Thrombotic Disorders Flashcards
Describe the pathology of Factor V Leiden Deficiency and the consequences
guanine substitutes for adenine, causing glutamine to replace arginine on position 506
Mutated Factor Va cannot be cleaved/ inactivated by protein C, leading to excessive clot formation
Describe the pathology and consequences of Prothrombin mutations
mutation of G20210A in the promoter region the gene leads to 30% increase in prothrombin serum levels , which promotes clot formation
Why is Protein C deficiency problematic?
Protein C usually cleaves factor 5a and 8a. In its absence, coagulation goes uninhibited
The patient is a risk for warfarin-induced skin necrosis
Describe the morphology of warfarin skin necrosis
fibrin thrombi within venules, accompanied by hemorrhagic necrosis
What is the purpose of Antithrombin III and what is the consequence of its deficiency
AT III neutralizes thrombin, factors 9a-12a. Without it clot formation is uninhibited
AT III deficiencies are resistant to heparin
What are acquired ways of becoming AT III deficient
- Liver disease leads to decreased production of the protein
- Nephrotic syndrome leads to increased clearance via urination
- DIC
- Surgery
- Acute thrombosis
- Estrogen therapy
whats enhances the affinity of thrombin and factors 9a-12a for AT III?
Heparin
What are acquired ways of becoming Protein C deficient
Liver disease
DIC
Acute thrombosis
Warfarin therapy
What are acquired ways of becoming Protein S deficient
Pregnancy
Liver disease
DIC
Inflammation
Acute Thrombosis
Warfarin therapy
estrogen therapy
Why is protein S deficiency problematic
Protein S is a cofactor for the activation of Protein C. Without it, there will be a protein C deficiency and factors 5a/ 8a will go uninhibited
Pathology and clinical presentation of antiphospholipid syndrome
Pathology: procoagulation antibodies target phospholipid-binding proteins that activate platelets and vascular endothelium, promoting hypercoagulability
Clinical Features: repeated episodes of thrombosis, miscarriages, thrombocytopenia ulceration, splinter hemorrhages, stroke, bowel infarctions
Diagnostics pf antiphospholipid syndrome
Prolonged PTT that is not corrected by a mxixing study
Lupus anticoagulants
anticardiolipin antibodies
anti Beta 2 glycoprotein antibodies
False positive RPR/VDRL
Pathology of HIT
antibodies recognize complexes of heparin and platelet factor 4 o the surface of platelets, resulting in the activation, aggregation, and consumption of platelets
Less likely when using LMWH compounds
How can malignancies contribute to thrombosis
Malignant neoplasms can release thrombogenic agonists (issue factor), leading to clot formation
Trousseau Syndrome (migratory superficial thrombophlebitis)
Thrombosis with chronic DIC
Nonbacterial Thrombotic Endocarditis
