs associated with sickle cell anemia?
Painful bony crisis Renal damage "punched out" leg ulcers Splenic infarcts aplastic crisis severe anemia developmental delays avascular necrosis of bones (femoral head) Abdominal pain/vomiting Neuro disturbances splenomegaly
What are the SSxs associated with sickle cell trait?
Myalgias, hematuria
How is sickle cell anemia diagnosed?
Normocytic anemia
Elevated bilirubin
Sickle cells on PB smear
Electrophoresis shows hetero (Hb A and Hb S) or homozygotic (only Hb S)
What is hemoglobin C disease?
Genetic hemoglobinopathy, more commin in Africans, maybe associated with sickle cell - highly variable
What SSxs, PE, and labs are associated with hemoglobin C disease?
bone pain splenomegaly jaundice normochromic anemia target cells, spherocytes, or nucleated RBCs Heterozygous may show no symptoms
What is thalassemia? What are the different types? Who is primarily effected?
Inherited defects in rate of synthesis of one or more globin chains causing ineffective erythropoesis/low RBC production
Major (homozygous) or minor (heterozygous)
Most commonly effecting mediterraneans, africans, SE asians, (where malaria is present)
What are the SSxs associated with thalassemia?
heart failure, failure to thrive, splenomegaly, jaundice, leg ulcers, gallstones
Thick malar eminences and cranial bones (in Major)
Rare to live long with thalassemia major, normal life with minor
What do labs show in thalassemia?
Microcytic normochromic anemia target cells basophilic stippling nucleated RBCs Anisocytosis Poikocytosis Elevated iron/ferritn Elevated bilirubin
What levels neutrophils are associated with neutropenia?
> 1200 in blacks and >1500 in whites is normal
1000 - 1500 = mild risk of infection
500 - 1000 = moderate risk
<200 = rapidly fatal infection
What type on infections do neutrophils protect against? What else is involved in defense against infection?
Bacterial and fungal infection
skin, mucosal/vascular integrity and nutritional status also influence immunity
What causes intrinsic neutropenia?
Defects in myeloid cells or precursors - rare
Congenital causes
Chronic idiopathic
What are some causes of secondary neutropenia?
Drugs Bone marrow infiltration (cancer/myelofibrosis) Hypersplenism Infections/sepsis (HIV) Alcoholism Autoimmune (SLE) Folate/B12 deficiency Leukemias Transfusions
What are some important things to consider in pt with neutropenia?
PE of mucosal surfaces, lungs, abdomen, urinary, skin/nails for infection
Bacterial/fungal blood cultures if acute and febrile
Chest xray for pts with neutrophils <500
Radiography sinuses
Determine mechanism of cause (meds, toxins, maybe bone marrow biopsy)
What is lymphocytopenia? What number of lymphocytes is diagnostic?
Reduction in lymphocytes
Either Tcells (75%) or Bcells (50%) - together make up 20-40% of WBCs
<1000 in adults, less than 3000 in children
What are causes of lymphocytopenia?
Congenital or acquired Infections (Viral - TB, HIV, SARS, Hep) Dietary deficiency Iatrogenic immunosuppression (chemo/rad) Autoimmune (SLE, RA, sarcoid) Cushing's EtOH
What are SSxs associated with lymphocytopenia?
Signs of primary illness Absent/diminished tonsils/lymph nodes LAD with tumors Jaundice, splenomegaly, pallor, petechiae if hematologic disease is cause Recurrent viral/parasitic infections
