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94 Cards in this Set

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What are 4 categories of reasons for why people might bleed?
1. Lousy vessels
2. Lousy platelets
3. Not enough platelets
4. Coagulation factor problems
What is the best screening test for investigating bleeding problems?
The patient history
What symptoms will be seen in platelet defects?
Mucosal bleeding
-Nose bleeds
-Menorrhagia
-Petechiae
What symptoms will be seen in coagulation defects?
Deep tissue bleeding
-Joints
-Muscles
What are 3 things to look for on the skin in patients with bleeding problems?
-Hematomas
-Petechiae
-Unusual scarring
What will be seen in patients with absence of Factor 13?
Their scars stretch
What is Joint laxity a sign of?
Ehler's danlos syndrome - abnormal collagen.
What are the 2 lab tests for platelet function?
-Platelet count
-PFA100 or bleeding time
What are the 4 lab tests for coagulation function?
-PT
-PTT
-Fibrinogen assay
-Mixing studies to assay for inhibitors
What does the bleeding time tell you?
If the platelets WORK.
When is the bleeding time useful?
Only when the plt count is >100,000/ul
What is a normal bleeding time?
<9 min
What does a prolonged BT indicate?
-Platelet dysfunction
-Fx 8:vWF defect
What is the problem with the BT?
The PPV and specificity are not good.
What is a better test for platelet function?
PFA100
What does the PFA100 tell?
Whether platelet function and vWF function are adequete and normal.
What are the drawbacks and advantages of the PFA100?
-More sensitive in vWF level and platelet function than BT
-Less sens/spcf than other 'good' screening tests
What are 2 variables that will affect the aperture endpoint in PFA100 tests?
-Anemia - low hematocrit
-Meds - taking aspirin
What are 2 further tests that would be done if there is an abnormal BT or PFA100?
-Test vWF to detect VWD
-Test Platelet aggregation studies and look for Ehlers danlos
But what do you look at before even doing the BT or PFA100?
The platelet count from the CBC
What are the screening tests for the coag cascade?
PT and PTT
What are the reagents for the PT?
-Tissue factor
-Phospholipid
-Calcium
What type of tube do you have to collect blood in for the PT/PTT?
Sodium citrate - blue top
What does the citrate do?
Chelates calcium to prevent coagulation before being able to run the test.
What factors does the PT test?
7, 10, 5, 2, and 1 (fibrinogen)
How are PT times standardized between labs?
By reporting the time in a unitless number, the INR
What is the INR? Why is it used?
A normalized result used for warfarin monitoring
What is the INR calculation?
Patient's PT
-----------
Mean normal PT time

-raised to the ISI
what is the ISI?
a factor specific for each bottle of tissue factor reagent.
What is a normal INR?
1
What is a normal INR in patients with venous thrombosis, A-fibrillation or tissue heart valves?
2.5
What is a normal INR for patients with mechanical heart valves?
3
What are the reagents for the PTT?
-Surface activator
-Phospholipid
-Calcium
What factors are tested by the PTT?
1,2, 5, 8-11
When a hemophiliac patient is missing Factor 8, why do they bleed?
Because even if they can initiate clotting via Fx VII, the thrombin generated can't activate the amplification mechanisms because they lack Fx VIII which is required for the intrinsic side.
Will a patient with Fx 12 deficiency have bleeding problems and an abnormal PTT?
No; they can still activate clotting, and Fx 12 does not get activated by Thrombin so amplification doesn't rely on Fx 12 - the rest of the intrinsic cascade is still intact.
What is the function of a mixing study?
To investigate a prolonged PT or PTT
What is mixed in a mixing study?
Patient plasma with normal plasma containing 100% of all factors
What is the likely diagnosis if
-Clotting time corrects
-Clotting time remains prolonged
Corrects: factor deficiency

No correction: inhibitor
What is the differential diagnosis for an isolated long PTT?
-Factor deficiency (8/9/11/12)
-von Willebrand disease
-Inhibitors
Will the patient have a bleeding problem if there is a factor 12 deficiency?
no
Why would vWD cause a prolonged PTT?
Because vWF is not able to function normally as a fx 8 carrier so Fx 8 depletes.
What are 3 types of inhibitors that prolong the PTT?
-Heparin
-Lupus anticoagulant
-Specific factor inhibitors
What does Heparin do?
Inhibits serum proteases - mainly AT3
What does Antithrombin III do?
Inhibits factor Tenase and Thrombin
So what is the effect of Heparin?
Accelerated inhibition of Tenase and Thrombin, so it prevents clotting.
Since Heparin inhibits components of the common pathway, how come only the PTT is prolonged and not the PT?
Because the reagents for the PT have specific heparin inhibitors so that you have a way of monitoring heparin therapy.
What is Lupus anticoagulant?
An antiphospholipid autoantibody
How does the lupus anticoagulant work?
By binding to Phospholipid Binding proteins and preventing them from sitting down on phospholipids to initiate clots.
What exactly do Lupus anticoagulants inhibit?
The clotting cascade IN VITRO
Do lupus anticoagulants inhibit clotting in vivo?
NO - lupus patients are actually hypercoagulative.
Why isn't the protime prolonged in patients with lupus anticoagulants?
It has a lot more phospholipid in it than the PTT; so it is not inhibited.
What is the differential diagnosis for patients with an isolated long PT?
-Factor deficiency
-Inhibitors
What factor deficiency would prolong the PT?
7 and vit K dependent factors
What are 3 things that would cause vit K dependent factor deficiencies?
-Coumadin
-Vit K deficiency
-Liver disease
What is the half life of Fx 7? What is its impact on which clot factor test will be abnormal?
Very short - so in the case of liver disease, the PT which is more sensitive to Fx 7 defic goes prolonged much sooner than the PTT would.
What poison could prolong the PT?
Rat poison
What factor deficiencies prolong both the PT and PTT?
1, 2, 5, and 10
What are 3 situations of multiple factor deficiency that will prolong both the PT/PTT?
-Severe liver disease
-Severe Vit K deficiency
-DIC
What isolated factor inhibitors will prolong both the PT/PTT?
Factor 2, 5, and 10
What drugs in high amts will prolong both the PT/PTT?
Heparin and Direct thrombin inhibitors
What are 2 inhibitors of fibrin polymerization that will prolong both the PT/PTT?
FDPs and Myeloma proteins
What are 4 factors NOT tested by the PT/PTT screens?
-Factor 13
-EC function
-Fibrinolytic system/regulators
-Physiologic anticoagulants - Fx V leiden, Proteins C/S, ATIII
What are the 3 flavors of Hemophilia?
A - VIII deficiency
B - IX deficiency
C - XI deficiency
What is the result of hemophilia?
Weak, friable clots with the tendency to rebleed.
What test shows hemophilia?
Isolated prolonged PTT
What is the inheritence pattern of hemophilia A/B?
X-linked
What are the 2 hallmarks of Hemophilia A and B?
Hemarthrosis and deep muscle bleeds
What are the family history tipoffs to hemophilia?
-Almost always in a male
-Parents usually generally fine
Can female hemophilia carriers have symptoms? How?
Yes - by abnormal lyonization of the good gene they have so that more bad gene is expressed.
How is a TcT done?
By adding thrombin to a patient's plasma
What will cause a prolonged TT?
-Fibrinogen deficiency
-abnormal fibrinogen polymerization
-Thrombin inhibitor (heparin)
Will the TT be abnormal in hemophilia?
no
What determines the severity of symptoms in hemophilia?
The degree of factor deficiency
What is the level of factor 8 in patients with:
-severe hemophilia
-moderate hemophilia
-mild hemophilia
Severe <1%
Moderate 1-5%
Mild >5%
What symptoms will patients with severe hemophilia exhibit?
Spontaneous bleeding episodes
What symptoms will patients with moderate hemophilia exhibit?
Bleeding with mild trauma
What symptoms will patients with mild hemophilia exhibit?
Bleeding with major trauma
What are the 2 functions of von Willebrand factor?
-Platelet adhesion
-Factor 8 carrier
What may abnormalities of vWF lead to?
Fx 8 deficiency
What is a way to differentiate a prolonged PTT being due to vWF dysfunction versus hemophilia?
vWD will present with mucosal bleeding and platelet abnormalities.
What type of inheritence is seen in vWD?
Autosomal dominant
What screening assays will be abnormal in vWD?
-Bleeding time
-PTT
Are the screening tests all that helpful for picking up a vWD?
No - the PTT will only be abnormal if vWF deficiency is severe.
How do you really detect a VWD?
By doing a vWF function test.
What is the test for vWF function?
Ristocetin cofactor assay
What are the Vit K dependent factors?
2, 7, 9, 10, proteins C/S
What is Vit K a cofactor for?
y-carboxylation of glutamic acid
What is y-carboxylation and calcium required for?
Factors to bind to phospholipid
What are 4 problems that cause vit K deficiency?
-Drugs
-Malabsorption/dietary defic.
-Liver disease
-Newborns
What is the treatment for Vit K deficiency?
-Give vit K
-FFP for emergencies
What problem do patients with liver disease and cirrhosis have in addition to factor deficiency?
Thrombocytopenia
Why does liver disease alter the PT more?
Because that's where vit K is stored
Where are Fx 8 and vWF made?
In endothelial cells! so they're preserved in liver disease.