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217 Cards in this Set
- Front
- Back
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Describe the regenerative response to a decrease in RBC mass.
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Renal cells sense decreased 02 tension release EPO and prod of RBCs by bone marrow increases
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What are the two main effects of EPO on bone marrow?
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-erythroid hyperplasia w/ increased prod of erythrocytes
-early release of reticulocytes |
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What is considered the hallmark of regeneration and describe
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reticulocytosis--increased number reticulocytes, which is detected 3-4 days after stimulation of marrow by EPO and preaks 7-10 days after stimulation
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What is special about horse's response to anemia?
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almost never release reticulocytes into peripheral blood
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What are aggregate reticulocytes?
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newly released reticulocytes w/ abndant ribosomes. Provides info on active bone marrow response. Ribosomes degrade w/in 12 hours.
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What are punctate reticulocytes?
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older reticulocytes. provides info on cumulative bone marrow response
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Are aggregate reticulocytes in cates and all reticulocytes in other species and same as polychromatophilic cells?
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yes
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If you see an increased reticulocyte count do you need to take a bone marrow aspirate? Why?
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No, because indicates increased erythroid hyperplasia in bone marrow (it is active)
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The more severe the anemia the higher/lower the reticulocyte count?
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higher
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what are the most common causes of chronic blood loss in adult animals?
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ulcers, neoplasms, blood-sucking parasites, IBD.
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Which neonates are at particular risk for iron def anemia?
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piglets
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Why is hypoproteinemia present w/ chronic blood loss?
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Seen in external blood loss b/c protein prod doesn't match protein loss
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What is the signal for RBC precursors to stop dividing?
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correct hemoglobin concentration
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What are the two fns of RBCs?
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Transport 02 from lungs to tissues
Transport CO2 from tissues to lungs |
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How do globin molecules of hemoglobin differ between mature and fetal?
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2 alpha and 2 beta in adult
2 alpha and 2 gamma globin molecules in fetal hemoglobin |
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Each globin molecule is linked to a ______ which binds ______
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heme. 02.
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What is erythron?
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The whole RBC mass, including stem cells, precursors, and mature cells in body
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What is erythropoietin?
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trophic hormone for RBC prodution. Specialized cells in kidney detect decreased 02 tension and prod and secrete EPO.
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How do RBCs differentiate?
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EPO acts on erythroid stem cells and they divide into rubriblasts. Rubriblasts produce mRNA and divide into prorubricytes and rubricytes. Hgb increases and cell mitotic activity decreases and metarubricyte. Mr kicks out nuclues (which is black and dead) and end up with reticulocyte which still has organelles (including ribosomes) Rt matures into erythrocyte.
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RBCs circulate for how long?
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100 days (dogs), 70 days (cats), 150 days (horses and cows)
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How do macrophages in the spleen remove senescent RBCs?
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heme molecules converted into unconjugated bilirubin, then secreted into blood, bound by albumin in plasma, and carried to liver. Bilirubin taken up by hepatocytes, conjugated, and excreted into canalicular space for delivery to intestine as part of bile. Iron stored as hemosiderin or feritin; globin degraded into constituent amino acids
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What is the main source of energy?
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glucose and anaerobic glycoloysis thru Embden-Meyerhof pathway generates ATP
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Enzymes that give energy to RBCs are ____ and w/o them end up with _____
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phosphofuctokinase (PFK) and pyruvate kinase (PK), hemolytic anemia b/c decreased ATP
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How do RBCs in spleen enter systemic circulation?
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splenic contraction
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Where do Mr (nRBCs) and reticulocytes go through maturation?
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spleen
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RBC concentration in blood is determined by what?
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production, destruction, and shift of RBCs in and out of spleen
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Define normocytic.
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RBCs of normal size for species
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Define anisocytosis
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Size variation abnormal for the species
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What is marcrocytosis?
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Increased number of RBCs w/ increased diameters
-should have increased MCV -common cause is regenerative anemia when bone marrow releases reticulocytes |
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What is microcytosis?
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Increased number of RBCs w/ decreased diameters.
-should correlate w/ decreased MV common cause is iron deficency anemia |
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what is crenation?
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An artifact that occurs when blood dries on the slide. RBCs have regularly spaced sharp projections (aka echinocytes)
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What are poikilocytes?
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General term meaning abnormally shaped RBCs
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What are schistocytes?
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fragmented RBCs (usually result from RBC shearing by fibrin deposition in blood vessels or by abnormal vessels)
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What are acanthocytes?
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RBcs w/ blunted surface projections that are unevenly spaced (ass w/ splenic and hepatic disorders. Sitting in abnormal lipid environment)
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What are spherocytes?
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spherical cells. Lack central pallor. normal volume. ass w/ IMHA.
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What are target cells?
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RBCs w/ excessive membrane that appear like target or bull's eye. Increased in regen anemia and have no significance under these cond.
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What are eccentrocytes?
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RBCs w/ hemoglobin shifted to one side of cell. On other side is clear area and thin membrane (indicative of oxidative damage)
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Ribosomes stain _____ and hemoglobin stains ____. When both are present in cell, cell stains _______ .
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Blue. Pink. Blue-gray.
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Increased polychromatophilic cells indicates what?
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regeneration
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What is hypochromasia?
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RBCs that are pale and have increased central pallow owing to decreased hemoglobin. Present in iron deficiency anemia
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What are ghost cells?
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RBC membranes w/ little or no hemoglobin content
-usually result from complement-mediated lysis of RBC |
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Why are nRBCs considered an inclusion?
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Even though the Mr is a normalcell, they should remain in bone marrow until they mature.
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What is a Howell-Jolly body?
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small round dark-staining inclusion
-represents remnant of extruded nucleus |
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What is basophilic stippling?
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Small basophilic granules, representing aggregated ribosomes
-normal in ruminant reticulocytes -also seen in dogs and cats w/ severe anemia that is regenerative -seen in lead poisoning |
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What is a Heinz body?
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denatured globin resulting from oxidation of hemoglobin
-seen on 10% cat RBCs -actual HBs large and single in cats, small and mult in dogs -better seen w/ new methylene blue stain |
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What does the direct antiglobulin test (DAT) or Coombs' test detect?
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anti-erythrocyte antibodies
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Who do reticulocytes appear in ruminants?
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Either polychromatophilic or basophilic stippling
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What indices does one look for in a regenerative RBC response?
2 things |
Increased MCV (macrocytosis) and decreased MCHC (hypochromia)
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What would one look for ain a wright's stained blood smear to find regenerative RBC response?
3 things |
anisocytosis (b/c both normal RBCs and macrocytic reticulocytes)
Macrocytosis (b/c macrocytic reticulocytes) Polychromasia |
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What are some additional features of regnerative response?
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Howell jolly bodies, nRBCs (sneak out when reticulocytes released), basophilic stippling (usually only in dogs and cats when anemia severe)
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How would one evaluate anemia in a horse? (4 things)
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History and clinical signs (hem or red maple leaves)
-plasma color and plasma protein concentration -MCV: even though no reticulocytes, RBCs can be larger -bone marrow aspiration to see if erythroid hyperplasia present |
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What is anemia?
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reduction in circulating RBC mass: decreased RBC count, decreased hemoglobin concentration, decreased PCV
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Clinical signs resulting from decreased oxygen carrying capacity are:
4 things |
Pallor (pale mucous membranes), lethargy (exercise intolerance, weakness, epression), increased respiratory rate (tachypnea), heart murmur (from decreased blood viscosity)
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What are the three classification systms of anemia?
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1. responsiveness of bone marrow: regenerative (hem or hemolysis) or nonregenerative ( intra-or extramarrow disease)
2. Alterations of MCV and MCHC 3. Pathophysiologic mech (blood loss, hemolysis, decreased prod of RBCs) |
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What kind of loss does hemorhagic anemia result in? 4 things
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volume, plasma, cells, and protein
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What happens in an internal hemorrhage?
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components resorbed or recyclesd w/ no net loss of iron or plasma proteins. This ic bleeding into the thoracic cavity or peritoneal cavity
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What happens in external hemorrhage?
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Components lost from body
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What happens in acute hemorrhage Immediately?
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Total blood volume decreased, but proportions don't change so PCV and TP concentration are w/in reference intervals
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What happens in chronic external hemorrhage?
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leads to iron deficiency anemia
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What happens in acute hemorrhage w/in hours
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intestitial fluid enters vasculature to restore volume, so blood components diluted, so PCV and TP decrease to reveal ANEMIA and HYPOPROTEINEMIA. If severe thrombocytopenia presnet it will be the cause NOT result of anemia
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What happens in acute hemorrhage after 3 days?
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regenerative rsponse evident
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What happens in acute hemorrhage after 7 days?
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peak reticulocyte response. Plasma protein normal
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What are the common causes of chronic external hemorrhage (CEH)?
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bleed into GI tract b/c of ulcers, neoplasm, blood-sucking parasites or IBD
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Anemia from CEH results from what?
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combination of blood loss and inadequate prod due to iron deficiency
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What are some lab features of CEH?
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hypoproteinemia (external blood loss and failure of protein prod to match loss), decreased MCV/microcytosis (signal for RBC to stop dividing is correct hemoglobin conentration, and w/o iron, hemoglobin production is inadequate, so see microcytes, decreased MCV)
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What is the RBC morphology in CEH?
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small and pale (microcytic and hypochromic). Poikilocytosis freq b/c iron-deficient RBCs more subject to oxidative damage. Shape changes include schistocytes, blister cells, applestem RBCs and keratocytes
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How are platelets affected in CEH?
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may be increased b/c of cytokines produced as part of inflammation ass w/ bleeding ulcer, neoplasm, or IBD
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How is bone marrow affected in CEH?
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Erythroid hyperplasia w/ ineffective erythropoiesis
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How are iron levels effeced in Fe deficiency CEH? (3 things)
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Decreased seum iron concentration, decreased serum transferrin saturation (transferrin is iron transport protein), decreased iron stores: ferritin (soluble) and hemosiderin (insoluble, stored in bone marrow macrophages. absent w/ anemia)
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How is Fe deficiency anemia diagnosed?
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microcytic, hypochromic andemia, decreased Fe levels, ID of source of blood loss. Platelet count hig b/c probaby have infection somewhere
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What is hemolysis?
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RBC destruction that may occur in vascular space (intravascular hemolysis) or in spleen, liver, bone marrow, orother organs (extravascular hemolysis)
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What are 4 general features of hemolytic anemia?
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-Only RBCs are lost (thru destruction), so TP doesn't change unless dehydrated so goes up
-more reticulocytes -fever may be present -plasma color may change |
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What is intravascular hemolysis
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RBCs lyse in circulation, releasing hemoglobin. Hemoglobin cleared from circulation when cmplx w/ plasma proteins (haptoglobin and hemopexin). Removed by liver where hepatocytes metabolize and conserve iron. If excessive, haptoglobin system saturated and get hemoglobinemia (hemoglobin in plasma) and hemoglobinuria
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What color is plasma with intravascular hemolysis
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pink or red
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What color is plasma from extravascular hemolysis?
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yellow or icteric
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What happens in extravascular hemolysis?
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splenic Macrophages 'digest' RBCs and metabolize components. Heme portion converted w/in macrophage to bilirubin. Bilirubin unconjugated, released by macrophage and enters to circulation. Binds to albumin. Travels to liver. Liver conjugates bilirubin and extretes into biliary system for delivery to small intestine in bile.
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What are 6 causes of hemolytic anemia?
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-IMHA from prod of anti-erythrocyte antibodies
-oxidative damage from drugs, chemicals, plants and some metabolic diseases -infection w/ erythrocytic microorganisms -fragmentation of RBCs by intravascular fibrin or travel thru abnormal vascular beds -Water intoxication -hypophosphatemia, bacterial infections, viral infections, hereditary |
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what is IMHA?
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attachment of anti-erythrocyte antibodies or immune cmplxes to RBC membranes.
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How often does IMHA occur?
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most common cause in dogs. Idiopathic (autoimmune) most common in certain breeds (cocker spaniels, poodles, collies) and females more affected
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Clinical signs of IMHA are what (3 things)?
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-signs ass w/ anemia
-splenomegaly (proliferation of macrophages in spleen) -icterus |
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Intravascular IMHA
5 things |
-caused by IgM antibodies
-complement fixation results in intravascular lysis of RBCs -hemoglobinemia and hemoglobinuria result -ghost cells -antibodies cross-link mult RBCs resulting in agglutination |
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Extravascular IMHA
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-caused by IgG antibodies
-antibody coated RBCs travel to spleen where Fc portion of antibody attaches to Fc receptor on splenic macrophages -splenic macrophage removes antibody and small portion of RBC and so see SPHEROCYTES THE HALLMARK extravascular IMHA -more rigid spherocyte gets stuck in spleen and phagocytized so entire RBC destoyed and anemia results -macrophages metabolize RBC components and icterus reults due to increased production of unconjugated bilirubin |
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How does CBC look in IMHA?
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-regenerative anemia (increased MCV, decreased MCHC, reticulocytosis)
-Total protein normal -Plasma color hemolysed if intravascular hemolysis or icteric if extravascular hemolysis |
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What is RBC morphology in IMHA?
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-morphologic changes ass w/ regeneration (anisocytosis, macrocytosis, polychromasia, nRBCs, HJB, and basophilic stippling)
-intravascular: ghosts and/or agglutination -extravascular: spherocytes |
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What do you see w/ WBC in IMHA?
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count is increased due to increased neutrophils and monocytes. Maybe see more immature neutrophils. This is b/c tissue damage from hypoxia or macrophages produces cytokines that increase WBC prod
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What do you see w/ platelets in IMHA?
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they are increased for same reason as WBC, but could also be decreased if prod of antibody against platelets
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What would you see in serum biochemical panel of IMHA?
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-hyperbilirubinemia (extravascular)
-increased liver enzyme is severly anemic and hypoxic damage of liver occurs |
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What would you see in urine analysis of IMHA?
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hemoglobinuria if intravascular and bilirubinuria if extravascular
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How would you dianose IMHA? (3 things)
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-signalment, history, clinical signs
-characteristic hematologic features -Direct antilobulin test (Coombs' test) Treated w/ immunosuppressive therapy |
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What is neonatal isoerythrolysis?
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common in foals. Mare sensitized to foal's RBCs produce antibodies against foal's RBCs which secreted into colostrum
-foal ingests colostrum and gets henolytic anemia |
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How would one detect oxidative damage in a blood smear?
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Heinz bodies and eccentrocytes. These cells are rigid and removed in spleen, resulting in hemolytic anemia (extravascular)
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What are causes of oxidative damage hemolytic anemia?
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acetaminophen, zenc, copper, onions/garlic, plants in bassica species, red maple leaves, propylene glycol
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What are lab feat of hemolytic anemia from oxidative damage?
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-regen anemia (increased MCV, decreased MCHC, reticulocytosis)
-total protein normal -plasma icteric or hemolysis -regen blood smear w/ heniz bodies and eccentrocytes -bilirubinuria in urinalsis if hemolyzed. |
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Describe hemotrophic mycoplasmas
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-epicellular organisms
-hemolysis predominantly extravascular -not always anemic |
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Describe anaplasma
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rickettsial organism
-intraerythrocytic -hemolysis predominantly extravascular |
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Describe protozoan organisms
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-intraerythrocytic
-hemolysis predominantly intravascular -babesiosis common -theileriosis and cytauxzoonosis also common |
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Describe fragmentation hemolysis
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schistocytes formed when traveling thru abnormal vascular bed or cross fibrin strands abnormally deposited in vasculature often secondary to disorder in coagulation
-often hemorrhaging as well -can also see spherocytes |
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What is nonregenerative anemia?
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reticulocyte response inadequate or absent. nomocytic/normochromic MCV and MCHC normal
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Intramarrow diseases cauing NRA is what?
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originate in bone marrow. Result in aplasia/hypoplasia, dysplasia, neoplasia of bone marrow cells. mult lineages affected
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Aplastic anemia
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intramarrow disease causing NRA. aplasia of all cell lines by radiation, drugs, toxins, hormones (estrogen)
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Pure red cell aplaia
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intramarrow disease causing NRA.
caused by immune-mediated destruction of erythroid precursors |
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Infectious diesease like FeLV
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intramarrow disease causing NRA. Causes supression of erythroid prod
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Leukemia
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intramarrow disease causing NRA. neoplastic transformation of clone of bone marrow cells that proliferate in bone marrow and crowd out normal hematopoietic cells. Myelophtheis='crowding out'
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Myelofibrosis
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intramarrow disease causing NRA. replacement of marrow space w/ fibrous tissue
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What is extramarrow nonregen anemia?
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disorders originate outside bone marrow and result in erythroid hypoplasia owing to decreased trophic hormones or nutrients or increased inhibitory cytokines ass w/ inflammation
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Chronic renal disease
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Extramarrow disease causing NRA. results in b/c decreased prod of EPO. also decreased responsiveness of marrow cells to epo, decreased lifespan of RBCs.
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hypothyroidism
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Extramarrow disease causing NRA. metabolic rate and req for O2 decreased, leading to decreased EPO prod
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Hypoadrenocorticism
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Extramarrow disease causing NRA. decreased glucocorticoids which may have stimulatory effects on RBC prod, cause mild anemia
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hyperestrogenism
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Extramarrow disease causing NRA. Toxic effect of estrogen on bone marrow
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What are key conepts of anemia of inflammation?
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Extramarrow disease causing NRA.
-cytokines inhibit release of iron from macrophage -decreased RBC lifespan and response of erythroid cells to EPO -usually mild -treatment directed at inflammatory disease |
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anemia of liver disease
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Extramarrow disease causing NRA
-seen in animals w/ chronic progressive liver diesease -usually normocytic/normochromic |
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What is inappropriate rubricytosis?
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nRBCs seen in absence of regen response
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What are some causes of inapprop rubricytosis? 3
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-marrow damaged by neoplasia, inflammation, necrosis, or hypoxia
-low number escap marrow and get trapped in spleen where undergo full maturation. If splenectomy or diseased spleen may mee nRBC -lead poisoning |
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What is polycythemia?
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increase in concentration of RBCs, hemoglobin concentration, or PCV. if severe, sludging of blood occurs resulting in porr perfusion of tissues
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What is relative polycytheia?
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offten seen w/ dehydration b/c plasma decreased so RBC and proteins concentrated. Also caused by splenic contraction which occurs when epinephrine released under excitement.
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What is relative polycythemia?
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Primary (from neoplasm or erythroid series) or secondary (resulting from increased EPO levels)
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What is hemostasis?
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The stoppage of blood. An interaction of blood vessels, platelets, and coagulation factors to achieve hemostasis w/o obstrcting blood flow
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How do platelets form?
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Stem cell differentiates into megakaryoblast. Megakaryoblast differentiates into megakaryocyte by endomitosis (nuclear replication w/o cellular division). Megakaryocyte located at sinus wall. Shed cytoplasm as long proplatelet processes directly into sinus lumen and then break into individual platlets.
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What is maturation time from megakaryoblast to platelet release?
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4-5 days
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What is the fn of thrombopoietin (TPO)? 3 things
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-stimulate megakaryocyte differentiation and platelet prod
-increase number, size and ploidy of megakaryocytes in bone marrow -decreased megakaryocyte maturation time in bone marrow |
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What is the lifespan of platelets?
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5-10 days
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How much of platelet mass is located in spleen?
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1/3
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What is the morphology of platelets?
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small granular discs w/ cytoseleton, alpha and dense granules, canalicular and tubular systems, membrane glycoproteins that act as receptors
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Do platelets have metabolic activity?
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yes, high metabolic activity
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What is the fn of platelets?
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formation of primary hemostatic plug (3-5 minutes)
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How do platelets form a plug?
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ADHERE to subendothelium, ACTIVATION (including shape change) SECRETE granules, AGGREGATE to form platelet plug (replaced by fibrin plug later)
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What are the adhesion factors of platelets?
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von Willebrand factor (vWf) and collagen. vWf binds to GP1b on platelet surface and serves as bridge twn platelets and collagen
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How do platelet shapes change?
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from smooth disc to spheres. Increases surface area of platelet and occurs in response to binding of thrombin and platelet surface
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Describe aggregation and secretion by platelets.
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secrete alpha granule products and dense granule products that recruit more platelets, mediate platelet aggregation, facilitate coagulation and mediate repari of vessel
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What are some examples of alpha granules?
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fibrinogen, factors V and VIII, growth factors
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What are some dense granules?
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ADP, thromboxane A2, Ca++
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What activates platelets?
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Thrombin, ADP, thromboxane A2
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What is the charge of the outer surface of platelet?
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negative phospholipid cmplx
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What happens to platelets as result of fibrinogen?
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Platelets irreversibly aggregate w/ help of Ca++. Then provide surface for formation and deposition of definitive fibrin plug
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What is the role of platelets in coagulation pathway? (3 precise things)
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localize coagulation and facilitate generation of thrombin (enzyme that converts fibrinogen to fibrin, the definitive hemostatic plug).
-aggregated platelets provide surface where coag rxn occurs -surface neg charged phospholipid cmplx (platelet factor 3) and platelet ca++ are important cofactors in coagulation -activated platelets bind coagulation factors/cofactors via high affinity binding sites |
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What is the role of platelets in inflammation? (3 things)
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-chemotaxis, ehancement of neutrophil fn
-antimicrobial activity -source of inflammatory mediators, vasoactive substances and mitogenic agents |
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Why is heparin lousy for a CBC?
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Inhibits fibrin so platelets still clump
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What is the normal number of platelets per filed?
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7-10 minimum. Horses are 4-10.
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What are large platelets called and what do they suggest?
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megathrombocytes, suggest active platelet production
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When does spontaneous hemorrhage begin for platelet count?
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<20,000-30,000
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What is MPV?
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Mean Platelet Volume. Indicates ave size platelets. increased if thrombopoiesis accelerated. Increased MPV=increased thrombopoiesis
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What is a fn-al platelet test?
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buccal mucosal bleeding time.
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What does prolonged BMBT suggest? (3 things)
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suggests platelets can't make plug
-platelet fn defect -vascular defect -von Willebrand Disease Thrombocytopenia can naturally result in prolonged bloeeding time, so only perform on animals w/ normal or increased platelet concentrations |
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What is thrombocytopenia?
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Decreased concentration of circulating platelets
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What are some clinical features of thrombocytopenia? (4)
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-mucosal surface bleeding (petechiation/eccymosis, melena, hematuria, epistaxis, gingeval bleeding, hyphema)
-spontaneous hem if platlet count <20,000-30,000 -anemia depending on degree and duration of bleeding -signs ass w/ primary disease (fever, lymphadenopathy) |
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What are the mechanisms of thrombocytopenia? (4)
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-decreased prod of platelets by bone marrow
-decreased platelet survival (destruction or consumption) -abnormal dist of platelets -pseudothrombocytopenia (false thrombocytopenia): not all platelets dectected bc clumping or exclusion by analyzer |
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What is thrombocytopenia w/ decreased prod of platelets by bone marrow associated with?
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Decreased numbers of of megakaryocytes in bone marrow
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What will cause decreased number of megakaryocytes in bone marrow? (3)
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-bone marrow hypoplasia, aplasia due to drugs, hormones, toxins, infectious agenents, immune mediated disease, idiopathic
-space occupying lesion in bone marrow (neoplasm) -myelonecrosis or myelofibrosis (marrow replaced w/ fibers) |
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What Causes thrombocytopenia: decreased platelet survival caused by platelet destruction? (2)
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-immune mediated destruction (most common)
-direct injury to platelets (drugs:quinine and heparin, infectious agents, physical damage from vascular disease) |
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How is IMT classified? 3 ways
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Pimary or idiopathic, secondary, or alloimmune thrombocytopenia from maternal alloimmunization
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Describe Primary/idopathic IMT (3 things)
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-antiplatelet autoantibody attaches to platelet membrane
-platelet cleared from circulation, primarily by plenic macrophages. Circulates to spleen and removed on 1st pass thru unlike w/ RBC which is spherocyte first. TPO increased bc decreased platelets so see increased megakaryocytes -may occur as part of systemic immune-mediated disorder (like lupus or IMHA) |
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Describe 2ndary IMT (2 things)
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-Platelets altered or coated by drugs, viruses, infectious agents, ciculating immune cmplxes ass w/ neoplasia
-increase in platelet ass immunoglobulin causing clearance of platelets from circulation |
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What is alloimmune throbocytopenia?
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predominantly in piglets and foals. Following maternal alloimmunization Neonates ingest colostrum containing antiplatelet antibodies
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What are 3 causes of thrombocytopenia: decreased platelet survival caused by consumption?
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-disseminated intravascular coagulation (DIC)
-vascultitis (FIP, inflammation of lining BV) -viral infection |
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What are 3 features of thrombocytopenia: decreased platelet survival caused by consumption?
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Platelet count in range of 50,000-150,000
-hem occur if thrombocytopenia sever or coag defect present -signs ass w/ primary disease |
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What is thrombocytopenia: abnormal dist of platelets
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reversible sequestration of platelets in large vascular bed, e.g. spleen, liver, dilated vessels, lung
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What are 4 causes of thrombocytopenia: abnormal dist of platelets
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-splenomegaly, splenic torsion, splenic neoplasia
-hepatomegaly, hepatic disease, portal hypertension -vasodilation in endotoxic shock (lung liver) -sever hypothermia |
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What are 3 features of thrombocytopenia: abnormal dist of platelets?
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Platelet count in range of 50,000-150,000
-hem occur if thrombocytopenia sever or coag defect present -signs ass w/ primary disease |
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How does aspirin effect platelets?
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cause acquired thrombocytopenia. Inhibits prod of thromboxane and lasts lifetime of platelets
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What 4 things can cause acquired disorder of platelets?
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-uremia (toxin in uremic plasma inhibit platelet fn)
-drugs: aspiring, phenybutazone, acetominophen, anesthetics, ca++ blocker -fibrin degradation products (FDP inhibit platelet fn when FDP increased in disease process) -paraproteins (in plasma cell myeloma, cloat platelet surface and inhibit fn. Plasma cell makes immunoglobin) |
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What are two types of inherited platelet disorder?
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-intrinsic platelet defects including absence of glyco protein receptors, ansence or reduction in platelet granules, and signal transduction defects
-von willebrand disease |
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What are the 3 types of vWD?
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Type 1 and 3 are deficiency and type two is abnormality. Results in reduced platelet adhesion
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What is VWF a carrier for?
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Factor VIII, coag factor. SOOOO...vWF makes platelet adhere to collagen and ALSO beinds coag factor VIII:C
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What would one see in vWD? (6)
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-mild to moderate severe bleeding
-platelet count normal -bleeding prolonged -vWf either reduced or absent -aPTT and ACT normal, but may be prolonged if VIII reduced a bunch -PT normal |
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What is thrombocytosis?
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Increased concentration of circulating platelets caused by increased prod of platelets or redist of platelets into circulation
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What is primary thrombocythemia?
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-marked elevation of platelet count from uncontrolled prod of platelets
-rare |
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What is secondary or reactive thrombocytosis?
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-ass w/ some disease processes (inflammatory diseases, Fe deficiency anemia, hem, IMHA, neoplasms)
-present in rebound from thrombocytopenia, post splenectomy, certain drugs, excitement/exercise -animals asymptomatic |
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What is coagulation?
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-generation of thrombin (enzyme that converts fibrinogen to fibrin) occurs as result of series of enzyme cmplxes assembling on surface of neg charged platelets. Termed 2ndary hemostasis
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Where are all coagulation factors synthesized?
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liver
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How do coag enzymatic factors circulate?
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enzymatic factors circulate as inactive proenzyme and activated at site of coagulation
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How do platelets aid in coagulation?
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-aggregated (activated) platelets express high-affinity binding sites for cofactors (nonenzymatic coag factors [tissue factor, VIIIa and Va]) that bind to platelet
-activated platelet has high density of neg charges on external membrane -ca++ attaches to neg charge on platelet membrane -vitamin K -dependent factors (enzymatic coag factors that act as proteases and substrates) are neg charged (carboxylated) and brought together by interacting w/ their cofactor and their attraction to calcium cations |
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What are the vitamin K dependent factors? 4
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II, VII, IX, X
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How do vit K-dependent factors work? 3 steps
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-vit K dep carboxylase in liver alters factors so have high density neg charge
-neg charges attracted to site of coagulation -non vitamin K-dep cofactors bring vit K-dep factors together |
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What are the 3 most important vit-K dep rxn?
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-extrinsic tenase:VIIa acts on X to yield Xa (cofactor is TF [III])
-intrinsic tenase: IXa acts on X to yield Xa. Cofactor is VIIIa -prothrombinase: Xa acts on prothrombin (II) to yield thrombin (IIa) (cofactor is Va) *all rns involve neg charged platelet surface and ca++ (IV) |
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What activates tissue factor [III]
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when expressed already active
These are cofactors brought to activated platelet membrane that brings neg charged vit k-dep protease and substrate |
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What activates factors V and VIII?
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activated by small amt thrombin generated initially
These are cofactors brought to activated platelet membrane that brings neg charged vit k-dep protease and substrate |
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What is an antiprotease?
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Inhibitor of activated coagulation factors
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What are 3 anti-proteases?
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-antithrombin: inactivates thrombin, IXa, Xa. ATIII activity enhanced by heparin (pharmacological)/heparan (in body)
-protein C: activated protein C (APC) inactivates factors Va and VIIIa -Tissue Factor Pathway Inhibitors (TFPI): inhibits further generation of Xa |
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What effect does the monocyte-macrophage phagocytic system have on coagulation?
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It inhibits coagulation. Removes activated factors,initiators of coagulation, microthrombi
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What is fibrinolysis?
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Degradation of the fibrin clot.
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What is the mechanism of fibrinolysis? 3 steps
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-plasminogen converted to plasmin by tissue plasminogen activator (TPA)released from endothelial cells
-plasmin degrades fibrin (also fibrinogen, Va, VIIIa, and vWf) -fibrin degradation products (FDP) produced, then clreaed by liver |
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How do you measure the intrinsic/common pathway? (2 ways)
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-activated partial thromboplastin time (aPTT)
-Activated clotting time (ACT) |
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How does aPTT work?
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Mesures time for fibrin clot formation in citrated plasma after addition of contact activator, calcium, and substitute for platelet phospholipid
-prolonged time means deficiency or inhibition of any 'intrinsic' or common pathway factor (70% defcinecy) or heparin therapy |
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How does ACT work?
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Measures time for fibrin clot formation in non-anticoagulated whole blood collected into specialized tube containing contact activator
-prolonged time means deficiency or inhibition of 'intrinsic' or common factor (95% deficiency) or severe thrombocytopenia can cause |
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How do you measure the extrinsic/common pathway? 2 ways
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one stage prothrombin time (PT) or screen test for viatmin K deficiency or antagonism b/c short have life of factor VII
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How does PT work?
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Measures time for fibrin clot formation in citrated plasma after add of TF, ca++, and sub for platelet phospholipid
-prolongation means factor VII deficiency (70%) |
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What does thrombin time measure? (TT)
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time for fibrin clot formation after thrombin added to citrated plasma. Converts fibrinogen to fibrin.
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What happens to coag if fibrinogen concentration decreased? 2
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-hypercoagulation (excessive conversion of fibrinogen to fibrin)
-decreased prod by liver |
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What happens to coag if fibrinogen concentration increase? 2
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inflammation, relative increase w/ dehydration
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What tests detect increased firinolysis? 2
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Fibrin degradation products (FDP)
D-dimer assays |
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What does increased FDP concentration indicate? 3 things
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increased fibrinolysis
severe internal hem w/ fibrinolysis Decreased clearance of FDP by liver |
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What affect will increased FDP have?
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inhibit platelet fn and fibrin polymerization, but only if pathologically increased like in DIC
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How do you measure antithrombin? AT
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measured as percent activity. Abnormal is <75-80%
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What are 3 general features of coagulation disorder?
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-may be acquired or congenital
-important to know age, breed, sex, and history -pattern of hem: major hemo, often mult sites ~sq, IM hematomas, large areas of ecchymosis ~bleeding into cavities, joints ~blood in stool, vomitus, urine ~petechiation |
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What is vitamin K deficiency and antagonism?
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acquired disorder of coagulation
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What are 4 causes of vit k def and ant?
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-poisoning with coumarin derivatives (warfarin, mycotoxin from sweetclover)
-fat malabsorption -dietary deficiency -antibiotics that cause decreased absorption or utilization by liver |
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How do anticoagulant rodenticides work?
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Vitamin K antagonist prevent conversion of vitamin K dep factors to appropriate (neg charged) forms
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What are clinical signs of anticoagulant rodenticide poisoning? 7
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-bleeding
-anemia, weakness, pallor -hypovolemia, shock -dyspnea -lameness -neurological signs -death |
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What are lab feat of antigoaculant rodenticide poisoning? 5
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-regen anemia (hem)
-leukogram variable -platelets normal but eventually may dev thrombocytosis -PT, aPTT, and ACT prolonged. PT good test bc short half life vactor VII -PIVKAassay indirectly detects abnormal forms of vit K dep factors, but not specific |
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How can you treat anticoag rodent poisoning? 6
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-blood transfusion
-correct hypovolemia, treat shock -avoid aggravation of bleeding (ie drugs that inibit platelet fn, IM injections, traumatic env) -vit K replacement -remove accumulations of blood -remove source of rodenticide |
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what is disseminated intravascular coagulation? (DIC)
4 points |
acquired disorder of coagulation
-syndrome caused by continued activation of both coagulation and fibrinolysis, resulting in thrombosis of microvasculature and bleeding from depletion of coagulation factors and platelets -always secondary to another disease process -also termed 'consumptive coagulopathy' -common coagulopathy in vet med |
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What are causes of DIC?
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-induction or exposure of tissue factor or other activators of coagulation thru sepsis, tissue necrosis, neoplasia
-endothelial damage exposing collagen -proteolytic enzymes (snake venoms, trypsin, from pancreatitis) -stagnant blood flow -hemangiosarcoma, metastatic tumors, systemic infections, endotoxemia, viral disease, shock, heat stroke, intravascular hemolysis, liver disease |
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What is the first phase of DIC?
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1st: hypercoagulable phase: characterized by thrombosis
consequence: blockage of microvasculature with thrombi causing ischemic necrosis and organ dysfunction |
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What is the 2nd phase of DIC?
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Consumptive phase: characterized by consumption of platelets, coagulation factors, and AT
consequence: bleeding |
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What happens in DIC?
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increased fibrinolysis bc increased amt of fibrin formed
Consequence is bleeding *LOOK AT CHART ON PAGE 28 OF NOTES* |
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What are the clinical signs of DIC? 3
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-signs of primary disease process
-signs of organ dysfn secondary to thrombosis -bleeding |
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What are some of the diagnostic and lab feat of DIC?
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-Presence of underlying disorder
-coagulation tests: consumptive phase ~thrombocytopenia ~prolonged PT, aPTT, ACT ~increased FDP/D-dimer concentration ~decreased fibrinogen ~schistocytes b/c fibrin laid down, but also have regn hem anemia w/ low TP ~decreased anthithrombin activity (AT) bc binds to all excess thrombin ~platelets decreased |
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What is the treatment of DIC?
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-identify and eliminate underlying disorder
-fluids to maintain circulatory volume and perfusion -transfusion therapy, replacement of factors, AT |
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is a coagulopathy ass w/ liver disease acquired or inherited?
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acquired coagulopathy
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What happens in coagulopathy ass w/ liver disease? 4 things
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-decreased synthesis of coagulation factors,inhibitors, and fibrinolytic factors
-thrombocytopenia -production of dysfn-al coag factors -decreased clearance of FDP and activated coag factors ~result in bleeding +/- thrombosis ~May be diff to dist from DIC |
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What are the clin feat of coag ass w/ liver disease? 3
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-tendency to bleed: severe only in advanced diseas
-clin feat of liver disease -screen for coag abnormalities b/f biopsy or surgery |
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What do vit K def, DIC and Liver disease all have in common?
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All acquired disorder of coag. All have prolonged PT and aPTT so need history and other lab tests
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What is Hemophilia A?
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Factor VIII:C deficiency only (not VWF)
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What is the mode of inheritance for HEMOPHILIA A?
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x-linked recessive in dogs, horses
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What are the clin and lab feat of hemophilia A?
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-bleeding
-coag studies ~platelet count and bleeding time normal ~aPTT, ACT prolonged if deficiency severe enough (intrinsic) ~PT is normal ~reducted % of factor VIII activity -CBC normal except of evidence of hem |
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What is hemophilia B?
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Factor IX deficiency (inherited coagulation disorder)
-signs and inheritance similar to hemophilia A |
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What is Hageman's disease?
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Factor XII defieciency (inherited coagulation disorder)
-seen in cats -NOT ass w/ bleeding, but prolonged aPTT |
