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Year : 2014  |  Volume : 1  |  Issue : 1  |  Page : 20-23

A Brief Review of High Altitude Thrombosis

1 Department of Vascular Surgery, King's College Hospital, London, United Kingdom
2 Department of Vascular Surgery, Army Hospital (R and R), New Delhi, India
3 Department of Vascular Surgery, Paras Hospital, Gurgaon, Haryana, India
4 Department of Vascular Surgery, Sir Ganga Ram Hospital, New Delhi, India

Date of Web Publication9-Oct-2014

Correspondence Address:
RPS Gambhir
King's College Hospital, London
United Kingdom
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0972-0820.142362

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Spontaneous vascular thrombosis may occur after a short climb or prolonged stay at high altitude (HA). Both venous and arterial thrombosis has been reported in the literature and cause significant morbidity and mortality. Diagnosis is often difficult; treatment delayed and postthrombotic sequelae disabling. Experimental evidence is limited and trials to prove thrombogenecity of HA are technically challenging to conduct. A greater understanding and awareness of its varied presentations and management is required by all those engaged in treating such patients.

Keywords: High altitude, hypercoagulability, hypoxia, thrombosis

How to cite this article:
Gambhir R, Anand V, Khatana SS, Bedi V S. A Brief Review of High Altitude Thrombosis. Indian J Vasc Endovasc Surg 2014;1:20-3

How to cite this URL:
Gambhir R, Anand V, Khatana SS, Bedi V S. A Brief Review of High Altitude Thrombosis. Indian J Vasc Endovasc Surg [serial online] 2014 [cited 2022 Dec 6];1:20-3. Available from:

  Introduction Top

Medical complications of climbs to high altitude (HA), such as acute and chronic mountain sickness, HA pulmonary edema, and HA cerebral edema have been well-reported and extensively studied. [1] Vascular thrombosis at HA is, however, not as well-understood. Hemoconcentration and hypercoagulability are major risk factors for thrombosis, and it has been suggested that hypoxia at HA activates a pro-coagulant state. [2]

A 30 times higher risk of spontaneous vascular thrombosis was reported among young male soldiers following mean stay of over 10 months at altitudes from 3000 m to 6500 m (extreme HA). Manifestations varied from deep vein thrombosis& (DVT) and pulmonary thrombo-embolism (PE) to stroke, mesenteric, splenic, portal vein thrombosis, retinal artery, and peripheral arterial thrombosis. [3] Even a shorter stay was associated with thrombotic occlusive hypertensive vascular disease. [4] The literature contains other reports describing cerebral sinus thrombosis and stroke during high-altitude climbing and training. [5],[6] Both arterial and venous thrombosis has been reported. [7],[8]

  Pathophysiology Top

Garvey et al. demonstrated that erythrocytosis in the setting of a hypobaric environment provoked procoagulability in rhesus monkey model. [9] Autopsy findings of thrombi in the pulmonary vasculature of climbers who had died of HA pulmonary edema led to the notion that hypoxia may be thrombogenic. Hypoxia stimulates production of erythropoietin by the juxtaglomerular apparatus of the kidney; hematocrit and hemoglobin levels increase exponentially with altitude, and may rise up to 20 g/dl, resulting in polycythemia, which is an independent risk factor for thrombosis. [10],[11] Jha et al. noted that 75% of their patients with stroke at HA had Hb ranging from 16.2 to 22 g/dl. [12]

Thrombosis has a multifactorial etiology. Several acquired and genetic risk factors are usually present simultaneously and interact with environmental and behavioral risk factors. [13] A number of hematological changes has been noted by various researchers on ascent to HA, or on simulation in hypobaric chambers, results varying with the duration of stay. [14],[15],[16] An initial transient hypercoagulability has been reported which settles down after a week. However, in individuals who stay for long a late hypercoagulability develops, which peaks at 5 months and persists for as long as the individual stays at HA. [7],[14]

Another important factor responsible for HA hypercoagulability is platelet dysfunction. Platelet counts are higher as is platelet adhesion, the rise in platelet counts is not thrombopoetin mediated. [17],[18] Increased release of thromboxane from platelets, endothelial cell damage, and activation of clotting cascade has also been reported due to hypoxic stress at HA. [19] In an elaborate prospective cohort study on 38 healthy lowlanders staying at HA for 8 months, Kotwal et al., found an increased platelet count, hematocrit, platelet activation factors, plasminogen activator inhibitor-I, and fibrinogen levels to account for the prothrombotic state. [20]

When an individual has a procoagulation disorder (such as protein C deficiency, fibrinolytic enzyme deficiency, or antiphospholipid antibody syndrome) thrombosis can develop even at a moderate altitude. [21]

There is now experimental evidence in mice that HA hypoxia promotes DVT. [22] Tyagi et al. using proteomic analysis of platelets and in vivo models of thrombosis have demonstrated that enhanced calpain activity, regulated by CAPNS1, significantly contributes to platelet reactivity and thrombosis under hypoxic conditions. These observations from animal models were supported by human data showing increased calpain activity and elevation in markers of platelet activation in the plasma of patients who developed DVT at HA. [23]

  Clinical Presentations Top

Manifestations of HA thrombosis are variable. Venous manifestations are more common than cereberovascular, arterial and retinal thrombosis, but all cause significant morbidity and mortality.

  Venous Top

Deep vein thrombosis is the most commonly reported vascular complication of HA stay. [2],[7],[24] Kumar noted a 24.5 times relative risk of developing DVT in HA. [7] He also described a higher incidence of PE in those staying longer and at higher altitudes, but the numbers were small. Clinical and radiological picture is no different from non HA DVT, though a greater delay in resolution of symptoms has been noted by the authors. Upper limb involvement with Axillary vein thrombosis is as often reported and may not be an effort induced thrombosis. Superficial thrombophlebitis is also frequently encountered, but it is often self-limiting.

Mesenteric or porto-systemic thrombosis involving the superior mesenteric, inferior mesenteric, splenic and portal vein thrombosis though rare can be very challenging to diagnose preoperatively. Presentation may vary from poorly localized abdominal pain, distension, and fever to vomiting and gastrointestinal bleeding. Clinical signs are nonspecific and may include diffuse tenderness, ascites, splenomegaly, and hepatomegaly. [25] At times, the diagnosis is made following an exploratory laparotomy for peritonism and the common finding is of gut infarction with vascular thrombosis.

Neurological symptoms due to cerebral sinus thrombosis depend on the vessels involved and the chronicity of development. Hemorrhagic infarction can occur secondary to cortical venous thrombosis Symptoms are more often subtle than catastrophic; a slow progression of symptoms over days is characteristic. Symptoms vary and may include throbbing frontal headaches made worse on bending forwards, gait disturbance, speech disturbance, dysequilibrium, articulation disorders, paresthesia, visual field narrowing, and coordination disorders. [5],[6],[26],[27]

  Arterial Top

Arterial thrombosis usually presents with acute limb ischemia, lower limb involvement being more common than the upper limb. [8],[28] Amputation rate is high as timely evacuation is often difficult. Risk of developing compartment syndrome remains high. Occasionally thrombotic aortic occlusion, classically juxtarenal leads to both the lower limbs being affected with disastrous consequences. Mesenteric artery thrombosis with small bowel gangrene carries a high mortality.

Another often unreported entity is the hypoxic damage to the muscles during prolonged treks/climbs in HA. These patients often manifest with hard fibrotic mass in the muscle belly of the calf muscle which usually resolves over 6 months. It could represent a form of chronic compartment syndrome.

Cerebral artery thrombosis leading to stroke has been reported in climbers and troops at HA. [3] However, there is no evidence of increased risk of strokes in population living permanently at moderate altitudes. [10],[29],[30]

It is not just the native vessels, but also stents, which may thrombose in HA. Stent thrombosis of a drug-eluting coronary stent at HA has been recently reported. [31]

  Investigations Top

Any thrombotic episode needs to be investigated thoroughly. For all accessible peripheral and extracranial vessels color Doppler examination remains the first line of radiological confirmation of thrombotic occlusion. In the abdomen, Doppler assessment of porto-systemic circulation will pick up collaterals as well as detect the direction of flow. Computed tomography or magnetic resonance angiography is essential for cerebral and pulmonary vasculature, and provides additional information for abdominal vasculature. Brain magnetic resonance imaging will reveal ischemic changes and occluded cerebral sinuses. Diagnostic digital subtraction angiography is rarely required.

Suggested full hematological workup in these cases includes hemoglobin, packed cell volume, prothrombin time, activated partial thromboplastin time. Fibrinogen, d-Dimers, lipid profile, homocysteine levels, antiphospholipid antibodies, lupus anticoagulants, anticardiolipin antibodies, coagulation factors (II, V, VIII, IX, X), protein C, protein S, antithrombin, factor V Leiden mutation, plasminogen activator inhibitor-I, platelet activation factors. [32],[33],[34],[35]

In view of recent evidence for enhanced calpain activity, in the future, a simple bioanalytic assay of "calpain" could be developed as an early diagnosis test for HA induced vascular thrombosis. [23]

It should be noted that the percentage of samples, which are positive for prothrombotic work up, is less than 20% in most reports for HA vascular thrombosis. [12],[25],[35] These tests have limited immediate applicability and should be done after 3-6 months. At times, the initial coagulation screen has been positive but a repeat after stopping anticoagulation after 6 months is negative. This may support the concept of reversible procoagulability in HA, which reverts to normal after stay at lower altitude. It is important that individuals diagnosed to have a pro-coagulant state do not go back to those extreme altitudes.

  Management Top

Anticoagulant therapy is initiated as soon as there is clinical suspicion and is continued after radiological confirmation of thrombosis. The patient is converted to oral anticoagulation once it is clear that no immediate surgical intervention is required. Oral anticoagulation is continued for at least 6 months, with strict INR control.

Low-molecular-weight dextran infusion to reduce the blood viscosity has been used by some in an acute setting, but its role remains equivocal and the benefit if any is little. It has been used in both cerebral sinus thrombosis and mesenteric vein thrombosis. [5]

Immediate treatment of cerebral thrombosis aims at correcting dehydration, anticoagulation, reducing intracranial pressure with osmotic diuretics, steroids, oxygen, and surgical craniotomy when indicated. [5] In the chronic phase, treatment of these patients is directed mainly toward rehabilitation and excluding an underlying prothrombotic state.

Arterial thrombosis requires surgical thrombo-embolectomy at the earliest to restore the flow. It is important to monitor for compartment syndrome and do a four-compartment fasciotomy in the leg whenever there is a clinical suspicion. All patients will require anticoagulation for 6 months. Those patients with extensive ilio-femoral DVT and leg swelling may benefit with thrombolysis and suction thrombo-embolectomy if they can be evacuated to a tertiary center immediately.

Most cases of DVT are managed by anticoagulation, though thrombolysis has a definite role if it can be done within 2-3 weeks. Some of these patients later go on to develop chronic venous hypertension with a 20% reported incidence of postthrombotic syndrome. [32] Thrombophlebitis normally is self-limiting, and these patients have traditionally been managed without anticoagulation, though recent guidelines recommend otherwise. [36]

Managing mesenteric vein thrombosis remains a challenging problem and may require gut resection. Results of mesenteric vessel thrombolysis or surgical thrombo-embolectomy are quite poor as often the diagnosis itself is made on exploratory laparotomy.

All individuals who are found to have a pro-coagulant state may require longer duration or even lifelong anticoagulation in some cases. They are best assessed and managed by a hematologist.

With the recent research focused on the enhanced calpain activity, regulated by CAPNS1, in the future, if we may develop drugs aimed at specifically preventing or treating HA thrombotic disorders. [37]

  Prevention Top

The cardinal principle for the prevention of HA illnesses is not to go too high too fast. It is important to avoid dehydration, immobility, cold, and constrictive clothing. There is no specific preventive strategy for vascular thrombosis though some authors advocate prophylactic antiplatelet agents, acetazolamide, or homocysteine-lowering vitamins in HA climbs. [33],[38],[39]

Patients with known or suspected cerebro-vascular problems such as transient ischaemic attack's, previous strokes or carotid artery stenosis, patients with bleeding or clotting problems, inherited risk factors, and patients on anticoagulation therapy for any reason should probably be advised against altitude travel and those on oral contraceptive pills should be cautioned about the risks.

  Conclusion Top

Thrombosis at HA is a reality and not a myth. It can affect the recreational climber as well be an occupational hazard for those deployed there. With its varied manifestations and lack of onsite investigative facilities, early recognition and prompt evacuation to an appropriate center can save life and limb.

  References Top

1.Wilson MH, Newman S, Imray CH. The cerebral effects of ascent to high altitudes. Lancet Neurol 2009;8:175-91.  Back to cited text no. 1
2.Bärtsch P. How thrombogenic is hypoxia? JAMA 2006;295:2297-9.  Back to cited text no. 2
3.Anand AC, Jha SK, Saha A, Sharma V, Adya CM. Thrombosis as a complication of extended stay at high altitude. Natl Med J India 2001;14:197-201.  Back to cited text no. 3
4.Singh I, Khanna PK, Lal M, Hoon RS, Rao BD. High-altitude pulmonary hypertension. Lancet 1965;1:146-50.  Back to cited text no. 4
5.Saito S, Tanaka SK. A case of cerebral sinus thrombosis developed during a high-altitude expedition to Gasherbrum I. Wilderness Environ Med 2003;14:226-30.  Back to cited text no. 5
6.Torgovicky R, Azaria B, Grossman A, Eliyahu U, Goldstein L. Sinus vein thrombosis following exposure to simulated high altitude. Aviat Space Environ Med 2005;76:144-6.  Back to cited text no. 6
7.Kumar S. High altitude induced deep venous thrombosis: A study of 28 cases. Indian J Surg 2006;68:84-8.  Back to cited text no. 7
8.Fagenholz PJ, Gutman JA, Murray AF, Noble VE, Wu A, Zeimer G, et al. Arterial thrombosis at high altitude resulting in loss of limb. High Alt Med Biol 2007;8:340-7.  Back to cited text no. 8
9.Garvey MB, Dennis LH, Hildebrandt PK, Conrad ME. Hypobaric erythraemia: Pathology and coagulation studies. Br J Haematol 1969;17:275-81.  Back to cited text no. 9
10.Jaillard AS, Hommel M, Mazetti P. Prevalence of stroke at high altitude (3380 m) in Cuzco, a town of Peru. A population-based study. Stroke 1995;26:562-8.  Back to cited text no. 10
11.Rao KS. Other medical illnesses aggravated by high altitude. In: Anand AC, Narula AS, Kakkar R, Kalra R, editors. Textbook of Environmental Emergencies. Pune, India: Department of Internal Medicine, Armed Forces Medical College; 2006. p. 26-9.  Back to cited text no. 11
12.Jha SK, Anand AC, Sharma V, Kumar N, Adya CM. Stroke at high altitude: Indian experience. High Alt Med Biol 2002;3:21-7.  Back to cited text no. 12
13.Rosendaal FR. Venous thrombosis: The role of genes, environment, and behavior. Hematology Am Soc Hematol Educ Program 2005:1-12.  Back to cited text no. 13
14.Singh I, Chohan IS. Blood coagulation changes at high altitude predisposing to pulmonary hypertension. Br Heart J 1972;34:611-7.  Back to cited text no. 14
15.Anand IS, Chandrashekhar Y, Rao SK, Malhotra RM, Ferrari R, Chandana J, et al. Body fluid compartments, renal blood flow, and hormones at 6,000 m in normal subjects. J Appl Physiol (1985) 1993;74:1234-9.  Back to cited text no. 15
16.Andrew M, O′Brodovich H, Sutton J. Operation Everest II: Coagulation system during prolonged decompression to 282 Torr. J Appl Physiol (1985) 1987;63:1262-7.  Back to cited text no. 16
17.Sharma SC. Platelet count and adhesiveness on induction to high altitude by air and road. Int J Biometeorol 1982;26:219-24.  Back to cited text no. 17
18.Hudson JG, Bowen AL, Navia P, Rios-Dalenz J, Pollard AJ, Williams D, et al. The effect of high altitude on platelet counts, thrombopoietin and erythropoietin levels in young Bolivian airmen visiting the Andes. Int J Biometeorol 1999;43:85-90.  Back to cited text no. 18
19.Le Roux G, Larmignat P, Marchal M, Richalet JP. Haemostasis at high altitude. Int J Sports Med 1992;13 Suppl 1:S49-51.  Back to cited text no. 19
20.Kotwal J, Apte CV, Kotwal A, Mukherjee B, Jayaram J. High altitude: A hypercoagulable state: Results of a prospective cohort study. Thromb Res 2007;120:391-7.  Back to cited text no. 20
21.Boulos P, Kouroukis C, Blake G. Superior sagittal sinus thrombosis occurring at high altitude associated with protein C deficiency. Acta Haematol 1999;102:104-6.  Back to cited text no. 21
22.Brill A, Suidan GL, Wagner DD. Hypoxia, such as encountered at high altitude, promotes deep vein thrombosis in mice. J Thromb Haemost 2013;11:1773-5.  Back to cited text no. 22
23.Tyagi T, Ahmad S, Gupta N, Sahu A, Ahmad Y, Nair V, et al. Altered expression of platelet proteins and calpain activity mediate hypoxia-induced prothrombotic phenotype. Blood 2014;123:1250-60.  Back to cited text no. 23
24.Gupta N, Ashraf MZ. Exposure to high altitude: A risk factor for venous thromboembolism? Semin Thromb Hemost 2012;38:156-63.  Back to cited text no. 24
25.Anand AC, Saha A, Seth AK, Chopra GS, Nair V, Sharma V. Symptomatic portal system thrombosis in soldiers due to extended stay at extreme altitude. J Gastroenterol Hepatol 2005;20:777-83.  Back to cited text no. 25
26.Cheng S, Chng SM, Singh R. Cerebral venous infarction during a high altitude expedition. Singapore Med J 2009;50:e306-8.  Back to cited text no. 26
27.van Veen JJ, Makris M. Altitude and coagulation activation: Does going high provoke thrombosis? Acta Haematol 2008;119:156-7.  Back to cited text no. 27
28.Rai S. Peripheral Arterial Disease in the Serving Soldier in the North Eastern sector: A Critical Analysis.(abstract) in Proceedings of 6 th International congress of Asian Vascular Society and 11 th Annual conference of Vascular society of India, November 3-6 th 2004, Bangalore, India. [Abstract number 191].  Back to cited text no. 28
29.Mahajan SK, Kashyap R, Sood BR, Jaret P, Mokta J, Kaushik NK, et al. Stroke at moderate altitude. J Assoc Physicians India 2004;52:699-702.  Back to cited text no. 29
30.Razdan S, Koul RL, Motta A, Kaul S. Cerebrovascular disease in rural Kashmir, India. Stroke 1989;20:1691-3.  Back to cited text no. 30
31.Basavarajaiah S, O′Sullivan M. Physical exertion at high altitude-another risk factor for coronary stent thrombosis? J Invasive Cardiol 2013;25:E66-8.  Back to cited text no. 31
32.Rosendaal FR. Venous thrombosis: A multicausal disease. Lancet 1999;353:1167-73.  Back to cited text no. 32
33.Kotwal J, Chopra GS, Kotwal A, Sharma YV, Bhardwaj JR. High altitude: A hyper coagulable state: Results of a prospective cohort study. Blood 2004;104:96b.  Back to cited text no. 33
34.Ashraf HM, Javed A, Ashraf S. Pulmonary embolism at high altitude and hyperhomocysteinemia. J Coll Physicians Surg Pak 2006;16:71-3.  Back to cited text no. 34
35.Gambhir RP, Gupta P, Chaudhry R. Prothrombotic work up in vascular thrombosis-are we guilty of underassessment? Br J Surg 2008;95 Supple 3:8.  Back to cited text no. 35
36.Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ, American college of chest physicians antithrombotic therapy and prevention of thrombosis panel. Executive summary: Antithrombotic therapy and prevention of thrombosis, 9 th ed: American college of chest physicians evidence-based clinical practice guidelines. Chest 2012;141:7S-47.  Back to cited text no. 36
37.Pawlinski R. Inhibit the calpain to climb the mountain. Blood 2014;123:1123-4.  Back to cited text no. 37
38.Peacock AJ. ABC of oxygen: Oxygen at high altitude. BMJ 1998;317:1063-6.  Back to cited text no. 38
39.Wright A, Brearey S, Imray C. High hopes at high altitudes: Pharmacotherapy for acute mountain sickness and high-altitude cerebral and pulmonary oedema. Expert Opin Pharmacother 2008;9:119-27.  Back to cited text no. 39

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