CASE REPORT
A CASE OF ANTIPHOSPHOLIPID SYNDROME FOR OPEN
CHOLECYSTECTOMY – ANESTHETIC CONCERN
Darshan M. S1, Sri Devi S2
HOW TO CITE THIS ARTICLE:
Darshan M. S, Sri Devi S. “A Case of Antiphospholipid Syndrome for Open Cholecystectomy – Anesthetic
Concern”. Journal of Evidence based Medicine and Healthcare; Volume 1, Issue 9, October 31, 2014; Page:
1231-1236.
ABSTRACT: The antiphospholipid (aPL) syndrome is an acquired disorder in which patients
manifest with either thrombotic events and/ or recurrent pregnancy loss showing laboratory
evidence of antibodies against phospholipid-proteins. The resulting hypercoagulable state can
affect any part of the vasculature and hence the disease has multi-organ involvement. Patient can
manifest with recurrent pregnancy losses, thrombocytopenia, early stroke, cerebral venous
thrombosis, coronary artery disease and so on. Hence we are presenting a case of aPL syndrome
coming for open cholecystectomy.
KEYWORDS: antiphospholipid syndrome, anesthesia, cholecystectomy.
CASE REPORT: 29 year old female was referred from surgical gastroenterologist for
cholecystectomy. Patient gave history of preeclampsia and delivery of a premature IUGR baby 4
years ago; six months after delivery she developed left sided weakness of upper and lower limbs
which on evaluation was found to be thrombotic stroke. Further evaluation of the patient
revealed to have primary aPL syndrome. Patient also gave history of yellowish discoloration of
skin and eyes one month ago and had got treatment for the same. No other significant history
was elicitable from the patient.
On examination of the patient; she was oriented to time, place and person; conscious and
co-operative with normal skin and eyes. No signs of deep vein thrombosis of lower limbs.
Systemic examination of the patient revealed right hypochondriac tenderness and murphy’s sign
was positive. Patient had power of 4/5 in left upper and lower limb and power of 5/5 on right
upper and lower limb, deep tendon reflexes were exaggerated on left side with plantar extensor
response on left side.
Hematologic investigations of the patient revealed hemoglobin of 9 g/dl with microcytic
blood picture normal bleeding time, clotting time, PT, APTT and INR. Blood urea, serum
creatinine, serum electrolytes and liver function tests were reported normal. IgM antiphospholipid
antibody which was taken 8 weeks apart was found to be 84 MPL and 86 MPL (strongly positive).
Ultrasound abdomen and CT abdomen revealed distended gall bladder with thickened wall and
multiple stones. CT brain revealed features of old infarct involving the caudate and putamen on
right side with gliosis. Cardiac evaluation of patient was uneventful.
Physician, neurologist and hematologist were consulted and it was decided to start Inj. UF
Heparin 5000 units subcutaneously twice daily, Tab. Prednisolone 60 mg and Tab Pantoprazole
40 mg per orally at once a day dosing. Physiotherapy was also started for the patient. It was
differed to take patient for laparoscopic cholecystectomy and patient was posted for open
cholecystectomy. Patient was assessed and was taken up for surgery 5 days after starting the
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CASE REPORT
medication. High risk informed consent was obtained from the patient. Inj. Heparin was stopped
12 hours prior to surgery. Adequate amount of blood and blood components were kept reserved.
Patient was advised to take Tab. Alprazolam 0.5 mg and Tab. Metaclopromide 10 mg orally night
prior to the surgery. Day before surgery Bleeding time, Clotting time, platelet count, APTT and
INR were repeated and found to be normal.
General anesthesia was the planned mode of anesthesia. After reassessing and reassuring
the patient she was connected to multi para monitor and, ECG, Oxygen saturation (Pulse
oximetry) and NIBP were monitored. Intravenous cannulation was carried out with 18G peripheral
venous catheter. Baseline vitals such as pulse rate, blood pressure and oxygen saturation were
recorded. Pre anesthetic check of Boyle’s apparatus was done, Ambu bag, Airway gadgets,
Emergency drugs were checked and kept available. TED (thrombo embolic deterrent) stockings
were applied to patient to prevent deep vein thrombosis.
Patient was pre medicated with Inj. Glycopyrrolate 0.2 mg, Inj. Midazolam 2 mg and Inj.
Fentanyl 100 microgram intravenously. After preoxygenating the patient for 3 minutes with 100%
Oxygen, Inj. Etomidate 15 mg i.v was given for induction of the patient Inj. Vecuronium 5 mg
was used to ease the intubation for the patient. A gas mixture of 1 litre of oxygen 2 litres of
Nitrous oxide and 1% sevoflurane was used for maintenance of anesthesia. Inj. Hydrocortisone
100 mg was given intravenously. Inj. Dexmeditomedine 50 microgram and Inj. Ondansetron 4
mg was given 20 minutes prior to the extubation, intra operative period was uneventful and
patient at the end of surgery was reversed and extubated on table.
Postoperatively Inj. Dexamethasone 8 mg iv was continued at frequency of twice daily.
Inj. Heparin 5000 units was restarted subcutaneously 4 hours after the surgery. On the 5th postop
day patient was switched over to Tab Prednisolone 60 mg from Inj.Dexamethasone and
subcutaneous heparin by Tab Warfarin 10 mg per orally. Patient was put on TED stockings till she
was mobilized on second postoperative day. Patient had uneventful perioperative period and was
discharged from the hospital on the seventh postoperative day. Patient was advised for a review
after 4 weeks for checking adequacy of anticoagulation and we aimed to keep INR between 2-3.
DISCUSSION: The antiphospholipid (aPL) syndrome is an acquired disorder in which patients
manifest with either thrombotic events and/ or recurrent pregnancy loss with laboratory evidence
of antibodies against phospholipid-proteins.[1] Disease has multi-organ involvement and is called
secondary aPL syndrome if they are associated with any major autoimmune disorders and called
primary aPL syndrome if they occur in absence of them. Deep veins of lower limbs are the
common site of thrombosis, but any part of vasculature either arterial or venous system can
undergo thrombosis. Also any organ can be affected because of thromboembolism. Disease
mimics Thrombotic Thrombocytopenic Purpura or DIC.
Antiphospholipid syndrome is also known by following synonyms, the anticardiolipin (aCL)
syndrome, aPL/cofactor syndrome, antibody-mediated thrombosis syndrome and Hughes
syndrome. aPL syndrome was first described by Prof. Graham R.V Hughes in 1980.
ETIOLOGY: It is said to be of autoimmune etiology. And the antibody recognizes protein
cofactors rather than the phospholipid itself hence known as aPL cofactor syndrome. Familial
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CASE REPORT
clustering suggest the concept of genetically susceptible host.[2,3] Strongest association of disease
with HLA-DR-53 haplotype and some association with HLA-DQ-7. Antigenic triggers noted which
includes varicella, hepatitis-C, cytomegalo virus and parvo B19 virus. Cellular apoptosis occurs
following viral infection and hence exposure of the anionic phospholipid on the surface triggers
the generation of antibodies.[4-6] Molecular mimicry between β2GPI-related synthetic peptides and
structures within bacteria, viruses, tetanus toxoid, and CMV has reportedly caused experimental
aPL syndrome.[7]
Pathogenesis:
Annexin A5 shield disruption
Altered eicosanoid synthesis
Endothelial damage
Induced production of endothelial cell adhesive molecules
Induction of tissue factor expression on monocytes and endothelial cells
Induction of apoptosis
Interference with protein C pathway
Antiphospholipid binding to proteins C and S
Acquired activated protein C resistance
Cross-reactivity with oxidized low-density lipoprotein
Increase of plasminogen activator inhibitor-1
Reduced fibrinolysis by impairment of autoactivation of factor XII and by
antibodies to tissue-type plasminogen activator
Platelet activation
Activation of complement
Antibodies against tissue factor pathway inhibitor
Concentration of prothrombin locally
Mechanism proposed for the pathogenesis of Anti-phospholipid Syndrome[1]
Arterial and venous thrombosis: DVT, thoracic abdominal and pelvic vein thrombosis.
Obstetric complications: Recurrent pregnancy losses, Preeclampsia, Growth retardation,
CVS manifestations: CAD, Valvular heart disease, Peripheral vascular disease
CNS manifestations: Stroke, Seizure, Chorea, Migraine, GB syndrome, dementia,
Acute transverse myelopathy
Hematologic manifestations: Bleeding, Thrombocytopenia, Hypoprothrombinemia,
Inhibition to factor VIII, Inhibition to platelet function.
Cutaneous manifestations: Livedo reticularis, Necrotizing vasculitis, Livedoid vasculitis,
Thrombophlebitis, Cutaneous ulceration, Necrosis, Erythematous macules, purpura, ecchymoses
Respiratory manifestations: Pulmonary hypertension, Pulmonary thromboembolism, NonJ of Evidence Based Med & Hlthcare, pISSN- 2349-2562, eISSN- 2349-2570/ Vol. 1/ Issue 9 / Oct. 31, 2014. Page 1233
CASE REPORT
inflammatory pulmonary vasculopathy
GIT manifestations: Budd-Chiari syndrome, Hepatic infarction, Esophageal necrosis, Intestinal
ischemia, Pancreatitis, Colonic ulceration, Primary biliary cirrhosis, Acute acalculous cholecystitis
Retinal manifestation: Cilioretinal artery occlusion, Optic neuropathy,
Severe vasoocclusive retinopathy
Renal manifestation: aPL syndrome nephropathy
Clinical presentation of aPL
Diagnosing criteria has been formulated by the International consensus statement on
preliminary classification criteria for definite antiphospholipid syndrome.[8] It states that for
diagnosing aPL if a minimum of one clinical and one laboratory criteria are met.
 Clinical
o One or more episodes of vascular thrombosis
o Pregnancy morbidities
 Laboratory
o aCL IgG and/or IgM antibody present in medium or high titer on two or more
occasions, at least 6 weeks apart, measured by standard ELISA for β2GPIdependent aCL antibodies
Anesthetic implications: Disease being having multi-organ involvement, evaluation in terms of
in-depth history from the patient, and laboratory evaluation enables to find functional status of
the patient. Immobilization of the patient and venous stasis following neuraxial procedure further
predispose the patient for venous thrombo-embolism (VTE.) Hence current concept of early
mobilization of patient is advocated. Physical and pharmacological strategies have been used to
prevent such VTE. Physical modalities like graded compression stockings and intermittent
pneumatic compression devices are used with risk reduction of around 45%. Pharmacologic
methods for prophylaxis against VTE are either parenteral or oral anticoagulant drugs. Heparin
which is most commonly used drug has a risk reduction of 60-70%.[9]
Some surgeries like ocular surgeries, dental procedures and dermatological procedures
can safely be conducted without discontinuing the anticoagulation therapy. Risk benefit ratio to
the patient determines whether these anticoagulant drugs need to be continued or stopped.
For the patient requiring discontinuation of the anticoagulant therapy bridging therapy is
initiated, if the risk of venous thromboembolism is moderate to high. Oral anticoagulation with
warfarin is stopped five days prior to surgery and 36 hours after discontinuation of the drug
heparin is started. Both unfractionated and fractionated forms of heparin can be used for
anticoagulation.
Both general and regional anesthesia can safely be initiated based on the requirements of
the patient. Though regional anesthesia reduces the risk of VTE, it requires the prophylactic
anticoagulant therapy. Since the patients have been put on anticoagulant drugs, for initiating
neuraxial techniques guidelines by American Society of Regional Anesthesia should be followed.
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CASE REPORT
CONCLUSION: Most of the patients suffering from antiphospholipid syndrome who are
undergoing surgery require a temporary interruption of the oral anticoagulant medication and
need to be bridged by Inj. Heparin either fractionated or unfractionated. Patients can safely
undergo both regional anesthesia and general anesthesia, adherence to the guidelines set by
ASRA will help for the safe practice of regional anesthesia on such patients.
REFERENCES:
1. Jacob H. Rand, The Antiphospholipid Syndrome, In: Williams Hematology, 8ed.
Marshall A. Lichtman, Thomas J. Kipps, Uri Seligsohn et al, The McGraw Hill company, New
York, 2010, 2145-62.
2. Sebastiani GD, Galeazzi M, Morozzi G, Marcolongo R: The immunogenetics of the
antiphospholipid syndrome, anticardiolipin antibodies, and lupus anticoagulant. Semin
Arthritis Rheum, 1996, 25: 414.
3. Goldstein R, Moulds JM, Smith CD, Sengar DP: MHC studies of the primary antiphospholipid
antibody syndrome and of antiphospholipid antibodies in systemic lupus erythematosus. J
Rheumatol, 1996, 23: 1173.
4. Eschwege V, Freyssinet JM: The possible contribution of cell apoptosis and necrosis to the
generation of phospholipid-binding antibodies. Ann Med Interne Paris 1996, 147(1): 33.
5. Price BE, Rauch J, Shia MA, et al: Anti-phospholipid autoantibodies bind to apoptotic, but
not viable, thymocytes in a beta 2-glycoprotein I-dependent manner. J Immunol, 1996, 157:
2201.
6. Pittoni V, Isenberg D: Apoptosis and antiphospholipid antibodies. Semin Arthritis Rheum,
1998, 28: 163.
7. Blank M, Asherson RA, Cervera R, Shoenfeld Y: Antiphospholipid syndrome infectious origin.
J Clin Immunol 2004, 24: 12.
8. Wilson WA, Gharavi AE, Koike T, et al: International consensus statement on preliminary
classification criteria for definite antiphospholipid syndrome: Report of an international
workshop. Arthritis Rheum 1999, 42: 1309.
9. Adriana Dana Oprea, Hematologic Disorders, In: Stoelting's Anesthesia And Co-Existing
Disease, 6th ed, Roberta L. Hines, Katherine E. Marschall, Elsevier Inc, Philadelphia, 2012,
407-36.
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CASE REPORT
AUTHORS:
1. Darshan M. S.
2. Sri Devi S.
PARTICULARS OF CONTRIBUTORS:
1. Assistant Professor, Department of
Anaesthesiology, Subbaiah Medical College,
Shimoga.
2. Assistant Professor, Department of
Anaesthesiology, Subbaiah Medical College,
Shimoga.
NAME ADDRESS EMAIL ID OF THE
CORRESPONDING AUTHOR:
Dr. Darshan M. S,
C/o. Vasavi Clinic, M. G. Road,
Chickmaglur, Karnataka 577101.
E-mail: drdarshanms@gmail.com
darshanms_jss@yahoo.com
Date
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Submission: 15/10/2014.
Peer Review: 16/10/2014.
Acceptance: 27/10/2014.
Publishing: 29/10/2014.
J of Evidence Based Med & Hlthcare, pISSN- 2349-2562, eISSN- 2349-2570/ Vol. 1/ Issue 9 / Oct. 31, 2014. Page 1236