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Year : 1999  |  Volume : 47  |  Issue : 2  |  Page : 155-6

Plasma antithrombin III deficiency in ischaemic stroke in the young.


Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, 560029, India.

Correspondence Address:
Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, 560029, India.

  »  Abstract

A deficiency of plasma antithrombin III has been identified as a potential risk factor for thrombosis. In a pilot study of 56 patients aged less than 40 years who presented with ischaemic stroke of unknown etiology, we detected only one case of plasma antithrombin III deficiency. Antithrombin III activity was estimated by a chromogenic assay. Hence, antithrombin III deficiency, though rare, should be considered while evaluating young patients with stroke of unknown etiology.

How to cite this article:
Nagaraja D, Christopher R, Tripathi M. Plasma antithrombin III deficiency in ischaemic stroke in the young. Neurol India 1999;47:155


How to cite this URL:
Nagaraja D, Christopher R, Tripathi M. Plasma antithrombin III deficiency in ischaemic stroke in the young. Neurol India [serial online] 1999 [cited 2020 Aug 7];47:155. Available from: http://www.neurologyindia.com/text.asp?1999/47/2/155/1630



Stroke in the young forms 20-30% of all ischaemic strokes in India.[1] The aetiology of a majority of ischaemic strokes in these young individuals is unexplained. A wide variety of coagulation abnormalities have been identified as potential risk factors for ischaemic cerebral infarction. Antithrombin III (AT III) is an inhibitor of plasma serine proteases. An important action of AT III is the inhibition of thrombin activation. Familial AT III deficiency is an autosomal dominant disorder in which patients are heterozygous for an abnormal gene and are predisposed to thrombotic events including stroke in the young.[2] Acquired deficiency of AT III in nephrotic syndrome or colitis may also predispose to thrombosis.[3] However, no published data is available in India on the association of such a deficiency, whether familial or acquired and stroke in the young. This led us to study this natural anti-coagulant protein in patients of stroke aged less than 40 years.

Consecutive 56 patients with completed stroke, aged 40 years and below, were included for the study. The exclusion criteria were the presence of haemorrhage on brain CT Scan, a cardiac source of embolism and stroke resulting from infections or collagen vascular disease. Patients who were on oral contraceptives or anticoagulant therapy were also excluded.

The plasma AT III activity was determined by a chromogenic assay (Spectrolyse AT III, Biopool, Canada). In this two stage method, thrombin was added to diluted plasma containing AT III in the presence of excess of heparin. After an initial incubation period, residual thrombin was determined with a thrombin-specific chromogenic substrate. The residual thrombin activity is inversely proportional to the antithrombin III concentration. Of the 56 young patients with cerebral infarcts studied, only one case of AT III deficiency was detected.

This 25 year young lady presented with a history of weakness of right side of the body of 24 hours duration. She had no history of a similar episode earlier. There was no past history of any known risk factor for stroke in the young. Her general physical examination, peripheral pulses, carotids, blood pressure and cardiac evaluation were within normal limits. Neurologically, she was drowsy but arousable and globally aphasic. She had right-sided hemiplegia of grade 0/5 with a right upper motor neuron facial palsy. Blood investigations, both haematological and biochemical, including the coagulation and lipid profile, liver and renal function tests, protein C and protein S were within normal limits. The serum antiphospholipid antibodies, both IgG and IgM types, RA factor and LE cells were negative. However, her plasma AT III activity was only 26% of the normal (control range 75-125%). The cranial CT showed an infarct involving the territory of left middle cerebral artery. The electrocardiogram and echocardiogram were normal.

Hereditary AT III deficiency, may be of the type 1, where there is a quantitative decreases of less than 50% of the normal plasma activity. This may result from either a gene deletion or from frameshift mutations resulting in a truncated protein. This truncated protein is unstable and therefore undetectable in assays. Qualitative defects resulting in functional deficiencies are present in type II deficiency and are due to point mutations. These mutations affect the protease binding function, heparin binding function or both. Most patients with hereditary AT III deficiency are heterozygous, although kindreds with homozygous deficiency have been reported. In familial AT III deficiency patients usually present with repeated episodes of venous thrombosis. Thrombosis of the leg or iliac veins has been observed in 90% of the reported cases.[4] Cases of cerebral thrombosis associated with AT III deficiency, although extremely rare, have been reported in the literature[5],[6],[7],[8],[9],[10] [Table I]. In all these cases the patients were young adults and large cerebral or precerebral arteries were involved. Arterial occlusive events associated with intracardiac thrombosis have also been reported.[11] Thrombotic events in patients with AT III deficiency are sometimes precipitated by other factors like surgery, trauma, pregnancy, oral contraceptive use, or infection.

Acquired AT III deficiency can result from an increased consumption of this protein resulting from the generation of pathologic levels of serine proteases as happens in disseminated intravascular coagulation, extensive deep vein thrombosis, massive pulmonary embolization and diffuse small and large venous and arterial thrombo-occlusive events. Loss of AT III from the intravascular compartment as may happen in some renal diseases and increased protein catabolism are the other conditions where deficiency of AT III can occur. Oestrogens may reduce AT III levels by about 15% and greater reductions are correlated with higher doses of oestrogens. This may be due to a specific binding between oestrogens and this protein.

Haemostatic abnormalities due to deficiency of plasma AT III may be associated with unexplained strokes in young patients. Hence it is worthwhile investigating the presence of AT III deficiency, while evaluating this group of patients. However, further studies on a larger patient group are required to find out the prevalence of this defect in young patients with stroke, where no other causative factor is detectable.
 

 

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