5. Coag 2 - Pathology Of Hemostasis

Front 1

What are 4 categories of reasons for why people might bleed?

Back 1

1. Lousy vessels
2. Lousy platelets
3. Not enough platelets
4. Coagulation factor problems

Front 2

What is the best screening test for investigating bleeding problems?

Back 2

The patient history

Front 3

What symptoms will be seen in platelet defects?

Back 3

Mucosal bleeding
-Nose bleeds
-Menorrhagia
-Petechiae

Front 4

What symptoms will be seen in coagulation defects?

Back 4

Deep tissue bleeding
-Joints
-Muscles

Front 5

What are 3 things to look for on the skin in patients with bleeding problems?

Back 5

-Hematomas
-Petechiae
-Unusual scarring

Front 6

What will be seen in patients with absence of Factor 13?

Back 6

Their scars stretch

Front 7

What is Joint laxity a sign of?

Back 7

Ehler's danlos syndrome - abnormal collagen.

Front 8

What are the 2 lab tests for platelet function?

Back 8

-Platelet count
-PFA100 or bleeding time

Front 9

What are the 4 lab tests for coagulation function?

Back 9

-PT
-PTT
-Fibrinogen assay
-Mixing studies to assay for inhibitors

Front 10

What does the bleeding time tell you?

Back 10

If the platelets WORK.

Front 11

When is the bleeding time useful?

Back 11

Only when the plt count is >100,000/ul

Front 12

What is a normal bleeding time?

Back 12

<9 min

Front 13

What does a prolonged BT indicate?

Back 13

-Platelet dysfunction
-Fx 8:vWF defect

Front 14

What is the problem with the BT?

Back 14

The PPV and specificity are not good.

Front 15

What is a better test for platelet function?

Back 15

PFA100

Front 16

What does the PFA100 tell?

Back 16

Whether platelet function and vWF function are adequete and normal.

Front 17

What are the drawbacks and advantages of the PFA100?

Back 17

-More sensitive in vWF level and platelet function than BT
-Less sens/spcf than other 'good' screening tests

Front 18

What are 2 variables that will affect the aperture endpoint in PFA100 tests?

Back 18

-Anemia - low hematocrit
-Meds - taking aspirin

Front 19

What are 2 further tests that would be done if there is an abnormal BT or PFA100?

Back 19

-Test vWF to detect VWD
-Test Platelet aggregation studies and look for Ehlers danlos

Front 20

But what do you look at before even doing the BT or PFA100?

Back 20

The platelet count from the CBC

Front 21

What are the screening tests for the coag cascade?

Back 21

PT and PTT

Front 22

What are the reagents for the PT?

Back 22

-Tissue factor
-Phospholipid
-Calcium

Front 23

What type of tube do you have to collect blood in for the PT/PTT?

Back 23

Sodium citrate - blue top

Front 24

What does the citrate do?

Back 24

Chelates calcium to prevent coagulation before being able to run the test.

Front 25

What factors does the PT test?

Back 25

7, 10, 5, 2, and 1 (fibrinogen)

Front 26

How are PT times standardized between labs?

Back 26

By reporting the time in a unitless number, the INR

Front 27

What is the INR? Why is it used?

Back 27

A normalized result used for warfarin monitoring

Front 28

What is the INR calculation?

Back 28

Patient's PT
-----------
Mean normal PT time

-raised to the ISI

Front 29

what is the ISI?

Back 29

a factor specific for each bottle of tissue factor reagent.

Front 30

What is a normal INR?

Back 30

1

Front 31

What is a normal INR in patients with venous thrombosis, A-fibrillation or tissue heart valves?

Back 31

2.5

Front 32

What is a normal INR for patients with mechanical heart valves?

Back 32

3

Front 33

What are the reagents for the PTT?

Back 33

-Surface activator
-Phospholipid
-Calcium

Front 34

What factors are tested by the PTT?

Back 34

1,2, 5, 8-11

Front 35

When a hemophiliac patient is missing Factor 8, why do they bleed?

Back 35

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.

Front 36

Will a patient with Fx 12 deficiency have bleeding problems and an abnormal PTT?

Back 36

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.

Front 37

What is the function of a mixing study?

Back 37

To investigate a prolonged PT or PTT

Front 38

What is mixed in a mixing study?

Back 38

Patient plasma with normal plasma containing 100% of all factors

Front 39

What is the likely diagnosis if
-Clotting time corrects
-Clotting time remains prolonged

Back 39

Corrects: factor deficiency

No correction: inhibitor

Front 40

What is the differential diagnosis for an isolated long PTT?

Back 40

-Factor deficiency (8/9/11/12)
-von Willebrand disease
-Inhibitors

Front 41

Will the patient have a bleeding problem if there is a factor 12 deficiency?

Back 41

no

Front 42

Why would vWD cause a prolonged PTT?

Back 42

Because vWF is not able to function normally as a fx 8 carrier so Fx 8 depletes.

Front 43

What are 3 types of inhibitors that prolong the PTT?

Back 43

-Heparin
-Lupus anticoagulant
-Specific factor inhibitors

Front 44

What does Heparin do?

Back 44

Inhibits serum proteases - mainly AT3

Front 45

What does Antithrombin III do?

Back 45

Inhibits factor Tenase and Thrombin

Front 46

So what is the effect of Heparin?

Back 46

Accelerated inhibition of Tenase and Thrombin, so it prevents clotting.

Front 47

Since Heparin inhibits components of the common pathway, how come only the PTT is prolonged and not the PT?

Back 47

Because the reagents for the PT have specific heparin inhibitors so that you have a way of monitoring heparin therapy.

Front 48

What is Lupus anticoagulant?

Back 48

An antiphospholipid autoantibody

Front 49

How does the lupus anticoagulant work?

Back 49

By binding to Phospholipid Binding proteins and preventing them from sitting down on phospholipids to initiate clots.

Front 50

What exactly do Lupus anticoagulants inhibit?

Back 50

The clotting cascade IN VITRO

Front 51

Do lupus anticoagulants inhibit clotting in vivo?

Back 51

NO - lupus patients are actually hypercoagulative.

Front 52

Why isn't the protime prolonged in patients with lupus anticoagulants?

Back 52

It has a lot more phospholipid in it than the PTT; so it is not inhibited.

Front 53

What is the differential diagnosis for patients with an isolated long PT?

Back 53

-Factor deficiency
-Inhibitors

Front 54

What factor deficiency would prolong the PT?

Back 54

7 and vit K dependent factors

Front 55

What are 3 things that would cause vit K dependent factor deficiencies?

Back 55

-Coumadin
-Vit K deficiency
-Liver disease

Front 56

What is the half life of Fx 7? What is its impact on which clot factor test will be abnormal?

Back 56

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.

Front 57

What poison could prolong the PT?

Back 57

Rat poison

Front 58

What factor deficiencies prolong both the PT and PTT?

Back 58

1, 2, 5, and 10

Front 59

What are 3 situations of multiple factor deficiency that will prolong both the PT/PTT?

Back 59

-Severe liver disease
-Severe Vit K deficiency
-DIC

Front 60

What isolated factor inhibitors will prolong both the PT/PTT?

Back 60

Factor 2, 5, and 10

Front 61

What drugs in high amts will prolong both the PT/PTT?

Back 61

Heparin and Direct thrombin inhibitors

Front 62

What are 2 inhibitors of fibrin polymerization that will prolong both the PT/PTT?

Back 62

FDPs and Myeloma proteins

Front 63

What are 4 factors NOT tested by the PT/PTT screens?

Back 63

-Factor 13
-EC function
-Fibrinolytic system/regulators
-Physiologic anticoagulants - Fx V leiden, Proteins C/S, ATIII

Front 64

What are the 3 flavors of Hemophilia?

Back 64

A - VIII deficiency
B - IX deficiency
C - XI deficiency

Front 65

What is the result of hemophilia?

Back 65

Weak, friable clots with the tendency to rebleed.

Front 66

What test shows hemophilia?

Back 66

Isolated prolonged PTT

Front 67

What is the inheritence pattern of hemophilia A/B?

Back 67

X-linked

Front 68

What are the 2 hallmarks of Hemophilia A and B?

Back 68

Hemarthrosis and deep muscle bleeds

Front 69

What are the family history tipoffs to hemophilia?

Back 69

-Almost always in a male
-Parents usually generally fine

Front 70

Can female hemophilia carriers have symptoms? How?

Back 70

Yes - by abnormal lyonization of the good gene they have so that more bad gene is expressed.

Front 71

How is a TcT done?

Back 71

By adding thrombin to a patient's plasma

Front 72

What will cause a prolonged TT?

Back 72

-Fibrinogen deficiency
-abnormal fibrinogen polymerization
-Thrombin inhibitor (heparin)

Front 73

Will the TT be abnormal in hemophilia?

Back 73

no

Front 74

What determines the severity of symptoms in hemophilia?

Back 74

The degree of factor deficiency

Front 75

What is the level of factor 8 in patients with:
-severe hemophilia
-moderate hemophilia
-mild hemophilia

Back 75

Severe <1%
Moderate 1-5%
Mild >5%

Front 76

What symptoms will patients with severe hemophilia exhibit?

Back 76

Spontaneous bleeding episodes

Front 77

What symptoms will patients with moderate hemophilia exhibit?

Back 77

Bleeding with mild trauma

Front 78

What symptoms will patients with mild hemophilia exhibit?

Back 78

Bleeding with major trauma

Front 79

What are the 2 functions of von Willebrand factor?

Back 79

-Platelet adhesion
-Factor 8 carrier

Front 80

What may abnormalities of vWF lead to?

Back 80

Fx 8 deficiency

Front 81

What is a way to differentiate a prolonged PTT being due to vWF dysfunction versus hemophilia?

Back 81

vWD will present with mucosal bleeding and platelet abnormalities.

Front 82

What type of inheritence is seen in vWD?

Back 82

Autosomal dominant

Front 83

What screening assays will be abnormal in vWD?

Back 83

-Bleeding time
-PTT

Front 84

Are the screening tests all that helpful for picking up a vWD?

Back 84

No - the PTT will only be abnormal if vWF deficiency is severe.

Front 85

How do you really detect a VWD?

Back 85

By doing a vWF function test.

Front 86

What is the test for vWF function?

Back 86

Ristocetin cofactor assay

Front 87

What are the Vit K dependent factors?

Back 87

2, 7, 9, 10, proteins C/S

Front 88

What is Vit K a cofactor for?

Back 88

y-carboxylation of glutamic acid

Front 89

What is y-carboxylation and calcium required for?

Back 89

Factors to bind to phospholipid

Front 90

What are 4 problems that cause vit K deficiency?

Back 90

-Drugs
-Malabsorption/dietary defic.
-Liver disease
-Newborns

Front 91

What is the treatment for Vit K deficiency?

Back 91

-Give vit K
-FFP for emergencies

Front 92

What problem do patients with liver disease and cirrhosis have in addition to factor deficiency?

Back 92

Thrombocytopenia

Front 93

Why does liver disease alter the PT more?

Back 93

Because that's where vit K is stored

Front 94

Where are Fx 8 and vWF made?

Back 94

In endothelial cells! so they're preserved in liver disease.