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What occurs in vitro and in vivo when Lupus Anticoagulant is present?
In vitro: acts as an anticoagulant
Prolong phospholipid-dependent clot-based tests (PT and PTT)
In vivo: Acts as a Procoagulant by:
Interferes with proteins that bind to Phospholipid
Blocks inhibitory proteins from binding, leading to thrombosis
Depends on protein blocked as to whether it disrupts anticoagulant or procoagulant reactions
associated with increased risk for thrombosis and miscarriage
What is the patient required to do before lab tests can be run for evaluation of thrombosis risk?
stop taking oral anticoagulants 10-14 days before testing
What is the prevalence of thrombosis?
What is the incidence of arterial thrombosis?
500,000 premature deaths in US
What are the major functions of the phospholipid in the coagulation cascade?
Required for most major steps in the coagulation reactions
Formation of multimolecular coagulation protein complexes on phospholipid cell surfaces
What is included in step three for diagnosis of APS?
Phospholipid dependent studies(DRVVT confirm or STACLOT LA): shortened clotting times with addition of extra phospholipid, to prove that inhibitor LA is sensitive by being neutralized by the increased amount of phospholipid
>1.2 seconds of DRVVT Screen/confirm =suspect LA but have to rule out VIII inhibitor
Define Thrombosis.
Inappropriate formation of platelet or fibrin clots that obstruct the blood vessels
may cause ischemia leading to necrosis
What are two examples of additional antiphospholipid antibodies? How do we test for them?
Anticardiolipin Ab and Anti Beta 2 glycoprotein
Immunoassays
When would you suspect a lupus anticoagulant?
When there is a prolonged PTT and the patient is not on oral anticoagulants and the fibrinogen is normal, and the initial mixing study is not corrected and the patient is not bleeding
What are the clinical symptoms of venous thrombi?
Heat, localized pain, redness, and swelling
List some non-disease risk factors for thrombosis aka acquired factors.
Age >50, immobilization, high fat diet, lipid metabolism imbalance, oral contraceptive, pregnancy, hormone therapy replacement, femoral or tibia fracture, hip knee gynecologic or prostate surgery, smoking, or chronic inflammation
What are the antigen targets of antiphospholipid syndrome?
Protein C and S, ***Prothrombin***, XI, XII, and Kininogens
What would cause you to suspect there is a congenital thrombosis issue?
When it occurs in young adults
occurs in unusual sites
is recurrent
occurs in patient with a family history
Define thrombophilia.
predisposition to thrombosis secondary to a congenital or acquired disorder
theoretical causes include physical, chemical or biological events
What is step 2 in the diagnosis of APS?
Non-correction of the mixing study,
Non-correction of DRVVT mixing study
What is the first step in the diagnosis of APS (antiphospholipid syndrome)?
aka phospholipid-dependent test
Test 1: Prolonged aPTT with LA sensitive reagent
Test 2: Prolonged Dilute Russel Viper Venom test (DRVVT)
Must do both since they evaluate different pathways, BOTH REAGENTS ARE LOW-PHOSPHOLIPID []
What is Factor V Leiden? What are the tests for it?
Factor V mutation, substitutes glutamine for arginine on factor V molecule, arginine is cleavage site for APC, mutation slows or prevents inactivation of factor V
Lab tests for APC resistance: PTT with factor V depleted plasma and patient plasma (make two tubes one with just cacl2 and the other with cacl2 and APC) APC resistance occurs when the CaCL2 APC tube has a reading of <54 seconds with 27 sec on the CaCl2 tube, OR Factor V leiden mutation assay (molecular testing)
DVT that has moved to the lungs, start as deep leg and calf vein emboli
entire leg can swell
List some diseases that increase your risk for thrombosis.
Antiphospholipid syndrome, myeloproliferative neoplasms, Hepatic disease, cancer (adenocarcinoma), leukemia, parasoxysmal nocturnal hemoglobinuria, and chronic inflammation
What can arterial thrombi cause if it moves to the brain?
dementia
What is the incidence of venous thrombosis in the US? What are the types of thrombi?
1 in 1000
Superficial leg veins, deep vein thrombosis DVT in iliac popliteal and femoral veins of upper legs and calves, large occlusive thrombi in veins of upper extremities, liver, spleen, intestines, brain or kidneys
Atherosclerotic plaque formation in vessel walls, activated platelets, monocytes, and macrophages embedded the plaque within the endothelial lining, Plaques rupture blocking arteries and releasing thrombotic mediators initiating thrombosis
What are the arterial thrombosis predictors?
Cholesterol (total cholesterol, High LDL and low HDL)
High sensitivity CRP(detects low levels of inflammation)
Plasma homocysteine (result of folate trap)
fibrinogen activity
Lipoprotein(a) in LDL
What are some inherited congenital thrombosis disorders?
AT(antithrombin) deficiency, PC (activated Protein C) deficiency, Free Protein S deficiency, APC resistance, Prothrombin G20210A, and Hyperfibrinogenemia
Explain the principles of the LA sensitive aPTT and the DRVVT.
PTT-LA: regular aPTT test with reagent sensitive to LA, Low dose phospholipid, prolonged if LA present
DRVVT: Russell viper venom activates factor X to initiate common pathway, minimal amount of phospholipid present (dilute), if LA present, it binds to phospholipid available prolonging dRVVT clotting time