Thrombotic Disorders Flashcards
Characterize arterial thrombosis, their composition, causes etc.
characterized by a platelet rich “white clot” formed under high shear stress in the presence of endothelial abnormalities (often atherosclerotic vessel disease)
arterial thrombosis can cause downstream ischemic necrosis and emboli
Characterize venous thrombosis, their composition, causes etc.
characterized by fibrin rich “red clot,” most commonly of the deep venous system of the lower extremities/pelvis
complications include edema, swelling, pain and inflammation, and sometimes pulmonary embolism (hypoxemia, shock and death) or paradoxical embolus
How are the risk factors for VTE related to Virchow’s triad?
VTE is a multi causal disease including both acquired and genetic factors, each factor can be organized as one of Virchow’s triad (venous stasis, endothelial/vessel injury and intrinsic hyper coagulability (often inherited)
advanced age is a risk factor for VTE
What factors/conditions that can be acquired, contribute to VTE?
immobilization due to surgery or injury CHF/ venous insufficiency (stasis) malignancy myeloproliferative disorders (esp P vera) pregnancy and exogenous estrogens antiphospholipid syndrome heparin induced thrombocytopenia
Describe what are antiphopholipid antibodies..
APA are a large category of phospholipid-dependent antibodies that are directed against a variety of epitopes and do not effect in vitro coagulation but can be associated with both arterial and venous thrombosis, recurrent fetal loss and autoimmune thrombocytopenia or hemolytic anemia
Lupus anticoagulants are a subset of APA that are associated with arterial or venous thrombosis as well as prolonged aPTT that does not correct with mixing studies
What causes heparin induced thrombocytopenia and how might you confirm HIT dx with tests?
caused by heparin dependent antibody, detected with a 50% reduction in platelet count (not severe thrombocytopenia)
Describe the mechanism of HIT.
IgG and heparin with PF4 form an immune complex that adheres to the platelet
platelets with immune complex are removed by splenic macrophages, immune complex also causes platelet activation and cytokine release
What genetic factors increase risk of VTE
complicated question: gene defects that cause hyper coagulability can increase the risk of VTE but they do not automatically confer disease, note that defects can act synergistically
Contrast the risk of common and uncommon genetic risk factors for VTE.
deficiency of major coagulation inhibitors is uncommon, but those with defect are at significantly increased risk (antithrombin, protein C and S deficiencies)
more common defects (factor V leiden, prothrombin polymorphism) confer a relatively low rate if increased risk
relative risk may be high but absolute risk is still considerably low
In someone with VTE, should you do genetic testing to determine risk of future clotting?
the occurrence of idiopathic VTE is a better predictor of recurrence than lab evaluation for hyper coagulable states
clot without precipitating event is a clinical risk factor, recurrence rates are in the 20-30% range
How is dx of venous thromboembolism made?
symptomatic and physical exam along with D-dimer levels can be suggestive of diagnosis, but it is critical to confirm with testing like MR venography or duplex doppler ultrasound; spiral CT is the key diagnostic tool of pulmonary embolism
Where are thrombus clot formation more common?
often begin forming behind valves and can grow and then break off, causing embolism
note that post clot there can occur a post-phelbetic condition that is caused by valvular disfunction and vessel scarred open, allowing the pooling of blood
How do you treat VTE?
initiate therapy with rapidly acting anticoagulant for at least 5 days, UFH or LMWH is used most often, also TSOAC possible;
NOT warfarin alone, the recurrence rate is higher due to transient hyper coagulability state
standard therapy continues for 3-6mo (often with warfarin alone, initiate with heparin overlap); there is indefinite therapy for selected patients
When would you consider “indefinite” anticoagulation for VTE? What are your considerations?
when the risk of recurrent VTE exceeds the risk of bleeding with long-term anticoagulation
consider: are events recurrent and idiopathic, are the emboli large, what is the age of presentation, family history?, ongoing-non-reverible factors? (antiphopholipid syndrome)
What is the first line treatment in the following patients?
HIT patients
patents with cancer associated VTE
patients with anticoagulation contraindication
HIT: direct thrombin inhibitor or fondaparnux until platelets normalize then transition to warfarin (very hyper coagulable, treat even without a clot)
cancer: lower reccurence rate with prolonged LMWH
contraindication to anticoagulation: IVC filter placement
