Coagulation Disorders: Thrombosis Flashcards
Define Hypercoagulability and thrombophilia. What is the mechanism of thrombophilia?
excessive coagulation in the absence of bleeding
Thrombophilia: inherited or acquired disorder associated with increased risk of venous thrombosis due to either:
- increase in procoagulant factors (prothrombin mutation)
- decrease in inhibitors of clotting (antithrombin deficiency, protein S deficiency, protein c deficiency, activated protein C resistance (APCR = factor V leiden mutation)
Define thrombosis, thrombus, and thromboembolism
Thrombosis is when blood clots block your vessels
thrombus is the clot itself
thromboembolismis is when thrombus travels (now called embolus) and blocks a vessel
What are the 3 physiological components responsible for thrombosis
- Venous stasis (decreased velocity of blood)
- activation of coagulation cascade
- vessel damage (so fibrin cells can stick to endothelial damage)
What is the difference between white and red thrombus? What are the risk factors for each?
White thrombus (platelets)
- occurs in arteries
- risk factors: atherosclerosis, age, HT, obesity, diabetes
- causes stroke and MI
Red Thrombus (RBC and fibrin)
- occurs in veins (more time needed to develop -> blood stasis is a cause)
- risk factors: stasis, surgery, cancer, factor V leiden mutation
- causes pulmonary embolus
What are the clinical manifestations of an inherited thrombophilia? Why is the diagnosis often missed?
Inherited thrombophilia clinical manifestations are:
- venous thromboembolism under age of 50
- recurrent VTE
- family history
- unusual sites of VTE
What are the 5 most common thrombophilia conditions? what are the lab investigations?
antithrombin deficiency (chromogenic or clot based method)
protein S deficiency (ELISA, immunoassay, clot based)
protein c deficiency (clot based method)
factor V leiden mutation (PCR)
prothrombin mutation (PCR)
What are the clinical presentation of homozygous Factor V leiden mutation, prothrombin, PC deficiency, PS deficiency, and antithrombin deficiency?
FV leiden: huge increase in risk for VTE 80X
Prothrombin: increased risk of VTE
PC: purpura fulminans
PS: purpura fulminans
antithrombin: lethal in utero
What are 4 secondary disorders leading to thrombosis?
Antiphospholipid syndrome
heparin-induced thrombocytopenia (low platelet count)
thrombotic microangiopathies
disseminated intravascular coagulation
Briefly describe APLS and the diagnosis
- presents as systemic vascular thrombosis and miscarriages
- autoimmune disorder -> lupus anticoagulant Ab, anticardiolipin Ab
- procoagulant mechanism
- anticoagulants inhibition: PC, prostacyclin, heparan, decreased TFPI
- Lab: diagnosis requires Ab against phospholipids , test for protein co-factors using ELISA
Briefly describe heparin-induced thrombocytopenia and the labs
- usually with unfractionated heparin
- platelet factor 4 bind to heparin during platelet activation, complex triggers immune response, binding of Ab causes even more platelet activation -> clots
- Lab: immunoassay or platelet activation assay
briefly describe Disseminated intravascular coagulation (DIC), what are the lab signs of DIC (EXAM)
DIC is a type of thrombotic microangiopathies
- systemic activation of coagulation
- caused by infection or injury
Lab signs: increased INR, prolonged PTT, decreased fibrinogen, low platelets
briefly describe thrombotic thrombocytopenic purpura (TPP)
type of thrombotic microangiopathies
- lack of cleaving factor for large VWF
- lab investigations: smear review (schistocytes), platelet count, check for cleaving factor ADAMTS-13
Describe heparin therapy, complications, and monitoring
heparin
unfractionated: affects antithrombin and factor Xa (monitor by aPTT and anti Xa activity)
low MW: affects only factor Xa (monitor by anti Xa activity)
complications: bleeding, heparin induced thrombocytopenia
what is the MOA of vit K antagonists (warfarin)
in general VKA target Vit K dependent proteins like Factors I, II, VII, IX (1972) and protein C and S
- prevents hepatic carboxylation
Describe 2 direct-acting oral anticoagulants (EXAM)
DOACs inhibit specific factors
Dabigatran (thrombin inhibitor): inhibit free and clot-bound thrombin (blocks conversion of fibrinogen to fibrin and blocks clotting initiated by thrombin). Affects the prothrombin time
Rivaroxaban (Xa inhibitor): oral selective factor Xa inhibitor. Affects Prothrombin time and PTT
compare DOAC and VKA
DOAC
- Pros: fixed dosing, no monitoring, few food and drug interactions, low bleed risk
- cons: need compliance, renal function effects, no reversal agents
Warfarin
- pros: reversible, safe in renal failure, less GI bleed
- cons: risk of bleed, many food and drug interactions, narrow therapeutic range
What are antiplatelet medications used for?
preventing white clots (arterial thrombosis) -> prevents MI and stroke
An example is Aspirin
-> these medications cause platelet dysfunction (can lead to bleeding)
briefly describe thrombotic microangiopathies
Thrombotic microangiopathies (TMA) are clinical syndromes defined by the presence of microangiopathic hemolytic anemia (destruction of red blood cells), low platelets, and organ damage due to formation of microscopic blood clots
