Coagulation Missed Questions Flashcards
1
Q
Which vWD causes platelet aggregation and
thrombocytopenia in response to DDAVP ?
A
- Type 2B
- Gain of function that causes it to bind to GP IB/V/IX more readily
- usually a transient thrombocytopenia that does not cause bleeding or thrombosis
2
Q
What is the main defect in vWD type 2A ?
A
- mutation in the vWF protease cleavage site
- leads to increased enzymatic cleavage
- lack of high and intermediate vWF multimers
3
Q
What is the main defect in vWD type 2M ?
A
- caused by a loss of function mutation in the vWF binding site on GP IB/V/IX
- leads to decreased binding of vWF to platelets
4
Q
What is the defect in vWD type 2N?
A
- mutation in the factor VIII binding site on vWF
5
Q
What is the mechanism of HIT ?
A
- antibodies to platelet factor four complexed to Heparin occur
- antibodies can form in response to unfractionated heparin and LMW Heparin, although less likely because of the smaller molecule size
- generally presents as an unexplained thrombocytopenia 4-14 days after heparin administration
6
Q
What is a Latex Immunoassay used for
in coagulation testing ?
A
- used for the quantitative detection of plasma proteins
- Process:
- latex is sensitized with reactant and the specimen
- provides a quantitative measurement by using light detection methods or turbidimetry (light absorption) or nephelometry (light scattering) to detect resultant antibody-antigen complexes
- IMP:
- this test does NOT measure activity levels
7
Q
What is a chromogenic assay used for ?
A
- it is a qualitative assay, meaning it checks function
- it is a good first step in evaluation of bleeding when there is normal PT, aPTT, and fibrinogen levels
- how do the assays work:
- chromogenic assays provide all components of the coagulation cascade needed to clot except for the factor being measured
- the end point is cleavage of synthetic substrate thorugh enzymatic reaction
- this is determined colorimetrically
- the assay precisely measures the activity of the protein being tested
8
Q
What sort of coagulation issue should be suspected in a newborn with
bleeding (post circumcision etc) with normal PT, aPTT, and fibriongen levels?
A
- Factor XIII functional deficiency or less likely quantitative deficiency
9
Q
How is PCR used in coagulation testing ?
A
- it is NOT used to measure activity or levels of coagulation factors
10
Q
How does a clotting assay work in coagulation testing ?
A
- these are modified PT and aPTT designed to make the factor of interest the rate-limiting step
- How it works:
- test plasma is compared with control plasma
- the amount of correction is then measured
- clot based assays give a broader view of the factor of interest function
- IMP
- activity of factor XIII cannot be detected by clot-based methods
- Clot stability is assessed through the use of 5M of urea or 1% monochloracetic acid
11
Q
How does an ELISA assay work
in coagulation testing ?
A
- measures quantitative levels of plasma proteins
- fluorescent labeled antibody is combined with the patient sample, then a labeled detection antibody is added
- the level of fluorescence, luminscence or optical density is then measured to provide an accurate level of the protein of interest
- IMP
- this test does not measure activity levels
12
Q
What are the different type of factor defects ?
A
- Type I: quantitative with reduced or absent amounts of factor
- Type II: qualitative with decreased activity despite normal numbers
- Acquired defects can behave as type I or II
- IMP
- when choose a PT or aPTT clot based assay vs. chromogenic assay remember levels of other proteins can affect the clot based assay results while chromogenic is not affected
13
Q
What can be a cause of Heparin resistance ?
A
- AT deficiency
- inherited or acquired
- AT deficiency affects Heparin therapy because heparin is not able to accelerate AT effectively if AT is present in low amounts
14
Q
Which factors are inactivated by Heparin binding to Antithrombin ?
A
- IIa (thrombin)
- IXa
- Xa
- XIa
Note: aPTT is usually used to monitor UFH therapy. If 25,000 to 35,000 IU of Heparin is administered in a 24 hour period without much affect on aPTT, then resistance should be considered.
IMP: if anti-Xa is elevated out of proportion to the measured aPTT then Heparin resistance should be considered
15
Q
What are common causes for Heparin resistance ?
A
- elevated factor VIII activity (acute phase reactant)
- congenital or acquired AT deficiency
- increased Heparin clearance
- increased Heparin binding to proteins
16
Q
What is the treatment for Heparin resistance ?
A
- switching to alternative anticoagulant
- Argatroban
- also can administer AT through infusion of plasma or AT concentrates
- monitoring with anti-Xa activity instead of aPTT
17
Q
What is the function of Heparin cofactor II?
A
- heparin cofactor II binds to Heparin which leads to inactivation of factor IIa
- increased cofactor activity does NOT cause heparin resistance
18
Q
Which hemoglobinopathies are associated with
sickling of the peripheral blood ?
A
- SS
- SC
- SD
- SO
- S/Beta Thalassemia
Note: Hb SG-Philadelphia behaves like a sickle cell trait.
Note: sickle cells are irreversibly damaged red cells. Boat cells are reversibly distorted and resume their discoid shape with oxygenation.
19
Q
What is the treatment for acquired Factor X deficiency
due to systemic amyloidosis ?
A
- FFP or prothrombin complex concentrates
- Acquired Factor X deficiency can be seen in:
- vitamin K deficiency or liver disease
- but in these instances it is usually not isolated (II, VII, IX, etc)
- respiratory infections
- thymoma
- malignancies (RCC, adrenal adenocarcinoma, AML)
- aquired inhibitors or congenital deficiencies are rare
- vitamin K deficiency or liver disease
20
Q
What does microhematocrit measure and how ?
A
- determines the PCV (percentage of red cells in whole blood) using a potassium EDTA whole blood sample
- how it works:
- a small volume of blood is taken up by the capillary action into a fixed bore capillary tube
- end of the tube is heat sealed and centrifuged for 5-10 minutes at a high rate
- sample separates into red cells, white cells, platelets, and plasma layer
- percentage of the column occupied by red cells (linear distance) compared with the total column is the packed cell volume
21
Q
What factors affect the microhematocrit PCV ?
A
- centrifugation time
- centrifugal force
- red cell size and deformability
- increased ESR
- anticoagulant type
- deoxygenation of Hgb
22
Q
How is the PCV by microhematocrit affected by SS disease, B-Thal,
decreased centrifugation time, increased ESR, and decreased centrifugal force ?
A
- SS Disease
- PCV is increased by microcytosis, SS disease and other causes of decreased RBC deformability
- B-Thal
- does not affect PCV
- Decreased centrifugation time
- PCV is increased because of excess plasma trapping
- Increased ESR
- causes falsely low PCV due to decreased plasma trapping
- Decreased centrifugal force
- PCV is increased because of incommplete reduction of plasma trapping
23
Q
What is the inheritance pattern of
Bernard Soulier syndrome and what are the main defects ?
A
- Autosomal Recessive
- defect in GP Ib/V/IX complex
- Symptoms:
- bleeding
- thrombocytopenia
- large platelets
- bleeding often starts in childhood with frequent nosebleeds, gum bleeding, and easy bruising
24
Q
How is the diagnosis of Bernard
Soulier made ?
A
- platelets fail to aggregate with ristocetin
- diagnosis can be confirmed with flow cytometry to analyze GPIb-alpha surface density
25
What is stored in the Weibel-Palade
bodies of endothelial cells ?
* vWF and P-selectin
* other proteins: IL-8, endothelin, tPA
* Weibel Palade bodies are secretory organelles found within endothelial cells
* they are oval or elongated with a whorled or fingerprint like appearance on EM
* vWF
* acts in primary hemostasis by binding platelets to the subendothelium and also stabilizes factor VIII in plasma
* P-selectin
* participates in leukocyte adhesion
26
Which is the preferred anticoagulant for a
CBC specimen ?
* K2EDTA
* Note:
* K3-EDTA can cause cell shrinkage and a slight dilution of the sample
* Na-Heparin: causes white cell clumping
* Na-Citrate: dilutes the blood sample and can also cause cell shrinkage
IMP: cell shrinkage causes a lower MCV and HCT
27
When diagnosing antiphospholipid antibody
syndrome what must be demonstrated ?
* antiphospholipid antibodies must be detected on two or more occasionas at least 12 weeks apart
* this is an acquired autoimmune condition
* symptoms include:
* thrombosis
* microvascular thrombosis usually manifest as catastrophic APS syndrome
* pregnancy loss
* persistent APS antibodies
28
What are the clinical criteria for
APS Syndrome ?
* vascular thrombosis: one or more episodes of venous, arterial or small vessel
* pregnancy morbidity
* one or more unexplained deaths of normal fetus at or. \>10 weeks
* one or more preterm births of normal neonate before 34th week of gestation due to eclampsia or pre-eclampsia
* 3 or more unexpalined consecutive spontaneous miscarriages before 10th week with other possible causes excluded (hormonal, chromosomal etc)
29
What are the laboratory criteria
for APS Syndrome ?
* LAC present in plasma on 2 or more occasions, 12 weeks apart of IgG or IgM isotype present at medium or high titer
* Anti-B2 glycoprotein 1 antibody of IgG or IgM isotype in serum or plasma on 2 or more occasions at least 12 weeks apart
* Prolongation of Phospholipid dependent tests on 2 or more occasions
* Demonstration of presence of an inhibitor
* Demonstration of the phospholipid dependence inhibitor
Note: LAC activity is an in vitro phenomenon that is prolongation of phospholipid dependent coagulation tests and not a specific inhibitor to coagulations factors
30
What are phsopholipid based tests that
can be used to test for LAC antibodies ?
* should always use two or more tests when testing for APS
* Tests
* low phospholipid concentration PTT
* dilute Russell viper venom time
* kaolin clotting time
* dilute PT
* Confirmator testing
* use a high phospholipid concentration test or LAC-insensitiv test to demonstrate phospholipid dependence
31
What test is used to look for
aCL and anti-B2-glycoprotein antibodies ?
* ELISAS
32
What lab findings can suggest an
alpha thalassemia trait ?
* presence of microcytosis
* normal hemoglobin fractions (normal A2 and F)
* normal iron studies (may be denoted by normal platelets and Ferritin levels)
Note: alpha thalassemias are most commonly caused by deletion of 1 or more alpha globin genes
33
How does delta-B Thalassemia present
with lab findings ?
* microcytosis by MCV
* elevated Hgb F
* normal Hgb A2
34
How does Hgb E trat present in the lab ?
* Microcytosis
* there is peak that elutes on HPLC in the A2 window
IMP: Hgb Lepore also presents in this way on HPLC
35
How does B-Thalassemia trait present
by HPLC ?
* microcytosis
* elevated Hgb A2
36
What are the percentages of hemoglobins by HPLC
for Sickle cell trait and S/B Thalassemia ?
* Sickle cell trait:
* Hgb A. \> Hgb S fraction
* S/B Thal
* Hgb S \> Hgb A
37
What are antifibrinolytic medications ?
* aminocaproic acid
* aprotinin
* tranexamic acid
38
What are Howell Jolly Bodies composed of. ?
* DNA
* think .....DNA is long and complex just like the name Howell Jolly Body
39
What is the size and distribution of the RBCs
on the RBC histogram in treated B 12 def, end stage liver disease,
pseudothrombocytopenia, B-thal trait, and treated Fe def anemia ?
* Treated B12
* macrocytosis
* ESLiver Dz
* macrocytosis
* Pseudothrombocytopenia
* platelet clumps are small and should not have a large distribution of microcytic cells
* B Thal trait
* uniformly distributed microcytic cells
* Fe Def anemia
* variable distribution with microcytes and the macrocytes represent reticulocytes that are being pushed out
40
What is the Coulter method for detection of
cells in the hematology analyzer ?
* electrical-impedence method
* cells are suspended in an electrolyte solution and passed through an aperture with an electrical field around it
* measures numbers of cells as well as size
* size is X axis, number of cells is Y axis
* IMP
* a dimorphic red cell histogram corresponds to two RBC populations
* dimorphic RBC s can represent treated Fe deficiency anemia, transfused RBCs, treated megaloblastic anemia, sideroblastic anemia, hemolytic anemias
41
What is the advantage of the red cell histograms ?
* the MCV may be normal in the presence of dimorphic red cell populations
42
How are Fe deficiency anemia and B-Thalassemia
differentiated on a RBC cytogram ?
* B thal trait
* microcytosis (downward shift) but the hemoglobin content per cell does not decreased
* Fe Def Anemia
* microcytosis and decreased hemoglobin content (leftward shift)
Note: sickle cell disease is usually normochromic, normocytic anemia
43
What are some general considerations with
Factor V Leiden ?
* inherited thrombophilia disorder with increased risk of VTE
* mutation of Factor V at 1691 G* APC is 10x slower at inactivating FVL than WT
* most common genetic risk factor for VTE, ~5% of caucasians
