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Journal of the association of physicians of india • vol 62 • october, 2014

Stroke in Young with Primary Protein –

S Deficiency
Narayana Pantam*, Mamatha Pulloori**, Keerthi Alugubelly***

Abstract
Stroke in young is a major health problem in developing countries along with CAD, according to various
Indian studies its prevalence is 25-34%. Thrombophilic disorders constitute aetiology in 60% cases of stroke
of undetermined aetiology. A 20 yrs old young female presented with symptoms of left PCA thrombosis
(P2 syndrome), on evaluation – Isolated Protein – S deficiency is noticed. In this case Protein-S deficiency
seems to be the only risk factor responsible for stroke.

Introduction

C erebral venous thrombosis and rheumatic heart disease are the leading causes
of stroke in young. World wide, thrombophilic factors have been implicated in
4-8% of the young strokes. These may be hereditary or acquired. Among hereditary
causes- factor-v leiden deficiency, coagulation factor like protein-C, S deficiency and
prothrombin gene mutation. Protein –S is a vitamin-K dependent anticoagulant, acts as
a cofactor for protein C coagulation pathway. In healthy individuals, approximately 60%
is bound to protein and 40% is in free active form. Around 1-5% of cases are associated
with venous thrombosis, < 0.5% with arterial thrombosis. 1

Case Proper
A 20 yr old young female, presented with blurring of vision and numbness of
right half of body since 4 days with no positive history to explain symptoms. On
general examination – pallor was noticed. Detailed neurological examination – higher
intellectual functions- normal, cranial nerve – 2nd shows homonymous hemianopia
with normal fundus and pupillary reaction, sensory system – pain and temperature
sensation decreased over the right half of body. Rest of the examination was normal.

Lab Investigations MRI Brain

Haemoglobin-6 gm/
dl, total leucocyte count –
8 0 0 0 c e l l s / m m 3, p l a t e l e t s
-4.4 lakh s, ESR-30 mm/hr.
Pe r i p h e r a l s m e a r s h o w i n g
microcytic hypochromic
anaemia. Complete urine
examination-normal. Total
protein:7.4, albumin:4.5,
g l o b u l i n : 2 . 9 , A / G - 1 . 5 , T.
bilirubin-0.6, D.B-0.2. ALT-15,
*
Head of Department, AST-17, ALP-79, GGT-14,
Assisstant Professor, ***Resident
**
blood urea-30mg/dl, serum
General Medicine, Chalmeda
creatinine -0.5. Ultra sound
Anand Rao Institute of Medical
Sciences, Karimnagar,
abdomen imaging – normal.
Andhra Pradesh HIV- negative, ECG- normal, Fig. 1 : T2 flair hyper intensities with restriction on
Received; 08.05.2013; Chest –X ray PA view –normal. diffusion weighted noted in left postero- temporal,
Revised: 11.06.2013; Fasting lipid profile – normal. left parieto-occipital region, splenium of corpus
Accepted: 18.06.2013 callosum and left thalamus
Journal of the association of physicians of india • vol 62 • october, 2014 75
MR Angiogram
Fig. 2 : Arrow shows clear narrowing of left posterior
cerebral artery ( p2 syndrome)
Coagulation Profile
1. APLA Ab’s-IgM, IgG normal; 2. Prothrombin
activity – Normal; 3. Fibrinogen- 362 mg/dl, 4.
Antithrombin activity-105%; 5. Factor-V - 88%;
6.Serum Homocystein-5.1 micmol/l, 7. Protein- S
activity- free form -27% (50%-140%); 8. Protein – C
activity -88.4%.We concluded arterial thrombosis as
a result of hereditary deficiency of protein-S. She was
managed with heparin and oral anticoagulants.
Discussion
Ischaemic stroke in young constitutes 10-15% of
cases among thrombophilic disorders. Most of these
are associated with venous thrombosis rather than
arterial thrombosis. Cerebral venous thrombosis and
rheumatic heart diseases are the most common causes
of stroke in young in developing countries. At present
there are no guidelines to screen for thrombophilic
disorders. Carod-Artal et al2 found that prothrombotic
conditions were more frequent among the young IS
patients classified as “strokes of undetermined cause”
The distinction between free and total protein
S levels is important and gives rise to the current
terminology regarding the deficiency states.
The congenital deficiencies of protein S 3 are
classified in three forms : 1) Type I deficiencies -
reduced antigen levels of both total and free protein
S. 2) Type II deficiencies - reduced protein S activity
but with normal antigen levels of both. 3) Type III
deficiencies are defined by a reduced antigen level
activity of free protein S but the antigen level of total
protein S remains normal.
Acquired protein S deficiencies are associated
with several clinical states: Oral warfarin therapy,
liver disease, disseminated intravascular coagulation,
oral contraceptives, oestrogen therapy, auto immune
disorders, pregnancy, HIV, sickle cell disease,
malignant tumours, Type-1 diabetes mellitus,
nephritic syndrome.
Protein S deficiency is a hereditary disorder, but the
age of onset of thrombosis is different in heterozygous
or homozygous state. Most venous thrombosis events
in heterozygous protein S deficiency occur in persons
younger than 40–45 years. The rare homozygous
patients have neonatal purpura fulminans, 4 with
onset in infancy. There were only few case reports
showing association with arterial thrombosis. 5 In
this case patient presented with blurring of vision
and hemi sensory loss. On clinical evaluation patient
has homonymous hemianopia, decreased pain and
temperature sensation on right half of body.
MRI Brain image : (Figure 1) Posterior cerebral
artery stroke (P2 syndrome). MRA (Figure 2) shows
clear narrowing of left posterior cerebral artery.
Initially we ruled out routine risk factors like
diabetes, hypertension, intake of oral contraceptive
pills, hypertriglyceridaemia and on screening for
thrombophilic disorders show decreased free form
of protein-s, other coagulation profile was normal.
We concluded that probably hereditary deficiency of
protein-s being the cause of stroke in this case.
Our interest of presenting a case of stroke in young,
enlightens us isolated protein-S deficiency is one of
the components of thrombophilic disorder causing
arterial thrombosis.
References
1. Amit Hooda, PD Khandelwal, Puneet Saxena. Protein S deficiency
: recurrent ischemic stroke in young. Annals of Indian Academy of
Neurology 2009;12:183-184.
2. Carod-Artal FJ, Nunes SV, Portugal D, Silva TV, Vargas AP. Ischemic
stroke subtypes and thrombophilia in young and elderly stroke
patients admitted to a rehabilitation hospital. Stroke 2005;36:2012
3. Wagh SB, Anadure R, Dutta V, Sandhu MS, Trehan R. Isolated
protein S deficiency presenting as catastrophic systemic arterial
and subsequently venous thrombosis. Australasian Medical Journal
2012;5:424-428
4. Edlich RF, Cross CL, Dahlstrom JJ, Long WB. 3rd. Modern concepts of
the diagnosis and treatment of purpura fulminans. J Environ Pathol
Toxicol Oncol 2008;27:191–6.
5. Eun Jae Ok, Hye Won Kim, Sang Dong Kim, et al. Multivessel
Thromboembolism Associated with Dysfunction of Protein. S Ann
Rehabil Med 2012;36:414–417.