Lecture 7: Thrombosis and Hemostasis Flashcards

1
Q

What is the most common cause of bleeding?

A

Thrombocytopenia

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2
Q

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

A
  • Extrinsic pathway
  • Prolonged in deficiencies of Factors II, V, VII, and X as well as fibrinogen
  • Prolonged in pt’s taking warfarin or dicoumarol
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3
Q

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

A
  • Assesss the intrinsic system
  • Prolonged in deficiencies of factors VIII, IX, XI, XII (8, 9, 11, 12)
  • Prolonged in pt’s on heparin
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4
Q

Platelet aggregation studies are important in determining what defects?

A

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

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5
Q

What is the most common cause of abnormal platelet function?

A
  • 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
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6
Q

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

A
  • Differentiates factor deficiency from presence of a factor inhibitor by mixing pt plasma w/ normal plasma
  • Factor deficiencies will correct with mixing
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7
Q

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

A
  • 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
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8
Q

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

A
  • 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!
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9
Q

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

A

One or two joints that patients have recurrent bleeds into

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10
Q

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

A

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

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11
Q

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

A
  • Meds = phenytoin, sulfa drugs, and penicillin
  • Autoimmune disorders = SLE and RA
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12
Q

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

A

Immunosuppressive therapy

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13
Q

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

A

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

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14
Q

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

A

Cryoprecipitate

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15
Q

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

A

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

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16
Q

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

A

Fresh Frozen Plasma

17
Q

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

A

Gram negatives

18
Q

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

A
  • Prolonged PT and PTT and thrombin time
  • High D-dimer titer
  • Reduced serum fibrinogen level and platelet count
19
Q

When would giving heparin be useful for DIC?

A

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

20
Q

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

A
  • Heparin
  • H2 blockers
  • Abx, particularly Cephalosporin and penicillins
  • Digoxin
21
Q

Which coagulation test will be prolonged with Vitamin K deficiency?

A

Prolonged PT (remember Vit K is extrinsic!)

22
Q

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

A

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

23
Q

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

A

Fresh frozen plasma

24
Q

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

A

Protein C deficiency

25
Q

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

A
  • Protein C: inactivates factors V and VII
  • Protein S: cofactor for protein C
26
Q

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

A
  • 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
27
Q

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

A

Antithrombin III deficiency

28
Q

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

A

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

29
Q

Diagnosis of antithrombin III deficiency requires what?

A

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

30
Q

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

A
  • 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
31
Q

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

A
  • Thromboembolic phenomena
  • Miscarriage
  • Pre-mature births
  • Cerebral ischemia and reccurent stroke (especially in young pt’s)
32
Q

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

A
  1. A prolonged PTT
  2. Lack of correction in mixing studies using normal plasma
  3. Neutralization of inhibitor with excess phospholipid
33
Q

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

A

Dilute Russell viper venom time (DRVVT)

34
Q

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

A
  • 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
35
Q

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

A
  • Pregnancy: you can anticoagulate with SC heparin
  • Hydroxychloroquine: may help ↓ thromboembolism in pt’s with APS and SLE
36
Q

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

A

Platelet levels since these can cause thrombocytopenia