Catastrophic Antiphospholipid Syndrome – Top 10 Series

1. What is antiphospholipid syndrome (APS)?

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder in which the patient’s immune system makes antibodies (antiphospholipid antibodies [aPL]) that increase the risk of blood clots (thickened blood) and pregnancy complications.

Antiphospholipid antibodies occur in otherwise healthy individuals or in patients with other autoimmune disorders such as systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA).

2. What is catastrophic antiphospholipid syndrome?

Catastrophic APS, sometimes referred to as, CAPS, is the most severe form of APS and is very rare. It is defined as APS in which multiple blood clots in small, medium, and large blood vessels occur over a short period (usually within a week.)

3. How common is catastrophic antiphospholipid syndrome?

Catastrophic APS occurs in less than 1% of APS patients. [1]

4. Why does catastrophic antiphospholipid syndrome occur?

It is not well known why the majority of APS patients develop single medium-to-large vessel clots, and only a few develop life-threatening rapidly progressive widespread clotting (catastrophic APS).

Nevertheless, the currently accepted hypothesis is that catastrophic APS occurs in genetically susceptible individuals in response to a “trigger” such as trauma, surgery, or infections (this is seen in about 50% to 60% of cases). [3]

5. What are the major clinical manifestations of catastrophic antiphospholipid syndrome?

Multiple blood clots can result in infarction (lack of oxygen in tissues) and failure of different organs, leading to “multiple organ dysfunction,” a life-threatening condition requiring intensive care unit (ICU) management. Although any organ can be involved in catastrophic APS, the most frequently affected organs are the kidneys, lungs, brain, skin, and heart.

In addition, patients can develop clots in unusual locations, such as the esophagus or ovaries, and may develop blood cell abnormalities such as low platelet counts (which can increase the risk of bleeding).

6. How is catastrophic antiphospholipid syndrome diagnosed?

A patient is diagnosed with "definite" catastrophic APS when he/she fulfills all of the following criteria:

• blood clots in three or more organs
• simultaneous development of blood clots or development of multiple blood clots in less than a week
• small vessel clots in at least one organ
• positive antiphospholipid antibodies:
  • lupus anticoagulant
  • anticardiolipin antibodies
  • anti-β2 glycoprotein-I antibodies

If a patient fulfills only three of the four criteria above, "probable" catastrophic APS is diagnosed.

Although early diagnosis of "definite" or "probable" catastrophic APS is very important for improved outcomes, the diagnosis can be challenging because: [4]

• Other diseases may resemble, or occur at the same time as, catastrophic APS (e.g., severe infections.)
• Antiphospholipid antibody test results may not be available at the early stage of the disease.
• Antiphospholipid antibody test results may not be reliable if patients have infections or are taking blood thinners.
• In critically ill patients, especially in those with low platelet counts, organ biopsy to demonstrate small vessel involvement may not be feasible.

7. How is catastrophic antiphospholipid syndrome treated?

Because catastrophic APS is so rare, it is not easy to design a clinical trial to study whether any given medication is an effective treatment. Current treatment recommendations are based on an analysis of published catastrophic APS cases [5] and have three clear goals:

• to treat any “trigger” factors (for example, early antibiotics if infection is suspected)
• to prevent and to treat existing blood clots
• to suppress excessive inflammation

If catastrophic APS is suspected, aggressive treatment should be started without delay. Commonly used medications in catastrophic APS, which are usually given in combination, include heparin, corticosteroids, plasma exchange, intravenous gamma globulin, cyclophosphamide, and rituximab. [5]

• Heparin (anticoagulant, blood thinner) inhibits blood clot formation and dissolves existing clots.
• High dose corticosteroids as an anti-inflammatory agent may also suppress the negative effects of aPL.
• Plasma exchange may temporarily remove both aPL, and certain proteins that cause inflammation, from the blood.
• Intravenous gamma globulin blocks autoantibodies and helps modulate inflammation.
• Cyclophosphamide, an immunosuppressive drug, may be helpful in patients who also have lupus and experience a lupus flare in addition to catastrophic APS.
• Rituximab, another immunosuppressive drug that targets the inflammatory cells that secrete aPL, has been used in a limited number of catastrophic APS patients, especially in those with low platelet counts.

8. What is the prognosis of catastrophic antiphospholipid syndrome?

Short Term: Analysis of the published catastrophic APS case reports shows that mortality from this condition has been decreasing since the year 2000. This is probably due to the increased recognition and early treatment of the disease. However, catastrophic APS remains a very serious life-threatening condition. In addition to the specific manifestations of catastrophic APS, patients may develop other complications during the acute period - such as infections or bleeding - which directly affect the prognosis.

Long Term: Based on one retrospective (looking back at collected data) study that analyzed long-term outcomes (up to six years) in catastrophic APS patients, approximately 70% of the patients who survived the initial catastrophic APS event and took warfarin (a blood thinner), remained free of blood clots. [7]

9. Can I lead a normal life after catastrophic antiphospholipid syndrome?

Following a catastrophic APS event, permanent damage may occur; the extent of this damage depends on the type and severity of the organs involved. After an acute event, catastrophic APS patients receive long term anticoagulation therapy. Patients should discuss the need for other medications with their physicians and follow important precautions to reduce the risk of a new clot.

10. Is there any ongoing research on catastrophic antiphospholipid syndrome?

The lack of prospective studies (those designed to follow a group of patients over time) due to the rarity of the disease, has encouraged the European Forum on Antiphospholipid Antibodies, coordinated by Dr. Ricard Cervera, to develop an international catastrophic APS registry. The purpose of this web-based registry is to organize all published case reports, as well as newly diagnosed catastrophic APS cases, from all over the world. The registry currently includes the clinical, laboratory, and treatment data of 282 patients.

Genetics of Thrombotic Storm is another multicenter study, which aims to identify the genetic characteristics of patients with Thrombotic Storm syndromes (diseases in which patients develop multiple blood clots), including catastrophic APS. [8]

Learn more about the University of Miami Miller School of Medicine's Thrombotic Storm study.

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Related articles

References:

1. Asherson RA, Cervera R, de Groot PG, Erkan D, et al. Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines. Lupus 2003; 12: 530–4.

2. R Cervera.  Catastrophic APS Registry. Lupus 2012; 21: 755–7.

3. Vora S, Asherson RA, Erkan D.  Catastrophic Antiphospholipid Syndrome. Journal of Intensive Care Medicine 2006; 21: 144-59.

4. Erkan D, Espinosa G, Cervera R.  Catastrophic antiphospholipid syndrome: Updated diagnostic algorithms. Autoimmunity Reviews 2010; 10: 74–9.

5. Erkan D.  Therapeutic and prognostic considerations in catastrophic antiphospholipid syndrome  Autoimmunity Reviews 2006; 6: 98–103

6. Bucciarelli S, Erkan D, Espinosa G, Cervera G.  Catastrophic Antiphospholipid Syndrome: Treatment, Prognosis, and the Risk of Relapse. Clinical Reviews in Allergy and Immunology, 2008. 

7. Erkan D, Asherson RA, Espinosa G, Cervera R, et al.  Long term outcome of catastrophic antiphospholipid syndrome survivors. Ann Rheum Dis 2003; 62: 530–3

8. Kitchens C, Erkan D, Brandão L, Hahn S, et al.   Thrombotic Storm Revisited: Preliminary Diagnostic Criteria Suggested by the Thrombotic Storm Study Group. The American Journal of Medicine 2011; 124: 290-6.