Catastrophic Antiphospholipid

Ajit Vyas
1
, Huseyin Kadikoy
1
, Waqar Haque
1
, Abdul Abdellatif
1,2
Departments of
1
Medicine and
2
Division of Nephrology, Baylor College of Medicine.
Houston, TX, USA
ABSTRACT
Context Antiphospholipid syndrome is often associated with systemic lupus erythematosus. Both syndromes have different clinical
manifestations based on organ involvement. Antiphospholipid syndrome commonly causes spontaneous abortions, cerebral vascular
occlusion, and deep venous thrombosis. Catastrophic antiphospholipid syndrome occurs when three or more organ systems are
affected by thromboses in less than a week. Case report We report a unique case of a young woman with a history of systemic lupus
erythematosus and antiphospholipid syndrome who presented with recurrent ischemic pancreatitis. Pancreatitis was refractory to
anticoagulation and low dose steroids. Secondary to recurrence of pancreatitis and other organ involvement, she was treated as a
presumed case of catastrophic antiphospholipid syndrome. Aggressive treatment with plasmapheresis, corticosteroids,
cyclophosphamide, and anticoagulation eventually led to her recovery. Conclusion Awareness of this rare, rapidly fatal medical
condition prompts vital, early intervention to improve patients’ survival. This case report aims to add to the limited therapeutic data
available as well as suggest a possible approach to treating this rare syndrome with very high morbidity and mortality.
INTRODUCTION
Antiphospholipid syndrome and systemic lupus
erythematosus are commonly associated. Systemic
lupus erythematosus is characterized by skin
manifestations such as malar rash, arthralgias, cardiac
manifestations including pericarditis and endocarditis,
neurologic manifestations, as well as hematological
and immunological changes. Antiphospholipid
syndrome is characterized by the presence of
antiphospholipid antibodies with characteristic clinical
manifestations. The antiphospholipid antibodies consist
of lupus anticoagulant, anti-cardiolipin, and anti-beta2-
microglobulin antibodies [1, 2]. The clinical
manifestations of antiphospholipid syndrome include
venous thromboses, arterial thromboses, thrombotic
microangiopathy, and recurrent fetal loss [3]. The
thromboses in antiphospholipid syndrome can affect
any vascular bed, so potentially any organ system in
the body can be involved. Catastrophic
antiphospholipid syndrome occurs when three or more
organ systems are affected by thromboses in less than a
week. Catastrophic antiphospholipid syndrome occurs
in only 1% of antiphospholipid syndrome patients [4].
However, it is an important clinical entity to consider
due to mortality rates up to 50%.
CASE REPORT
A 20-year-old African American woman presented to
the emergency center with abdominal pain, nausea, and
vomiting. Her medical history is significant for
systemic lupus erythematosus and antiphospholipid
syndrome. Systemic lupus erythematosus was
diagnosed four years prior to presentation on the basis
of fever, malar rash, arthralgias, and alopecia. The
patient also has hypertension and chronic kidney
disease with a baseline creatinine of 3 mg/dL
(reference range: 0.8-1.5 mg/dL) secondary to her
underlying disease. Antiphospholipid syndrome was
diagnosed one year prior to admission when she
presented with a deep venous thrombosis. She has been
placed on subcutaneous low-molecular weight heparin
for anticoagulation for the past year, but she has not
been fully compliant.
Two months prior to admission, the patient was
hospitalized for acute pancreatitis. For a differential
diagnosis of pancreatitis see Table 1. During her
hospital course, she developed methicillin-resistant
Staphylococcus aureus bacteremia, acute renal failure,
and a right brachial deep venous thrombosis. Renal
biopsy
confirmed
lupus
nephritis
with
microangiopathic disease (Figure 1). She was
discharged after re-initiation of anticoagulation with
Received July 15th, 2009 - Accepted August 11th, 2009
Key words Antiphospholipid Syndrome Lupus Erythematosus,
Systemic; Pancreatic Diseases; Pancreatitis; Pancreatitis, Acute
Necrotizing
Correspondence Abdul Abdellatif
Division of Nephrology, Department of Medicine, Baylor College
of Medicine, One Baylor Plaza, BCM 620, Houston, TX 77030,
USA
 

Page 2
JOP. J Pancreas (Online) 2009 Sep 4; 10(5):566-569.
JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 10, No. 5 - September 2009. [ISSN 1590-8577]
567
subcutaneous low-molecular weight heparin and
warfarin and being apparently asymptomatic.
Upon current presentation, her abdominal pain was
localized to the epigastric and periumbilical regions
without radiation. The pain was sharp, stabbing, and
intermittent. She had vomited every other day for two
weeks prior to admission, with her vomitus being non-
bloody and consisting primarily of food contents. She
also had diarrhea with three non-bloody, watery bowel
movements the day prior to admission. Her blood
pressure was elevated at 157/110 mmHg.
Her laboratory data revealed lipase was 231 U/L
(reference range: 6-51 U/L); amylase was 159 U/L
(reference range: 30-110 U/L); anti-nuclear antibody
was positive; Anti DNA titer was 1:80 (negative if less
than 1:40) and equal to, or higher than, 1/2,560
SSA/Ro (positive if higher than 1/8); IgG level was
normal (670 mg/dL; reference range: 751-1,560
mg/dL); C3 was 79 mg/dL (reference range: 79-152
mg/dL); C4 was 22 mg/dL (reference range: 16-38
mg/dL). Duplex ultrasound of the abdomen showed no
biliary dilatation, no calculi or wall thickening in the
gallbladder, negative sonographic Murphy’s sign, and
no portal vein or splenic vein thrombosis. A non-
contrast CT of the abdomen and pelvis after her
admission was limited, but showed inflammatory
changes around the pancreas with small amounts of
peripancreatic fluid, thickening of the stomach wall,
and free fluid in the pelvis, all consistent with
pancreatitis (Figure 2). She was also found to have
worsening kidney function with a creatinine of 5.3
mg/dL. APACHE II score was calculated to be 22,
indicating 28.6% mortality. SLEDAI (systemic lupus
erythematosus severity index) was calculated to be 29.
The patient was treated as presumed catastrophic
antiphospholipid syndrome. Initial treatment included
six sessions of plasmapheresis without intravenous
immunoglobulin to avoid further kidney damage, and
Figure 1. The biopsy specimen showing markedly thickened vessels,
sclerotic glomeruli, and glomeruli with Class IV glomerulonephritis.
Table 1. Differential diagnosis of common causes of pancreatitis.
Toxic
Methanol, ethanol, scorpion venom
Metabolic
Hypercalcemia, hyperlipidemia
Mechanical
Pancreatic cancer, gallstones, periampullay
diverticulum, duodenal stricture
Infection
Hepatitis B, CMV, HIV, leptospira, salmonella,
cryptosporidium
Drugs
Metronidazole, salicylates, estrogen, penatmidine
Congenital
Pancreas divisum
Trauma
Trauma to the abdomen, blunt damage to abdomen
Genetic
CFTR mutations
Vascular
Systemic lupus erythematosus vasculitis,
atheroembolism, ischemia
Miscellaneous Alpha-1-antitrypsin deficiency, pregnancy
Figure 2. CT scan showing inflammatory changes around pancreas
with small amounts of peripancreatic fluid, thickening of stomach
all, and free fluid in the pelvis, all consistent with pancreatitis.

Page 3
JOP. J Pancreas (Online) 2009 Sep 4; 10(5):566-569.
JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 10, No. 5 - September 2009. [ISSN 1590-8577]
568
one dose of cyclophosphamide. After six sessions of
plasmapheresis, the patient showed significant clinical
improvement with resolution of her abdominal pain.
Kidney function also improved with creatinine
returning to baseline. Her blood pressure was difficult
control, but eventually stabilized on a combination of a
beta blocker, a calcium channel blocker, and a loop
diuretic. The patient was discharged 4 weeks after
initial presentation on prednisone 30 mg once per day,
metoclopramide 5 mg every 6 hours, clonidine 1 patch
per week, nifedipine 60 mg twice per day, and
hydroxychloroquine 400 mg once per day. A repeat
abdominal CT scan 5 week after the acute event
showed complete resolution of pancreatitis (Figure 3).
The patient remains free of recurrence of ischemic
pancreatitis at 16 month follow-up.
DISCUSSION
Antiphospholipid antibodies have a high prevalence in
the general population. Some estimates place their
prevalence among asymptomatic, healthy subjects at 1
to 5%, and much more common in patients with
systemic lupus erythematosus, with 30-40% prevalence
[5]. Lupus anticoagulant antibodies are actually a
heterogeneous set of antibodies that are identified by
prolongation of coagulation cascade assays. Although
they delay coagulation in the assay, lupus anticoagulant
antibodies are often prothrombotic in vivo as well.
Similarly, the anti-cardiolipin and anti-beta2-
microglobulin antibodies are defined by their ability to
bind phospholipids or phospholipid-binding proteins on
immunoassays [2, 6].
However, in certain individuals, these antibodies are
active and cause clinical manifestations, primarily
thromboses and fetal loss. The clinical manifestations
against the background of these antibodies give rise to
the antiphospholipid syndrome [7]. This condition is
typically manageable using standard anticoagulation
therapy. However, in a subset of individuals with
antiphospholipid syndrome, the thromboses are
widespread and affect several organ systems
simultaneously, leading to a high rate of mortality. This
entity has been termed catastrophic antiphospholipid
syndrome [8]. In catastrophic antiphospholipid
syndrome, the thromboses tend to be in the form of
thrombotic microangiopathy, in contradistinction to the
predominantly venous thromboses seen in antiphospho-
lipid syndrome. Definitive catastrophic antiphospho-
lipid syndrome occurs when three or more organ
systems are affected by thromboses in less than a week
in patients who have tested positive for
antiphospholipid antibodies twice at least six weeks
apart. There should also be confirmation by
histopathology of small vessel occlusion in at least one
organ or tissue. Patients who meet most but not all
criteria are labeled as having probable catastrophic
antiphospholipid syndrome [9].
Our patient displayed many features of catastrophic
antiphospholipid syndrome, given that she also has
systemic lupus erythematosus. In addition to her
pancreatitis and worsening kidney function, she had
worsening hypertension that required multiple anti-
hypertensive medications to manage. Given her clinical
picture and our high clinical suspicion, we decided to
treat her as if she had catastrophic antiphospholipid
syndrome. Due to the aggressive nature of the
syndrome, the high mortality rate, and the lag time in
obtaining full laboratory results, treatment should be
instituted as soon as the syndrome is suspected.
There are several treatment options for catastrophic
antiphospholipid syndrome, but no definitive regimen.
As the number of patients with catastrophic
antiphospholipid syndrome worldwide is small, there
are no prospective, randomized, controlled trials on
Figure 3. CT scan showing normal pancreas with no fluid
accumulation in the pelvis, and normal stomach wall.

Page 4
JOP. J Pancreas (Online) 2009 Sep 4; 10(5):566-569.
JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 10, No. 5 - September 2009. [ISSN 1590-8577]
569
therapeutic strategies [10]. First line therapies include
anticoagulants and corticosteroids. Plasmapheresis and
intravenous immunoglobulin are second line
treatments. Given our patient’s history and lack of
clinical response to anticoagulation, plasmapheresis
was attempted. Other treatments have been described
in the literature, such as the use of rituximab, an anti-
CD20 monoclonal antibody that acts against B-cells
[11, 12]. However, the use of these alternate modalities
has been limited to a few small case series.
In light of the association between antiphospholipid
syndrome and systemic lupus erythematosus, it is
interesting to consider how catastrophic antiphospho-
lipid syndrome manifests itself in systemic lupus
erythematosus patients. As Bayraktar et al. have
shown, patients with catastrophic antiphospholipid
syndrome in systemic lupus erythematosus are more
likely to be female and younger, have cerebral and
pancreatic involvement, receive corticosteroids and
cyclophosphamide, demonstrate a lower prevalence of
high IgG anti-cardiolipin, and have a higher risk for
mortality after adjusting for age, sex, organ
involvement, and treatment [13]. Patients with
catastrophic antiphospholipid syndrome in systemic
lupus erythematosus who were treated with a
combination of plasmapheresis, corticosteroids, and
anticoagulation had a survival rate of 65% [14]. Our
patient fit these criteria fairly well, as she was female,
young, had pancreatic involvement, and responded
well to plasmapheresis.
CONCLUSION
This case reaffirms the heightened degree of clinical
awareness required to treat patients who present with
signs of organ failure and have a history of systemic
lupus erythematosus and antiphospholipid syndrome.
Fortunately for our patient, her clinical picture
improved after six cycles of plasmapheresis,
corticosteroids, and cyclophosphamide. The patient has
not had recurrent pancreatitis for 18 months of follow-
up. However, given her multiple comorbidities, it is
important to retain a high degree of suspicion for
ischemic complications and catastrophic antiphospho-
lipid syndrome due to its high mortality rate.
Conflict of interest The authors have no potential
conflicts of interest
References
1. Levine JS, Branch DW, Rauch J. The Antiphospholipid
Syndrome. N Engl J Med 2002;346:752-763. [PMID 11882732]
2. Asherson RA, Cervera R, de Groot PG, Erkan D, Boffa M-C,
Piette J-C, et al. Catastrophic Antiphospholipid Syndrome Registry
Project Group. Catastrophic antiphospholipid syndrome:
international consensus statement on classication criteria and
treatment guidelines. Lupus 2003; 12:530-534. [PMID 12892393]
3. Wang CR, Hseih HC, Lee GL, Chuang CY, Chen CY.
Pancreatitis associated to antiphospholipid antibody syndrome in
patient with systemic lupus erythematosis. J Rheumatol 1992;
19:1123–1125. [PMID 1512770]
4. Yeh TS, Wang CR, Lee YT, Chuang CY, Chen CY. Acute
pancreatitis related to anticardiolipin antibodies in lupus patients
visiting an emergency department. Am J Emerg Med 1993; 11:230–
232. [PMID 8489664]
5. Love PE, Santor SA. Antiphospholipid antibodies:
anticardiolipin and the lupus anticoagulant in systemic lupus
erythematosus (SLE) and non-SLE disorders. Ann Intern Med 1990;
112: 682-698. [PMID 2110431]
6. Asherson RA, Khamastha MA, Ordi- Ros J. Primary
antiphospholipid syndrome: major clinical and serological features.
Medicine 1989; 68: 366-374.
7. Uthman I, Godeau B, Taher A et al. The hematologic
manifestations of the antiphospholipid syndrome. Blood Rev 2008;
22: 187-194.
8. Bortolati M, Marson P, Fabris F et al. Recovery from
catastrophic antiphospholipid syndrome by a plasma exchange
procedure: report of four cases and review of the literature.
Autoimmun Rev 2009; 8: 297-301.
9. Espinosa G, Bucciarelli S, Asherson RA et al. Morbidity and
mortality in the catastrophic antiphospholipid syndrome:
pathophysiology, causes of death, and prognostic factors. Semin
Thromb Hemost 2008; 34: 290-4.
10. Spencer HL. Primary antiphospholipid syndrome as a new cause
of autoimmune pancreatitis. Gut 2004 Mar;53(3):468; author reply
468.
11. Erkan D. Therapeutic and prognostic considerations in
catastrophic antiphospholipid syndrome. Autoimmunity Reviews
2006; 6:98-103.
12. Harris EN, Pierangeli SS. Primary, secondary, and catastrophic
antiphospholipid syndrome: what’s in a name? Semin Thromb
Hemost 2008; 34: 219-26.
13. Rubenstein E, Arkfeld DG, Metyas S, Shinada S, Ehresmann S,
Liebman HA. Rituximab Treatment for Resistant Antiphospholipid
Syndrome. J Rheumatol 2006; 33(2):355-357.
14. Bayraktar UD, Erkan D, Bucciarelli S, Espinosa G, Asherson R,
Catastrophic Antiphospholipid Syndrome Project Group. The clinical
spectrum of catastrophic antiphospholipid syndrome in the absence
and presence of lupus. J Rheumatol 2007; 34(2):346-352.

There are no products listed under this category.