The Hazardous Headache of
Nephrotic Syndrome
Amy Dickey, MD
Resident, Department of Internal Medicine
Priyanka Duggal MD
Attending, Department of Internal Medicine
University of Washington, Seattle, WA
The Case
 A 20yo female presented to the hospital with
a severe headache. It is a bilateral frontal,
throbbing headache, associated with emesis,
photophobia, and fatigue.
 Three months earlier, she was diagnosed with
minimal change disease by renal biopsy. Her
initial symptoms of lower extremity edema
and decreased exercise tolerance improved
with immunosuppressive therapy; however,
she was then started on a steroid taper. Two
weeks prior to presentation, she noticed
increased edema and breathlessness with
exercise.
Prior History
• Past medical history: minimal change disease, onset
approximately 4 months prior, diagnosed by renal biopsy
• Medications:
– prednisone 20mg po qday,
– lasix 40mg po tid
– KCL 20meq po qday
• Family medical history:
–
–
–
–
Great grandfather – Wegener’s granulomatosis
Grandmother – migraine headache
Father – hypothyroidism
Mother – migraine headache
• Social:
– No history of alcohol, tobacco, or drug use
– Currently a college business student
– Previously ran triathlons
Physical Exam
• T 36.5 HR 55 BP 116/66 R 18 O2 sat 98%
• CONSTITUTIONAL/GENERAL APPEARANCE: tired appearing female
• MENTAL STATUS/NEURO: alert and oriented x4, CN II-XII intact,
PERRL, strength 5/5 symmetric throughout, reflexes 2+ throughout
• EYES: PERRL, significant peri-orbital edema
• NECK: trachea midline, edema of neck and jaw
• RESPIRATORY: clear to auscultation bilaterally
• CARDIOVASCULAR: normal rate, regular rhythm, no murmurs
• ABDOMEN/GI: soft, slight tenderness in epigastric region, no
rebound
• MUSCULOSKELETAL: no joint swelling, ROM preserved, trace LE
edema
• SKIN: no rashes
Initial Laboratory Data
23
286
22.28
52
133
92
16
136
3.4
32
0.75
Lipids: Tchol 418, Trig 118, LDL 244, HDL 136
Urinalysis: 3+ blood, 3+ protein
Protein/creatinine ratio 19.7
LP – Opening pressure of 31mmHg, otherwise
normal
Non-contrast head CT – slit ventricles, otherwise
normal
1.4
20
5.4
59
0.8
27
1.0
CT Venogram – superior sagittal and
straight sinus thrombosis and …
Bilateral transverse sinus thrombosis
CT venogram venous thrombosis of the
superior sagittal sinus, bilateral transverse
sinuses, and the straight sinus.
The Anticoagulation
Obstacle
•
•
•
•
Baseline PTT 27. Started heparin drip at 6pm.
430am – PTT 36
1030am – PTT 36
130pm – anti-Xa heparin activity assay 0.05
(therapeutic range 0.5-0.7)
• 6pm – anti-Xa activity 0.55 – therapeutic!
• An initial therapeutic heparin drip rate was
1700U/hr. Several days later, this was decreased
to 1200U/hr. At that time, her proteinuria had
resolved on high dose steroids.
A Happy Ending!
• A complete work-up for other predisposing
factors contributing to thrombosis was
negative
• Duplex scans of renal arteries, veins and
vessels of the legs and arms all negative
• MRI of the brain negative for infarction
• Her headache resolved, and she was
discharged on subcutaneous enoxaparin with
no residual neurological deficits.
Nephrotic Syndrome and
Venous Thrombosis
• In adults with nephrotic syndrome, there is an absolute
risk of venous thromboembolism at 1.02% per year.
• Risk of VTE is especially great in the first 6 months,
approximately 9.85%!
• With nephrotic syndrome there is increased
prothrombotic factors (fibrinogen, factor VII, platelet
adhesions), decreased antithrombotic factors
(antithrombin, protein C and S levels)
• Heparin complexes with antithrombin, increasing its
inactivation of factors II and X.
• In nephrotic syndrome, lower circulating antithrombin,
results in decreased responsiveness to heparin
References
• Glassock R. Prophylactic Anticoagulation in Nephrotic
Syndrome: A Clinical Conundrum. Circulation 2008;
117:224-30
• Mahmoodi B, et al. High Absolute Risk and Predictors
of Venous and Arterial Thromboembolic Events in
Patients with Nephrotic Syndrome. J Am Soc Nephrol
2007; 18:2221-2225
• Sung S, et al. Central Venous Thrombosis In Patients
with Nephrotic Syndrome: Case Reports. The Journal of
Vascular Diseases 1999; 50: 427-432
Thank you!
Annual Incidence of Types of
Thromboembolism Among Patients
with Nephrotic Syndrome
The incidence of
cerebral venous
thrombosis in adults
with nephrotic
syndrome is extremely
low and has not been
quantified.
Nephrotic Syndrome and AntiCoagulation
• Other contributors – volume depletion,
diuretic or steroid therapy, venous stasis,
immobilization, activation of the clotting
cascade
• In nephrotic syndrome, LWMH preferred over
warfarin because of unreliable kinetic in
patient with hypoalbuminemia