Antiphospholipid Syndrome: The Risk of Travel at High Altitudes

Additional studies have demonstrated an independent, increased risk of thrombosis with prolonged (longer than four hours) air, bus, car or train travel described by some to be equivalent to the risk of thrombosis with oral contraceptives.^6-10 Further analysis of risk factors demonstrates the need to address the role of comorbidities, such as diabetes, coronary artery disease and hyperlipidemia, in having a greater risk of sudden cardiac death at higher altitudes.¹¹

Despite published literature demonstrating the specific association between hypoxia and VTE, contrasting results have also been described.^4,12-16 In a crossover study mimicking air pressure in a flight cabin by evaluating changes in hemostatic markers in individuals exposed to a hypobaric chamber for eight hours compared with normobaric normoxia, William D Toff, MD, and colleagues could not find a difference in the clotting risk between the study groups.¹⁷

The continued debate over whether thrombosis prevention is indicated in prolonged travel in the general population is based on a known incidence of VTE of one per 1,000 individuals per year and the absolute risk of thrombosis in air travel of one per 6,500 passengers.¹⁸ This—combined with the limited evidence for the utility of compression stockings and exercise, as well as the independent risk of bleeding with medicinal prophylaxis—offsets the value of thromboprophylaxis in the general low-risk population. However, such recommendations applied to individuals predisposed to clotting at baseline may be worthy of consideration.

In addition to being exposed to low atmospheric oxygen, those traveling in planes also sit for prolonged periods of time without actively moving their legs, another known risk factor for the development of a DVT. A cross-sectional comparison of incident VTE was reported in individuals exposed to seated immobility at work compared with those exposed to long-haul flights greater than eight hours in duration.¹⁹ Of 61 patients with VTE who completed the questionnaire, 21 patients reported seated immobility at work (defined as sitting for at least eight hours in one day and at least three hours consistently without standing). One of these 21 patients was subsequently diagnosed with APS and seven others with the factor V Leiden mutation, factor VIII deficiency, or prothrombin gene mutation. The criteria of the number of hours of seated immobility were chosen as such because risks of VTE begin to increase at flight duration greater than four hours, peaking beyond eight hours.²⁰

Antiphospholipid Syndrome

APS is characterized by antibody formation against phospholipids or phospholipid-bound protein cofactors in the blood. Through a series of events, antiphos­pholipid antibodies increase the risk of arterial and venous thrombosis that typically require lifelong anticoagulation. Although recommendations for anti­coagulant thromboprophylaxis have been made, no formal guidelines are set. The Sapporo classification criteria for APS implicate the diagnosis if one clinical criterion (vascular thrombosis or pregnancy morbidity) and one laboratory criterion (anti-cardiolipin antibody, anti-β2 glycoprotein-I antibody or lupus anticoagulant) are met (see Table 1).^21,22