Antiphospholipid Antibodies Flashcards
what are antiphospholipid antibodies?
a group of antibodies that attack phospholipids, including those in cell membranes
they either target the phospholipids directly or the proteins that are bound to them
currently unclear what causes these antibodies to be formed
what causes antiphospholipid antibodies to form?
- idiopathic
- secondary to systemic autoimmune diseases, most commonly systemic lupus erythematous (SLE)
- various types of infections and medications
what autoimmune disease can lead to the formation of antiphospholipid antibodies?
systemic lupus erythematous (SLE)
20-40% of patients with SLE have anti-phospholipid antibodies
what’s the clinical significance of anti-phospholipid antibodies?
can cause excess blood clot formation
exact mechanism of this is unclear but people think that the antibodies alter the coagulation pathway in various ways which promote hypercoagulability
BUT not everyone with anti-phospholipid antibodies actually end up developing blood clots
what is antiphospholipid antibody syndrome?
APS
an autoimmune disorder characterized by the presence of antiphospholipid antibodies along with thromboembolic events
once someone with anti-phospholipid antibodies starts to have symptoms like recurrent thrombosis or fetal loss it’s considered APS
what’s the two hit theory for APS?
the presence of anti-phospholipid antibodies alone does not lead to APS so researchers have proposed what is called a “two hit theory”
at least two “hits” are required for the full-blown manifestation of a disease
the first “hit” would be the presence of antiphospholipid antibodies, which by itself would not cause APS
second hit: any additional risk factor for hypercoagulability such as smoking, surgery, diabetes, pregnancy, malignancy, etc.
what parts of the body does APS effect?
can affect any organ in the body,
makes sense because phospholipids are everywhere
what are the clinical features of APS?
- venous/arterial thrombosis**
- pulmonary embolism
- stroke
- livedo reticularis
- fetal loss**
- heart valve disease
- nephropathy
what are the hallmark clinical features of APS?
- vascular thrombosis
2. pregnancy morbidity
what is the presentation of vascular thrombosis in APS?
may be venous or arterial, and it may occur in any tissue or organ
what is the presentation of pregnancy morbidity in APS?
- premature birth
- multiple miscarriages
- preeclampsia during the second or third trimester
- fetal growth restriction
how do you diagnose APS?
must test for the presence of antiphosphoslipid antibodies
what is livedo reticularis?
discoloration of skin in a reticular pattern due to obstruction of superficial capillaries
what are the two characteristic lab findings in APS?
- prolonged PTT
2. thrombocytopenia
why is PTT prolonged in APS?
seems paradoxical that PTT/PT would be prolonged in a person who is in a hypercoagulable state
Anti-phospholipid antibodies bind to, and inhibit, the reagent (thromboplastin) used in the PTT, falsely prolonging the PTT
this happens though because anti-phospholipid antibodies interfere with the reagents in coagulation studies
this means that the antibodies act to inhibit coagulation in vitro while they may act as procoagulants in vivo
prolonging the PTT
what is PTT and PT?
PT = prothrombin time = measures the speed of clotting by means of the common and extrinsic pathway
PTT = partial thromboplastin time = measures clotting speed by means of the common and intrinsic pathways
what is lupus anticoagulant?
one of the anti-phospholipid antibodies
it delays coagulation
what is a mixing study?
the patient’s plasma is mixed with normal plasma, and the PTT assay is run again on this mixture of blood
the point of this study is to determine if the prolonged PTT is caused by a coagulation factor deficiency or by the presence of an inhibitor (such as antiphospholipid antibodies)
if a coagulation factor deficiency is present, then adding normal plasma (which has that coagulation factor in it) will result in a normal (“corrected”) PTT
If an inhibitor (or antiphospholipid antibody) is present, then the PTT will still be prolonged (it will not “correct”), because the inhibitor in the patient’s sample interferes with the reagent used in the test
what do you do if the mixing study shows that an antiphospholipid is present?
if the mixing study shows an uncorrected PTT, phospholipids may be added to the sample to try to “sop up” some of the antiphospholipid antibodies, preventing them from interfering with the PTT reagent
correction of clotting time upon addition of phospholipids confirms the presence of anti-phospholipid antibodies
what assays are commonly used to detect anti-phospholipid antibodies?
Viper venom test (DRVVT)
Silica clotting time (SCT)
what additional tests can be done after the the presence of anti-phospholipid antibodies is confirmed?
ELISA
this test can identify the nature of the antibody more specifically
***sidenote: it’s important to repeat anti-phospholipid antibodies testing after at least twelve weeks in order to confirm the diagnosis, as acute infection and medications have been known to cause false positive results
What are the main steps in anti-phospholipid antibody testing?
- Mixing study with normal plasma that shows no correction of PTT
- Correction of prolonged PPT with addition of phospholipids
A 25-year-old woman has recently been diagnosed with APS. Which additional conditions is this woman most likely to have?
systemic lupus erythematous
A 31-year-old woman with a history of DVT and two miscarriages who is otherwise healthy presents to the clinic. You suspect antiphospholipid antibody syndrome. Which laboratory findings would be consistent with APS?
Elevated PTT
