1. 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

2. 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.

3. 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

4. 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

5. Initial Laboratory Data23 20 59
0.8
5.4
1.4
22.28 52
286
133
3.4 92 16 32
0.75
136
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
1.0 27

6. CT Venogram – superior sagittal and straight sinus thrombosis and …

7. Bilateral transverse sinus thrombosis
CT venogram venous thrombosis of the superior sagittal sinus, bilateral transverse sinuses, and the straight sinus.

8. 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 )
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.

9. 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.

10. 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

11. 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:
Sung S, et al. Central Venous Thrombosis In Patients with Nephrotic Syndrome: Case Reports. The Journal of Vascular Diseases 1999; 50:

12. Thank you!

14. 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.

16. Nephrotic Syndrome and Anti-Coagulation

17. 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