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92 Cards in this Set

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Q: Describe the pathophysilogoy for hemolytic anemias.
-intrinsic defects, extrinsic defects and it’s a systemic disease
Q: How does hemolytic anemia present clinically?
-may be asymptomatic, has either an acute or gradual onset
-has diverse symptoms including (severity of anemia, amount of compensation, cause of anemia, and additional underlying disease)
Q: What are the CBC findings for hemolytic anemia?
-anemia
-WBC, platelets, indices, and RBC morphology dependent on type of disease
Q: What happens to the retic count during hemolytic anemia?
-usually INC in moderate to severe hemolytic anemia, usually takes 2-3 days for response to appear
Q: Describe the bilirubin levels during hemolytic anemia.
-both the total and indirect bilirubin levels are elevated
Q: Describe the levels of lactic dehydrogenase (LDH) during hemolytic anemia.
-INC in LDH, LDH1 normally present in RBC’s (as well as in muscle), hemolysis -> INC serum LDH (LDH 1-2 flip)
-can be artificial increased by traumatic venipuncture or improper specimen handling resulting in in-vitro hemolysis, i.e. delay in separation of cells.
Q: What happens to serum haptoglobin levels during hemolytic anemia?
-haptoglobin is an alpha-2-globulin that binds free hemoglobin released into the bloodstream from hemolysis, is classified as an acute phase reactant, levels of serum haptoglobin DEC during hemolytic anemia
Q: What happens to levels of plasma methemalbumin during hemolytic anemia?
-methemalbumin appears after binding of haptoglobin is exhausted, free Hgb in plasma combines with albumin to form methemalbumin
-its presence indicates a considerable amount of intravascular hemolysis
Q: Describe the levels of plasma methemalbumin in hemolytic anemia.
-minute or trace amounts are “normally” present in plasma or serum (some hemolysis is unavoidable in drawing and processing specimens)
-occurs in larger amounts when all protein-binding capacity (including albumin) has been exhausted
-indicates severe intravascular hemolysis, if traumatic phlebotomy can be ruled out
Q: What is a direct Coombs test (DAT) used for?
-helpful in diagnosis of hemolytic disease, indicates Ab on patients RBCs
Q: What are some intrinsic defects in hemolytic anemia?
-membrane defects, RBC enzyme defects
Q: What are some membrane defects that occur in hemolytic anemia?
-congenital spherocytosis, paroxysmal nocturnal hemoglobinuria (PNH), hereditary elliptocytosis (ovalocytosis), congential stomatocytosis, abetalipoproteinemia
Q: Describe congenital spherocytosis.
-it is an autosomal dominant disease that has a deficiency of membrane protein, spectrin, leads to loss of surface area, decreased surface-to-volume ratio, and renders RBC’s less deformable
-can get extravascular hemolysis by spleen (500-800 grams) (splenomegaly) splenectomy largely eradicates the problem but does not cure the defect
-also get pigmented gallstones with cholecystectomy at an early age, 25% of individuals are asymptomatic
Q: What is the best screen for congenital spherocytosis?
-osmotic fragility test is best screen
Q: What are the lab findings associated with congenital spherocytosis?
-normocytic anemia (50 – 60%)
-no WBC changes
-RBC morphology includes spherocytes, polychromasia and Howell Jolly bodies
-the retic index >3%, MCHC INC suggests diagnosis but indices may be normal
Q: Describe Paraoxysmal Nocturnal Hemoglobinuria (PNH).
-is a stem cell disorder that involves all cell lines (RBCs, WBCs and platelets), have slight acidosis leading to intravascular destruction
Q: Describe the pathophysilogy of PNH.
-mutation of phosphotidylinositol glycan A gene
-abnormal cell membrane anchor glycosylphosphatidylinositol (GPI)
-results in deficiency of GPI-linked proteins which inactivate complement (decay accelerating factor (CD55), membrane inhibitor of reactive lysis (CD59), C8 binding protein)
Q: What else is associated with PNH?
-pancytopenia (DEC in RBC, WBC and platelet number)
Q: What are the clinical signs/symptoms associated with PNH?
-morning urine is dark
-iron deficiency from chronic iron loss in urine
-Budd Chiari syndrome - resulting from platelet aggregator release (platelet destruction
Q: What are the normal lab values associated with PNH?
-retic index > 3%
-bone marrow: often hypocellular
-sugar water test (screen)
-Ham’s test (confirmatory)
-low serum haptoglobin
-urine hemosiderin
-low leukocyte alkaline phosphatase (LAP)
Q: Describe hereditary elliptocytosis (ovalocytosis).
-usually a mild hemolysis that is largely compensated and has mild or no anemia, shows an autosomal dominant pattern
-normal population has up to 15% elliptocytes
Q: Describe stomatocytosis.
-autosomal recessive disease, mild anemia
Q: Describe abetalipoproteinemia.
-autosomal recessive disease where 40-80% of RBCs are acanthocytes (spur cells) with irregular sized spicules on their surfaces
-get demyelinization of posterior column of CNS
-serum lacks chylomicrons, VLDLs, and LDLs
Q: What are some examples of RBC enzyme defects?
-G6D deficiency, G6PD Mediterranean, pyruvate kinase deficiency
Q: Describe the pathophysiology of G6PD deficiency.
-RBC membranes vulnerable to injury from oxidants, damage to RBC leads hemolysis
-can be caused by certain drugs, antimalarials especially primaquine and other compounds (fava beans)
Q: Why does G6PD deficiency cause hemolysis?
-because glutathione (reduced state) protects RBCs and their membranes from such oxidants
Q: Describe the epidemiology of G6PD deficiency.
-most common and most important hemolytic anemia, >> 100,000,000 worldwide
-there are over 100 genetic variants known (most represent amino acid substitutions, they have different electrophoretic mobilities)
-has a sex-linked pattern, affects 22% of U.S. blacks, females are asymptomatic
-older RBCs usually affected, young RBCs tend to have normal or near normal levels
Q: Describe the Mediterranean version of G6PD deficiency.
-caused by fava beans, certain drugs
-DEC enzyme activity throughout life span of RBCs
-drug + Hb leads to production of H2O2, accumulating H2O2 injures RBC leading to hemolysis, denatured hemoglobin (Heintz bodies) precipitates in RBCs
Q: Describe Pyruvate kinase deficiency.
-second most common enzyme defect, is autosomal recessive
-enzyme necessary to produce pyruvate – energy producing step
-ATP necessary for maintaining the Na-K pump
Q: What are some extrinsic defects associated with hemolytic anemia?
-autoimmune hemolytic anemia, traumatic (microangiopathic hemolytic anemia), alloimmune hemolytic anemia, anemia of blood loss, non-immunologic hemolytic anemia
Q: What are some examples of autoimmune hemolytic anemia?
-warm agglutinins, cold agglutinins, drug induced, paroxysmal cold hemoglobinuria (PCH)
Q: Describe warm agglutins.
-affects the IgG class, is a clinical disease more common than cold types
-approximately 50% are idiopathic, also associated with collagen vascular diseases (SLE), CLL, malignant lymphoma (especially Hodgkin’s), viral infections, often directed against Rh antigen on Rh complex
Q: What are the lab findings associated with warm agglutins?
-spherocytes
Q: Describe cold agglutinins.
-affects the IgM class
-causes include: Mycoplasma pneumoniae, infectious mononucleosis, CLL, drugs
-Raynaud’s phenomenon common
Q: What are the laboratory results assoacitged with cold agglutinins?
-DAT usually positive, cold agglutinin titer INC (normal ≤ 32), spherocytes often absent
Q: What are the different ways that drugs can induce autoimmune hemolytic anemia?
-antibody (IgG) to drug binds to RBC membrane, penicillin is the prototype drug, others include hapene (benzyl penicilloyl), leads to extravascular hemolysis, test with direct coombs (is +)
-can be an “innocent bystander,” drug–anti-drug immune complex, IgG (extravascular hemolysis) or IgM (intravascular hemolysis) bind complement, example drugs include quinidine, quinine, INH, sulfonamides
-membrane alteration leading to nonspecific binding of plasma proteins, durgs include Keflex
-true autoimmune antibody, drug includes Aldomet (alpha methyldopa), affects 1-2% of patients, minimum 3 – 6 month treatment for hypertension, also associated with Rh antigens being altered leading to production of antibodies
Q: Describe paroxysmal Cold Hemoglobinuria (PCH).
-acquired IgG antibody with anti-P specificity, bithermal, Donath Landsteiner antibody
-binds to RBC, antibody complement fixation in cold, hemolysis when body warms
-shows a positive DAT (direct antiglobulin test = direct Coombs)
Q: What are the symptoms associated with PCH?
-similar to hemolytic transfusion reaction, fever, chills, cramps, leg and back pain, idiopathic or following viral illness
Q: Describe traumatic (microangiopathic hemolytic anemia).
-is a hemolytic disease associated with production of many schistocytes
-the #1 example is disseminated intravascular coagulation (DIC), RBCs get damaged by fibrin buildup or clots in small vessels
-other causes include artificial heart valves, thrombotic thrombocytopenia purpura
Q: Describe alloimmune hemolytic anemia.
-can be due to transfusion reaction-donor and recipient blood is incompatible, get intra- and/or extravascular hemolysis, free hemoglobin toxic to kidney cells
-laboratory findings for transfusion reaction includes-DAT, anemia depending on severity, total and indirect bilirubin elevated, haptoglobin decreased, LDH increased
-can also be due to hemolytic disease of the newborn (HDN)-maternal antibodies directed against baby's RBCs, leads to anemia and hyperbilirubinemia
-laboratory findings for HDN includes positive DAT, elevated total and indirect bilirubin, LDH increased, anemia (initially hematocrit and hemoglobin may be within normal limits)
Q: Describe the acute version of anemia of blood loss.
-48-72 hours to restore blood volume with severity of the anemia not properly reflected in Hgb or Hct until then
-reduced oxygenation in tissues leading to INC erythropoietin production, this causes INC in erythropoiesis
-reticulocyte count may reach 10% - 15% after several days, e.g. G.I. bleeding, fractures of hip, severe epistaxis
Q: Describe the chronic version of anemia of blood loss.
-produces anemia when blood loss exceeds regenerative capacity of bone marrow (ordinarily 6x-8x normal), but anemia occurs before that in most cases
-often complicated by Fe deficiency, e.g. hypermenorrhea, CA of colon, chronic gastric or duodenal ulcer
Q: What are some causes of non-immunologic hemolytic anemia?
-hypersplenism, microangiopathic hemolytic anemia (MAHA), microorganisms (malaria, babesia, Clostridium perfringens), snake venoms (cobra venom), chemical (plumbism), or physical (burns)
Q: Describe anemia associated with renal disease (uremia).
-usually normochromic and normocytic, often with mild anisocytosis, sometimes hypochromic, microcytic
-burr cells are present, shrunken RBCs with irregular pointed surface projections (echinocytes)
-usually present when BUN is twice normal
Q: What are some possible mechanisms underlying uremia?
-hemolysis from impaired renal excretion
-coagulation defects (in severe disease) leading to blood loss
-bone marrow suppression
-impaired erythropoietin production from renal endocrine failure
Q: Describe anemia with neoplasia.
-usually normochromic and normocytic with normal reticulocyte count, unless there is blood loss, hemorrhage or a myelophthisic process
-mild hemolytic component often present, may be severe with some lymphomas, possibly due to the altered endothelium of malignant tissues (also acts as a set-up for DIC)
Q: Describe anemia of infection.
-mild to moderate anemia, fairly common with subacute and chronic infections
-usually normochromic and normocytic
Q: What are the mecfhanisms involved in anemia of infection?
-poorly understood, may involve decreased rate of erythropoiesis, failure to utilize iron properly and decreased RBC survival
Q: What happens with serum iron levels in anemia of infection?
-low to low normal, low serum iron binding capacity (SIBC)
-examples include bronchiectasis, severe chronic pyelonephritis, visceral or deep abscess, SBE, Tb
-anemia of chronic disease, i.e. rheumatoid arthritis and collagen diseases
Q: What else can cause hemolytic anemias of infection?
-bacterial toxins (Clostridium perfringens) and malaria
Q: Describe intravascular hemolysis.
-Within the vessels, red cell lysis in peripheral blood cell via cell lysis mediated by complement (lysis in the blood), due to infection process (bacteria can release toxins and hemolysis into peripheral blood stream that can lyse the cell)
Q: Describe alloantibody and cell lysis involved with it.
-directed against antigens that are not self, ex: Blood transfusion
-Donated blood must be the same type otherwise it is perceived as nonself and get antibody response
Q: Describe autoantibodies and cell lysis involved with it.
-directed against self, Antigen-ab reaction, complement reaction, and cell lysis
-Antibody class: IgG and IgM, these are complement activators, complement gets activated by Ig when there is cross-linking
-IgM is more efficient because it is a pentamer, can cross link faster, IgG is a monomer, so need two of them sitting next to each other
Q: What happens when the cell lyses?
-Free Hb released and serum haptoglobulin is depressed., Antigen is probably binding to the RBCs and it is becoming non-self, Antigen can get on RBC as an infectious process via toxins
Q: Describe RhD antigen.
-have red cells that are RhD positive, add Ab and patient’s Ab bind to red cell, but don’t get vascular hemolysis even if you saturate the cell with RhD antigens, complement activation doesn’t occur, why? Because the IgG molecules are so spaced out and don’t cross link, even if you saturate with antigen. However if it was an IgM antibody, then you’ll fix complement
Q: Describe Clostridium perfringens.
-anaerobic bacteria, produces extracellular enzymes and toxins that will cause cell lysis, so if get those in blood stream, big trouble! Malaria causes hemolysis. Can also be due to prosthetic valve.
Q: Describe extravascular hemolysis.
-Removal of red cells by macrophages in spleen, liver, Recognition of those cells by spleen macrophages is mediated by: deformities, G6PD, but mostly due to macrophages having Fc recognition sites to bind to IgG on red cells
Q: What role do macrophages have on cell lysis?
-Macrophages don’t have Fc receptors for IgM, Macrophages can break down the red cells
Q: What role do the Igs have on cell lysis?
-If have a red cell membrane with IgG, macrophage has Fc Receptors to recognition sites, and these can bind to the Fc portion of the molecule and lead to phagocytosis
-macrophages don’t have FcIgM recognition sites, so how do they recognize an RBC with IgM bound? Activation of complement leads to C3b release, which binds to cell membrane of the red cell, and now they can be removed from blood stream by liver macrophages. IgM fixes complement and releases C3b. Most macrophages that recognize gammaFc are from spleen, and most that recognize C3b are from liver.
Q: Describe the haptoglobulin test for hemolysis.
-Controlled extravascular hemolysis, won’t see free Hb in the blood stream, look for the haptoglobulin levels. Controlled means the body is compensating or medication is helping. Decreased haptoglobulin means the hemolysis is very severe.
-We don’t test for free Hb in the blood stream, instead we look for serum haptoglobulin if hemolysis is severe, will find that it is decreased, this occurs for intravascular hemolysis as well
-Haptoglobulin is made in liver, and it takes 2-3 days for the liver to make the levels normal again when the hemolysis is fixed.
Q: What is the use of LDH in hemolysis testing?
-5 fractions of LDH are used for diagnosis, not a good test in general because doesn’t elevate quickly
-LDH is a good test for MI’s, but it takes 3 days to detect by that time you’re dead or bed ridden
Q: Describe the importance of LDH 1-2 flip in hemolysis.
-normally 2nd fraction of LDH is higher than 1st. Someone with heart attack, see fraction 1 higher than 2 after 3 days. Red cells are rich in LDH1, so if do this test on hemolysed blood, get a 1,2 flip, mimics a heart attack. Don’t want to run some of these tests on hemolysed blood, because will look like an MI.
-LDH is not a good test also because can get bad testing due to traumatic blood draw or if the sample sits too long. So there are a number of cases when we don’t want to run this test.
Q: Describe the role of methalbumin in testing for hemolysis.
-if all haptoglobulin is bound already, get an increase in methalbumin, but usually don’t run this test because haptoglobulin levels are sufficient.
-Methmalbumin is free Hb bound to albumin, binds after Hb binds to haptoglobulin
Q: Describe the changes in bilirubin that occur after hemolysis.
-Bilirubin will be increased (indirect – unconjugated) if there is hemolytic process. Get premature red cell destruction, increase in indirect levels, assuming the liver is functioning normally. Must look at increased bilirubin if the liver is functioning correctly. Liver is conjugating as much as it can and as quickly as it can, but there is still unconjugated floating around it is because red cells are being destroyed.
Q: Describe the levels of urobilinogen in hemolysis.
-Also see an increase in urobilinogen: bilirubin is carried by albumin to liver where it gets conjugated and leaves liver bile caniliculi to common bile duct to duodenum, 40% is reabsorbed at the small intestine to the portal system -> central vein -> vena cava -> blood stream -> kidneys -> excreted as urobilinogen.
-Urobilinogen is a product of the conjugated bilirubin. Newborns with jaundice have a lot of bilirubin, called kernicterous, babies are normally born with a lot of bilirubin.
Q: Can bilirubin be used as a marker for premature red cell destruction?
-yes, The more red cell destruction you get, the more bilirubin is formed, urobilinogen levels get elevated and assuming the liver is functioning at max, then get more conjugated bilirubin, so get more urobilinogen (more absorbed) and more excreted, this can be used as a marker for premature red cell destruction (hemolytic process)
Q: What are the lab findings in hemolytic anemia?
-elevation in LDH1, urobilinogen (urine), and anemia, DEC in serum haptoglobulin
-in peripheral blood smear will see shift retics and depending on how severe anemia is, nucleated reds, assuming the bone marrow is doing its job
-Shift retics on peripheral smear are polychromatophilic cells (bluish)
-If bone marrow is doing its thing, the reticulocyte count will be elevated and if there is anemia, must correct for it!
Q: What are some examples of acquired hemolytic anemias?
-PNH, malaria, clostridium perfrinogens
Q: What are some examples of inherited hemolytic anemias?
-sickle cell, beta-thalassemia, G6PD deficiency
Q: Describe beta-thalassemia as a hemolytic anemia.
-not traditional in the sense that don’t get excessive red cell removal in peripheral blood stream, but get destruction of reds in the bone marrow, more immature red cells
Q: Describe G6PD deficiency as a hemolytic anemia.
-this enzyme increases NADPH and reduces GSH to protect the Hb from developing disulfide bridges and losing its tertiary structure
-Iron in ferrous state is functional state, if in ferric state won’t carry oxygen, called the met-Hb reduction system (second system of RBC energy production), called methemoglobin reductase system.
Q: What is methemoglobin?
-Met-Hb is iron in the +3 state, met-Hb reductase state maintains it in the +2 form. If have G6PD deficiency, this system may kick in to keep the iron reduced, but the Hb still can’t maintain the disulfide bridges, due to lack of GSH reduction, so can’t protect the sulfhydral groups in Hb and the red cells, so Hb is unstable due to changes in tertiary structure and red cell membrane integrity
Q: What happens with patients who have G6PD deficiency?
-patients will have unstable Hb, which can be recognized by looking for intracellular inclusions, called Heinz bodies, which are indicators of unstable Hb
-Heinz bodies are not recognizable on Wright stain, different from Howell Jolly bodies, which CAN be seen on Wright stain.
Q: What test is used to check for G6PD deficiency?
-can run the Heinz body test
-The test to run to see if someone has G6PD deficiency, look at slide to see if Heinz bodies are present then may be hemolysis. Can quantify the amount of enzyme in the blood cell to determine if they are actively or inactively hemolyzing. If there is high G6PD in the red cell + Heinz bodies = means past incidence, if low G6PD, means current occurrence of hemolysis.
Q: is there a way to quantitate the amount of enzyme in the red cell?
-Can also order a test that will quantitate the amount of enzyme in the red cell (seen in patient that is not actively hemolyzing but may be due to drugs)
-Primaquin (antimalarial) was given to GIs in Korean war, and they got hemolytic anemia, due to G6PD deficiency
Q: Describe congentical spherocytosis.
-Genetic disease that causes a decrease in spectrin and ankyrin in the membrane, which decreases the membrane integrity and decreased surface area to volume ratio. MCV is low – normal. MCHC are elevated because red cells are packed with Hb. More than 50%, probably close to 70% of the blood cells will be spherocytes. Needs to be recognized early in life, red cells are abnormal and they are removed extravascularly. Complication of this is the formation of gall stones, which are JET BLACK, with a primary constituent of bilirubin.
Q: What test is run to check for congenital spherocytosis?
-Can run a test called osmotic fragility test, where you put the cell in a hypotonic solution, and see if it breaks. So if decrease the isotonic solution to a hypotonic solution, they will burst much sooner than a typical red cells.
Q: What are the steps involved in osmotic fragility test?
-Get a series of 12 tubes with decreasing salt concentrations and add the patient’s serum and look to see which concentration gives cell lysis. In congential spherocytosis get increased lysis at lesser hypotonic solutions as compared to normal red blood cells. Opposite of what happens to people with sickle cell, which will take up more fluid faster.
-Solution is more hypotonic than cell, so fluid rushes inside and causes cell lysis
Q: Blood smear with Polychromatophilia, macrocytes, and spherocytes, some microcytes.
-should see elevated RDW. MCV may be in the normal range and have at least 2 populations of the cells, normal along with some big and small.
-Polychormatophila means the bone marrow is putting out retics early, see shift retics. Elevated retic count means bone marrow is compensating, so get shift retics
Q: Patient comes in complaining of dark urination. Hct/Hb are 32 and 10.5, second day 30 and 10, third day it is 27 and 9. What does this mean?
-patient is losing blood
-Ddx: Autoimmune hemolytic anemia, antibody against drug, or alloimmune hemolytic anemia. G6PD, congential spherocytosis, PNH (polysomal nocturnal hemolysis)
Q: How do you test to see if a hemolytic process is due to an Ab?
-Coombs test
Q: What is the difference between a direct and indirect Coombs test?
-Coombs direct test: order if you want to know if there are Abs bound to red cell
-Indirect Combs test: antibodies in the serum
-Someone with hemolytic anemia, we want to order a direct Coombs, want to know if it is hemolytic anemia, antibody related. If it is positive, do an indirect Coombs to find out which antibody it is. Can also take the red cell and elute the antibody on it and determine which one it is.
Q: Describe the functioning of the bone marrow during a hemolytic anemia.
-The patient’s bone marrow is NOT working properly in hemolytic processes, if it is pumping out nucleated reds. If take a patient’s bone marrow with spherocytosis, see shift retics, spherocytes because spleen removing extra deformed cells and bites the membrane but it reforms into a sphere.
-In any hemolytic anemia, get spherocytes because spleen is removing the red cells but not efficiently
Q: How would the blood smear look for MAHA (microangiopathic hemolytic anemia?
-would see 30% shistocytes and some spherocytes, most of the cells are macrocytic
Q: Describe HDN.
-Same as Erythroblastosis fatalis, There are antibodies in the mother’s blood that attack the newborn’s RBCs, these antibodies are IgG, which is the only one that crosses the placental barrier.
-very severe, lots of macrocytes, spherocytes, occasional shistocytes, and nucleated reds, Presence of nucleated reds suggests that this is a very severe anemia, and that there are polychromatophilic cells (shift retics)
Q: How does the body compensate for severe anemia?
-Someone with a very severe anemia will have the body compensating by releasing more red cells, kidney makes more erythropoietin, cardiac output is increased, tachycardia, oxygen dissociation curve goes to the right, let go of oxygen easier because release for BPG, get decreased peripheral resistance. When bone marrow puts out young cells, it is activated to the max, and the M:E ratio is lower because have more red cells leading to Increased erythorpoiesis, so get hyperplasia and low M:E ratio of bone marrow, because see more red cells than white cells!
Q: Describe PNH.
- acquired disease with intrinsic problems with cell membrane (only diseases of this type because all other diseases with cell membrane are inherited)
-Mutant gene, called PIGA, is required for synthesis of intramembranous glycolipid anchor (phosphatidyl inositol glycan)
Q: What happens when there is a problem with the GPI anchor like seen in PNH?
-Problem with the GPI anchor which is a receptor site for 3 proteins, which prevent the complement from binding. CD55 (decay-accelerating factor), CD59 (membrane inhibitor of reactive lysis), and C8 (binding protein). CD59 is the most important one. If can’t anchor these proteins, can’t prevent the complement from working so get overactive complement system.
Q: What’s wrong with a overeactive complement system?
-In this disease, the red cells have increased susceptibility to slight changes in the pH, mild acidosis. Mild acidosis will initiate the complement pathway and because these cells don’t have a mechanism to limit complement activity, this leads to a chronic and continued lysis of red cells. It is a chronic disease, and only about 20-25% of the time these patients will have brown urine, which is an indicator that something is wrong. But only a small % of these ppl will have these symptoms, most patients will have symptoms of chronic anemia. If this goes on long enough, get red cell lysis and will get release of iron in urine as urinesideron, which tests for chronic hemolysis. If this goes on long enough, these patients may develop iron deficiency anemia. (In US, most common cause of iron deficiency is chronic bleeding).
Q: What is a major complication of PNH?
-Major complication is venous thrombosis, Budd Chiari disease, in which get hepatic vein thrombosis and can be life threatening in patients, initiated by PNH. Not only are red cells affected, but ALL are (wbcs and platelets). When platelets are destroyed, get platelet aggregation factors that gives platelet aggregation and thrombosis. Not a common disease.
Q: How is PNH diagnosed?
-screening test is the sugar water test, if this is positive, then go to a confirmatory test, i.e. the Ham test. Sugar water test – sugar water enhances complement attachment to RBCs so will lyse faster is positive as in PNH.
-Ham test: take patient’s red cells, put in serum and acidify them. If those cells lyse randomly, then + test, confirmation this patient has PNH. Can also test for presence or absence of the CD receptor sites, make Ab’s against them and test for them but it is very expensive and not always done because it takes forever.
Q: Can the screening test for PNH have false positives in it?
-Screening test could have some false positives, specificity not good, but sensitivity is very good, don’t want people with the disease filtering through, so capture a lot of people plus people without disease.
-Confirmatory test: specificity is increased.