8 Hematology in Older Persons Flashcards
Genetically determined syndromes with features of accelerated aging
Hutchison-Guilford (early-onset progeria), Werner (adult-onset progeria), and Down syndromes
Single gene mutation in Werner syndrome
chromosome 8
Encodes a protein containing a helicase-like domain
A mutation in the lamin A (LMNA) gene localized to chromosome 1 causes
Hutchison-Guilford syndrome
Hypothesis that a random or stochastic accumulation of damage, either to DNA or protein, that leads eventually to dysfunctional cells, cell death and subsequent organ dysfunction, and ultimately death.
Somatic mutation theory
Proposes that spontaneous or endogenous mutations occur at different rates in different species and that this accounts for the variability observed in lifespan
Intrinsic mutagenesis theory
Disorders involving one or a subset of repair mechanisms could lead to accumulation of DNA damage and dysfunction.
DNA repair theory
It is suggested that random errors in protein synthesis occur, and when the proteins involved are those responsible for DNA or RNA synthesis
Error catastrophe theory
Critical enzyme is necessary for maintaining telomere length and cell replicative potential
Telomerase
In vitro cellular senescence is associated with diminished telomerase activity but whether this relates to aging of the organism as a whole remains controversial.
This theory offers that aging is the result of DNA and protein damage (eg, mutagenesis or crosslinking) by atoms or molecules that contain unpaired electrons (free radicals).
Free radical hypothesis
Proposes that the decrements in neuronal and associated hormonal function are central to aging.
Neuroendocrine theory
After a finite number of divisions, normal somatic cells invariably enter a state of irreversibly arrested growth, a process termed _________________
Replicative senescence
The percentage of marrow space occupied by the hematopoietic tissue declines from _______at birth to a level of approximately _______at age 30 years and _______at age 70 years
90% at birth
50% at age 30 years
30% at age 70 years
The most apparent change seen in the marrow with aging is
Decreased cellularity
___________ (type of cell) numbers increase with age.
Monocyte
In humans, alterations occur in the phenotype and cell surface markers of monocytes: “nonclassical” CD14+CD16+ are increased compared with “classical” CD14+CD16- monocytes.
Nonclassical monocytes secrete proinflammatory cytokines but with unknown consequences.
By immunophenotyping of lymphoid and myeloid cell markers in humans, there are a preservation of numbers of myeloid cells and a decrease in B-lymphoid cells, resulting in _______________ predominance (lineage)
Myeloid predominance
It is the occurrence of two genetically distinct populations of cells within an individual (eg, aneuploidy or deletions in large relevant areas of the chromosome), was found to be strongly associated both with increasing age
Somatic chromosomal mosaicism
The presence of a somatic driver mutation associated with hematological malignancy without cytopenias
Clonal hematopoiesis of indeterminate potential (CHIP)
Clone size, or variant allele fraction (VAF) must be at least
2%
The most commonly mutated driver genes seen in CHIP are
DNMT3A, TET2, and ASXL1
TRUE OR FALSE
CHIP may indeed represent a preneoplastic phase of hematologic malignancy; however, the majority of people with CHIP do not develop a hematologic malignancy with an overall risk of progression of just 0.5% to 1% per year
TRUE
CHIP may indeed represent a preneoplastic phase of hematologic malignancy; however, the majority of people with CHIP do not develop a hematologic malignancy with an overall risk of progression of just 0.5% to 1% per year
Mutations that have been associated with worse long-term clinical outcomes in patients with heart failure.
DNMT3A and TET2
Characteristic of unexplained anemia in elderly
Mild (hemoglobin concentration in the 100–120 g/L range), normocytic, and hypoproliferative (low reticulocyte count)
INCREASE OR DECREASE in AGING
Serum erythropoietin
Serum erythropoietin: INCREASE
Result of age-associated shortened red cell survival or reduced sensitivity of erythroid progenitor cells to the erythropoietin signal
INCREASE OR DECREASE in AGING
Neutrophil count
Neutrophil count:INCREASE
INCREASE OR DECREASE in AGING
Lymphocyte count:
Lymphocyte count: DECREASE
A mild decrease in the blood lymphocyte count is first noticeable in the fourth decade of life with a gradually progressive decrease thereafter throughout the remainder of the lifespan
INCREASE OR DECREASE in AGING
Platelet count
Platelet count: DECREASE
Small but definite quantitative drop in platelet number with a modest change in platelet function
INCREASE OR DECREASE in AGING
Factor VII coagulant activity and antigen and factor VIII:c, von Willebrand factor,fibrinogen, fibrinopeptide A, and tissue plasminogen activator antigen:
Activated factor VII, activation peptides of prothrombin, factors IX and X, and thrombin–antithrombin complex:
Protein C and free protein S:
Antithrombin:
D-dimer and plasmin–antiplasmin complexes:
Factor VII coagulant activity and antigen and factor VIII:c, von Willebrand factor,fibrinogen, fibrinopeptide A, and tissue plasminogen activator antigen: INCREASE
Activated factor VII, activation peptides of prothrombin, factors IX and X, and thrombin–antithrombin complex: INCREASE
Protein C and free protein S: INCREASE
Antithrombin: DECREASE in MEN and INCREASE in women
D-dimer and plasmin–antiplasmin complexes: INCREASE
TRUE OR FALSE
Older patients may show an exaggerated anticoagulant response to warfarin.
TRUE
Older patients may show an exaggerated anticoagulant response to warfarin.
An acquired variant of von Willebrand disease (VWD) occurs in association with certain cardiovascular diseases, such as
Aortic stenosis and hypertrophic obstructive cardiomyopathy, and in patients on mechanical circulatory support systems that generate excessive high shear stress
***Cause excessive cleavage of von Willebrand factor multimers, resulting in a loss of HMW multimers and a syndrome that resembles VWD type 2A.
INCREASE OR DECREASE in AGING
D-dimer and IL-6:
D-dimer and IL-6:INCREASE
INCREASE OR DECREASE in AGING
Coagulation and decreased fibrinolytic activity in association to depression and psychological stress:
Coagulation and decreased fibrinolytic activity in association to depression and psychological stress: INCREASE
TRUE OR FALSE
Within the T-helper (TH) cell fraction, there is a shift to the TH2 subset and away from TH1, thereby influencing cytokine production and overall immune response
TRUE
Within the T-helper (TH) cell fraction, there is a shift to the TH2 subset and away from TH1, thereby influencing cytokine production and overall immune response
TRUE OR FALSE
In aging, there is decline in the paracortical and medullary zones and increased deposition of fat within the germinal centers
TRUE
In aging, there is decline in the paracortical and medullary zones and increased deposition of fat within the germinal centers
Unexplained anemia (UA) accounts for up to ________ of cases of anemia in older patients, and its frequency increases with advancing age
One-third
