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Deep vein thrombosis is an entity that can have
multiple predisposing factors. Identification of each of these is essential for
better outcomes and requires a holistic approach. Here we report the case of a
41 year old female who presented with deep vein thrombosis in whom the initial
diagnosis was vitamin B-12 deficiency with secondary hyperhomocysteinemia was
made beyond doubt. However, since she had one spontaneous first trimester
abortion, loud P2 suggesting possible pulmonary hypertension with history
suggestive of recurrent pulmonary embolism, a coexistent APLA syndrome was also
suspected clinically, which was confirmed by prolonged aPTT, positive VDRL and
ANA positivity. The case is reported to highlight importance of looking for
other etiological factors for any clinical syndrome, if the clinical
indications are strong. Hence the presence of one definite etiologic factor
does not necessarily indicate the absence of others. A holistic clinical
approach is absolutely essential to help the patients rather than believing
only the laboratory.
INTRODUCTION
Deep vein thrombosis (DVT) is a major
preventable cause of morbidity and mortality. It has to be prevented by all
possible means but when it develops, prompt clinical diagnosis and early
management should not be delayed even if radiological evidence is not available
since the sensitivity of ultrasound Doppler is poor especially for distal deep
vein thrombosis. While early recognition of the condition is important, equally
important is the identification of possible etiological factors. Each patient
with venous thrombosis has multiple factors responsible for venous thrombosis.
Hence a holistic approach in the form of detailed history, including dietary
history, adequacy of hydration, immobilization, travel, prolonged unusual
postures and physical examination and necessary investigations are needed to
solve the clinical problems.
CASE
DESCRIPTION
41 year old female who was apparently normal
before the onset of symptoms presented with 2 weeks history of insidious onset
progressive right lower limb oedema and pain mainly confined to the leg and
dorsum of foot not associated with fever (Figure
1). There was no history of any trauma/wound in the concerned limb. There
was no history of prolonged immobilisation/recent surgeries. There was no
history of polyarthralgia/skin lesions/oral ulcers or hematuria. There was no
history of weight loss/fever. She was not on any medications. Two days after
she was admitted for evaluation, she developed sudden onset breathlessness as
well after walking a few steps. She gave a history suggestive of similar two
episodes in the past few years although the severity of the present episode was
much higher. She was a pure vegetarian and her dietary history suggested poor
intake of fruits and green leafy vegetables as well. She also gave a history of
tingling sensation of her lower limbs for the past few years. As far as her obstetric
history was concerned, she had one spontaneous abortion in first trimester of
her pregnancy at the age of 20. Her next two pregnancies were uneventful. There
was no history of any similar complaints in her family to her knowledge. On
examination she was overweight with a BMI of 27. Pallor was present. She had a
pulse rate of 100/min and
normal blood pressure. Her respiratory rate was 24/min. Her right lower leg was
swollen and tender with no local rise in temperature or redness. Chest was
clear on auscultation. Cardiac auscultation revealed loud P2. Abdominal and
pelvic examination was normal. Neurological examination was normal except for
absent ankle jerk. Hence the provisional diagnosis was deep vein thrombosis
with possible pulmonary venous thromboembolism
with
an
Thus it was clear that the patient had
vitamin B-12 deficiency and hence she was started on parenteral
hydroxycobalamine and other oral multivitamins as well in addition to the
necessary dietary advice. Five days after inpatient care, she was
symptomatically better with regard to her lower limb edema and dyspnea. By this
time a diagnosis of probable APLA, suspected upon clinical grounds, was
reaffirmed as the aPTT was prolonged, VDRL was reactive and ANA was positive.
Although the APLA antibodies came out to be negative, the clinical history
together with indirect laboratory evidence of anti-cardiolipin antibody
(positive VDRL) was sufficient enough to make an early diagnosis of APLA
syndrome in this patient so that early intervention to prevent further
thrombotic events could be initiated. Hence the patient was started on
steroids, Azathioprine and Dabigatran as well in addition to the necessary
dietary advice for weight reduction and was discharged to be kept under follow
up. On follow up she has been asymptomatic for the last one year. There have
not been any further episodes suggestive of thrombotic events.
DISCUSSION
Deep vein thrombosis is a clinical diagnosis.
Venous Doppler should not be relied upon for a diagnosis of DVT since the
sensitivity of the same is poor especially for distal vein thrombosis [1].
Hence its significance in a clinically evident case of deep vein thrombosis is
questionable since the absence of radiological evidence can misguide us in the
diagnosis and most importantly would cause a delay in the diagnosis and
management of the condition. There was no alternative diagnosis in this patient
other than DVT and recurrent pulmonary embolism after history and physical
examination. Hence this patient was started on heparin soon after admission.
This patient was a pure vegetarian with low intake of vegetables and fruits.
Thus it was clear that she was having vitamin B-12 and folic acid deficiency
which was suggested by her hemogram showing anemia with high MCV. Even her
vitamin B12 levels were low, although it is not necessary to assess the same as
vitamin B-12 assay can be normal in some patients with vitamin B-12 deficiency.
Thus ultimately, what led us to the diagnosis of vitamin B-12 deficiency in
this patient was her dietary history and hem orgasm. Vitamin B-12 deficiency is
a well-recognized cause of hyperhomocysteinemia and the latter is a well-recognized
cause of thrombosis [2]. Among the various biochemical function of vitamin B-12,
the one involved in the synthesis of methionine from homocysteine is clinically
important with regard to the occurrence of hyperhomocysteinemia and subsequent
predisposition to venous thrombosis in patients with vitamin B-12 deficiency
[3]. Hyperhomocysteinemia causes venous thrombosis by variety of mechanisms
such as endothelial dysfunction, increase in synthesis of thromboxane and
impaired fibrinolysis.
Vitamin B12 deficiency is extremely common in
India. The reasons for this are too many and related to diet, lifestyle and
social and cultural issue. In spite of it being a common disorder, its
recognition is delayed or missed because the manifestations are diverse in nature,
affecting all organs and systems and is often subclinical [4].
Hence, she was started on parenteral
hydroxycobalamine, folic acid and other oral multivitamins in addition to the
dietary modifications. Although we identified one definite risk factor for
thrombosis in this patient, there was still a suspicion of an additional
underlying APLA syndrome since she had recurrent episodes of exertional
dyspnea, loud P2 on auscultation and one spontaneous abortion at the age of 20
years. Hence aPTT, APLA antibodies and VDRL was tested. The aPTT was prolonged
and VDRL was positive although IgG APLA was negative. ANA-IF was positive as
well. Thus a diagnosis of probable APLA based on clinical clues and indirect
evidence of anti-cardiolipin antibody was made. Here again APLA syndrome
secondary to an underlying collagen vascular disorder was diagnosed in the
setting of a thrombotic event and suggestive clues in history, examination and
investigations. One should not wait for all the laboratory criteria to be satisfied
in such a case. There have been case reports of seronegative APLA syndrome as
well [5]. For the same reason, she was started on azathioprine and tapered
regimen of steroids. Thus we could identify vitamin B-12 deficiency and APLA
syndrome as two potential risk factors in this patient with venous
thromboembolism.
CONCLUSION
Clinical evaluation and decision making should remain the cornerstone in the diagnosis and management of any patient. Radiological investigations and laboratory criteria should not be heavily relied upon when the diagnosis is obvious clinically since the patient may benefit remarkably from early intervention. Finally, identifying a potential risk factor for venous thrombosis does not necessarily obviate the need to look for other additional factors contributing to the same.
1. Goodacre
S, Sampson F, Thomas S, van Beek E, Sutton A (2005) Systematic review and
meta-analysis of the diagnostic accuracy of ultrasonography for deep vein
thrombosis. BMC Med Imaging 5: 6.
2. den
Heijer M, Koster T, Blom HJ, Bos GMJ, Briët E, et al. (1996)
Hyperhomocysteinemia as a risk factor for deep-vein thrombosis. N Engl J Med
334: 759-762.
3. Oger
E, Lacut K, Le Gal G, Couturaud F, Guénet D, et al. (2006) Hyperhomocysteinemia
and low B vitamin levels are independently associated with venous
thromboembolism: Results from the EDITH study: A hospital-based case-control
study. J Thromb Hemost 4: 793-799.
4. Sasidharan
PK (2017) B12 deficiency in India. Arch Med Health Sci 5: 261-268.
5. Nayfe
R, Uthman I, Aoun J, Saad Aldin E, Merashli M, et al. (2013) Seronegative anti-phospholipid
syndrome. Rheumatology 52: 1358-1367.
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