Anemias Flashcards
Anemia of Chronic Disease
Normocytic, normochromic
- Occurs due to increased destruction of RBCs by factors released from damaged tissue; BM is suppressed by inflammatory cytokines
- Defective reutilization of iron leads to an accumulation in phagocytes
Lab: Ferritin =» Increased
TIBC =» Decreased
% Saturation => Decreased
*Hepcidin released by the liver limits iron transfer and EPO to decrease the available iron for bacteria (logic behind this)
Megaloblastic Anemias
Folate or Vit-b12 deficiency
- Pancytopenia
- Megloblastic , hypercellular BM w/ giant bands and nuclear asynchrony
- PB: Macroovalocytes, hypersegmented PMNS, and anisopoikolocytosis
Treatment: Give B12 injection and Folate supplements (folate will not treat neurological symptoms of B12 deficiency)
Vitamin B12 deficiency
Commonly caused by pernicious anemia
- Dietary deficiency only occurs in vegans, pregnancy, hyperthyroidism, tumorigenic states
- Typically assoc. w/ AI disease, possibly gastritis =» parietal cell destruction
***Will see neurologic defects due to demyelination of nerves; also see glossitis and increased methlymalonic acid
-Can diagnose w/ the Schilling Test
Treat w/ B12 supplements; folate supplements sorta work but will not correct neurologic symptoms)
Folate Deficiency
- Typically due to diet lacking green, leafy vegetables or fish; increased demand during pregnancy
- Glossitis, increased homocysteine
Schilling Test
Stage I: Give pt. oral radiolabeled B12 and inject B12 intramuscularly; if radiolabel seen in urine, there is no IF-deficiency and it is probably dietary
If no radiolabel in urine, then…
Stage II: Give oral radiolabeled B12 AND IF
=» If still not in urine, probably general malabsorption issue
Macrocytic Anemias (other than B12/Folate)
Caused by alcoholism, chemotherapy, liver disease, hypothyroidism
Aplastic Anemia
Damage to hematopoetic stem cells causing pancytopenia w/ NO resulting reticulocytosis; BM will be hypocellular resulting in a dry tap
Clinical: Anemia, weakness, pallor, prone to bleeding and infections, no spleen abnormalities
*Can be caused by CHLORAMPHENICOL, alcohol, benzene, radiation therapy
Treatment: Supportive G-CSF; if severe enough, BM transplant or immunosuppression if indicated
Fanconi’s Anemia
AR defect in the DNA repair mechanism that is a potential cause of aplastic anemia
Clinical: Hypoplastic thumbs and organs
-Pre-malignancy
Diamond-Blackfan Syndrome
Pure red cell aplasia caused by AI mediated destruction of red cell precursors
- Pure red cell aplasia also caused by parvovirus B19, chloramphenicols, thymomas, SLE
- Chronic, severe anemia characterized by no reticulocytosis but normal myeloid and platelets
Treatment: Immunosuppresion, IVIG (parvovirus), thymic resection
Sideroblastic Anemia
Failure to incorporate heme into protoporphyrin IX ring =» presence of ringed sideroblasts and basophilic stipling
-Mild, dimorphic anemia w/ ineffective erythropoesis
Labs: Increased Ferritin
Increased Transferrin
Decreased TIBC
Increased % saturation
*Hereditary = ALA-synthase deficiency Acquired = **Isoniazid therapy, myelodysplasia, hemochromatosis, lead toxicity (painters)
Treatment: Pyridoxine (Vit B6); treatment of underlying problem
Ringed Sideroblasts
Iron-laden mitochondria w/ iron collections in erythroid precurors
-Seen in sideroblastic anemia
Hemolytic Anemias
Acute: Jaundice, SOB, fever, lower back pain
Chronic: Gallstones, fractures, abnormal bone growth
Labs: Increased LDH
Decreased haptoglobin
Increased unconj. bilirubin
PB: Spherocytes, schistocytes, polychromasia, reticulocytosis, Howell-Jolly bodies
Intravascular Hemolysis
Releases free Hgb =» Hemoglobinuria, hemoglobinemia, decreased serum haptoglobin
-Usually occurs in burn pts., immune disorders, microangiopathic conditions
Extravascular Hemolysis
Occurs in the spleen, liver, macrophages
-Usually due to inherited defect in Hgb prod., RBC membrane, enzymes
Lab: Increased unconj. bilirubin w/ no schistocytes, anemia
Beta-Thalassemia Major
Microcytic, hypochromic anemia w/ codocytes due to gene mutation on chromosome 11; common in people of Mediterranean descent
If B zero/B zero =» No B-globin produced=» MOST SEVERE
Clinical: Onset 6 months after birth after HbF levels normally decrease in favor of HbA
=»Ineffective erythropoesis causes hepatosplenomegaly, bone malformations, organ damage, Howell-Jolly bodies (ppt. of a-chains), basophilic stipling, NRBCs, iron overload, **CREWCUT appearance of skull
*Electrophoresis: Decreased HbA, Increased HbA2 and HbF
Treatment: Chronic transfusions
Beta Thalassemia Minor
One normal and one abnormal gene on chromosome 11
*Must differentiate from iron deficiency anemia
=»B-thalassemia minor will not improve w/ iron supplementation
*PB will also have basophilic stipling
Alpha-Thalassemia
COMPLETE deletion of a-genes on chromosome 16
4 gene deletion: Hydrops fetalis =» tetramers of y-chains that have an increased affinity for Hgb
3 gene deletion: severe anemia assoc w/ Hemoglobin H (tetramer of B-chains); ppt. as Heinz bodies and can produce “Bite cells” after passing thru the spleen
Alpha-Thalassemia Trait (2 gene deletion)
Alpha-thal-1: cis deletion of genes on same chromosome
-Hb Bart at birth: Hb H during life
Alpha-thal-2: trans deletion of genes on opposite chromosomes
-Hb Bart at birth; No Hb-H during life
Sickle Cell Anemia
Valine=»Glutamic Acid on gene 6 of the B-globin chain causes the prod. of HbS
-Sickled cells form spectrin dimers that are dense and not easily deformable therefore posing a risk for small vessel occlusion and increasing the viscosity of blood
Clinical: Chronic hemolysis and vaso-occlusive crises
Autosplenectomy
Chronic leg ulcers
Organ infarction
Gallstone formation
Dactylitis (swelling of hands and feet)
Basophilic stippling/Howell-Jolly bodies
Labs: Increased HbF (~10%)
Sickling test (+) -Metabisulfate
⭐️⭐️Dehydration, acidosis, thalassemia all induce increased sickling
Iron Deficiency Anemia
Hypochromic, microcytic anemia
*Most common nutritional deficiency worldwide; also very common cause of thrombocytosis
Caused by: menorrhagia in females and peptic ulcers in males; malabsorption (duodenal problem); nutritional deficiency; other forms of chronic blood loss
*Colonic adenocarcinoma
*Pts. appear w/ pallor, koilonychia, pica
Labs: Ferritin =» decreased
TIBC =» Increased
% saturation =» Decreased
Treatment: Give iron supplements; find source of bleeding
Hereditary Spherocytosis
Microcytic, hyperchromic RBCs w/ decreased lifespan
Caused by mutations in ankyrin gene which anchors spectrin to the RBC membrane =» spherical, less deformable shape
Clinical: Slight anemia, jaundice, splenomegaly, anemic crises
Labs: Osmotic fragility test (+); Increased MCHC; reticulocytosis
-OF test will shift curve to the right although reticulocytes can persist; may also be necessary to incubate the cells for 24hrs to accentuate fragility
Treatment: Splenectomy; Howell-Jolly bodies will now emerge on smear
G6PD deficiency
Lack of G6PD causes the denaturation of Hgb (and formation of Heinz bodies) during times of oxidative stress; induced by fava beans, drugs (***Dapsone, chloramphenicol, sulfonamides, antimalarials), and viral infecion
Clinical: Intravascular & Extravascular hemolytic symptoms (chills, fever, back pain, SOB, pallor)
Treatment: Attacks are self-limiting (only old RBCs affected) so therapy is supportive
*B/w attacks, PB is NORMAL
Warm Autoimmune Hemolytic Anemia
Due to IgG abs reactive at warm temperature of the central body; spleen destroys ab-coated RBCs
-Assoc. w/ lymphatic malignancies and AI disorders
*Includes Drug-Induced WAHA which occurs due to:
Methyldopa (against Rh-ag)
Penicillin-hapten
Cephalosporins/Tetracyclines
Treatment: Immunosuppression, splenectomy, treat underlying disorder, blood transfusions
Cold Autoimmune Hemolytic Anemia
IgM binds to RBCs and induces agglutination during exposure to cold temperature in the limbs; also causes opsonization by C3 and phagocytosis in the spleen BUT no splenomegaly
Acute: Due to Mycoplasma pneumoniae (I-Ag) or infectious mononucleosis (i-Ag)
Chronic: Lymphoid malignancy
Treatment: Keep warm; treat underlying illness
Paroxysmal Cold Hemoglobinuria
Due to Donath-Landsteiner IgG that binds RBCs in cold temperatures (limbs) and binds complement in warm temperatures (torso) =» hemolysis
- Assoc. w/ skiing or recovery from illness
- Characterized by biphasic nature of the antibody
Labs: Chill antibody, heat it, check for lysis
Treatment: Keep pt. warm
Microangiopathic Hemolytic Anemia
Due to abnormalities in vessel circulation resulting from DIC, HUS, TTP, Preeclampsia
Labs: Predominance of schistocytes on PB
Alcoholic Liver Disease
Abnormal lipid structure of RBC membrane =» acanthocytes, spur cells, and target cells
Paroxysmal Nocturnal Hemoglobinuria
Caused by mutations in the Phosphatidyl-inositol glycan class A gene (pig-A); codes for GPI anchor required for CD55 and CD59
*CD59-inhibits lysis by complement; CD55-DAF
=»Increased susceptibility to complement destruction
Screen: Sucrose lysis test (+)
Confirmatory Ham’s Test (+)/ Flow for CD55 (-)
Treatment: Iron supplements; prednisone; BM transplant
*Can progress to AML
Secretion products of platelets
a-granules: Fibrinogen, P-selectin, PDGF, Factors V, VIII, Platelet Factor 4
delta granules: ADP, ATP, Ca2+, Serotonin, epinephrine
Point at which primary hemostasis is reversible to
Until Thrombin binds to protease-activated receptor (PAR) on the platelet membrane w/ ADP and TXA2
(Aggregation)
Last step in formation of platelet plug
Fibrinogen binding to GpIIIa/IIb receptors on platelet
Anti-platelet properties of endothelial cells
ADPase
NO and PGI2 (vasodilators)
ATIII (II, X, XII, XI)
TFPI (inhibits VIIa and Xa)
t-PA (activates Plasminogen)
Thrombomodulin (activates Protein C)
Virchow Triad
- Endothelial Injury (exposes vWF, releases TF)
- Abnormal Blood Flow (Increased coagulants)
- Hypercoaguability (Coag Factor deficiencies/mutations)
- describes the cases in which thrombosis can occur
Factor V Leiden
Arginine =» Glutamine substitution makes Factor V much more resistant to cleavage by Protein C
-Many pts. w/ recurrent DVTs have this
Homocystinuria
Mutation in the MTHFR gene (motherfucker) causes a variation in a THF-reductase gene elevating homocysteine
Homocysteine inhibits ATIII and thrombomodulin
*Clinical: MR, thrombosis, long-slender fingers
Antiphospholipid Antibody Syndrome
Abs bind to epitopes exposed by phospholipids; can be primary or secondary
-Causes recurrent DVTs, thrombocytopenia, prolonged PTT, cardiac vegetations
Treatment: Anticoagulants, immunosuppressants
Arterial Thrombi
Usually occlusive, overlies an atherosclerotic plaque and grows retrograde to blood flow
Venous thrombi
Always occlusive; typically in the lower extremities, and grows anterograde to blood flow
Post-mortem clots
Usually not attached to the vessel wall and the dependent portion is dark red
-Yellow, gelatinous supernatant
Superficial Venous Thrombi
Causes edema distal to the obstruction; predisposes overlying skin to injury
-Rarely embolizes
Deep Venous Thrombi
Above the knee: Most likely will embolize
Below the knee: Make sure it doesn’t move above the knee
Treatment: Anticoagulants
Pulmonary Thromboembolism
Greater than 60% go asymptomatic; obstruction of end arteries causes infarct
- Hemorrhage can occur due to dual circulation of the lung
- Saddle embolus=most serious
Systemic thromboembolism
Typically from the left heart; sometimes the left if it bypasses pulmonary circulation
*Typically go down to the legs
Fat embolism
Occurs 1-3 days after broken bone;
Clinical: Pulmonary insufficiency, anemia, thrombocytopenia, **neurological defects
Air embolism
Often caused by thoracentesis, neck injury, obstetric procedures, AND decompression sickness
=»Air breathed in @ increased pressure has increased N2 content; bubbles out when rapidly surfacing causing pain around the joints
Amniotic Fluid Embolism
Uncommon occurrence of infusion of amniotic fluid at delivery
Clinical: Severe dyspnea, hypotensive shock, pulmonary edema, DIC
-Very fatal, yes
