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Antiphospholipid syndrome

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Antiphospholipid syndrome

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Antiphospholipid syndrome

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USMLE® Step 1 style questions USMLE

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A 52-year-old woman, para 4 gravida 2 aborta 2, comes to the clinic for a follow-up appointment after a hospitalization. Two weeks ago, she had an incident of acute, severe abdominal pain and bloody stools. She was diagnosed with portal vein thrombosis. She denies similar episodes in the past. Medical history is notable for Legg-Calvé-Perthes disease as a child. She does not smoke, drink excessive alcohol, or use illicit drugs. She had 2 spontaneous abortions in the first trimester, following 2 successful pregnancies. Family history is remarkable for DVT in her maternal uncle and colon cancer in her father. The physician suspects an inherited condition. Which of the following will prompt further evaluation in this patient?  

Transcript

Content Reviewers:

Rishi Desai, MD, MPH

In antiphospholipid syndrome, individuals produce antiphospholipid antibodies, which attack the phospholipids in the cell membrane of their own cells, or attack proteins that are bound to those phospholipids.

So antiphospholipid syndrome, or APS, is an autoimmune disease.

Antiphospholipid syndrome can be primary or secondary. Primary antiphospholipid syndrome occurs by itself, whereas secondary antiphospholipid syndrome occurs with other autoimmune diseases, especially systemic lupus erythematosus.

And just like most autoimmune diseases, antiphospholipid syndrome is more common in young females.

The exact cause of antiphospholipid syndrome isn’t known, but there are some known genetic and environmental factors.

For instance, the HLA-DR7 gene encodes a specific type of a protein called major histocompatibility complex or MHC class II, which sits on the surface of the B cell.

These surface proteins help activate B cells so that they can start producing antibodies.

Now, having a mutated HLA-DR7 gene predisposes individuals to activate B cell production of antiphospholipid antibodies.

But the presence of the mutated HLA-DR7 gene alone isn’t enough to develop antiphospholipid syndrome - an environmental trigger must also be present.

There’s a variety of potential triggers - some common ones include infections - like syphilis, hepatitis C, HIV, and malaria - drugs, like some cardiovascular drugs - including procainamide, quinidine, propranolol, and hydralazine - or antipsychotic drugs like phenytoin and chlorpromazine.

The main antiphospholipid antibody is anti-beta2-glycoprotein I, which targets the protein beta2-glycoprotein I, also called apolipoprotein H.

This protein binds to phospholipids and inhibits agglutination which is when platelets clump together to form blood clots.

So when anti-beta2-glycoprotein I binds beta2-glycoprotein I, it’s not free to do its job, and that leads to clot formation.

Another antiphospholipid antibody is anti-cardiolipin, which targets a lipid in the inner mitochondrial membrane called cardiolipin which binds beta2-glycoprotein I.

Anti-cardiolipin antibodies are also present in syphilis, and that can cause a false-positive test for syphilis.

Autoantibodies might also target blood components.

If platelets are targeted, it can lead to thrombocytopenia, and if red blood cells are targeted it can lead to anemia.

So the antiphospholipid antibodies lead to a hypercoagulable state, meaning that they cause thrombosis or blood clots to form within arteries and veins.

Arterial thrombosis is more common in males, and can cause a heart attack, stroke, or limb ischemia.

In addition, individuals might develop Libman-Sacks endocarditis, which is where vegetations form, which are a mixture of immune cells and blood clots - usually on the mitral valve.

Venous thrombosis is more common in females, and typically presents as a deep vein thrombosis.

Sometimes, a part of the main clot may break free and become an embolus, which is where a blood clot travels downstream.

Since lung capillaries are very small, this embolus could get stuck, causing a pulmonary embolism.

This is a life-threatening situation because it literally blocks blood from getting into the lungs to pick up oxygen.

Another organ with very small capillaries is the kidneys, so individuals might develop renal failure.

Sources
  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
  3. "Harrison's Principles of Internal Medicine" McGraw-Hill Medical Publishing (2004)
  4. "Antiphospholipid syndrome" Best Practice & Research Clinical Rheumatology (2020)
  5. "Antiphospholipid syndrome" Thrombosis Research (2017)
  6. "Diagnosis and Management of the Antiphospholipid Syndrome" New England Journal of Medicine (2018)
  7. "Antiphospholipid syndrome" Translational Research (2020)