Antiphospholipid Antibodies

Question 1

what are antiphospholipid antibodies?

Answer 1

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

Question 2

what causes antiphospholipid antibodies to form?

Answer 2

1. idiopathic
2. secondary to systemic autoimmune diseases, most commonly systemic lupus erythematous (SLE)
3. various types of infections and medications

Question 3

what autoimmune disease can lead to the formation of antiphospholipid antibodies?

Answer 3

systemic lupus erythematous (SLE)

20-40% of patients with SLE have anti-phospholipid antibodies

Question 4

what’s the clinical significance of anti-phospholipid antibodies?

Answer 4

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

Question 5

what is antiphospholipid antibody syndrome?

Answer 5

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

Question 6

what’s the two hit theory for APS?

Answer 6

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.

Question 7

what parts of the body does APS effect?

Answer 7

can affect any organ in the body,

makes sense because phospholipids are everywhere

Question 8

what are the clinical features of APS?

Answer 8

• venous/arterial thrombosis**
• pulmonary embolism
• stroke
• livedo reticularis
• fetal loss**
• heart valve disease
• nephropathy

Question 9

what are the hallmark clinical features of APS?

Answer 9

1. vascular thrombosis

2. pregnancy morbidity

Question 10

what is the presentation of vascular thrombosis in APS?

Answer 10

may be venous or arterial, and it may occur in any tissue or organ

Question 11

what is the presentation of pregnancy morbidity in APS?

Answer 11

• premature birth
• multiple miscarriages
• preeclampsia during the second or third trimester
• fetal growth restriction

Question 12

how do you diagnose APS?

Answer 12

must test for the presence of antiphosphoslipid antibodies

Question 13

what is livedo reticularis?

Answer 13

discoloration of skin in a reticular pattern due to obstruction of superficial capillaries

Question 14

what are the two characteristic lab findings in APS?

Answer 14

1. prolonged PTT

2. thrombocytopenia

Question 15

why is PTT prolonged in APS?

Answer 15

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

Question 16

what is PTT and PT?

Answer 16

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

Question 17

what is lupus anticoagulant?

Answer 17

one of the anti-phospholipid antibodies

it delays coagulation

Question 18

what is a mixing study?

Answer 18

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

Question 19

what do you do if the mixing study shows that an antiphospholipid is present?

Answer 19

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

Question 20

what assays are commonly used to detect anti-phospholipid antibodies?

Answer 20

Viper venom test (DRVVT)

Silica clotting time (SCT)

Question 21

what additional tests can be done after the the presence of anti-phospholipid antibodies is confirmed?

Answer 21

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

Question 22

What are the main steps in anti-phospholipid antibody testing?

Answer 22

1. Mixing study with normal plasma that shows no correction of PTT
2. Correction of prolonged PPT with addition of phospholipids

Question 23

A 25-year-old woman has recently been diagnosed with APS. Which additional conditions is this woman most likely to have?

Answer 23

systemic lupus erythematous

Question 24

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?

Answer 24

Elevated PTT

Question 25

You order the plasma mixing study for the patient suspected of having APS. Which
of the following laboratory findings is consistent with APS?

A. Addition of normal plasma corrects PTT

B. Addition of normal plasma does not change PTT

C. Addition of normal plasma further prolongs PTT

D. Addition of phospholipids does not change PTT

E. Addition of phospholipids further prolongs PTT

Answer 25

Addition of normal plasma does not change PTT

The correction of PTT upon addition of normal plasma is consistent with coagulation factor deficiency

In APS, PTT stays uncorrected because the antibodies are still inhibiting the reagents

The addition of excess phospholipids neutralizes the antibodies and result in correction of PTT