LT37-39
43 important questions on LT37-39
What is chronic hypoxemia? In which diseases?
COPD
Right to left shunts
Smoking
HIgh altitude
What is inadequate erytropoietin secretion? In which diseases?
- renal tumors
- paraneoplastic (lung cancer)
What is the definition of anemia in males? and in females?
Females: Hb < 7.5 mmol/L
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What are classifications for anemia?
- impaired production
- increased loss or destructino
Anemia of impaired erythropoiesis - Lack of essential components?
Vitamin deficiency
General malnutrition, protein deficiency
How is iron deficiency related to anemia?
- chronic blood loss
-- menstruation
-- gastric ulcer
-- colorectal cancer
- nutritional
- anemia of chronic disease
-- chronic inflammation
-- cancer
How is vitamin deficiency related to anemia?
Vit B12 deficiency
- pernicious anemia: antbiodies against parietal cells or intrinsic factor
- nutritional
- gastrectomy, ileum resection
- diphyllobothium latum
Folid acid deficiency
How is gneeral malnutrition related to anemia?
inflammatory bowel disease
staration
Anemia through increased destruction of erythrocytes; hemolysis?
- immune: autoimmune (IgG, IgM), alloimmune (AB0 incompatibility, Rh incompatibility)
- infection: malaria, septicemia, other
- chemical: toxic, osmotic
- mechanical: microtraumatic (marching), foreign bodies (heart valves), extracorporal circulation
Corpuscular:
- acute hemorrhage
- inherited
- acquired
What are autoimmune haemolytic anemias?
These anemias are characterized by the presence of a positive direct antiglobulin -> The Coomb's test, which detects autoantibodies on the surface of the patient's red blood cells.
What is the indirect antiglobulin test?
Normal RBC -> patient's serum/plasma --> anti-human globulin? You get agglutination
What is the direct antiglobulin test?
If there is an immune mediated hemolysis, red cells are covered with autoantibodies. If you get agglutination, you know that the direct test is positive.
AIHA is divided into warm and cold types. Explain.
Warm AIHA: IgG and complement or only complement, coomb's test strongly opsitive, idiopathic as cause of primary condition
Cold AIHA: IgM, leaving complement which is detcted by C3d , coomb's test positive, idiopathic as cause of primary condition
What are causes of secondary conditions in warm and cold AIHA?
- autoimmune rheumatic disorders, such as SLE
- chronic lymphocytic leukaemia
- lymphomas
- Hodgkin's lymphoma
- Carcinomas
- drugs, many including methyldopa, penicillins, cephalosporins, NSAIDs, quinine, interferon
Cold:
- infections, such as infectious mononucleosis, mycoplasma pneumoniae, or other viral infections (rare)
- lymphomas
- paroxysmal cold: haemoglobuineria IgG
What is extravascular hemolysis?
What is intravascular haeolysis?
Waar kijk je naar bij een analysis of abnormal leukocyte counts
Loss omhoog of omlaag
Destruction omhoog
Leukocytes
Neutrophilic granulocytes
What is physiological/reactive left shift?
What is a pathological left shift?
What is a hiatus leucamicum?
Inherited neutropenia, production decreased, why?
Severe congenital neutropenia (SCN)
- Kostmann's syndrome (elastane 2 (ELA2) mutation) - autosomal recessive
Cyclicla neutropenia
Glycogen storgae disease
What are acquired causes of production decrease?
- building blocks: vitamin D, folic acid, copper
- drugs: chemotherapy, drug-induced
- irradiation
- replacement: metastasis solid tumor, granulomatous diseases, acute leukemia, idiopathic myelofibrosis
- cellular/humoral mechanisms:
--- Viral: HIV, EBV, HBV
--- Severe aplastic anemia
--- LGL (large granular lymphocytosis); MTCN (mature T cell neoplasm)
Intrinsic: myelodysplastic syndrome
What are acquired causes of destruction/removal increase?
overwhelming infection
immune mediated: systemic immune disorder, drug-induced, neonatal allo-immune, TRALi
Complement activation: ECMO, hemodialysis, leukapheresis, acute respiratory distress syndrome
What are causes of increase plateletcounts?
reactive or neoplastic
What are causes of decreased platelet counts?
insufficient production, loss or destruction
What are cuases of thrombocytosis?
Neoplastic: myeloprolifertive neoplasms: essential thromboytosis, polycythemia vera, myelofibrosis
What is immune thrombocytopenic purpura? (ITP)
Exclusion of the causes of low platelets
Usually no active bleeding, only petechia or bruising
Why do we perform hematopoietic stem cell transplantation?
as a rescue procedure after high dose chemotherapy or irradiation to ensure hematopoiesis
as a way to reset the immune system
to perform allogeneic cellular immune therapy for malignant disorders
How do we harvest a stem cell graft?
Mobilized peripheral blood
REcruitment of stem cells from marrow to peripheral blood by G-CSF treatment
Measurement of the appearance of stem cells in the blood by analysis of marker CD34.
Harvest of the cells via leukapheresis, with a device isolating leukocytes, while returning other blood celles
How do we perform allogeneic stem cell transplantation?
Treatment of patient resulting in:
- immune ablation of the patient to allow acceptance of donor cells
- making space for donor stem cells in the marrow
optional modificiation of stem cell product
establishment of donor hematopoiesis in the patient
establishment of a novel immune system or treatment of the disroder with donor immune cells
What is host versus graft / graft versus host disease?
Graft versus host: immune cells in the graft coming from the donor can react with cells from the patient
How do we prevent graft rejection?
Removal of T cells from the patient by treatment with monoclonal antibodies, such as globulin and alemtuzumab.
T cells cause the immunorejection of the graft.
Antibodies which specifically reac tiwht T cells are therefore given
Which diseases are treated by allogeneic stem cell transplantations?
Acquierd stem cell failure syndromes
Hematological malignancies
Why don't we perform an autologous SCT to treat hematological stem cell malignancies?
Leg het verschil uit tussen donor T cells and donor T cells newly developing in the patient>
Donor T cells present in the graft are educated in the donor and may recognize tissues from the patient as foreign = GVHD. THey may also recognize malignant cells as foreign, this gives GVL.
What is mixed chimerism?
What do we do when there is a relapse after transplantation?
Infuse donor T cells to induce an immune respone.
AFter infusion of T cells, you can stimulate the immune respone by giving the drug interferon alfa.
An immune modulatory drug, which increases the activaiton of t cells and helps to induce an alloimmune respones, also inducing the risk of GVHD
What is GVHD? What is GVL?
GVL: T cell responding to haematopoietic-restricted minor histocompatibility antigen
What are strategies to separate GVL from GVHD?
Manipulation of the inflammatory environment of the patient
IN vitro selection of T cells, preferentially recognizing patien hematopoietic cells
What is an opportunistic infection often after T cell depleted alloSCT?
How does CMV infection work in transplantation?
Memory T cells are activated and detect CMV infected cells and clear those cells.
In the first 3 to 6 motnhs, there are hardly any T cells present int he patient.
You treat it with drugs, treatment with T cells for long term control
What organs are targeted by CMV disease?
Brain (encephalitis)
Eye (retinitis)
Lung (pneumonia)
Stomach and intestines (gastroenteritis)
HOw to treat CMV reactivation?
Donor lymphocyte infusion (donor must be CMV+
CMV specific T cells (donor must be CMV+
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