Lecture 7: Thrombosis and Hemostasis

Question 1

What is the most common cause of bleeding?

Answer 1

Thrombocytopenia

Question 2

Which pathway does the prothrombin time (PT) assess; deficiencies of which factors and drugs cause prolongation?

Answer 2

• Extrinsic pathway
• Prolonged in deficiencies of Factors II, V, VII, and X as well as fibrinogen
• Prolonged in pt’s taking warfarin or dicoumarol

Question 3

Which pathway does the partial thromboplastin time (PTT) assess; deficiencies of which factors and drugs cause prolongation?

Answer 3

• Assesss the intrinsic system
• Prolonged in deficiencies of factors VIII, IX, XI, XII (8, 9, 11, 12)
• Prolonged in pt’s on heparin

Question 4

Platelet aggregation studies are important in determining what defects?

Answer 4

Platelet abnormalities when platelets are normal in numbers i.e., “qualitative platelet defects”

Question 5

What is the most common cause of abnormal platelet function?

Answer 5

• Meds such as aspirin or NSAIDS due to impaired arachidonate metabolism
• Very important to make sure pt has not taken these drugs for at least 7 days prior to doing a platelet aggregation study

Question 6

What is the utility of using a 1:1 mixing study in pt with bleeding abnormality?

Answer 6

• Differentiates factor deficiency from presence of a factor inhibitor by mixing pt plasma w/ normal plasma
• Factor deficiencies will correct with mixing

Question 7

What is the diagnostic testing utilized for Von Willebrand Disease (wWD)?

Answer 7

• Platelet function analysis (PFA) –> may be normal in mild cases
• vWF antigen level, vWF activity assay, factor VIII level
• Platelet aggregation tests are abnormal –> especially to ristocetin

Question 8

What is first-line tx for Von Willebrand Disease (wWD); what else can be given?

Answer 8

• Desmopressin; administered IV or intranasally
• Can give intermediate-purity factor VIII concentrates, which contain vWF
• Cryoprecipitate is rich in wWF but carries risk of transfusion-transmitted infection!

Question 9

In regards to Hemophilia A and B, what does the term “target joints” refer to?

Answer 9

One or two joints that patients have recurrent bleeds into

Question 10

Acquired inhibitors of coagulation factors are most likely to manifest how clinically?

Answer 10

As a life-threatening bleed; pt’s may present w/ severe soft tissue bleeding, but not hemarthrosis

Question 11

Acquired inhibitors of coagulation is often seen in association with what meds and underlying disorders?

Answer 11

• Meds = phenytoin, sulfa drugs, and penicillin
• Autoimmune disorders = SLE and RA

Question 12

Long-term management of acquired inhibitors of coagulation requires what therapy?

Answer 12

Immunosuppressive therapy

Question 13

Which laboratory test for coagulopathy is sensitive indicator of hepatic synthetic function?

Answer 13

PT; due to the short half-life of factor VII, which a failing liver cannot maintain

Question 14

Which therapy is useful in liver disease if the the fibringoen level is <100 mg/dL?

Answer 14

Cryoprecipitate

Question 15

Which clotting factors and proteins requires Vitamin K-dependent gamma-carboxylation for full activity?

Answer 15

Factors II, VII, IX, and X, as well as protein C and protein S

Question 16

In patient with vitamin K deficiency what is used when urgent correction is required?

Answer 16

Fresh Frozen Plasma

Question 17

Sepsis associated with what organisms is the most common infection associated with DIC?

Answer 17

Gram negatives

Question 18

Diagnosis of DIC is based on which PT, PTT, thrombine time, D-dimer titer, fibrinogen and platelet level?

Answer 18

• Prolonged PT and PTT and thrombin time
• High D-dimer titer
• Reduced serum fibrinogen level and platelet count

Question 19

When would giving heparin be useful for DIC?

Answer 19

Only given if overt thrombosis is recognized, unfortunately thrombosis is often masked

Question 20

What are the “big 4” drugs associated with thrombocytopenia?

Answer 20

• Heparin
• H2 blockers
• Abx, particularly Cephalosporin and penicillins
• Digoxin

Question 21

Which coagulation test will be prolonged with Vitamin K deficiency?

Answer 21

Prolonged PT (remember Vit K is extrinsic!)

Question 22

Hereditary hemorrhagic telangiectasia is due to a defect in gene coding what?

Answer 22

Endoglin (CD105) a membrane glycoprotein strongly expressed on endothelial cells

Question 23

Which treatment can be used in the short-term to replace coagulation factors in pt with liver disease?

Answer 23

Fresh frozen plasma

Question 24

Which inherited deficiency is the cause of Warfarin-induced skin necrosis in some patients?

Answer 24

Protein C deficiency

Question 25

What is the role of protein C and protein S in the coagulation pathways?

Answer 25

- **Protein** **C**: inactivates **factors V** and **VII** - **Protein S**: cofactor for **protein C**

Question 26

Which therapy is used to decrease the risk of thromboembolic disease in patients with Protein C and S deficiency; why must you be careful?

Answer 26

- **Warfarin** - Must be careful because the **most common** cause of **hypercoagulable** state from deficiency of these proteins is **initiation** of **warfarin** therapy!!! - Pt needs to be on **heparin** first, and therapeutically **anticoagulated** before beginning **warfarin**

Question 27

Which acquired thrombotic disorder is often characterized by recurrent lower extremity thrombophlebitis and DVT, venous insufficiency and chronic leg ulcers?

Answer 27

**Antithrombin III deficiency**

Question 28

Antithrombin III deficiency is associated with a significantly increased risk of DVT in whom?

Answer 28

**Pregnant** pt's - due in part to pregnancy causing **induced hypercoagulability**

Question 29

Diagnosis of antithrombin III deficiency requires what?

Answer 29

Demonstration of **diminished** levels of AT-III in **serum** (**\<50% of normal activity**)

Question 30

What is the treatment approach for AT-III deficiency, prophylactically and those with DVT; what about pt's who do not respond?

Answer 30

- **Prophylactic** tx w/ **anticoagulants** - Pt's with DVT should receive **heparin** but **much higher doses** required - **AT-III replacement therapy** available for known AT-III deficient pt's with DVT who **do not respond** initially to heparin

Question 31

What are some of the common clinical presentations of someone with antiphospholipid syndrome?

Answer 31

- **Thromboembolic phenomena** - **Miscarriage** - **Pre-mature births** - **Cerebral ischemia** and **reccurent stroke** (especially in **_young_** pt's)

Question 32

Which 3 tests/findings are used to diagnose antiphospholipid syndrome?

Answer 32

1. A **prolonged PTT** 2. **Lack** of correction in **mixing studies** using normal plasma 3. **Neutralization** of **inhibitor** with **excess phospholipid**

Question 33

Which screening test for antiphospholipid syndrome may be more specific than a PTT-related test?

Answer 33

**Dilute Russell viper venom time (DRVVT)**

Question 34

What is the recommended tx for pt with antiphospholipid syndrome and no hx of thromboembolic disease vs. pt with a hx?

Answer 34

- **No hx**: the current recommendation suggests **no** benefit for anticoagulation; just observation - **Prior hx**: lifelong anticoagulation (**warfarin**) - don't base off a single test! Multiple positive tests over a 3-12 month period are **required** for dx

Question 35

Which drug therapies can be used for antiphospholipid syndrome during pregnancy and pt's with concurrent SLE?

Answer 35

- **Pregnancy**: you can anticoagulate with **SC heparin** - **Hydroxychloroquine**: may help ↓ thromboembolism in pt's with **APS** and **SLE**

Question 36

Levels of what should be routinely monitored in pt's with anticardiolipin antibodies or lupus anticoagulant?

Answer 36

**Platelet levels** since these can cause **thrombocytopenia**