|Year : 2021 | Volume
| Issue : 3 | Page : 274-276
Homocysteinemia-induced upper-extremity deep-vein thrombosis: A sinister at high altitude
Saurabh Sud1, Yogesh Kumar2, Saurabh Bhardwaj3, Deepak Dwivedi4
1 Department of Anaesthesia and Critical Care, Siachen Military Hospital, Ladakh, India
2 Department of Medicine, Siachen Military Hospital, Ladakh, India
3 Department of Aviation Medicine, Siachen Military Hospital, Ladakh, India
4 Department of Anaesthesia and Critical Care, Armed Forces Medical College, Pune, Maharashtra, India
|Date of Submission||02-Aug-2020|
|Date of Decision||07-Aug-2020|
|Date of Acceptance||01-Sep-2020|
|Date of Web Publication||6-Jul-2021|
Department of Anaesthesia and Critical Care, Siachen Military Hospital, Ladakh
Source of Support: None, Conflict of Interest: None
Hyperhomocysteinemia is a rare condition which predisposes to arterial and venous thrombosis. Plasma homocysteine levels are influenced by many genetic factors and environmental factors. Increased levels of homocysteine at high-altitude areas (HAA) can predispose to upper-extremity deep-vein thrombosis (UEDVT). Therefore, awareness by the medical authorities regarding this entity at HAA as a sole cause of UEDVT needs to be established. Prompt reduction in the homocysteine level can be therapeutic as well as prophylactic in preventing the morbidity.
Keywords: Altitude, anticoagulant, folate, homocysteinemia, thrombolysis, upper-extremity deep-vein thrombosis
|How to cite this article:|
Sud S, Kumar Y, Bhardwaj S, Dwivedi D. Homocysteinemia-induced upper-extremity deep-vein thrombosis: A sinister at high altitude. Indian J Vasc Endovasc Surg 2021;8:274-6
|How to cite this URL:|
Sud S, Kumar Y, Bhardwaj S, Dwivedi D. Homocysteinemia-induced upper-extremity deep-vein thrombosis: A sinister at high altitude. Indian J Vasc Endovasc Surg [serial online] 2021 [cited 2021 Jul 25];8:274-6. Available from: https://www.indjvascsurg.org/text.asp?2021/8/3/274/320609
| Introduction|| |
Upper-extremity deep-venous thrombosis (UEDVT) involves the thrombosis of one or more deep-venous segments, with subclavian (18%–67%) being the most common followed by axillary (5%–25%), brachial (4%–11%), the percentages have been mentioned as per the reference article 1, 1.5% has been added for the internal jugular internal jugular, brachiocephalic, radial, and ulnar veins. UEDVT forms only 10% of all deep-vein thrombosis (DVT) and has an annual incidence of 0.4–1 case per 10,000 people. UEDVT is classified as primary (25%–33%) and secondary (67%–75%). Causes of primary UEDVT are Paget–Schroetter syndrome and thoracic outlet syndrome and can be idiopathic, whereas secondary UEDVT is due to endogenous or exogenous causes. Endogenous causes include coagulation abnormalities such as protein C and protein S deficiencies, antithrombin, hyperhomocysteinemia, antiphospholipid antibody syndrome, and factor V Leiden gene mutation. Exogenous risk factors include central venous catheters (93%), malignancy (40%), cardiac pacemakers, intracardiac defibrillators, previous or concurrent lower-extremity deep-vein thrombosis, pregnancy, oral contraceptives, old age, immobilization, and high altitude (HA). Swelling (80%) and pain (40%) are the most common symptoms of UEDVT at presentation. Postthrombotic syndrome (7%–46%) is the most significant complication of UEDVT followed by recurrent DVT and pulmonary embolism. Increased homocysteine levels of >22 μmol/L are associated with four times increase in the incidence of DVT.
| Case Report|| |
We present the case of a 42-year-old male (body mass index 24.6 kg/m2) who developed UEDVT involving the right internal jugular, axillary, and subclavian veins due to intermediate hyperhomocysteinemia. The patient was staying at 13,000 feet for the last 86 days when he developed an insidious, gradually progressive, nonpainful swelling on the right side of the neck which progressed from the neck to the whole right arm within a week. There was no significant contributory history except prolonged stay at HA. The common differential diagnosis of swelling in the upper limb such as contusions, superficial phlebitis, hematoma, lymphatic edema, muscle tears, and venous compression were ruled out. Vitals and systemic examination were within normal limits. Local examination revealed a nontender firm swelling, free from the skin, over the right side of the neck along the course of the internal jugular vein (IJV) extending up to the entire right upper limb. The mid-arm circumference of the right arm was 18 cm, whereas that of the left arm was only 10 cm [Figure 1]. There was no erythema, warmth, and tenderness over the swelling. Routine blood investigations and detailed procoagulant workup showed elevated levels of homocysteine, D-dimer, and fibrin degradation products and deranged prothrombin time/international normalized ratio. Venous duplex ultrasound showed noncompressible right IJV [Figure 2], axillary, and subclavian veins with the presence of thrombus throughout the length with no flow on color Doppler and computed tomography scan neck. The patient was treated with full anticoagulation, subcutaneous low-molecular-weight heparin, and oral warfarin for 3 months. Repeat Doppler ultrasound after 3 months showed complete resolution of the thrombosis and flow of blood.
|Figure 2: Thrombosed right internal jugular vein on ultrasound in both short-axis and long-axis views|
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| Discussion|| |
Homocysteine is a sulfur-containing, nonessential amino acid formed during the metabolism of methionine, by two metabolic pathways (remethylation and trans sulfuration), which are dependent on vitamins (folate, Vitamin B12, and Vitamin B6) as cofactors or cosubstrates. Homocysteine blood levels in humans are normally <15 mmol/L and levels >15 mmol/L is hyperhomocysteinemia. Hyperhomocysteinemia occurs due to various genetic and acquired causes. The genetic causes include deficiency of the enzyme cystathione ß-synthase, inborn errors of folate and cobalamine metabolism, absorption, and transportation. Acquired causes include deficiencies of folate, Vitamin B6, and Vitamin B12. Other causes include chronic renal failure, renal dysfunction, proliferative disorders, hypothyroidism, pernicious anemia, rheumatoid arthritis, drugs (sex hormones, insulin, antiepileptic drugs, lipid-lowering drugs, and metformin), increasing age, male gender, alcohol consumption, and smoking. Hyperhomocysteinemia leads to coronary artery disease, myocardial infarction, stroke, peripheral artery disease, arterial and venous thrombosis, neuropsychiatric diseases, neural tube defects, and placental vasculopathy.
Kang et al. classified hyperhomocysteinemia on the basis of blood fasting levels of homocysteine into moderate (15–30 mmol/L), intermediate (30–100 mmol/L), and severe (100 mmol/L). Homocysteinemia causes DVT by free radical oxidative damage of vascular endothelium, leading to endothelial dysfunction and decreased nitric oxide production. Other mechanisms involved are increased fibrinolysis, activation of clotting cascade, and increased platelet aggregation. Our patient had intermediate hyperhomocysteinemia (43 mmol/L) without any genetic or acquired causes. The treatment provided by us was as per the guidelines issued by the American College of Chest Physicians for the treatment of UEDVT. These guidelines recommend anticoagulant therapy over thrombolysis as primary treatment. Thrombolysis is only recommended for patients with severe symptoms, whereas our patient had only mild symptoms. The treating physicians at HA areas should have a high degree of suspicion for hyperhomocysteinemia in patients presenting with UEDVT, as even an increase of homocysteine levels by 5 mmol/L can cause 27% increased incidence of thromboembolism.
To conclude, it is imperative on the part of medical authorities to spread awareness regarding the presence of hyperhomocysteinemia in HA, and it should be kept as one of the differential diagnoses while managing UEDVT. They should also aim for meticulous management of hyperhomocysteinemia by rapid reduction in homocysteine levels, as even a decrease of 0.8 mmol/L can lead to decrease in the risk of myocardial infarction by 16%, stroke by 24%, and venous thrombosis by 25%. The treatment of hyperhomocysteinemia is simple and effective as shown by Naurath et al., demonstrating a reduction of 49.5% in the mean homocysteine level with high-dose multivitamins (folate, Vitamin B6, and Vitamin B12).
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Mustafa J, Asher I, Sthoeger Z. Upper extremity deep vein thrombosis: Symptoms, diagnosis, and treatment. Isr Med Assoc J 2018;20:53-7.
Kucher N. Clinical practice. Deep-vein thrombosis of the upper extremities. N Engl J Med 2011;364:861-9.
Hollberg J. What is the best approach to treat an upper-extremity DVT? Hospitalist 2011;10:1-9.
Sule AA, Chin TJ, Khien LH. Recurrent unprovoked venous thromboembolism in a young female patient with high levels of homocysteine. Int J Angiol 2012;21:95-7.
Ekim M, Ekim H, Yilmaz YK, Kulah B, Polat MF, Gocmen AY. Study on relationships among deep vein thrombosis, homocysteine & related B group vitamins. Pak J Med Sci 2015;31:398-402.
Eldibany MM, Caprini JA. Hyperhomocysteinemia and thrombosis: An overview. Arch Pathol Lab Med 2007;131:872-85.
Kang SS, Wong PW, Malinow MR. Hyperhomocysteinemia as a risk factor for occlusive vascular disease. Annu Rev Nutr 1992;12:279-98.
Undas A, Brozek J, Szczeklik A. Homocysteine and thrombosis: From basic science to clinical evidence. Thromb Haemost 2005;94:907-15.
Naurath HJ, Joosten E, Riezler R, Stabler SP, Allen RH, Lindenbaum J. Effects of Vitamin B12, folate, and Vitamin B6 supplements in elderly people with normal serum vitamin concentrations. Lancet 1995;346:85-9.
[Figure 1], [Figure 2]