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CASE REPORT

ABSTRACT

Systemic lupus erythematosus (SLE) has numerous

manifestations. Haematology is the common system inuenced

by the disease. The antibody antiphospholipid syndrome,

secondary hematology disorder in SLE, is related to high

incidence of thrombosis. The thrombosis events like myocardial

infarction and stroke are high in mortality. We reported

a-36-year old woman treated for lung tuberculosis (TB) with

secondary infection, nephritis lupus, and pancytopenia. The

general condition has improved and the patient was planned

to discharge while she suddenly fell down, unconscious and

had seizure. The CT-scan showed an area of hypodensity on

the left thalamus. Haematology results showed high level

of brinogen and D-dimer as the signs of thrombosis. The

anticardiolipin antibody was intermediately positive for IgG

and IgM, but lupus anticoagulan was weakly positive. The

serial test within 2 months still showed positive IgG. The

patient received supportive treatment , heparinization,neurotropic drugs and anticonvulsant. She was discharged

in good condition while continuing oral anticoagulant to

prevent recurrent seizure.

Key words: cerebral thrombosis, systemic lupus erythemato-

sus, antibody antiphospolipid syndrome.

INTRODUCTION

Antiphospholipid antibodies are the family of

autoantibodies that present a broad range of target

specificities and affinities, all recognizing various

combinations of phospholipids, phospholipids binding

protein or both.1 The term antiphospholipid syndrome

was first coined to denote the clinical association

* Department of Internal Medicine, School of Medicine University

of Indonesia/Cipto Mangunkusumo Hospital, ** Division of

Rheumatology, Department of Internal Medicine, School of Medicine

University of Indonesia/Cipto Mangunkusumo Hospital, *** Division

of Hematology and Oncology, Department of Internal Medicine, School

of Medicine University of Indonesia/Cipto Mangunkusumo Hospital,

Jakarta.

between antiphospholipid antibodies and syndrome

of hypercoagulability in which venous or arterial

thrombosis, or both, may occur. Systemic lupus

erythematosus (SLE) is the most common disease

related to the secondary antiphospholipid syndrome(APS). Current diagnosis criteria for antiphospolipid

syndrome are using a consensus statement, provide

simplied criteria for diagnosis of the APS.1-5

There are several mechanisms that have been

acknowledged in the pathogenesis of thrombosis in APS.

Inhibition of natural anticoagulant, platelet activation,

disorder of fibrinolytic and coagulation activation,

have played an important part in hypercoagulation

condition. Lupus anticoagulant (LA) is a stronger risk

factor for thrombosis than anticardiolipin antibodies

(ACA) in APS.1, 5-7

Systemic lupus erythematosis is a complex disorder

that may affect multiple organs or systems. Most of

the cases found in women, usually of childbearing age.

Prevalence of SLE varies, depends on race and genetic

inheritance. In white women the prevalence is 1:1000.8-11

Among patients with SLE antiphospholipid

antibodies are reported in 2055% of cases. The

Manifestation of APS in SLE varies in different condi-

tions. Stroke related to APS is one of the central nervous

system complications. The estimation of cerebrovascular

accident was 10 times higher in 18 to 44 years old women

with SLE compared to those without SLE.1, 12-15

CASE ILUSTRATION

Mrs. R, 36 years old, presented to RSCM with

shortness of breath since 4 days prior to admission. She

had been admitted to another hospital 2 days before,

where the diagnosis of tuberculosis and suspected lupus

were established. The patient was presently on anti TB

drug therapy. She had 1-month history of cough, some-

times with green coloured sputum. She also had a uctuat-

ing fever, night sweats, loss of appetite, weight loss, and

Cerebral Thrombosis in Systemic Lupus Erythematosus

with The Antibody Antiphospholipid SyndromeDidi Kurniadhi*, Pujiwati*, Linda K. Wijaya**, Bambang Setiyohadi**,

Djumhana Atmakusuma***


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Vol 39 Number 2 April - June 2007 Cerebral Thrombosis in SLE with The Antibody Antiphospolipid Syndrome

nausea. Since one year ago, she had had recurrent

ulcers in the mouth, hair loss and ushing on the face due

to sunlight exposure. No other signicant history.

On physical examination, the patient looked severely

ill and fully alert. Blood pressure (BP) was 130/80

mmHg, regular pulse rate at 88x/min, temperature was

36.6oC, respiratory rate (RR) 24x/min. The height was158 cm and body weight (BW) was estimated 40 kg. The

conjunctivas were pale, sclera were not icteric, there was

a sign of Malar rash and stomatitis, no palpable lymph

nodes. Vesicular breath sound with rales in both lungs.

The rest of the physical examination were normal.

On laboratory examination, Hb 9.2 g/dl, Ht 27%,

leukocyte 2100/uL, platelet count 73000/uL, diff count

0/0/0/91/7/2 and positive coombs test. Urinalysis

leukocyte 2-3, erythrocyte 20-25, protein 2+, blood

2+, BJ 1.030 and the others were normal. Ureum 92

mg/dl, creatinin 2.6 mg/dl, estimated GFR by Cockcroft

and Gaul was 23.6 ml/min, random blood glucose 155

mg/dl, AST 45 U/L, ALT 40 U/L, albumin 1.9 g/dl,

globulin 2.8 g/dl, Na 143 meq/L and K 3.6 meq/L. The

results of blood gas analysis (BGA) was pH 7.5, pO278,

pCO2

22, HCO3

17.5 and O2

sat. 96.8 %.

Normal ECG with tachycardia (QRS rate 100x/min).

CXR showed inltrate in both lungs dominantly on

the right.

Based on all data, the problems of this patient were

(1) lung TB with secondary infection, (2) lupus nephritis,

(3) pancytopenia caused by SLE, (4) SLE. Lung TB

with secondary infection was differentiated with lupuspneumonitis based on history of cough, with green

coloured sputum, uctuating fever, night sweats, loss of

appetite, loss of weight and nausea. Rales in both lungs

and CXR showed inltrate in both lungs especially on the

right. We planned to check ESR, AFB smear 3x, MOR,

Gram and consulted to the Pulmonary division. We

continued the anti TB drugs R/H/Z/E 450/300/1000/750,

vitamin B6 3 x 10 mg and we added Ceftriaxone

1 x 2gr for secondary infection. As for supportive

treatment, we administered the normosaline uid/12-h

and oxygenation 3lt/min.

Lupus nephritis was based on blood ureum 92 mg/dl,

creatinin 2.6 mg/dl, estimated GFR 23.6 ml/min and

urinalysis leukocyte 2-3, erythrocyte 20-25, protein

2+, blood 2+ and because she suffered from SLE. We

planned to perform measured GFR, 24-h quantitative pro-

tein urine and renal biopsy. The treatments were restricted

protein (32 gram) diet with normal calories intake; steroid

(prednisone) 1.5 mg/kgBW. The later was switched to

methylprednisolon with converting dose (3 x 4 tab) due

to slightly increased level of liver function test. We

assumed it was caused by anti TB drugs, proved by

previous data of normal liver function. We planned to

perform serial liver function test.

Pancytopenia caused by SLE was based on

decreasing Hb, leukocyte, platelet count and positive

direct Coombs test. SLE was based on a sign of malarrash, stomatitis, photosensitivity, haematologic disorders

and renal abnormality. For conrmation we examined

ANA, anti Ds-DNA and C3/C4. We treated the patient

with methylprednisolon 3 x 4 tab and ranitidine 2 x

1amp as gastric protector.

On the 4th day of hospitalization, the general

condition was improved, she looked moderately ill, RR

was 20x/min and other vital signs were within normal

limit. On laboratory nding, creatinin level returned to

normal (0.9 mg/dl), measured GFR 71.9 ml/min, 24-h

protein urine 3780 mg, Hb 8 g/dl, leukocyte 7400/uL,

Ht 24%, platelet count 85000, ESR 115 mm/hour, reticu-

locyte 13o/oo

, total bilirubin 0.8 mg/dl, direct bilirubin 0.5

mg/dl, indirect bilirubin 0.3 mg/dl, cholinesterase 5529

U/L, ANA positive with titer 1 : 1000 and anti Ds-DNA

positive 573 IU/ml. The BGA also improved, pH 7.439,

pCO226.2, pO

288.6, HCO

317.5 and O

2sat. 97.5%. The

Pulmonary Division was agreed to continue the anti TB

drugs, and adjusted the Etambutol dosage to 2 x 250

mg, by reason of lupus nephritis.

On day-10, the ureum and creatinin were already

normal (23mg/dl and 0.8mg/dL, respectively), AST 110

U/L, ALT 61U/L, Hb 9.6 g/dl, leukocyte 3800/uL, Ht28.3%, and platelet count 83000. Due to the increasing

level of liver function test and by the advice from the

Pulmonary division, we stopped giving Pyrazinamide

temporally and performed liver function monitoring.

Due to nancial reasons, renal biopsy and other tests

could not be completed. By signicant improvement of

general condition, clinically and laboratory, the Nephrol-

ogy Division suggested to discharge the patient and

evaluate in polyclinic. We added Captopril 2 x 12.5 mg

and liver protector. On the day-12, urinalysis nding

showed proteinuria 1+ and the other was normal. TheFigure 1. Chest X-ray


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Didi Kurniadhi, et al Acta Med Indones-Indones J Intern Med

decision to discharge the patient was also agreed by

Pulmonary and Rheumatology Division.

On the 13th day, early in the morning, the patient fell

down in the bathroom, unconscious and had repeating

convulsions. She was somnolent, BP 160/80 mmHg,

RR 28x/min, temperature 40oC and pulse 100x/min.

Random blood glucose 134 mg/dl, electrolyte and blood

gas analysis were within normal limit. The Neurology

Department suspected an intracerebral hemorrhages and

suggested to perform brain CT. The brain CT yielded a

subacute infarction on the left thalamus. We diagnosed

the unconsciousness caused by cerebral infarction with

other problems of lung TB with secondary infection with

suspected sepsis, lupus nephritis, pancytopenia caused by

SLE and SLE. We planned to check haemostatic and blood

culture. We performed also supportive treatment such

insertion of nasogastric tube with liquid diet 6 x

250cc, catheter urine and oxygenation. We switchedCeftriaxone to Ceftazidim 2 x 1 gr and oral to injection

Methylprednisolon 2 x 250 mg. The neurologist suggested

to give Fenitoin 3 x 100 mg and intravenous Citicholine

2 x 500 mg.

On day-14, haemostatic signs were PT 13.6

(control 13.2), APTT 30.3(control 31.2), brinogen

670 mg/dl and D-dimer 700 ng/dl. Haematology division

agreed to start heparinization with target of APTT

1.52.5x control. After 3 days, there was signicant

improvement on general condition, the patient looked

fully alert, vital signs were normal. We put off the nasog-

atric tube, overlapped heparin with simarc, switchedsteroids into oral and Pulmonary division suggested to

switch Ceftazidim to Levooxacin drip 1x500 mg. The

laboratory ndings were ACA positive of both IgG and

IgM, lupus anticoagulant positive and C3/C4 within

normal limit (75 mg/dl and 15 mg/dl, concecutively).

On the 21st day, general condition was good, she

was able to mobilize. As the AST and ALT returned to

normal, we started again the pyrazynamide and added

Aspirin. Albumin level increased to 2.77 g/dl, butINR level did not yet attain the target (1.4), so we

increased the dosage of simarc. On the 23rd day, she

was discharged in good condition.

DISCUSSION

Pulmonary infection in this case, as mentioned in

the litterature, is one of the co-morbid manifestation in

systemic lupus erythematosus, because of immuno

compromise status. The involvement of multi organ

disorders in SLE gives a severe clinical condition.

The disease is characterized by periods of relative

quiescences and periods of exacerbations, which may

involve any organ or system in various combination.

The uncontrolled SLE activity put a coincidence of

active SLE and the acute infection became serious

complications. As we know the infection is still the

most common cause of death in SLE.

The target organs involved in this patient were

kidney, hematology system, skin and musculosceletal.

Positive results of ACA and LA were common in SLE

with haematology manifestation and related with the

disease itself.

On the beginning, we analyzed the cause ofunconsciousness and repeated convulsion were

intracerebral hemorrhage due to head trauma or cranial

injury. That was because she had a history of fall down

and the status of on-steroid therapy would decrease the

possibility of having cerebral lupus.

The latest data of brain CT and hemostastic supported

the evidents of cerebral thrombosis as the cause of

this condition. Our treatment included supportive

therapy, adequate antimicrobial drug to eliminate

infection, neurotropic drugs and anticoagulant with

heparinization. Decision to start heparinization was

consulted and approved by Haematology and Oncology

division with target of APTT 1.5 2.5x control. As we

know, the management of SLE includes glucocorticoids,

antimalarial agents and immunosuppressant drugs. SLE

patients with APS should also receive antiplatelet and

anticoagulant. After aggressive treatment and intensive

monitoring, the condition was improved.6, 9-11,13, 16, 17

Antiphospolipid antibody syndrome was secondary

in systemic lupus erythematosus condition. From the

laboratory results we found positive lupus anticoagulant

antibodies and anticardiolipin antibodies of both IgGFigure 2. Brain CT-scan


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Vol 39 Number 2 April - June 2007 Cerebral Thrombosis in SLE with The Antibody Antiphospolipid Syndrome

and IgM. Those positive results had correlation with

increasing risk and incidence of thrombo-embolic events.

Criteria for antiphospholipid antibody syndrome

in this patient were supported by the incidence of

thromboembolic event (cerebral thrombosis) with

positive results of both antiphospholipid antibodies.Persistence of positive ACA (IgG) after 2 months has

fullled the criteria of APS.

As there was evidence of thrombosis, the patient

required an oral anticoagulant (Warfarin) as maintenance

treatment. The target of INR for arterial thrombosis

should be at least 2.5, but it varies in the literature. The

Haematology and Oncology division recommended to

maintain INR level between 1.5 2.5, and continued the

evaluation in the next few days in polyclinic.

CONCLUSION

Eventhough infection is the most dangerous

complication related to death in SLE, multi organ

involvement has made consideration of any other

possibility of complication and manifestation. Similar

to APS, the complication associated with SLE, which

found in many organs or systems such as venous

thrombosis, cardiac event and central nervous system.

Venous thrombosis is the most common clinical

manifestation of antiphospholipid antibody syndrome.

This complication could also have serious consequences,

if not managed seriously.1, 3, 12-15

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