T h e n e w e ng l a n d j o u r na l o f m e dic i n e

C or r e sp ondence

Venous Thrombosis during Spaceflight
To the Editor: Approximately 2 months into an
International Space Station mission, obstructive
left internal jugular venous thrombosis was suspected in an astronaut during an ultrasoundexamination that was performed as part of avascular research study. The astronaut reported
no headache or worsening of the facial plethorathat is common in conditions of weightlessness.
The astronaut had no personal or family historyof venous thromboembolism. The physical examination revealed a prominent ipsilateral external
jugular vein. Follow-up ultrasound examination
performed by the astronaut, guided in real-timeand interpreted by two radiologists on Earth,confirmed the presence of venous thrombosis
with subacute characteristics (Fig. S1A in the
Supplementary Appendix, available with the fulltext of this letter at NEJM.org); the contralateralinternal jugular vein and the bilateral subclavian,axillary, popliteal, and femoral veins were unremarkable.
Multispecialty discussions ensued, weighing
the unknown risks of thrombus embolism andretrograde extension into the sinus and cerebral
veins against those of anticoagulation. Twenty
vials containing 300 mg of enoxaparin each wereavailable in the pharmacy of the space station,
but no anticoagulation-reversal agent was available. Treatment with enoxaparin at a dose of
1.5 mg per kilogram of body weight once daily
was started; the dose was reduced to 1 mg perkilogram once daily after 33 days to extend
therapy until oral apixaban could be delivered tothe space station with a supply spacecraft. Prota­
mine and prothrombin complex concentrate werealso sent to the space station. Transition to
apixaban at a dose of 5 mg twice daily occurred
42 days after the diagnosis of venous thrombo-n engl j med 382;1

sis, and the dose was reduced to 2.5 mg twice
daily 3 months after diagnosis.
Sonographic surveillance at 7-to-21-day intervals showed progressive organization and volume
reduction of the thrombus (Fig. S1B and S1C).
Flow through the affected internal jugular segment was first noted on treatment day 47, but
only on augmentation by Müller maneuver (inwhich after a forced expiration, inspiration isattempted with a closed mouth and nose — i.e.,
the reverse of a Valsalva maneuver) (Fig. S1D andS1E); spontaneous flow was still absent after 90
days of anticoagulation. Apixaban treatment wasstopped 4 days before the return to Earth. On
landing, a point-of-care ultrasound examination
revealed spontaneous flow in the supine position with residual thrombus flattened to thevessel walls (Fig. S1F), a finding consistent withimages taken on the space station during theMüller maneuver; further anticoagulation wasdeemed unnecessary. Follow-up examinations
revealed a small volume of residual thrombus 24
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January 2, 2020

The New England Journal of Medicine
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89T h e n e w e ng l a n d j o u r na l o f m e dic i n e

LaunchLanding
Approximately 6-mo mission in weightless environment

Enoxaparin, once daily
1.5 mg/kg

Ultrasound1 2
Examination
Treatment Day
Thrombosis
suspected
on researchultrasoundexamination

34

1
Thrombosis Treatment
diagnosed
startedafter clinical <24 hr after
ultrasounddiagnosis
examination

1.0 mg/kg

56733

On EarthApixaban, twice daily5.0 mg

82.5 mg91043

90

Apixabandeliveredto the spacestation

Decisionmade tocontinue
therapybeyond90 days1112 13

Anticoag- Spontaneousulation
flow shown
stopped on landing;
4 daysno further
beforetreatment
landing
necessary

Figure 1. Timeline of Diagnosis and Treatment of Venous Thrombosis.

hours after landing and no thrombus 10 days
after landing. A subsequent thrombophilia workup was unremarkable. On follow-up 6 months
after the return to Earth, the astronaut continued to be asymptomatic. A summary timeline isshown in Figure 1.
Internal jugular venous thrombosis on Earth istypically associated with cancer, a central venous
catheter, or ovarian hyperstimulation; unprovoked isolated venous thrombosis of the internal jugular vein is uncommon.1-3 This case ofvenous thromboembolism in spaceflight highlights unique complexities of space medicine,such as the need for non–evidence-based clinicaldecision making; the need for patient-performed,
radiologist-guided telemedicine ultrasonography;
and a limited pharmacy in which long-term anticoagulation is not supported, syringes are alimited commodity, and drawing liquids fromvials is a significant challenge because of surface-tension effects. Medical decisions in this casewere implemented through concerted efforts
across multiple space agencies to overcome thenumerous logistic and operational challenges.
In addition, the observed blood-flow anomalies reveal gaps in our understanding of circulatory and hemostatic physiology.4 Although cervicocranial venous overcapacity is a known effectof spaceflight, the resultant changes in floworganization, local whole-blood viscosity, andprothrombotic risk need exploration. Active
astronaut surveillance and experimental models

90n engl j med 382;1

are critical to the development of prevention andmanagement strategies for venous thromboembolism in weightlessness, especially with futureplans for prolonged space travel to the Moonand Mars.
Serena M. Auñón-Chancellor, M.D., M.P.H.
Louisiana State University Health Science Center
Baton Rouge Campus
Baton Rouge, LAsaunon@lsuhsc.edu

James M. Pattarini, M.D., M.P.H.
National Aeronautics and Space Administration Johnson
Space Center
Houston, TX

Stephan Moll, M.D.
University of North Carolina School of Medicine
Chapel Hill, NC

Ashot Sargsyan, M.D.
KBR
Houston, TX
Disclosure forms provided by the authors are available atNEJM.org.
1. Gbaguidi X, Janvresse A, Benichou J, Cailleux N, Levesque H,Marie I. Internal jugular vein thrombosis: outcome and risk factors. QJM 2011;104:209-19.
2. Ascher E, Salles-Cunha S, Hingorani A. Morbidity and mortality associated with internal jugular vein thromboses. Vasc
Endovascular Surg 2005;39:335-9.
3. Sheikh MA, Topoulos AP, Deitcher SR. Isolated internal
jugular vein thrombosis: risk factors and natural history. VascMed 2002;7:177-9.
4. Marshall-Goebel K, Laurie SS, Alferova IV, et al. Assessmentof jugular venous blood flow stasis and thrombosis during
spaceflight. JAMA Netw Open 2019;2(11):e1915011.
DOI: 10.1056/NEJMc1905875

nejm.org

January 2, 2020

The New England Journal of Medicine
Downloaded from nejm.org at STEPHEN F AUSTIN ST UNIV on January 1, 2020. For personal use only. No other uses without permission.
Copyright © 2020 Massachusetts Medical Society. All rights reserved.