Year : 2014 | Volume
: 1 | Issue : 1 | Page : 20--23
A Brief Review of High Altitude Thrombosis
RPS Gambhir1, Vembu Anand2, Surinder Singh Khatana3, VS Bedi4,
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
King«SQ»s College Hospital, London
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.
|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;1:20-23
|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 2021 Jan 26 ];1:20-23
Available from: https://www.indjvascsurg.org/text.asp?2014/1/1/20/142362
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.  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. 
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.  Even a shorter stay was associated with thrombotic occlusive hypertensive vascular disease.  The literature contains other reports describing cerebral sinus thrombosis and stroke during high-altitude climbing and training. , Both arterial and venous thrombosis has been reported. ,
Garvey et al. demonstrated that erythrocytosis in the setting of a hypobaric environment provoked procoagulability in rhesus monkey model.  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. , Jha et al. noted that 75% of their patients with stroke at HA had Hb ranging from 16.2 to 22 g/dl. 
Thrombosis has a multifactorial etiology. Several acquired and genetic risk factors are usually present simultaneously and interact with environmental and behavioral risk factors.  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. ,, 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. ,
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. , Increased release of thromboxane from platelets, endothelial cell damage, and activation of clotting cascade has also been reported due to hypoxic stress at HA.  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. 
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. 
There is now experimental evidence in mice that HA hypoxia promotes DVT.  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. 
Manifestations of HA thrombosis are variable. Venous manifestations are more common than cereberovascular, arterial and retinal thrombosis, but all cause significant morbidity and mortality.
Deep vein thrombosis is the most commonly reported vascular complication of HA stay. ,, Kumar noted a 24.5 times relative risk of developing DVT in HA.  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.  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. ,,,
Arterial thrombosis usually presents with acute limb ischemia, lower limb involvement being more common than the upper limb. , 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.  However, there is no evidence of increased risk of strokes in population living permanently at moderate altitudes. ,,
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. 
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. ,,,
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. 
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. ,, 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.
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. 
Immediate treatment of cerebral thrombosis aims at correcting dehydration, anticoagulation, reducing intracranial pressure with osmotic diuretics, steroids, oxygen, and surgical craniotomy when indicated.  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.  Thrombophlebitis normally is self-limiting, and these patients have traditionally been managed without anticoagulation, though recent guidelines recommend otherwise. 
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. 
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. ,,
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.
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.
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