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Macedonian Journal of Medical Sciences. 2011 Jun 15;
4(2):192-195.
doi:10.3889/MJMS.1857-5773.2011.0178
Case Report
Antiphospholipid Syndrome in Patient with Portal Venous Thrombosis: Case Report
Ljubinka Damjanovska1, Ruse Rajcevski2
1University Rheumatology Clinic, Faculty of Medicine,
University “Ss Cyril and Methodius”, Skopje, Republic of Macedonia; 2General
Hospital “8 of September”, Transfusiology, Skopje, Republic of Macedonia
Antiphospholipid syndrome (APS) is defined by the presence of arterial and
venous thrombosis, recurrent fetal death, cerebrovascular accidents,
hemolytic anemia, thrombocytopenia and various manifestations on different
organs in the presence of anticardiolipin antibodies (aCL) and or lupus
anticoagulant (LA).
It was reported in early 1980’s. This syndrome is the most common cause of
acquired thrombophilia. There is no consensus for treatment among
physicians. Overall there is a general agreement that patients with
recurrent thrombotic episodes require life-long anticoagulation therapy and
those with recurrent spontaneous abortions require anticoagulation therapy
(low molecular weight heparin) and low dose aspirin during most of
gestation. Immunosuppresion seems to be ineffective exept in patients with
fulminate multiple organ failure i.e. catastrophic antiphospholipid syndrome
where plasmapheresis can also be used.
We present a case of 31 year old woman with primary APS and portal venous
thrombosis (PVT), without any recognizable autoimmune disease. She has 4
spontaneous abortions, calf thrombosis, gangrene of one toe, refractory
cutaneous ulcer on the heel and livedo reticularis. She is positive for aCL
and LA, with hypergammaglobulinemia.
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Citation: Damjanovska L, Rajcevski R. Antiphospholipid Syndrome in
Patient with Portal Venous Thrombosis: Case Report. Maced J Med Sci. 2011
Jun 15; 4(2):192-195. doi.10.3889/MJMS.1957-5773.2011.0178.
Key words: antiphospholipid syndrome (APS); portal venous thrombosis
(PVT); anticoagulant therapy; anticardiolipin antibodies (aCL); lupus
anticoagulant (LA).
Correspondence: Dr. Ljubinka Kiril Damjanovska. University
Rheumatology Clinic, Faculty of Medicine, University “Ss Cyril and
Methodius”, Vodnjanska 17, 1109 Skopje. Republic of Macedonia. Phone:
38923147366. E-Mail: ldamjanovska@gmail.com
Received: 09-May-2011; Revised: 23-May-2011; Accepted: 24-May-2011; Online
first: 01-Jun-2011
Copyright: © Damjanovska L. This is an open-access article
distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any
medium, provided the original author and source are credited.
Competing Interests: The author have declared that no competing
interests exist.
Antiphospholipid syndrome (APS) is characterized
by venous or arterial thromboses, fetal losses and thrombocytopenia, in the
presence of antiphospholipid antibodies (aPL) (namely lupus anticoagulant
(LA)), anticardiolipin antibodies (aCL) or antibodies directed to various
proteins, mainly beta 2 glycoprotein I (beta2GPI), or in the presence of all
three. Both lupus anticoagulant (LA) and anticardiolipin (aCL)
immunoglobulin isotype G (IgG) and M (IgM) are maintained as laboratory APS
criteria, and IgG and IgM anti-b2 glycoprotein-I (anti-b2GPI) assays are
added in the revised criteria. Laboratory criteria should be positive on two
or more occasions at least 6 weeks apart and anticardiolipin (aCL) antibody
of IgG and/or IgM isotype in serum or plasma, present in medium or high
titer (i.e. >40 GPL or MPL (or > the 99th percentile) [1].
Diagnosis is based on the presence of at least
one clinical and laboratory criterion each, according to International
Consensus Statement on preliminary classification criteria. However, APS can
be diagnosed in individuals even in the absence of some of the
classification criteria [2].
APS occurs 2-5 times more frequently in women
than in men. Currently, two major forms are recognized: primary and
secondary APS. Primary form exists without associated underlying illnesses,
while the secondary form is associated with definable underlying illnesses
or inciting factors. It can be found in 10-40% patients with SLE.
Nowadays, it is not recommended to use the terms primary and secondary APS
because secondary APS is usually associated with SLE [3].
Women with serologically positive IgG aPL
antibody and/or LAC, and/or thrombosis may lose approximately 80% of all
subsequent pregnancies. Criteria have recently been proposed for APS and
pregnancy. They suggest that women with positive aCLs greater than or equal
to 20 GPL or LA and any of the following should be diagnosed with APS: One
or more otherwise unexplained fetal death at 10 weeks or more of gestation,
loss of one or more morphologically normal neonates due to complications of
prematurity after delivery because of severe preelampsia or evidence of
severe placental insufficiency, three or more consecutive pre-embryonic or
embryonic losses, without anatomic, genetic, and hormonal abnormalities.
Early fetal loss, late fetal loss, premature births, and pre-eclampsia are
the most frequent fetal and obstetric manifestations [4].
Deep vein thrombosis is the most frequently
reported manifestation in this syndrome. Conversely, cerebrovascular
accidents are the most common arterial thrombotic manifestations [5].
Major-vessel occlusion has been described in
virtually every vessel, including the aorta, branches of the aorta, inferior
vena cava, hepatic vein, portal vein, intra-abdominal and intracranial
vessels, and the peripheral vasculature of the extremities (organ
infarctions). Liver thrombosis was a feature of the original clinical
description of the syndrome. Liver function abnormalities are common in APS
patients.
Approximately 40 % of patients will present with
cutaneous manifestation as the first indicator of the APS. These are as
follows: livedo reticularis, superficial thrombophlebitis, cutaneous
necrosis, digital ischemia and gangrene, stasis ulcers of the ankles,
epidermal atrophy, splinter hemorrhages of the nailbeds, non-necrotizing
purpura, and blue-toe syndrome [6].
Cardiac lesions may occur in as many as 22% to
36% of patients. Demonstrable lesions on echocardiography include aortic and
mitral regurgitation, valvular thickening, diminished valvular mobility, and
valvular vegetations.
Neurological symptoms such as dyplopia, memory
loss, headache, ataxia and “multiple sclerosis like syndrome”, are also
frequent.
Antiphospholipid antibodies correlate with
lesions of renal small-artery vasculopathy and chronic renal ischemia.
Platelet counts in APS may vary from normal to severe thrombocytopenia [1].
Accurate laboratory investigations are crucial
for APS diagnosis and treatment. LA measured by diluted viper venom test
(dRVVT) and activated thromboplastin time assay (aPTT) are among the most
sensitive tests. Lupus anticoagulants increase the risk of venous and
arterial events to the same extent, particularly if cerebral stroke and deep
vein thrombosis are considered. Anticardiolipin antibodies are not such
strong risk factors for thrombosis as lupus anticoagulants. They are
associated with cerebral stroke and myocardial infarction but not with deep
vein thrombosis.
All aCL assays detect antibodies to negatively
charged phospholipids bound to a plasmatic cofactor with natural
anticoagulant activity known as b 2-glycoprotein 1 or apolipoprotein H (b
2-GP or apo H). It seems that the pathogenic antibodies are those directed
towards beta 2-GP 1. Anti-b2GPI antibodies are an independent risk factor
for thrombosis and pregnancy complications. Anticardiolipin antibodies and
anti-b 2GP 1 are detected with ELISA technique. Patients may also have
anti-protrombin antibodies [1, 7].
We present a case of 31 years old white Muslim female, who presented with
primary APS with portal vein thrombosis.
The data were taken from the patient, from her family and from her past
medical records.
Identification: 31-year-old, white Muslim female.
Chief complaints: Fatigue, abdominal pain, pain and tenderness in her right
calf, painful ulcer on the bottom of the right feet. The ulcer resolved few
times with periods of rest, antibiotics, and local care. The current ulcer
has been treated without improvement with oral and topical antibiotics.
History of the present illness: She suffered 3 spontaneous abortions in her
second trimester of pregnancy, during 1996/1997 in a period of 15 months.
Once she was noted to have blighted ovum and missed abortion. After her
third abortion she developed recidivant right calf thrombosis, and because
of that she was treated with parenteral and oral anticoagulant therapy (warfarin)
for a total period of 3 years.
The fourth spontaneous abortion happened in 2001 in the 12-th week of her
pregnancy. Eight months before this admission her right calf became tender
and painful, and she noticed a painful ulcer on the bottom of her right
feet. Since then she suffers from malaise and feels frank pain in her right
flank. In addition due to arterial thrombosis she suffered gangrene on the
second toe of her left foot, which was amputated.
This time she was referred to specialist because of recidivated calf
thrombosis, prolonged aPTT, and coagulation factor deficit. She was not
taking anticoagulants for 4 years and her family physician suspected hepatic
lesion and APS.
Psychosocial History: Housewife, married since 1996 without any children,
she finished elementary school. She denies cigarette smoking and alcohol
drinking. She does not take any drugs.
Physical Exam. General: Conscious white female, lying comfortably supine in
the bed. Vital signs: Temp 37 DC, Respirations. 20, HR 100, BP 110/70. Skin:
pale, livedo reticularis on the extremities, ulcer on the bottom of the
right feet, measuring 2 x 2 cm, with fibrinoid debris over the ulcer
surface. Head, ears nose and throath (HEENT): Normal without lesions. Neck:
Full range of motion, no masses or lymphadenopathy. Chest: Symmetrical
expansion. FP equal bill. Lung fields clear to percussion. Breathing sounds
normal. Heart: No cardiac impulse visible. Normal S1, S2, no murmurs, no
rub. Abdomen: Distended, diffuse tenderness, without splenomegaly and
hepatomegaly. Musculoskeletal exam: No joint swelling, warmth and
tenderness. Range of motion within normal limits.
Peripheral vascular: Right calf tenderness, Homans’s sign positive, palpable
pulses on a. dorsalis pedis ECG: HR 100, normogram, sinus rhythm. Chest
X-ray: Without any abnormalities.
Dopler echosonography of the abdomen: Old portal thrombosis with numerous
varicosities with slow circulation around the liver, gall bladder and
pancreas.
Laboratory results: ESR: 79…105 mm/h, HGB: 107…88 g/L, Er 3.7 x 10/12/L Htc:
0.33…0.29 Le 4.1x10/9/L, Plt 126x10/3/L Urine analysis: Negative.
Protrombin time 17 sec. (RV 15 sec ), Thrombin time normal, aPTT prolonged
95 sec (RV 32 sec) FDP: <250 (RV 0-250).
Lupus anticoagulant – positive (APTT based assay), cardiolipin IgG antibody
22 gpl ( < 20) Coagulation factors : Factor II Prothrombin 45 % ( 60-120%),
Factor V Proaccelerin 42%, Factor VIII AHG 8.7%, Factor XI Christmas 13
%.Blood Group: O, Rh positive.
SMA-12: AP 31 U/L, SGOT: 32 U/L SGPT: 45U/L, LDH 21 U/L; CPK 22 U/L,
Glucose: 4.8 mmol/L Urea: 3.3 mmol/L Creatinin 55 mcg/mL, Total proteins: 86
g/L, Albumin 47, Globulin 49, IgG 23, cryoglobulines negative, C3 0.64, C4
0.06, CIK 0.13, ANA negative, Lupus cells phenomenon - negative, RF 320 IU/L
(> 30 IU/L), CRP negative.
Treatment: The patient was further referred to hematologist who treated her
with oral anticoagulants and aspirin.
We presented a case of the 31 year old white female with primary APS and
portal venous thrombosis, without any recognizable autoimmune connective
tissue disease. She had 4 spontaneous abortions in the first and second
trimester, deep venous thrombosis, arterial thrombosis manifested as a
gangrene of one toe, refractory cutaneous ulcer on the heel and livedo
reticularis.
She presented with mild anemia, thrombocytopenia, prolonged a-PTT, and she
was positive for LA, aCL and anti - CMV antibodies.
Systemic arterial and vein thrombosis are typical features of APS. Vianna et
al reported typical cases of arterial thromboses in deep vein thrombosis in
54% of cases and arterial occlusions in 44%. However, portal vein thrombosis
in APS is rare [8].
Portal vein thrombosis (presinusoidal venous obstruction) is the second most
common cause of portal hypertension after cirrhosis. It may develop in a
variety of hypercoagulable states (polycythemia vera, essential
thrombocytemia, deficiencies of protein C, S or antithrombin III ),
including APS. Normal pressure in the portal vein is low -10 to 15 cm saline
(portal hypertension > 30 mmHg saline). The major clinical manifestations of
portal hypertension include hemorrhage from gastroesophageal varices,
splenomegaly with hypersplenism, ascites and hepatic encephalopathy. Therapy
is directed towards surgical and non surgical decompression (TIPS).
Beta-adrenergic blockade with propranolol (propranolol reduces cardiac
output and has vasodilatatory effects on both splanchnic arterial bed and
the portal venous system) can be used [9-11].
The treatment of APS still remains controversial and it should be
individualized depending on the clinical manifestations and the underlying
disease.
It is consensus to indicate life-long oral anticoagulation therapy with
warfarin with an INR target of 2.5-3.5 for those with recurrent venous
thrombosis and INR of 3-4 for those with past arterial thrombosis. These
patients should also receive low dose 65-100 mg of ASA. The combination of
low molecular weight heparin and low dose aspirin is recommended in pregnant
patients with past thrombosis or fetal loss, because of significantly higher
rate of live births in the patients who received both aspirin and heparin
[13].
Glucocorticoids have been associated with increased maternal and fetal
morbidity. They sometimes may be useful in PVT with esophageal varices.
The treatment of patients with APS and portal venous thrombosis is difficult
because of the risk of bleeding and the recurrent thrombosis if they don’t
receive appropriate long-term anticoagulant therapy [10, 11].
Prophylactic anticoagulation therapy is not justified in patients with high
titers of aPL with no history of thrombosis. Treatment of associated risk
factors (avoidance of smoking, oral contraceptives, obesity, invasive
vascular procedures, treatment of hypertension and hypercholesterolemia,
avoidance of prolonged immobilization etc.) should be recommended [14].
This case report suggests that APS has heterogeneous clinical presentation
and a high index of suspicion for any signs of abdominal involvement should
be considered in patients with APS. In addition screening for aPL should be
carried out in patients who present with hepatic vein occlusion and
unexplained signs of intestinal angina.
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RH, DE Groot PG, Koike T, Meroni PL, Reber G, Shoenfeld Y, Tincani A,
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update of the classification criteria for definite antiphospholipid syndrome
(APS). J Thromb Haemost. 2006;4:295-306.
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