Other CP Flashcards
___ testing is performed on all amniotic fluids having elevated AFP concentrations.
AChE testing is performed on all amniotic fluids having elevated AFP concentrations. The odds of having a fetus with a NTD are considerably greater if both the AFP is elevated and the AChE is positive.
Antiphospholipid antibody syndrome.
APS is a common cause of acquired thrombophilia defined by venous or arterial thromboembolism and/or obstetric complications and the presence of antiphospholipid antibodies detected in patient plasma. APAs are acquired autoantibodies directed against phospholipid-protein complexes. Currently recognized laboratory criteria for APS include lupus anticoagulant (LA), IgG or IgM anticardiolipin (aCL) antibodies, or IgG or IgM anti-beta-2 glycoprotein I antibodies (anti-B2GPI). Lupus anticoagulants are IDd by clot-based coagulation tests, whereas aCL and anti-B2GPI Abs are IDd by ELISA. Abs should be demonstrable on at least 2 occasions separated by 12 weeks (this is to exclude transient APAs, which are often secondary to intercurrent infection or other acute illness). Despite the prolongation in clotting times in patients with LA Abs, APS is mostly a prothrombotic disorder and bleeding is uncommon. LAs prolong phospholipid-dependent coagulation tests due to antagonism of reagent phospholipids. The prolongation of clotting times is a laboratory phenomenon due to limited phospholipid in the test reagents. Among APAs, LA positivity carries the strongest risk for thromboembolic events or pregnancy morbidity.
Androgen receptor.
The androgen receptor is a nuclear receptor that localizes to the nucleus following phosphorylation and dimerization promoted by ligand binding, where it functions as a transcription factor.
List some antiplatelet agents and their mechanisms of action.
Antiplatelet agents include aspirin, clopidogrel (Plavix), prasugrel (Effient), ticagrelor (Brilinta), and glycoprotein IIbIIIa inhibitors. Are indicated for many conditions in which platelet aggregation leads to arterial thrombosis, such as MI, angina, stroke, diabetes in those over age 30, and PAD. Aspirin blocks thromboxane A2 synthesis irreversibly. Clopidogrel, prasugrel, and ticagrelor produce inhibition of platelet ADP receptors. The IV drugs abciximab (Reopro), eptifibatide (Integrilin), and tirofiban (Aggrastat) block glycoprotein IIbIIIa receptors.
Cancer-associated myositis?
Dermatomyositis is more frequent than polymyositis. Greater risk in males than females, age >60 years old. Patients with myositis and cancer tend to have more severe weakness and rashes, lower levels of serum creatine kinase, and higher ESRs. The MC associated malignancies are adenocarcinomas of the lungs, breast, GI tract, and ovaries, as well as lymphoma.
Chlamydia trachomatis serovars.
There are 18 known serovars. Serovars A, B, Ba, and C usually cause trachoma. Serovars D-K are usually sexually transmitted. Serovars L1-L3 are the causative agents of lymphogranuloma venereum.
Dermatomyositis?
Has a peak age of onset of 7 years in children and 30-50 years in adults. Relatively more frequent in children than adults. Is characterized by mild to moderate weakness, and more common in children are dystrophic calcifications, cutaneous and GI ulcerations, and lipodystrophy. 5 year survival in adult dermatomyositis is 75-90% and in juvenile dermatomyositis is >95%. Initial immune processes include activation of the complement cascade through C3 and deposition of the complement C5b-9 membrane attack complex on the endomysial vasculature, with resultant capillary destruction, muscle ischemia, and dilatation of the remaining capillaries. These processes lead to infiltration of B lymphocytes, CD4 helper T cells, and plasmacytoid dendritic cells in perimysial areas of muscle fascicles and in small blood vessels. The MHC class I antigen and intracellular adhesion molecules are upregulated on the cell surfaces of damaged fibers and in perivascular areas, respectively.
EGFR protein.
EGFR is a transmembrane tyrosine kinase that belongs to the HER/ErbB protein family. Ligand binding results in receptor dimerization, autophosphorylation, activation of downstream signaling, and internalization. The adaptor protein GRB2 binds activated EGFR phosphorylated at Tyr1068; this binding is necessary for the stimulation of EGFR-induced Ras/MAPK signaling.
Ethylene glycol (1,2-ethanediol), isopropyl alcohol (isopropanol), methanol (wood alcohol). Anion gap? Osmolal gap? What enzyme metabolizes it into what metabolites?
Ethylene glycol: anion gap acidosis +, osmolal gap +, no increase in ketones. Metabolized by alcohol dehydrogenase initially into glycolic acid, then to oxalate. The glycolic acid is responsible for the CNS manifestations and for the anion gap acidosis. The oxalate binds calcium to produce calcium oxalate, which is deposited in tissues and can be found in renal tubules and urine. Methanol: anion gap acidosis +, osmolal gap +, no increase in ketones. Metabolized by alcohol dehydrogenase to formaldehyde then formic acid. These metabolites result in ocular toxicity and the anion gap acidosis. Isopropyl alcohol: no anion gap acidosis, osmolal gap +, no increase in ketones. Is metabolized to acetone. Ethanol will have -/+ anion gap acidosis, osmolal gap +, and -/+ increase in ketones. Direct laboratory tests for methanol and ethylene glycol are not widespread, so the osmolal gap is a surrogate marker; ingestion is suspected if the osmolal gap exceeds 10, and is strongly suspected if it exceeds 20.
Hemoglobin makes up approximately (#)% of the cytoplasmic protein in a RBC. Hemoglobin is composed of (#) alpha-globins and (#) non-alpha-globins that are conjugated to (#) heme molecules that each contain (#) iron atom. Each hemoglobin molecule is capable of reversibly binding and transporting (#) oxygen molecues.
Hemoglobin makes up approximately 98% of the cytoplasmic protein in a RBC. Hemoglobin is composed of 2 alpha-globins and 2 non-alpha-globins (usually beta-globin in adults) that are conjugated to 4 heme molecules that each contain 1 iron atom. Each hemoglobin molecule is capable of reversibly binding and transporting 4 oxygen molecues.
HER2 gene.
Cell membrane surface-bound receptor TK, encoded by HER2/neu, a proto-oncogene. The gene is on 17q21-q22. HER2, neu, and ErbB-2 are all the same gene.
Human cases caused by the following domestic arboviruses are nationally reportable to the CDC:
West Nile, St. Louis encephalitis, Powassan, eastern equine encephalitis, western equine encephalitis, and California serogroup viruses (i.e., La Crosse, Jamestown Canyon, California encephalitis, Keystone, snowshoe hare, and trivittatus).
Idiopathic inflammatory myopathies or myositis syndromes?
The most common forms are polymyositis, dermatomyositis, and inclusion body myositis.
In prenatal screening tests, what is included in the first trimester panel and second trimester panel?
The first trimester panel includes total or free beta-hCG, PAPP-A (Pregnancy Associated Placental Protein-A), and NT (Nuchal Translucency). The second trimester panel can be a quadruple panel or a triple panel. The quadruple panel includes MSAFP (Maternal Serum Alpha-FetoProtein), uE3 (unconjugated estriol), beta-hCG, and DIA (Dimeric Inhibin-A). The triple panel is the quadruple panel minus the DIA.
In testing for lupus anticoagulant, what aspects of blood collection and processing must be paid attention to?
Anticoagulant meds such as heparin, direct thrombin inhibitors, and vitamin K antagonists such as warfarin can interfere with LA testing due to their effects on coagulation assays. Heparin and DTIs are of particular concern b/c they prolong phospholipid-dependent coagulation tests and behave as inhibitors in mixing studies, potentially mimicking an LA. A thrombin time, or other means of IDing heparin, should be routinely performed on test plasma to ID the presence of heparin or DTIs. The commercial dilute Russell viper venom time reagents used for LA testing contain heparin neutralizers; however, if the content of heparin in the test plasma exceeds the reagent neutralization capacity (typically greater than 0.8-1.0 U/mL), it can give rise to a false-positive LA result. Activated partial thromboplastin time reagents generally do not neutralize heparin. LMW heparin has less effect on LA testing than unfractionated heparin. In general, blood for LA testing should be collected before starting anticoagulant drugs or after their discontinuation. For vitamin K antagonists, wait 1-2 weeks after discontinuation or until the INR is <1.5. For processing, double centrifugation is recommended to ensure that the plasma is platelet-poor, b/c contaminating platelets can neutralize the Abs, resulting in a false-negative result. Plasma filtration introduces variables such as loss of VW factor and is not recommended. To prevent the loss of coagulation factors, the plasma should be tested or frozen as quickly as possible following collection. The sample should be thawed at 37 C for 5 minutes to avoid formation of cryoprecipitate and mixed thoroughly before testing.
Inclusion body myositis?
Is seen mainly in older white males. Is characterized by slowly progressive weakness primarily involving the quadriceps and finger flexors, rapid development of muscle atrophy, and dysphagia. 5 year survival is 100%, but there is much functional disability. Immune processes include a predominant cytotoxic T lymphocyte mediated process involving perforin, with CD8 T cells accompanied by smaller numbers of macrophages surrounding and invading otherwise normal-appearing myocytes in endomysial areas. The MHC class I antigen is upregulated on the surface of the majority of muscle fibers, even those not affected by inflammation. These immune processes are the same as in polymyositis.
Indirect and direct measurements of serum sodium.
Most modern high-throughput analyzers use indirect ion-selective electrodes to estimate electrolyte concentrations in serum samples. This analysis is preceded by a dilution step of the sample. If the water concentration is altered by the presence of increased lipid or protein, the dilution step and subsequent calculation of concentration by the analyzer results in a falsely low sodium value. Other indirectly measured analytes, such as potassium, calcium, and chloride, are subject to the same effects as sodium. Although the relative effect on all aqueous solutes is the same, the absolute change in sodium is far greater in view of its higher concentration in serum. With the use of indirect sodium measurement of routine analysis, measurements using a direct-reading ISE (direct potentiometry) should be undertaken under the following circumstances: 1) If the specimen is overtly lipemic or hyperviscous. However, correlation between visual turbidity and the concentration of triglycerides is poor. 2) If there is a significant discrepancy between measured osmolality and calculated osmolality. 3) Any low sodium in a patient with DM and hyperglycemia (pseudohyponatremia secondary to associated hyperlipidemia, in these patients, should be differentiated from true hyponatremia secondary to the positive osmotic effects of hyperglycemia). If a direct-reading instrument is not available, the serum water fraction can be calculated by the equation: serum water fraction = {99.1 - (0.001 x lipid concentration in mg/dL) - (0.7 x protein concentration in g/dL)} / 100 and then used in the equation: corrected sodium value = (indirect sodium value x 0.93) / calculated serum water fraction.
Lineweaver-Burke plots, competitive inhibition, noncompetitive inhibition, uncompetitive inhibition.
Lineweaver-Burke plots are a means to express a non-linear asymptotic concept (how the rate of the reaction varies with the substrate concentration) in a linear fashion by using the reciprocals of substrate concentration (1/[S]) and reaction rate (1/v). The x intercept is -1/Km, the y intercept is 1/Vmax, and the slope is Km. In competitive inhibition, the enzyme’s substrate and the inhibitor compete for the same binding site. This type of inhibition can be overcome by increasing substrate concentration. On the Lineweaver-Burke plot, the y intercept is unchanged and the slope is increased. In noncompetitive inhibition, the inhibitor binds the enzyme at a different site from the substrate binding site, effectively decreasing the amount of useful enzyme without affecting the binding of substrate to enzyme. On the Lineweaver-Burke plot, the Km (a function of binding) is unaffected, but the reaction rate decreases. In uncompetitive inhibition, the inhibitor binds and stabilizes the enzyme-substrate complex. On the Lineweaver-Burke plot, the Km is decreased (can’t bind enzyme if it’s in a stable complex), and the Vmax is decreased (product can’t be formed if the substrate and enzyme are stuck together).
Microscopic examination of stool for WBCs?
Microscopic examination of a nonconcentrated wet or stained preparation is the traditional means for identifying and quantifying WBCs in fresh or fixed stool. The test can produce false-negative results if the WBCs have degenerated. Prolonged transportation time, collection of stool a on swab, and storage at room temperature can all negatively affect morphology. WBCs can also be lysed by toxin-producing organisms such as C. difficile. Fecal lactoferrin can be used in place of, or in addition to, a traditional slide exam. Fecal lactoferrin is an iron-binding glycoprotein found in the secondary granules of neutrophils and is therefore an alternative marker of fecal PMNs. This compound remains stable in feces despite leukocyte deterioration. Commercially available fecal lactoferrin antigen detection methods are rapid, accurate, and easy to perform. However, the tests are not quantitative, so microscopic examination is still needed to quantify fecal leukocytes. Lactoferrin is present in mother’s milk and the test can be positive in nursing infants who do not have intestinal inflammation.
Monitoring patients on LMW heparin.
Because LMW heparin is more predictable in its effect, typically no monitoring is done. Notable exceptions are for obesity and low body mass, impaired renal function, pregnancy, and for patients on long-term therapy. In these cases, monitoring is done with the anti-factor Xa assay, using a target of 0.5-1 U/mL. Another important indication for monitoring is a pregnant patient previously on warfarin. Since warfarin causes birth defects, these women are switched to LMW heparin. However, as the fetus grows, it metabolizes LMW heparin faster than the mother, so the dose must often be increased as the pregnancy progresses.
Oncotype DX (Genomic Health Inc.), MammaPrint (Agendia), Mammostrat (Clarient). How do they work?
Oncotype DX is a real-time RT-PCR assay measuring RNA expression in 16 cancer-related genes and five reference genes, using paraffin-embedded tissue. Results are given as a recurrence score between 0 and 100, which are translated as low risk (a score of 18 or lower), medium risk (19 to 30), or high risk (31 or above). MammaPrint microarray measures expression of 70 genes in fresh or FFPE tissue; it categorizes patients as either high risk, (a so-called poor signature), or low risk (a so-called good signature) for recurrence. Mammostrat is an IHC test measuring five markers: p53, HTF9C, CEACAM5, NDRG1, and SLC7A5. The results are combined into a quantitative risk index: low, moderate, and high. Oncotype DX and MammaPrint are send-out tests, with TATs of 10-14 days, while results from the IHC-based Mammostrat, also a send-out test, are available to local pathologists within 48-72 hours. As of 3/2014, only MammaPrint has FDA clearance.
Plasmapheresis vs. plasma exchange?
In plasmapheresis, plasma is removed and replaced with a mixture of normal saline and 5% albumin. In plasma exchange, plasma is removed and replaced with allogeneic plasma.
Polymyositis?
Is seen mainly in adults, with peak onset at age 30-50 years. Is characterized by moderate to severe weakness, interstitial lung disease, and cardiac disease (including heart failure, arrhythmias, ventricular dysfunction). 5 year survival in adults is 75-94%. Immune processes include a predominant cytotoxic T lymphocyte mediated process involving perforin, with CD8 T cells accompanied by smaller numbers of macrophages surrounding and invading otherwise normal-appearing myocytes in endomysial areas. The MHC class I antigen is upregulated on the surface of the majority of muscle fibers, even those not affected by inflammation. These immune processes are the same as in inclusion body myositis.
Possible causes of a prolonged PTT?
A deficiency of Factor VIII, IX, XI, XII, prekallikrein, or high-molecular-weight kininogen. A lupus anticoagulant. Heparin. A direct thrombin inhibitor (such as argatroban, hirudin, or bivalirudin). A specific factor inhibitor (ie an antibody against Factor VIII, IX, XI, or XII).
Pseudohyponatremia, pseudonormonatremia, and pseudohypernatremia.
Hyponatremia occurs on a backdrop of hyperosmotic, isoosmotic, and hypoosmotic plasma; hence measurement of plasma osmolarity is important in the assessment of hyponatremia. For example, in the presence of hyperlipidemia or hyperproteinemia, measured serum sodium can also be depressed without concomitant depression of serum osmolarity. This artifact of measurement is termed pseudohyponatremia in the context of physiologically normal sodium levels and pseudonormonatremia when the result masks physiologically increased sodium. The phenomenon of pseudohypernatremia can occur as a result of severe hypoproteinemia.
Solid organ transplant-associated acute graft-versus-host disease.
The occurrence of an immunologically mediated and injurious set of reactions by cells genetically disparate to their host is known as GVHD. Acute GVHD is most commonly associated with hematopoietic stem cell transplantation (35-50%). With solid organs, the highest occurrence is with small intestine transplantation (5.6%), followed by liver transplantation (1-2%). Cases have also been reported after kidney, pancreas, heart, lung, and multivisceral transplants. The clinical presentation of solid organ transplant-associated GVHD includes skin rash (red to violet maculopapular rashes which may coalesce) and diarrhea (green, mucoid, watery, sometimes bloody), and most cases quickly advance to become a multisystem disease affecting bone marrow and other nontransplanted solid organs. The patient often dies of bleeding and infection from bone marrow failure. The mortality rate of solid organ transplant-associated GVHD ranges from 30 to >75%. In the rare reported cases after lung or pancreas transplant, the mortality rate reaches 100%. The diagnosis is based on clinical symptoms, characteristic histopathologic findings on biopsied tissues, and evidence of microchimerism of donor T cells. Solid organ transplant-associated GVHD often occurs between 2-6 weeks after liver transplantation, although this is variable with late-onset cases seen in other transplant settings.
Tube for collecting joint fluids for analysis?
Synovial fluid from inflamed joints can clot when collected and therefore should be collected into an anticoagulant for accurate cell counts, differential counts, and crystal analysis. It can be transported and stored at room temperature but should be examined as soon as possible, and definitely within 24 hours, because cellular degeneration will occur. Sodium heparin or EDTA tubes can be used for crystal analysis. Lithium heparin can form rhomboid crystals that can mimic calcium pyrophosphate dihydrate crystals, and oxalate will cause the formation of calcium oxalate crystals, so these 2 should not be used. If there is sufficient volume, chemistry studies such as glucose, protein, CH50, C3, and C4 can be performed on tubes without anticoagulant, or in the case of C3 and C4, with EDTA. A fluoride tube can also be used for glucose. Synovial fluid for culture should be collected into SPS (Sodium Polyanethol Sulfate) tubes without anticoagulant, or at least with an anticoagulant that does not have a suppressive effect on bacterial growth.
What diseases are antiphospholipid antibodies seen in conjunction with?
SLE, RA, Behcet syndrome, hematolymphoid malignancies, MGUS, Waldenstrom macroglobulinemia, and liver disease. Certain infections such as hepatitis C, HIV syndrome, HTLV-1 associated spastic paraparesis, Q fever, and malaria may also be associated with APAs.
What is Non-HDL-C?
Non-HDL-Cholesterol, which includes all atherogenic particles: LDL, very-low-density-lipoprotein, intermediate-density lipoprotein, and chylomicrons.
What is the LAP score?
Alkaline phosphatase activity is found in the cytoplasm of neutrophils, osteoblasts, vascular endothelial cells, and some lymphocytes. The alk phos level of peripheral blood neutrophils is quantitated by the leukocyte alkaline phosphatase (LAP) score and is a useful screening test to differentiate chronic myelogenous leukemia from leukemoid reactions and other myeloproliferative disorders. The LAP score is usually performed using the Kaplow procedure. The LAP score is determined by evaluation of the staining intensity (ranging from 0 to 4+) of 100 counted neutrophils or bands. Normal LAP scores range from 15 to 130, but there may be variation in these ranges between laboratories. Entities with a low LAP score (130): Infections, growth factor therapy, myeloproliferative disorders other than CML, inflammatory disorders, pregnancy, oral contraceptives, stress, drugs (lithium, corticosteroids, estrogen). There is rapid loss of alk phos activity in samples drawn in EDTA anticoagulant. The test is optimally performed on fresh capillary blood fingerstick smears or on blood anticoagulated with heparin and should be performed within 48 hours after collection of the sample. The blood smears may be held in the freezer for 2-3 weeks with little loss of activity.
What patient information do prenatal screen requisitions require?
The patient’s EDC (Estimated Date of Confinement), date of LMP, or EGA by US dating. Maternal birth date (to calculate the patient-specific risk for Down syndrome). Patient race (Black women have ~10% higher MSAFP levels than White women, ~57% higher PAPP-A, and ~8% lower DIA). Maternal weight (The average concentration of all analytes used for screening decreases with increasing maternal weight, since maternal blood volume increases with weight). History of patient receiving medication for DM (since pregnant women who have diabetes prior to conception have 12% lower MSAFP levels than nondiabetics of the same gestational age, but a higher birth prevalence of NTDs). Clinical evidence of multiple gestations. If this sample is an initial screen or a repeat test (since the interpretation of a repeat maternal serum sample may be different from the interpretation of an initial serum specimen).
What are phase 0, phase I, and phase II deficiencies in a CAP laboratory inspection checklist?
Each checklist requirement bears a designation of Phase 0, Phase I or Phase II. Phase 0 deficiencies do not require a formal response though should be corrected by the laboratory. Deficiencies to Phase I requirements do not seriously affect the quality of patient care or significantly endanger the welfare of a laboratory worker. If a laboratory is cited with a Phase I deficiency, correction and a written response to the CAP are required, but supportivedocumentation of deficiency correction is not required. A Phase I requirement may also be a new checklist requirement, which in subsequent checklist editions may be changed to Phase II. Deficiencies to Phase II requirements may seriously affect the quality of patient care or thehealth and safety of hospital or laboratory personnel. All Phase II deficiencies must be corrected before accreditation is granted by the Accreditation Committee. Correction requires both a plan of action and supporting documentation that the plan has been implemented.
