Today, I review, link to, and excerpt from The Curbsiders’ #421 Antiphospholipid Syndrome with Dr. Arielle Langer.* January 8, 2024 | By Malini Gandhi
*Gandhi MM, Langer A, Williams PN, Watto MF. “#421: Antiphospholipid Syndrome with Dr. Arielle Langer”. The Curbsiders Internal Medicine Podcast. thecurbsiders.com/category/curbsiders-podcast Final publishing date January 8th, 2024.
All that follows is from the above outstanding resource.
Transcripts available via YouTube
Conquer your fear of antiphospholipid syndrome! Dr. Arielle Langer leads us through what clinical features raise suspicion for antiphospholipid syndrome, how to interpret laboratory testing, and the nuances of antiphospholipid syndrome management.
- Case from Kashlak
- What is antiphospholipid syndrome?
- Clinical features that raise suspicion for antiphospholipid syndrome
- Laboratory testing and diagnosis of antiphospholipid syndrome
- Management of antiphospholipid syndrome: initial treatment
- Management of antiphospholipid syndrome: managing recurrent thrombosis
- Return to Case: Pregnancy in patients with a history of thrombotic APLS
- Obstetric APLS
- Final questions
Antiphospholipid Syndrome Pearls
- Three clinical buckets that raise suspicion for APLS include patients who are clotting through anticoagulation, patients clotting in unusual locations, or patients with a history of autoimmunity. These three buckets also help inform when to perform antiphospholipid antibody laboratory testing.
- Antiphospholipid antibody laboratory testing indicates whether antibodies are present that recognize clotting proteins, not that they actually have the special property that enables them to activate the clotting cascade. Thus, false positive testing is a challenge. In particular, transient false positives are common in the setting of acute inflammation, which is why diagnostic criteria require that testing is persistently positive for at least 12 weeks.
- Several trials indicate that warfarin is superior to DOACs for treatment of APLS. For patients who are experiencing breakthrough thrombosis on warfarin, some options include addition of aspirin to warfarin, switching to enoxaparin, addition of hydroxychloroquine, or addition of eculizumab.
- Patients may have thrombotic APLS only, obstetric APLS only, or both, depending on whether their antiphospholipid antibodies recognize clotting proteins only, placental trophoblasts only, or both.
- Patients with a history of thrombotic APLS should be switched from warfarin to enoxaparin for the duration of a pregnancy. Patients with a history of obstetric APLS only should be managed during a future pregnancy with aspirin +/- prophylactic-dose enoxaparin (guidelines vary).
- Every patient with antiphospholipid syndrome should have a hematologist!
Antiphospholipid Syndrome – Show Notes
What is antiphospholipid syndrome?
Dr. Langer typically describes antiphospholipid syndrome to patients as follows: Antiphospholipid syndrome (APLS) is an autoimmune disorder in which the body produces antibodies that recognize certain self clotting proteins. In most autoimmune conditions, antibodies cause the destruction of the self proteins they recognize. However, antiphospholipid antibodies have a special property that causes them to activate these clotting proteins, resulting in acceleration of the clotting process (Garcia et al, 2018). There is heterogeneity in how much these antiphospholipid antibodies turn on the clotting cascade from person to person, meaning there is a spectrum of how difficult it is to stop patients from clotting. There is also heterogeneity in terms of the accuracy of the testing: the laboratory testing just indicates whether antibodies are present that recognize the clotting proteins, not that they actually have the special property in which they recognize and activate these clotting proteins.
Clinical features suspicious for antiphospholipid syndrome
Dr. Langer describes three big buckets that raise her suspicion for antiphospholipid syndrome:
- Patients who are clotting through anticoagulation
- Patients that are clotting at unusual sites (ex. Arterial beds without another clear explanation such as atherosclerosis; splanchnic thrombosis; central venous sinus thrombosis)
- Patients with a history of autoimmunity (most commonly lupus); sometimes the autoimmune disorder is diagnosed concurrently with antiphospholipid syndrome
Other manifestations of antiphospholipid syndrome include obstetric complications (described in more detail below), as well as rarer microvascular manifestations such as livedo racemosa and nephropathy (Garcia et al, 2018). Catastrophic APLS is a rare entity characterized by widespread microvascular and large vessel thrombosis throughout the body, causing devastating complications such as renal injury, stroke, myocardial infarction, and adrenal hemorrhage (Cervera et al, 2020; Cervera et al, 2018).
Laboratory testing and diagnosis of antiphospholipid syndrome
There are three core tests used in the diagnostic work-up of antiphospholipid syndrome: lupus anticoagulant*, anti-cardiolipin IgG / IgM, and B2-glycoprotein IgG / IgM.
The revised Sapporo criteria (Miyakis et al, 2006) state that patients must meet the following clinical and laboratory criteria to be diagnosed with APLS:
- Clinical criteria: History of vascular thrombosis (arterial or venous) or pregnancy morbidity (described in more detail below)
- Laboratory criteria: at least one of the following positive laboratory results: positive lupus anticoagulant, positive anti-cardiolipin IgG or IgM (titer >40), or positive B2-glycoprotein (titer >40). (Titers between 20-40 can be labeled as positive or intermediate positive in some labs, which often yields confusion). Notably, at least one laboratory test must be positive around the time the event occurred as well as persistently positive at least 12 weeks later.
The pattern of laboratory results can help in risk stratification. A higher number of positive tests and higher antibody titers are both associated with higher risk (Pengo et al, 2010; Garcia et al, 2018). Positive IgG is more of a concern than IgM (Kelchtermans et al, 2016). Positive lupus anticoagulant has classically been shown to be a stronger predictor of future clotting than anti-cardiolipin and B2-glycoprotein in patients who have not yet clotted (Galli et al, 2003) (However, Dr. Langer points out that lupus anticoagulant is unique in that it can be influenced by the presence of anticoagulation, which can complicate results).