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127 Cards in this Set
- Front
- Back
Peripheral smear: macro-ovalocytes and hypersegmented PMNs
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megaloblastic anemias
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what are the 2 defining characteristics of megaloblastic anemias
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1. impaired DNA synthesis and 2. ineffective hematopoiesis
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what are the 2 characteristics of impaired DNA synthesis seen in megaloblastic anemias?
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1. delayed nuclear maturation and 2. DNA abnormalities - chromatin strand breaks
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what does the marrow look like in megaloblastic anemias?
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hyperproliferative, but many cells die within marrow
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what cells are affected in megaloblastic anemia?
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all dividing cells in the body - bone marrow: anemai or pancytopenia; GI: mucosal atrophy, glossitis; skin: hyperproliferative - constantly shedding, thin skin, fine hair
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what are the 4 main causes of megaloblastic anemias?
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1. B12 deficiency, 2. folate deficiency, 3. antifolate drugs - methotrexate, trimethoprim/sulfa antibiotics, 4. nucleoside inhibitors (AZT)
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what are 3 anti-folate drugs that can cause megaloblastic anemia?
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1. methotrexate, 2. trimethoprim, 3. sulfa antibiotics
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what is pernicious anemia?
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cobalamin deficiency due to autoimmune gastritis
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what are the 5 most common causes of macrocytic anemia?
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liver disease, reticulocytosis, meylodysplasia, alcoholism, hypothyrodism
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what is the important function of folate?
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transfer of one carbone fragments in many chemical reactions
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what are the dietary sources of folate?
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vegetables, fruits, cereals, and dairy products - heat liable, destroyed by cooking
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what is the daily requirement and body stores of folate?
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50 micrograms daily requirement; 5-10 milligrams body stores (stores can be depleted in a few months)
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what happens to the body stores of folate if the enterohepatic circulation is interrupted?
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the body stores can be depleted much more quickly
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what is the most common cause of folate deficiency?
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inadequate diet - tea and toast or alcoholism
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what are the the less common causes of folate deficiency?
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malabsorption, hemodialysis, AEDs, oral contraceptives, nitrous oxide (laughing gas)
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what are 3 conditions where there is increased need for folate?
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1. chronic hemolytic anemias (hemoglobinopathies and HS), 2. psoriasis, 3. pregnancy
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what is associated with folate deficiency in pregnancy?
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neural tube defects
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what are the primary sources of cobalamin?
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meat, eggs, dairy products
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what is the daily requirement and body store of cobalamin?
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0.1 microgram/day requirement; 2-4 miligrams - body stores; takes years to deplete body stores
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what is the most common cause of cobalamin deficiency?
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malabsorption
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what are the less common causes of cobalamin deficiency?
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dietary deficiency - strict vegans, infants of vegetarian mothers; congenital - deficiency of IF or transcobalamin II
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what is key in cobalamin absorption?
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intrinsic factor - produced by gastric parietal cells
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where is cobalamin absorbed?
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in the terminal ileum - absorbed efficiently as complex with IF
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how can pancreatic insufficiency cause cobalamin deficiency?
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pancreatic enzymes are needed to digest R-factors that are bound with cobalamin preventing the binding of IF - no pancreatic enzyme no binding sites for IF
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what is the function of transcobalamin II?
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it carries B12 in the blood and delivers it to tissues - ONLY carrier that can deliver it!)
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what is the most common cause of cobalamin malabsorption?
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pernicious anemia
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what is blind loop syndrome?
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stasis of the gut causes overgrowth of bacteria that compete for B12 causing malabsorption of B12
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what parasite can cause B12 deficiency?
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fish tapeworm - Diphyllobothrium latum
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when I say Diphyllobothrium latum, you say:
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cabalamin malabsorption
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what happens to the gastric mucosa in pernicious anemia?
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it is thinned, gastric crypts are destroyed and there is inflammation
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what antibodies are specific for pernicious anemia?
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anti-intrinsic factor - but they are not very sensitive
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what antibodies are sensitive for pernicious anemia?
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anti-parietal cell Ab - but they are not specific
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what is tetrahydrofolate required for?
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DNA synthesis - the conversion of dUMP to tUMP by thymidylate synthetase
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what is cobalamin required for?
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the regeneration of methylene-FH4 - it functions to regenerate the folate needed for DNA synthesis
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what is the reaction that requires both folate and B12?
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the conversion of homocysteine to methionine by methionine synthetase
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what are the signs and symptoms of megaloblastic anemia?
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weakness, fatigue, painful tongue and mouth, weight loss, loss of appetite, N&V, loose stools, pollor, angular cheilitis, dry smooth skin, smooth 'beefy' tongue, silvery or premature gray hair \
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what is the rule of fives in megaloblastic anemia?
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hypersegmented neutrophils on perihperal smear have > 5 nuclear lobes or >5% of neutorphils have 5 lobes
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what is megaloblastic maturation?
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nuclear-cytoplasmic asynchrony = large, immature nuclei in late erythroid precursors found in bone marrow
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when are giant bands and metamyelocytes found?
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in megaloblastic anemia
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what are 3 supplimental lab findings in megaloblastic anemia?
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1. increased LDH, 2. increased unconjugated bilirubin, 3. decreased haptoglobin
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what are the early neurologic signs of cobalamin deficiency ?
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paresthesias of distal extremities - reduced vibration and position sensation
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what are the later neurolgoic signs of cobalamin deficiency?
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clumsiness, ataxia, weakness, hyperrflexia, positive babinski and romberg signs
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what is the pathology behind the neurological manifestations of cobalamin deficiency?
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myelin degeneration (SAM is required for myelin production), loss of axons in dorsal and lateral columns of spinal cord and cerebral cortex
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what are the cortical manifestations of cobalamin deficiency?
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denemtia, altered metnal status and bizarre behavior
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what is the treatment of the neurologic manifestations of cobalamin deficiency?
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B12 supplementation may reverse all neurologic manifestations - long standing change may not be reversible
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what can happen if you give folate to a cobalamin deficient patient with neurological signs?
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folate may accelerate the neurological progression
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what are the 3 primary lab tests to distinguish folate or cobalamin deficiency?
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1. serum cobalamin, 2. serum folate, 3. erythrocyte folate level
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what are the secondary lab tests to distinguish folate or cobalamin deficiency?
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serum methymalonic acid (MMA) and serum homocysteine levels
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what are the lab findings for 1. serum B12, 2. serum folate, 3. RBC folate, 4.serum MMA and 5. homocysteine in cobalamin deficiency?
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1. serum B12 - ↓, 2. serum folate - normal/increased, 3. RBC folate - ↓, 4.serum MMA - ↑, 5. homocystein - ↑
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what are the lab findings for 1. serum B12, 2. serum folate, 3. RBC folate, 4.serum MMA and 5. homocysteine in folate deficiency?
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1. serum B12 - normal, 2. serum folate - ↓, 3. RBC folate - ↓, 4.serum MMA - normal, 5. homocystein - ↑
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of RBC folate, serum MMA and homocysteine levels, which one differs between folate and cobalamin deficiencies?
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MMA - in cobalamin it is increased, in folate it is normal; other two have identical changes in both deficiencies
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is serum folate or RBC folate a more stable lab value?
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RBC folate - reflects last few weeks. Serum can reflect last meal
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what test is most sensitive for cobalamin deficiency?
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increased MMA is most sensitive for cobalamin deficiency
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what is the possible effect fo folate of cobalamin deficiency on iron?
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either may decrease iron absorption due to atrophy of the GI tract
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what picture would you see if you had a folate or cobalamin deficiency + an iron deficiency?
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MCV may be normal, may see dimorphic RBC population, hypersegmented neutrophils may be present
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what is the treatment for folate deficiency?
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oral therapy
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what is the treatment for cobalamin deficiency?
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parenteral therapy (loading) followed by oral supplements - must follow up!!
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what are the consequences of HbSC?
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retinopathy, aseptic necrosis of femoral head, acute chest syndrome in 3rd trimester
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how is G6PD deficiency inherited?
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x-linked recessive
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polychromasia with bite or blister cells and Heinz bodies
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G6PD deficiency
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how is HS inherited?
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Ad
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what is the etiology of HS?
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verticle attachment problem - ankryin defect
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what is the etiology of hereditary elliptocytosis?
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hornizontal problem - spectrin problem
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what can cause normocytic, normochromic hypoproliferative anemia?
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hypothyroidism and hypogonadism
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what is seen with HbS beta-thal
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similar to sickle cell anemia
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microcytosis with traget cells and normal Hb (or slightly decreased)
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homozygoud HbE
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mild microcytic anemia with spherocytes and target cells
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HbCC
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what is "splenic conditioning"?
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seen in HS - spleen participates in membrane loss and spheocytic transformation
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what are the characteristics of intravascular hemolysis?
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direct complement mediated - formation of MAC, IgG or IgM
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what are the characteristics of extravascular hemolysis?
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IgG or complement on surface (not MAC) - opsonization leads to phagocytosis by macrophages or spleen and sometimes the liver
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what Ig is involved in col hemolytic anemia?
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IgM - fixes complement; usually extravascular but if enough complement are fixed can by intravascular
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what infections are associated with cold hemolytic anemia?
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mycoplasma pneumonia, EBV(mono)
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what Ig is associated with warm hemolytic anemia?
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IgG - may or may NOT fix complement
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what is idiopathic autoimmune hemolytic anemia?
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usually warm IgG hemolytic anemia that is directed against an Ag in the Rh system present in all non-Rh-null pts
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how do you diagnose idiopathic autoimmune hemolytic anemia?
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incrased reticulocyte count, LDH and unconj. Bilirubin; decreased hepatoglobin; POSITIVE DAT, has low ANA titer
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what happens in drug absorption type immune hemolytic anemia?
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(penicillin type): dose dependent reaction where drug binds to RBC surface; usually not severe
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what happens in neoantigen type drug related hemolytic anemia?
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combo of drug bound to RBC antigen - Ab fixes complemetn, MAC forms = intravascular hemolysis; not dose related (can occur at low doses); cephalosporins!
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what happens in autimmune (Aldomet) drug-related hemolytic anemia?
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drug induces autoimmune state that is like IAHA - does not require presence of drug; associated with T-cell dysfunction
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define TTP
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intravascular thrombi composed of vWF and platelets that fragemtn RBCs as they pass through the thrombi
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what causes TTP?
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deficiency of vWF cleaving enzymes; ADAMTS13
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what causes HUS?
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shiga-Toxin produced by E.coli (0157:H7), shigella;
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what are the symptoms of HUS?
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renal insufficiency, hematuria, vairable micorangiopathic hemolysis, thrombocytopenia
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what are the characteristics of pregnancy associated mechanical hemolysis?
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microangiopathic lymolysis, often HTN, edema and proteinuria
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what is HELLP?
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mechanical hemolysis in pregnancy: Hemolysis, Elevated Liver enzymes, Low Platelets
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what must be matched for RBC transfusion?
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must give units that lack any ABO Ag that a pt has Ab against
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what must be matched for plasma transfusion
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must give units that lack Ab against ABO on patient's RBC
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what mismatch causes the most serious transfusion reaction?
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when Type O pt gets Type A RBCs
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what type of transfusion reaction occurs with Anti-D (Rh) Ab?
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usually delayed and extravascular
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when is "type and screen" used?
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for pt with low probability of needing transfusion
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what are the 3 indications to give RBCs?
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1. provide oxygen carrying capacity, 2. replace blood lost acutely, 3. treat severe anemia in normovolemic pts
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what are the indications to give platelets?
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active bleeding with platelet <50K, not bleeding, platelet <10K, pt who is bleeding and needs surgery, pt who was on cardiac bypass pump
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what are the contraindications of giving platelets?
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1. TTP, heparin induced thromboyctopenia; avoid in ITP
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what Ag do platelets have?
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ABO and HLA; not Rh
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which blood component is the most dangerous?
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platelets - must be kept at room temp = bacterial contamination
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what does fresh frozen plasma contain?
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all clotting factors - Factor VIII loses activity the most in 5 days
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what do you need to match for FFP transfusion?
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ABO, Rh doesn't matter
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how much FFP do you need to give?
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at least 10-20 ml/kg
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what are the indications of FFP?
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multiple factor deficiency, rapid correction of warfarin, treat TTP, DIC
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what are the contraindications of FFP
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not for volume replacement
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what is not inactivated in FFP?
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viruses
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what is in cyroprecipitate?
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fibrinogen, factor VIII, vWF, XIII and fibronectin - fibrinogen is most important
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what are the indications of cryprecipitate?
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low fibrinogen, facotr XII deficiency; not indicated to replace VIII or vWF
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what is cyroprecipitate tested for?
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infeciton but not treated; not treated to inactivate viruses
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what cause acute intravascular hemolytic transfusion reaction?
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type 2 HS - due to ABO mismatch - usually clerical error
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what is the cause of delayed immune hemolytic transfusion reaction?
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atypical Abs - Kidd; extravascular
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what causes febrile non-hemolytic transfusion reaction?
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Ab against WBC in unit or can be do to cytokines; A type 2 HS rxn
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what is the most common transfusion reaction?
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allergic
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what causes allergic transfusion reaction?
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Ab against plasma protein in the unit
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what do you give for allergic reactiosn?
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diphenhydramine = benadryl
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what causes anaphlyatic shock reaction post-transfusion?
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IgA in unit given to pt who has a IgA deficiency and thus Anti-IgA Abs
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define transfusion associated acute lung injury
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non-cardiogenic pulmonary edema during or shortly after transfusion
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what causes transfusion associated acute lung injury?
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high titer anti-HLA or anti-leukocyte Ab in transfused plasma reacting against WBC in recipients blood - activated WBC cause lung injury
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what is the number one cause of death due to transfusion?
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transfusion associated acute lung injury
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what causes transfusion associated circulatory overload?
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rapid infusion of large volume can precipiate CHF or pulmonary edemia in pts with compromised cardaic fucntion
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what is the cause of GVHD?
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immunocompontent lymphocytes (T-cells) are transfused into a severely immunocompromised pt with malignancy or after receiving certain drugs - causes transfused cells to attack host
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what is the risk of transfusions from closely related persons?
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the recipient's immune system doesn't recognize transfused WBC as foreign BUT transfused WBC DO recognized recipient as foreign - and attack them
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what are the consequences of transfusion associated GVHD?
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bone marrow failure and apasltic anemia
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what in irradiated blood indicated?
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fetus, neonates, congential immune deficiencies, allogenic and autologous BMT, hemtalogic maligancies, aplastic anemia, solid tumors, HLA matched platelets, granulocyte transfusion and related/directed tumors
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what cells cause GVHD?
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t cell mediated
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what are blood units tested for?
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HIV, HBV, HCV, syphilis, west nile virus, HTLV-1; some tested for chaga
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what infections are not screen in blood units?
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CMV (most commonly passed on), malaria, vCJD, parovirus, babesiosis
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thalassemia: microcytic anemia + normal Hb electrophoresis
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alpha-thal trait
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thalassemia: microcytic anemia + decreased HbA and increased HbA2 and HbF
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beta-thal minor
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thalassemia: microcytic anemia + no synthesis of HbA
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beta-thal major
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thalassemia: microcytic anemia + >90% HbF
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beta-thal major
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thalassemia: no anemia + 50% HbA and 50% HbS
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sickle cell trait
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thalassemia: microcytic anemia + HbS and HbF
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sickle cell disease
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