Scribd
Upload
87 views24 pages

Catastrophic APS

This document summarizes catastrophic antiphospholipid syndrome (APS), a rare but severe subtype of APS associated with high mortality. It discusses triggers of catastrophic APS including infection and surgery. Presentation can involve multiple organ systems including the central nervous system. Diagnosis is based on preliminary classification criteria. Management involves anticoagulation, corticosteroids, plasma exchange or IVIG with limited evidence. Cyclophosphamide may benefit those with SLE. Refractory cases may be treated with rituximab or eculizumab though evidence is limited to case reports. Biopsy is not routinely recommended for diagnosis.

Uploaded by

Jiayu Yang
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PPTX, PDF, TXT or read online on Scribd
87 views24 pages

Catastrophic APS

This document summarizes catastrophic antiphospholipid syndrome (APS), a rare but severe subtype of APS associated with high mortality. It discusses triggers of catastrophic APS including infection and surgery. Presentation can involve multiple organ systems including the central nervous system. Diagnosis is based on preliminary classification criteria. Management involves anticoagulation, corticosteroids, plasma exchange or IVIG with limited evidence. Cyclophosphamide may benefit those with SLE. Refractory cases may be treated with rituximab or eculizumab though evidence is limited to case reports. Biopsy is not routinely recommended for diagnosis.

Uploaded by

Jiayu Yang
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PPTX, PDF, TXT or read online on Scribd
You are on page 1/ 24

Catastrophic

Antiphospholipid Syndrome
Antiphospholipid Antibodies

Ruiz-Irastorza et al. Lancet.


2010 Oct 30;376(9751):1498-
509.
Primary vs. Secondary
• Cervera et al. Ann Rheum Dis. 2015 Jun;74(6):1011-8.
• 10 year prospective multicentre study in Europe w/ 1000 patients

• Primary
• 53.1% of all patients

• Secondary: concomitant systemic autoimmune disease


• Most commonly SLE: 36.2% of all patients
Presentation
• Arterial + venous thrombosis
• Pregnancy-related complications

• Multiple other clinical manifestations:


• Hematological: hemolytic anemia, thrombocytopenia, TMAs
• Neurological: cognitive deficits, white matter lesions
• Cardiac: valvular heart disease
• Cutaneous: livedo reticularis
• Etc.
Diagnosis
• Sapporo Criteria (1999) -> Revised Sapporo/Sydney Criteria (2006)

Lim W. Hematology Am Soc Hematol Educ Program. 2013;2013:675-80.


Issues with Diagnosis
• Lupus anticoagulant testing affected by anticoagulation.

• Antiphospholipid antibodies fluctuate with clinical status.

• Lupus anticoagulant is a stronger risk factor. Anti-cardiolipin not


shown to be consistently associated with thrombosis in
prospective/retrospective studies.

• Patients with “non-criteria” manifestations. Patients with low titres.


Management
• Briefly summarized from EULAR recommendations:
• ASA 1o ppx:
• Asymptomatic, high risk antiphospholipid Ab profile
• Can consider if SLE, asymptomatic, low risk profile (isolated low-med +ve anti-cardiolipin or anti-beta 2
glycoprotein)
• Non-pregnant women with hx obstetric APS
• VKA 2o ppx:
• Definite APS, 1st venous thrombosis
• If provoked, tx for standard duration, assess for longer duration depending on RFs
• Can consider adding ASA or increasing INR target if recurrent thrombosis. Can consider
switching to LMWH if recurrent arterial thrombosis.
• Obstetric APS:
• Consider ASA during pregnancy if asymptomatic w/ high risk profile
• ASA + ppx heparin during pregnancy recommended. Can consider if clinical “non-criteria.”
DOACs in APS
• TRAPS 2018:
• Open label, non-inferiority RCT, n=120
• Rivaroxaban (n=59) vs. warfarin in triple +ve APS
• Thrombosis/major bleed/vascular deaths: 11 (rivaroxaban) vs. 2 (warfarin)
• Stopped prematurely
• ISTH recommendations:
• DOACs can be considered in discussion w/ pt for single/double +ve APS
• already on DOAC x several months w/ good adherence for VTE or
• intolerant to VKA.
• EULAR recommendations:
• DOACs can be considered in pts unable to achieve target INR despite
adherence or if VKA contraindicated.
• No rivaroxaban for triple +ve APS.
Hydroxychloroquine in APS
• Wang et al. Hematology Am Soc Hematol Educ Program. 2016 Dec
2;2016(1):714-716.
• 11 studies: 4 prospective, 6 retrospective, 1 meta-analysis. No RCTs.
• 9 assessed 1o prevention in pts w/ SLE. 5/9 showed significant
reduction in thrombosis.
• 2 remaining studies:
• Small sample size, retrospective design, unbalanced characteristics, combined
analysis of ASA w/ HCQ
• Prospective non-randomized trial: n = 40, 30% recurrent thrombosis w/
standard anticoagulation, 0% w/ anticoagulation + HCQ
• Ultimately recommended HCQ for 1o ppx in secondary APS w/ SLE
only
Catastrophic APS
• Triggers

• Presentation
• CNS involvement

• Diagnosis
• Should patients be biopsied?

• Management and evidence


• Management of refractory disease
Triggers of Catastrophic APS
• Cervera et al. J Autoimmun. 2009;32:240-245.

• CAPS Registry:
• 65.4% of cases attributable to trigger
• Infection: 46.7%
• Malignancy: 17.6%
• Surgery: 16.8%
• Sub-therapeutic anticoagulation: 10.9%
Presentation of Catastrophic APS
• Term proposed in 1992: “Widespread
coagulopathy, strongly antiphospholipid
antibody related, but totally distinct and
separate from any of the other
recognized inherited/acquired
coagulopathies”
• <1% of all APS pts, mortality ~50% (now
~40%)

• Bucciarelli et al. Autoimmune Rev


2006;6:72-5.
• Chart review. N=250 from CAPS Registry
until Feb 2005 for mortality.
• Huang et al. J Rheumatol. 2009 Mar;36(3):651.
• Case report of 28F with poorly controlled “schizophrenia”
• Initially admitted w/ fever + diarrhea. Developed limb weakness, AKI, PEs.
Antiphospholipid Abs confirmed on investigations.
• Initial MRI normal. LOC normal -> comatose in 1 day. Repeat MRI diffuse
marked cortical edema with herniation, attributed to ischemic change.
Diagnosis of Catastrophic APS
• Preliminary Criteria for Classification for the Catastrophic APS (2003)

Lim W. Hematology Am Soc Hematol Educ


Program. 2013;2013:675-80.
Should patients be biopsied to confirm the
diagnosis?
• McMaster RARE-Bestpractices project group recommendations (2018)
• Objective: Provide proof of principle that guidelines can be developed for rare
diseases.
• 10 recommendations made: all very low certainty of evidence, most are
conditional recommendations.
• No studies comparing biopsy vs. no biopsy. No articles documenting
sensitivity and specificity of biopsy.
• Adverse effects depending on organ involved
• Recommended using biopsy to diagnose in select cases
Management of Catastrophic APS
• Kazzaz et al. Curr Opin Rheumatol. 2016 May;28(3):218-227.
• Anticoagulation
• Antiplatelets
• Corticosteroids
• PLEX, IVIg
• Cyclophosphamide
• Refractory disease
• Rituximab
• Eculizumab
Anticoagulation
• Two studies w/ total n=325 pts from CAPS Registry
• Significantly lower mortality in anticoagulated patients
• OR 0.18, 95% CI 0.09-0.38
• Anticoagulation received: UFH, LMWH, warfarin
• No clear role for DOACs
• 3 studies on antiplatelets n=275 (262 from CAPS Registry) suggestive
of lower mortality
• OR 0.79, 95% CI 0.36-1.73
• Recommended as add on therapy by McMaster RARE-Bestpractices project
group
Corticosteroids
• Generally used in combination. Little data to support
independent use.
• Analysis of 242 pts from CAPS registry, 190/242 received
corticosteroids (pulse, 1-2mg/kg/d):
• Ignoring concomitant therapy: no difference in recovery (55.8% vs.
56.9%)
• 11 pts w/ corticosteroid monotherapy: 2 survived
• Used in combination w/ anticoagulation >99% of time
• No evidence-based dosing regimen, high doses per expert
consensus
PLEX + IVIg
• PLEX
• Retrospective data shows survival 77.8% for anticoagulation +
steroids + PLEX (n=18), survival 55.4% otherwise
• Separate series: PLEX in 21 pts, 16/21 complete control, 3/21
partial response

• IVIg
• Analysis of 342 pts: 160/342 w/ anticoagulation + steroids + PLEX
OR IVIg improved survival p=0.04
Cyclophosphamide
• Analysis of 103 pts w/ SLE, cyclophosphamide decreased
mortality (47%)
• OR 0.20, 95% CI 0.06-0.71, p=0.013

• 126 pts without SLE, cyclophosphamide associated w/


increased mortality (although given to pts w/ more severe
disease)
• OR 8.5, 95% CI 1.91-37.83, p=0.005
Refractory Disease
• Rituximab
• 2 studies:
• Rituximab n=1
• Non-comparative study: n=20, 13/20 recovered, 4/20 died
• CAPS Registry: n=30, 5/30 deaths. Comparative odds ratio w/
contemporaneous patients 0.41, 95% CI 0.15-1.11.

• Eculizumab
• Limited to case reports only
In Summary
• Catastrophic APS is rare with a high mortality
• Clinical manifestations can be varied
• Mainstays of therapy: anticoagulation (no role for DOACs) +
steroids + PLEX/IVIg
• Evidence is generally poor
• Cyclophosphamide can be considered for patients with SLE
• Rituximab and eculizumab can be considered in refractory
disease
Thank you!
References (not already cited)
• Chaturvedi et al. Hematology Am Soc Hematol Educ Program.
2015;2015:53-60.

You might also like