Anemia Flashcards
Thrombophilia
hypercoagulopathy, Thrombophilia is a risk factor for pathologic formation of an intravascular blood clot (thrombosis)
risk factors for thrombosis
stasis and vascular wall abnormalities, Thrombosis is usually a multifactorial condition
virchows triad
endothelial damage, hypercoaguability, stasis
Reasons for endothelial damage
smoking, htn, surgery, PICC lines, trauma
Reasons for hypercoaguability
heredity: factor V, prothrombin, protein C deficiency. acquired: cancer, chemo, pregnancy, obesity
Reasons for stasis
immobility, polycythemia
Inherited (autosomal dominant) causes
Protein C, protein S deficiency (inhibits f. V, VIII)
Factor V Leiden* most common (mutation f. V > resistance to inactivation)
Acquired causes
Malignancy (20% of all VTE occur in patients with cancer)
Pregnancy up to 2 months postpartum
Oral contraceptives or estrogen replacement therapy
Clinical features of inherited thrombophilia
Thrombosis before age < 50 years
Recurrent venous thrombosis DVT and PE
Family history of thrombosis before age 50
Thrombosis is more often when other factors are present (pregnancy, oral contraceptives, immobility)
Testing for inherited thrombophilia
ROUTINE thrombophilia testing is NOT recommended ( doesn’t affect management)
Available testing:
Protein C activity essay (abnormal in protein C deficiency)
Protein S activity essay (abnormal in protein S deficiency)
Protein C resistance essay (abnormal in factor V mutation)
PT/INR (normal)
Platelets (normal)
Thrombophilia therapy
Treat DVT/PE with anticoagulation therapy (Warfarin, direct oral anticoagulants ) for a minimum of 3 months (optimal length of the treatment is unknown)
IVC filter if there is a contraindication to anticoagulation
Anemia
Anemia is a deficits in the mass of circulating RBC ( the capacity to deliver oxygen is compromised) Measured as RBC count, concentration of Hgb (g/dl), % of Hct
What is hemoglobin
is a protein contained in RBC that is responsible for delivery of oxygen to the tissues Hct is a % of the volume of RBC in the total volume of a blood sample
Hgb: Hct
1:3
Normal Hgb
13.5-17.5 g/dl (male), 12-16 g/dl (female)
Hgb suggestive of anemia
Hgb concentration <14 g/dl in men and <12 g/dl in women suggests anemia
Symptoms of anemia
oxygen-caring capacity: tiredness, exercise intolerance, poor concentration, pallor, angina
cardiac compensation ( stroke volume, HR): palpitations, dyspnea on exertion, systolic murmur (hemic murmur)
Sx are minimal when
it is gradual and mild
MCV range
80-100
Microcytic
< 80
Macrocytic
> 100
Normocytic
80-100
Microcytic anemias (low MCV)
Small RBC (microcytosis) 90% of RBC volume composed of hgb. Hgb is a major contributor to the cell size Due to decreased production of Hgb
Hemoglobin made of
Made of Heme and Globin
Heme is mainly composed of iron ( that binds O2)
Reduction in any of these components will result in microcytic anemia
Microcytic anemia etiology
Iron deficiency anemia (IDA)
Anemia of chronic disease (ACD)
Thalassemia
IDA
Most common reason for anemia worldwide
Deficiency is due to
dietary lack : meat (better absorption), sunflower seeds, nuts, whole grains, dark leafy greens
poor iron absorption in duodenum (rare, Celiac disease)
increased iron demands (pregnancy)
blood loss (most common cause in adults, GI)
Manifestation of IDA – iron deficiency
Pica (ice, clay)
Restless leg syndrome
Manifestation of IDA – Low hemoglobin
Tiredness Generalized weakness Shortness of breath Pallor Hemic murmur
Diagnosis of IDA: CBC is an initial test – results on the CBC:
Low Hgb/Hct
Low MCV < 80 fL
Low MCHC (mean corpuscular hemoglobin concentration= the amount of Hgb per unit volume) < 33 g/dl
Increased RDW (red cells distribution width) > 15%
Low reticulocyte count
IDA blood smear
Low MCV on CBC MICROCYTOSIS on the blood smear
Low MCHC on CBC HYPOCHROMIA on blood smear
IDA blood smear red blood cells
Increased RDW on CBC ANYSOCYTOSIS on blood smear
Diagnosis of IDA : iron study (diagnostic)
Low serum iron (N 50-150 ng/dl)
Low ferritin (N 20-300 ng/dl)
Low % transferrin saturation (N 20-50%)
High TIBC (Total Iron Binding Capacity) (N 25-450 ng/dl)
Low reticulocyte (“young cells” just released from bone marrow) count
Stages of IDA – stage 1
(1) : Iron storage is depleted without causing anemia (ferritin) – asymptomatic
stage 2
(2) : Normocytic anemia (Hgb, normal MCV and normal reticulocyte count) – asymptomatic or mild symptoms of anemia
stage 3
(3) : Microcytic hypochromic anemia (low MCV, low MCHC, low reticulocyte count)- symptomatic
Management of IDA
Determine ETIOLOGY of iron deficiency and bleeding:
History of menorrhagia/ abnormal uterine bleeding, melena, hematochezia, hematuria
No obvious source of bleeding, consider occult GI bleeding (fecal occults blood, upper endoscopy, colonoscopy)
Severely symptomatic patients (myocardial ischemia)
RBC transfusion
Stable patients can get this
Oral iron supplementation (IV iron if absorption problems, intolerable GI effects of oral iron)
Oral iron supplementation side effects
nausea, constipation, heartburn, black stool Safe handling ( in a locked cabinet) : iron supplements account for 30% of fatal medication overdoses in children
Absorption is optimal if taken
30 min before meals with ascorbic acid (absorption can be reduced by 40-50% if taken with food)
How long is iron treatment for
Treat for 4-6 months or until ferritin level is normalized
Oral iron supplementation – what increases absorption?
Vitamin C (orange juice)
Oral iron supplementation – what decreases absorption?
Antacids Caffeine Calcium and calcium-containing foods (milk) H2 blockers PPIs
Response to iron supplementation, an increase in reticulocyte count (7-10 days) Is a response by the
marrow
increased Hgb (1-2 months into treatment ) indicates what
resolution of anemia
increased ferritin (4 months into treatment) indicates what
restoration of iron stores
Screening for IDA
Asymptomatic pregnant women should be screened for IDA at the first prenatal visit :
Anemia on screening 60 to 120 mg of oral iron per day
No anemia 30 mg/day of oral iron as primary prevention
Anemia of chronic disease (ACD)
Inflammatory mediators keep iron is storage sites (liver)
Low available iron> low Heme > low Hgb> microcytic anemia
Functional iron deficiency ( iron unavailable for erythropoiesis)
Anemia of chronic disease (ACD) causes
chronic infection (TB, HIV, osteomyelitis) cancer chronic inflammation ( RA, SLE) chronic kidney disease (+ erythropoietin deficiency)
Diagnosis of ACD : CBC (initial test)
Normal MCV ( initially) »_space; low MCV
Low Hgb/ Hct
Normal MCHC (initially)»_space; low MCHC
Normal RDW
Diagnosis of ACD: iron studies (diagnostic test)
Elevated ferritin
Low TIBC
Elevated transferrin saturation
Low serum iron
Management of ACD
Treat underlying disease
Thalassemia
Inherited genetic disorder
Inadequate PRODUCTION of globin> low Hgb> microcytic anemia
Thalassemia subtypes
Alfa and Beta
Alpha thalassemia
Genes that code for alpha globin are affected (inadequate production of alpha chains)
Beta thalassemia
Genes that code for beta globin are affected (inadequate production of beta chains)
Alpha chains are encoded by
4 genes (2 genes from mother, 2 from father) Severity of anemia depends of number of deleted genes (1 gene deleted – asymptomatic, 4 genes absent –incompatible with life)
Beta chains are encoded by
2 genes (1 from mother, 1 from father) Autosomal recessive inheritance. Severity of anemia variable: one abnormal gene – mild disease, two abnormal genes—moderate to severe
Thalassemia minor s/s
Asymptomatic
Signs of anemia
Thalassemia major s/s
Transfusion-depended anemia
Symptoms appear within first year of life: severe anemia , failure to thrive, irritability, pallor, bones hyperplasia and deformities.
Average life expectancy is 17 years
Beta thallasemia bone changes
Bone medullar expansion» deformities (“chipmunk face”)
Diagnosis of thalassemia initial diagnostic testing
CBC: VERY Low MCV Low Hgb normal RDW (all produced cells are small) Iron studies: NORMAL
Most accurate thalassemia testing to diagnose
Hgb electrophoresis (separate chains) to confirm the diagnosis
Mgmt thal. minor
Usually no treatment necessary, genetic counseling
Mgmt thal. major
transfusion-dependent (+ chelation therapy to prevent iron overload)
Macrocytic anemias
MCV > 100 fL “Bad DNA“ Not enough material for DNA synthesis and replication > arrest of cellular division> macrocytic anemia (immature cells are larger) Normal iron, Hgb synthesis is not affected > normochromic (normal MCHC) RDW increased
Major causes of macrocytic anemia
Folate deficiency
Vitamin B12 (cobalamin) deficiency
Alcoholism
Hypothyroidism
Dietary sources of b12
Meat, fish and milk (Only animal products ! )
Dietary deficiency in strict vegans
Stores are large (3 years)
Folate sources
Animal and non-animal products including green leafy vegetables, beans, fruits (bananas), mushrooms, yeast
Stores are limited (3 months)
causes of b12 deficiency
Malabsorption due to deficiency of intrinsic factor (pernicious anemia) –most common cause, Malabsorption due to gastric, bariatric, ileac surgery or Crohn’s disease
Causes of folate deficiency
Dietary lack (elderly and alcoholics, “ tea and toast” diet) - most common cause
Malabsorption (absorbed in jejunum)
Increased demand (pregnancy, cancer )
Drugs (methotrexate, antiepileptic drugs, Bactrim)
Pernicious anemia
Autoimmune disease
Autoimmune destruction of parietal cells > IF deficiency > Vit B12 deficiency
Because B12 is efficiently stored, it takes 2-3 years to develop anemia
Folate deficiency and pregnancy
Folate deficiency is teratogenic
Associated w/ neural tube defect ( spina bifida)
Recommendation: women planning pregnancy ( capable of conception) 0.4-0.8 mg/d for 3 month prior to conception
Women who has hx of giving birth to a child w. neural tube defect
4 mg/d 3 month before conception through 3 months of pregnancy
b12 deficiency manifestations
weakness, fatigue, atrophic glossitis, stomatitis
Neurological (parasthesia first , ataxia, loss of vibratory sense, + Romberg sign, dementia )
Folate deficiency manifestations
weakness, fatigue, atrophic glossitis, stomatitis
dx b12 deficiency
MCV > 100 fL, low RBC
Low reticulocyte count
Low serum B12
Elevated serum methylmalonic acid (B12 breaks out methylmalonic acid)
dx Folate deficiency
MCV > 100 fL, low RBC
Low reticulocyte count
Low serum folate
Normal level of methylmalonic acid
tx b12 deficiency
Parenteral (IM) therapy weekly > monthly (malabsorption) for the rest of life
Watch for hypokalemia
Hematological response is rapid ( retic.count 7 days). Full hematologic recovery takes 2 months
Neurological changes are irreversible if prolonged
tx folate deficiency
Oral folate replacement daily (1 mg po daily)
Hematologic response is rapid
Normocytic anemias
Normal MCV
Normal iron studies
Low RBC, low Hgb
Normocytic anemias definition
Destruction of RBCs or loss of RBCs due to: Hemolysis (sickle cell anemia, autoimmune hemolytic anemia)
Acute blood loss
Hemolytic anemias symptoms
Weakness, tiredness, pallor
Jaundice
Lab values hemolytic anemia
Normal MCV Low hemoglobin Elevated reticulocyte count Elevated indirect bilirubin Elevated LDH
Sickle cell disease (SCD)
Inheritance of abnormal (mutated) gene of beta chain of Hgb»_space; abnormal beta chain structure not quantity. Autosomal recessive: two beta chains are abnormal disease, one beta chain is abnormal trait
SC trait manifestations
SC trait individuals carriers only one abnormal gene
Clinically asymptomatic
SCD diagnosis
Blood smear to detect red blood sickle cell (initial)
Electrophoresis to detect HgS (most accurate)
SCD treatment
Exchange blood transfusions for serious complications (stroke, acute chest syndrome, priapism) Vaccinations (pneumococcal, meningococcal, Hemophylus influenza) Hydroxyurea (increases HgF level) – reduces sickling episodes. Painful crises- hydration, oxygenation, pain control. Genetic counseling for carriers (SCD trait)
Hydroxyurea increases
fetal hgb
