Lecture 7: Thrombosis and Hemostasis Flashcards
What is the most common cause of bleeding?
Thrombocytopenia
Which pathway does the prothrombin time (PT) assess; deficiencies of which factors and drugs cause prolongation?
- Extrinsic pathway
- Prolonged in deficiencies of Factors II, V, VII, and X as well as fibrinogen
- Prolonged in pt’s taking warfarin or dicoumarol
Which pathway does the partial thromboplastin time (PTT) assess; deficiencies of which factors and drugs cause prolongation?
- Assesss the intrinsic system
- Prolonged in deficiencies of factors VIII, IX, XI, XII (8, 9, 11, 12)
- Prolonged in pt’s on heparin
Platelet aggregation studies are important in determining what defects?
Platelet abnormalities when platelets are normal in numbers i.e., “qualitative platelet defects”
What is the most common cause of abnormal platelet function?
- 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
What is the utility of using a 1:1 mixing study in pt with bleeding abnormality?
- Differentiates factor deficiency from presence of a factor inhibitor by mixing pt plasma w/ normal plasma
- Factor deficiencies will correct with mixing
What is the diagnostic testing utilized for Von Willebrand Disease (wWD)?
- 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
What is first-line tx for Von Willebrand Disease (wWD); what else can be given?
- 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!
In regards to Hemophilia A and B, what does the term “target joints” refer to?
One or two joints that patients have recurrent bleeds into
Acquired inhibitors of coagulation factors are most likely to manifest how clinically?
As a life-threatening bleed; pt’s may present w/ severe soft tissue bleeding, but not hemarthrosis
Acquired inhibitors of coagulation is often seen in association with what meds and underlying disorders?
- Meds = phenytoin, sulfa drugs, and penicillin
- Autoimmune disorders = SLE and RA
Long-term management of acquired inhibitors of coagulation requires what therapy?
Immunosuppressive therapy
Which laboratory test for coagulopathy is sensitive indicator of hepatic synthetic function?
PT; due to the short half-life of factor VII, which a failing liver cannot maintain
Which therapy is useful in liver disease if the the fibringoen level is <100 mg/dL?
Cryoprecipitate
Which clotting factors and proteins requires Vitamin K-dependent gamma-carboxylation for full activity?
Factors II, VII, IX, and X, as well as protein C and protein S
In patient with vitamin K deficiency what is used when urgent correction is required?
Fresh Frozen Plasma
Sepsis associated with what organisms is the most common infection associated with DIC?
Gram negatives
Diagnosis of DIC is based on which PT, PTT, thrombine time, D-dimer titer, fibrinogen and platelet level?
- Prolonged PT and PTT and thrombin time
- High D-dimer titer
- Reduced serum fibrinogen level and platelet count
When would giving heparin be useful for DIC?
Only given if overt thrombosis is recognized, unfortunately thrombosis is often masked
What are the “big 4” drugs associated with thrombocytopenia?
- Heparin
- H2 blockers
- Abx, particularly Cephalosporin and penicillins
- Digoxin
Which coagulation test will be prolonged with Vitamin K deficiency?
Prolonged PT (remember Vit K is extrinsic!)
Hereditary hemorrhagic telangiectasia is due to a defect in gene coding what?
Endoglin (CD105) a membrane glycoprotein strongly expressed on endothelial cells
Which treatment can be used in the short-term to replace coagulation factors in pt with liver disease?
Fresh frozen plasma
Which inherited deficiency is the cause of Warfarin-induced skin necrosis in some patients?
Protein C deficiency
What is the role of protein C and protein S in the coagulation pathways?
- Protein C: inactivates factors V and VII
- Protein S: cofactor for protein C
Which therapy is used to decrease the risk of thromboembolic disease in patients with Protein C and S deficiency; why must you be careful?
- 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
Which acquired thrombotic disorder is often characterized by recurrent lower extremity thrombophlebitis and DVT, venous insufficiency and chronic leg ulcers?
Antithrombin III deficiency
Antithrombin III deficiency is associated with a significantly increased risk of DVT in whom?
Pregnant pt’s - due in part to pregnancy causing induced hypercoagulability
Diagnosis of antithrombin III deficiency requires what?
Demonstration of diminished levels of AT-III in serum (<50% of normal activity)
What is the treatment approach for AT-III deficiency, prophylactically and those with DVT; what about pt’s who do not respond?
- 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
What are some of the common clinical presentations of someone with antiphospholipid syndrome?
- Thromboembolic phenomena
- Miscarriage
- Pre-mature births
- Cerebral ischemia and reccurent stroke (especially in young pt’s)
Which 3 tests/findings are used to diagnose antiphospholipid syndrome?
- A prolonged PTT
- Lack of correction in mixing studies using normal plasma
- Neutralization of inhibitor with excess phospholipid
Which screening test for antiphospholipid syndrome may be more specific than a PTT-related test?
Dilute Russell viper venom time (DRVVT)
What is the recommended tx for pt with antiphospholipid syndrome and no hx of thromboembolic disease vs. pt with a hx?
- 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
Which drug therapies can be used for antiphospholipid syndrome during pregnancy and pt’s with concurrent SLE?
- Pregnancy: you can anticoagulate with SC heparin
- Hydroxychloroquine: may help ↓ thromboembolism in pt’s with APS and SLE
Levels of what should be routinely monitored in pt’s with anticardiolipin antibodies or lupus anticoagulant?
Platelet levels since these can cause thrombocytopenia
