Low Rate Call Girls Pune Esha 9907093804 Short 1500 Night 6000 Best call girl...
Poikilocytosis diagnostic criteria and tests
1. Biochemical basis of MBA:
•MBA is a type of anemia characterized by impaired DNA
synthesis.
•DNA synthesis requires polymerization of 4 deoxyribonucleoside
triphosphates, and FA deficiency impaires thymidylate synthesis
which is a crucial step in DNA synthesis as this step need methylin
THF polyglutamate.
•B12 required to achieve the active form of folate inside the cells.
•So deficiency of any vitamin will lead to impair in DNA synthesis.
2. Clinical features of MBA
• May be asymptomatic.
• Usually insidious onset with signs and symptoms of anemia.
• Mild jaundice (due to intramedullary destruction of red cell
precursors).
• Epithelial tissue changes as glossitis and angular stomatitis.
• NTD (neural tube defect ) in FA deficiency and may occur with B12
deficiency.
• Neurological manifestations only with B12 deficiency due to defect
in methylation of myelin, it is usually symmetrical affecting lower
limbs more.
• Psychiatric abnormality.
3. Pernicious anemia
• It is MBA due to B12 deficiency
• It is caused by autoimmune attack on gastric mucosa
• characterized by gastric atrophy, with plasma cell and lymphoid
infiltrate in lamina properia
• reduced or absent intrinsic factor with achlorhydria.
• It is more in females, mostly a disease of the elderly, more in
patients with autoimmune mediated disorders like autoimmune
thyroid disease.
• Increased risk of gastric carcinoma 2-3%.
• Not common in Iraq, common in north Europe.
• Mostly it is autoimmune in nature with presence of serum
antibodies like anti-IF Ab, anti-parietal cells Ab and anti-gasrtin
receptor Ab.
4. Laboratory findings of MBA:
Hematological findings:
•Variable degree of anemia, may be severe Hb < 6 gm/dl.
•MCV increased >100 fl, may be up to 135 fl.
•Increase MCV, MCH, and normal MCHC.
•Increase RDW.
•Low retic count.
•Leucocytes may be reduced, platelets may be moderately reduced
(pancytopenia).
•Blood film: oval macrocytes, hypersegmented neutrophils,
leukoerythroblastic picture may found.
5. G6PD deficiency
• More than 400 variants due to point mutations or deletions of the enzyme G6PD
have been characterized which show less activity than normal.
• Worldwide over 400 million people are G6PD deficient in enzyme activity.
• The inheritance is sex-linked, affecting males, and carried by females.
• The main races affected are in West Africa, the Mediteranean, the Middle East,
and South East Asia.
6. Laboratory finding
• Between crises blood count is normal.
• The enzyme deficiency is detected by
• One of a number of screening tests or
• By direct enzyme assay on red cells.
• During the crisis, the blood film may show contracted and fragmented cells, bite
and blister cells. Heinz bodies (oxidized denatured hemoglobin) may be seen in
reticulocyte preparation.
• There are features of intravascular haemolysis
7. Acquired Hemolytic Anemias
•Immune Hemolytic Anemias
Antibody mediated hemolysis is an important cause of acquired
hemolytic anemia.
Antibodies may be:
Autoantibodies produced by the patiet’s own immune system &
directed against his own red cell antigens.
Alloantibodies produced by the patient & directed against antigens not
present on his own red cells but introduced either by transfusion or
secondarily acquired as in drug induced hemolysis.
8. Autoimmune hemolytic anemia (AIHA)
•Characterized by a positive Coombs test or DAT, which detects
antibody, with or without complement, on the red blood cell surface.
•AIHA is classified into warm and cold types, depending on whether
the antibody reacts more strongly with red blood cells at 37°C or at 4°
C and whether IgG (warm) or IgM (cold) autoantibody predominates.
9. Warm autoimmune hemolytic anemia
>The autoantibodies are polyclonal & IgG in type.
>They react best at 37C.
>Red cells coated with IgG are taken up by macrophages especially in
the spleen which have receptors for the Fc fragment. Part of the
coated membrane is lost so the cell becomes progressively more
spherical and prematurely destroyed predominantly in the spleen.
10. Laboratory Finding
• Anemia is usually normochromic normocytic.
• The retic count is extremely reduced.
• Leucopenia. There is selective neutropenia usually but not always to below
1.5 x 109
/L. The neutrophils appear normal.
• Thrombocytopenia is always present & in severe cases is less than
50x109
/L.
• There are no abnormal cells in the peripheral blood.
• Bone marrow shows hypoplasia with loss of hemopoietic tissue &
replacement by fat cells >75%. Bone marrow biopsy is essential & may
show patchy cellular areas in a hypocellular background.
11. Types of normal Hemoglobins
• All Normal Haemoglobins consists of two pairs of
globin chains, at the centre of each is one heme
group.
• Hb A ( Adult Hb) : α2 β2 (~96%).
• HbF (Fetal Hb) : α2 γ2 (0.1-<2.0%).
• Hb A2 (minor Adult Hb) : α2 δ2(1.8-3.5%).
12. Hemoglobinopathies
Disorders of globin synthesis rather than
hem synthesis.
Qualitative Disorders
-Abnormal hemoglobins are formed when the sequence of
globin chain amino acids is altered. There is usually only a
single amino acid substitution in one of the globin
(polypeptide) chains.
Quantitative Disorders
-Thalassemia result from a lack of production of globin
chains to maintain adequate Hb levels.
13. β- Thalassaemia
• β-Thalassaemias are inherited defects in the rate of synthesis
of β-globin chains of Hb, which are widely distributed
throughout the world, with considerable frequencies in certain
areas particularly the Mediterranean and Middle Eastern
countries, including Kurdistan and Iraq.
14. Genetics of β thalassemia
• There is one β- globin gene on each chromosome 11 in
human genome.
• This form of thalassaemia is mostly caused by point
mutations involving various points in and around the beta
globin gene.
• The inheritance of this disorder is autosomal recessive, so
that heterozygous are usually symptomless, while
homozygotes are severely or moderately affected.
• β0 denotes absent β chain synthesis, while β+ means
reduced synthesis of β chain .
15. Most of the coagulation factors are synthesized from the liver.
Half-life of all factors range from 10-65 hrs except FVII of shorter
half-life5-7 hrs.
Coagulation pathways of old version depend on extrinsic, intrinsic and
common pathways.
Coagulation pathways of new version consist of:
•Initiation: TF binding to VII and form VIIa.
•Amplification:thrombin activate platelets bound Va,VIIIa and IXa
•Propagation : convertion of large amounts of prothrombin into
thrombin
Feedback inhibition by TFPI, anti-thrombin and activated protein C.
Fibrinolysis system.
Coagulation Factors
16. •Petechiae is pinpoint flat round red spots caused by intradermal
hemorrhage, less than 2 mm in diameter and do not blanch when
pressed upon.
•Purpura is extravasation of RBC into skin and subcutaneous tissue, 2-10
mm.
•Ecchemosis is purpura > 10 mm.
•Hematoma: bleeding in the muscle.
•Hemarthrosis: bleeding in the joint.
•Hemoptesis, hematemesis, hematuria, conjunctival hemorrhage,
epistaxis.
Note that:
•Erythema: mean redness of skin due to increase blood flow blanch
with pressure.
•Talengiectasia: dilated superficial capillaries blanch with pressure.
Any simple bleeding may be a presentation to dangerous disorder.
17. Investigations of bleeding tendency
Sample use in investigation of coagulation:
•Preparation of citrated plasma by using special tube contain sodium
citrate as anticoagulant mixed with proper amount of blood.
•Sample collected in EDTA tube cannot be use.
•Serum cannot be use.
Investigations include:
•1st line investigations (Basic screening tests )
•2nd
line investigations
18. Basic screening tests for bleeding disorders
(1st line investigations for bleeding disorders)
•CBC (complete blood count) and blood film.
•BT (bleeding time) or PFA100 .
•PT (prothrombin time).
•APTT (Activated Partial Thromboplastin Time).
•FNG (Fibrinogen assay).
•According to the result of 1st line investigation, the diagnosis made by 2nd line
investigations of bleeding disorder like factor assay, PLT aggregometry and
many other investigations.
• for a prolonged PT or aPTT , mixing study is done to distinguishes factor
deficiency(will be corrected) from the presence of inhibitors.