PAI-1 polymorphism as a cause of severe high altitude associated arteriovenous thrombosis

Abstract

We present a 34-year-old man who developed disseminated intra-arterial and venous thrombosis following exposure to extreme high altitude. On evaluation, the patient was found to have thrombosis involving the aorta, bilateral iliac arteries and middle cerebral artery. On detailed evaluation for the cause of recurrent seizures, he was also found to have cerebral venous thrombosis of the superior sagittal sinus. The patient underwent amputation of 3 limbs due to gangrene. Procoagulant work up revealed increased plasminogen activator inhibitor-1 activity with 4G/4G polymorphism. This case highlights the life-threatening and limb-threatening thrombosis secondary to a rare inherited thrombophilia on exposure to extreme high altitude.

Investigation of Plasminogen Activator Inhibitor‐1 (PAI‐1) 4G/5G promoter polymorphism in Indian venous thrombosis patients: A case‐control study

“…These data support findings of previous studies. 10,12,13 However, in the presence of inherited thrombophilia like FVL 13,14 or acquired risk factors such as high altitude 15 and obesity, 16 4G/4G genotype may contribute to the risk of CVT.…”

Frequency of hereditary prothrombotic risk factors in patients with Down Syndrome

“…PAI-1 gene 4G / 4G and 4G / 5G polymorphism types have been found to be associated with an increased risk of coronary artery disease, MI and ischemic stroke (20)(21)(22). In the stroke and MI / PAOD groups, heterozygous PAI rates were 49.3% and 38.7%, while homozygous PAI rates were 30.3% and 35.5% (14).…”

Epidemiology and pathophysiology of vascular thrombosis in acclimatized lowlanders at high altitude: A prospective longitudinal study

“… 38 PAI-1-6754G/5G and MTHFR677C/T were over-represented in ICs compared to CG, which is concordant with our group's earlier report of this association with VTE among Indian subpopulations. 39 , 40 However, in the absence of other thrombophilic defects, cardiovascular and metabolic disorders, the PAI-1-6754G/5G variant has a poor association with thrombosis in the healthy population. 41 Genes for Factor V Leiden, prothrombin, TFPI, EPCR, and ACE were found monomorphic in both CG and ICs suggestive of partial and restrained penetrance of these genetic mutation for thrombotic manifestation in Indian subpopulations.…”