CB Flashcards
What is a complete blood count?
It is a first level analysis that allows us to quantify and Lear some characteristics of the cells present in the blood such as RBC, WBC and thrombocytes.
We asses hematocrit which is the amount volume of blood composed of RBC, we also asses hemoglobin.
This exam can be done to a healthy patient to asses their overall health status, to diagnose a wide range of medical conditions, to monitor health conditions and treatements.
The CBC also allows us to discriminate differential counts of WBC such as neutrophils, basophils, eosinophils, lymphocytes and monocytes.
What is the mean corpuscular volume?
It informs us on the mean volume of the RBCs in the sample. Normal values are between 80-100 femtoliters. It is not really measured as it is a formula given by hematocrit/ n of RBCs x 10.
What is mean corpuscular hemoglobin?
MCH, also referred as mean corpuscular hemoglobin is measured in picograms and is calculated by (hgb/RBC) x 10.
According to MCH values: hypochromic (if MCH is lower than normal), normochromic (if MCH is normal) or hyperchromic (if MCH is higher than normal limit) anemia.
What are anisocytosis and poikilocytosis?
Anisocytosis—> RBC of different sized but with preserved shape.
Poikilocytosis—> RBCs with different shapes.
What could a high or low reticulocytes production index indicate?
Anemia with reduce RPI indicated impaired RBC production. If the MCV is normal and the RBC shape is normal the issue could be hypoproliferation caused by tumors, aplasia, metabolic defects.
Increased RPI in anemia suggests RBC loss rather than impaired production.
What are myeloproliferative neoplasms? Different types?
MPNs encompass a group of heterogeneous diseases characterized by clonal, cancerous alterations occurring in stem cells or early progenitors. These genetic alterations affect peripheral WBCs, platelets, RBCs, or a combination of them. While the rate of growth is not rapid, compensatory mechanisms delay symptom manifestation until a significant number of neoplastic cells are present. Unlike other clonal diseases, the mutations in MPN stem cells do not hinder differentiation, resulting in mature cells with the same molecular signature as the stem cell.
Main types in include CML characterized by BCR/ABL translocation, polycythemia vera marked by elevated RBC count and hemoglobin levels, essential thrombocythemia presents with significant increase in platelet count, primary myelofibrosis which exhibits bone marrow fibrosis.
CML genetics? Symptoms? Diagnosis?
We have a reciprocal translocation between ch9 and ch22 and BCR/ABL is the fusion gene. This leads to the transcription of a completely new protein with a tyrosine kinases activity.
Symptoms include a specific symptoms like, weakness, fever, sweating weight loss. Splenomegaly can be useful during physical exam.
Diagnosis is bases on CBC and blood smear evaluation where we may find increase WBC, variable RBC, PLT, immature cells in peripheral blood. Cytogenetic for Philadelphia chromosome. Conventional cytogenetic with FISH.
Why is a single mutation in CML able to cause cancer?
In oncology there is the hypothesis you need more than one mutation to transform a cell. The reason BCR/ABL is abele to cause cancer resides in the plethora of substrates that can be phosphorylated by this kinase.
They will activate RAS, PI3K and cytoskeletal proteins.
The mutation is not always the same, depending on the site of cut we can have classical p210kD, p230kD or p190kD.
Why do we use both conventional cytogenetics and FISH?
Conventional cytogenetics provide an over view of the entire genome, an detect small chromosomal changes and complex rearrangements, is less expensive. Although it is time consuming, labor intensive, limited sensitivity and cell culture may induce ch abnormalities not present in vivo.
FISH is very rapid, high sensitivity, a targeted analysis and does not require cell culture. On the other hand it has limited coverage, expensive, requires expertise, may not detect complex ch rearrangements.
Both techniques are used as they are complementary and allow for better observation.
What is first line therapy for CML?
Imatinib which is TKI, it works by blocking the activity of BCR/ABL. It is less expensive than other treatment and has a very good 10 year survival rate. Other options are dasatanib and ponatinib.
Second line is HSCT.
Important mutations in myeloproliferative disorders?
The most common one is JAK2. Other important mutation is calreticulin and MPL.
What is CAR T?
Engineered T cell by lentiviral or retroviral vectors. T cells are used because they are the easiest, very abundant in the blood. We can use two approaches :
CAR T—> CARs are chimeric antigen receptors that do not exist in nature, they recognize cancer cells using Abs rules so they recognize surface antigens. They can recognize glycoproteins, sugars, lipids etc..
TCR T—> they exist in nature and are devoted to activate T cell upon antigen recognition. They recognize protein that could be surface, cytoplasmic, mitochondrial and even nuclear.
The major advantage of TCR T is that they induce the survival of T cells, but better clinical responses have been seen with CAR T.
Why has CD19 been chosen for B cell tumors?
It is a B cell lineage antigen expressed by all B cells very strongly. It is very homogenously expressed.
How may we lose CD19 or any other lineage? How can we confront these problems?
It is called antigen loss.
- genomic alteration leading to variants not recognized by therapy.
- alternative splicing, the exon response for the protein that is recognizes has been spliced off.
- lineage switch, has been observed in ALL.
We can modify the CAR T. The most successful has been to use CAR T for both CD19 and CD22
CAR T toxicities?
- On target of tumor—> due to the recognition of the antigen by CAR T cell. For example B cell depletion for CD19.
- Cytokine release syndrome.
- Off target off tumor—> depends on the length of the hinge con the CAR T cell.
Cytokine release syndrome pathogenesis? Clinical markers?
Once CAR T- cells see the antigen on the tumour cells, tend to upregulate CD40 ligand and bind CD40 on macrophages, leading to their activation. Thus, macrophages will lead to the release of cytokines, including IL-6, IL-1, as well as NO, leading to a generalized status of hyperinflamma’on in the patient.
Clinical markers—> cytopenia, high ferritin, high CRP, high IFN, high IL-6.
How is cytokines release syndrome categorized? Treatment?
It is graded based on fever, hypotension and hypoxia and a there are 4 grades, the 5th being death.
Treatment include antipyretics, analgesics, tocilizumab, vasopressors, steroids, mechanical ventilation.
