This document contains a summary of a noon conference presentation on hypertensive emergencies and thrombotic thrombocytopenic purpura (TTP). It includes two multiple choice questions about appropriate blood pressure reduction goals in hypertensive emergencies and the classic pentad of TTP symptoms. The document also discusses a patient case of a 28-year-old man who presented with hypertensive emergency and was later found to have IgA nephropathy on renal biopsy. It provides prognostic factors and outcomes for IgA nephropathy as well as an illness script comparing the pathophysiology, epidemiology, clinical presentation, diagnosis, and treatment of TTP versus IgA nephropathy.
2. Question 1
What is the goal rate of reduction in blood
pressure in hypertensive emergencies?
A) 5-10% in the first hour and by a further 5-10% over the next 23 hours
B) 10-20% in the first hour and by a further 5-10% over the next 23 hours
C) 15-25% in the first hour and by a further 5-10% over the next 23 hours
D) 10-20% in the first hour and by a further 10-20% over the next 23 hours
3. Question 1
What is the goal rate of reduction in blood
pressure in hypertensive emergencies?
A) 5-10% in the first hour and by a further 5-10% over the next 23 hours
B) 10-20% in the first hour and by a further 5-10% over the next 23 hours
C) 15-25% in the first hour and by a further 5-10% over the next 23 hours
D) 10-20% in the first hour and by a further 10-20% over the next 23 hours
4. Patient Case
7/1
Mr. R dx’ed with
kidney stones
Mr. R awoken
with HA/N/V, mild
confusion, unable
to go to work
7/8
7/9
Presents to VMMC
with BP 240/120,
started on nicardipine
gtt amodipine,
lisinopril, HCTZ
Mr. R– 28yo M w/ no PMHx p/w hypertensive emergency
7/10
Patient’s BP stabilizes
with multidrug therapy.
24h protein is 6g.
Nephrology consulted.
REVIEW:
In this case,
what are the
three reasons
renal biopsy is
recommended?
5. TTP?!
Our patient presented with:
- confusion, headache
- thrombocytopenia
- hemolytic anemia
- acute renal failure
(1) George JN, Nester CM. Syndromes of thrombotic microangiopathy. N Engl J Med 2014; 371:654.
(2) Laszik ZG, Kambham N, Silva FG. Thrombotic microangiopathies. In: Heptinstall's Pathology of the Kidney,
Jennett JC, D'Agati VD, Olson JL, Silva FG (Eds), Lippincott-Raven, Philadelphia 2014.
6. Question 2
Which of the following is not considered part of
the classic pentad of TTP?
A) Microangiopathic hemolytic anemia
B) Thrombocytopenia
C) Fever
D) Neurologic Abnormalities
E) Renal Failure
F) Elevated PT/PTT
7. Question 2
Which of the following is not considered part of
the classic pentad of TTP?
A) Microangiopathic hemolytic anemia
B) Thrombocytopenia
C) Fever
D) Neurologic Abnormalities
E) Renal Failure
F) Elevated PT/PTT
8. TTP?
S/Sx of TTP?
Yes
Severe
thrombocytopenia,
normotensive +/-
ADAMTS13 deficiency
Urgent plasma
exchange for suspected
TTP
Mild
thrombocytopenia,
high MAP, severe renal
dysfunction
Consider HTN induced
TMA
No Search for other
etiologies
(1) Khanal et al. Differentiating malignant hypertension-induced thrombotic microangiopathy from thrombotic
thrombocytopenic purpura. Ther Adv Hematol. 2015 Jun; 6(3): 97–102.
9. Patient Case
7/1
Mr. R dx’ed with
kidney stones
Mr. R awoken
with HA/N/V, mild
confusion, unable
to go to work
7/8
7/9
Presents to VMMC
with BP 240/120,
started on amodipine,
lisinopril, and
nicardipine gtt
Mr. R– 28yo M w/ no PMHx p/w hypertensive emergency
7/10
Patient’s BP stabilizes
with uptitration of
lisinpril. Nephrology
consulted.
Renal biopsy performed;
shows IgA deposits in
glomerular mesangium
7/12
10. Prognosis
(1) Berthoux F, Mohey H, Laurent B, Mariat C, Afiani A, Thibaudin L. Predicting the risk for dialysis or death in IgA
nephropathy. J Am Soc Nephrol. 2011;22(4):752. Epub 2011 Jan 21.
(2) Alamartine E, Sabatier JC, Guerin C, Berliet JM, Berthoux F. Prognostic factors in mesangial IgA
glomerulonephritis: an extensive study with univariate and multivariate analyses. Am J Kidney Dis.
1991;18(1):12.
• 50% slow progression to ESRD
• Prognostication factors:
• Hypertension >140/90
• Elevated creatinine
• Persistent protein excretion above 1000mg/day
• Reduction in presenting GFR
• Acute onset nephrotic syndrome
• Modifiable risk factors: obesity, hypertriglyceridemia, smoking
11. Prognosis
(1) Berthoux F, Mohey H, Laurent B, Mariat C, Afiani A, Thibaudin L. Predicting the risk for dialysis or death in IgA
nephropathy. J Am Soc Nephrol. 2011;22(4):752. Epub 2011 Jan 21.
(2) Alamartine E, Sabatier JC, Guerin C, Berliet JM, Berthoux F. Prognostic factors in mesangial IgA
glomerulonephritis: an extensive study with univariate and multivariate analyses. Am J Kidney Dis.
1991;18(1):12.
• 50% slow progression to ESRD
• Prognostication factors:
• Hypertension >140/90
• Elevated creatinine
• Persistent protein excretion above 1000mg/day
• Reduction in presenting GFR
• Acute onset nephrotic syndrome
• Modifiable risk factors: obesity, hypertriglyceridemia, smoking
Death or Dialysis
(in 20 years)
2%
(proteinuria
<1000mg/day w/
treatment)
67%
(proteinuria
>1000mg/day w/
treatment)
12. Illness Script
TTP IgA Nephropathy
Pathophysiology Deficiency of ADAMTS13 no cleavage of von
Willebrand factor ultralarge vWf multimers
accumulate on endothelial surfaces where
platelets attach and accumulate
Immunoglobulin A (IgA) nephropathy is characterized
by predominant IgA deposition in the glomerular
mesangium.
Epidemiology Median age: 41
females>males, black race
2:1 male to female ratio
MC in caucasians, asians
Time Course Acute Varies
Clinical
Presentation
Fatigue, dyspnea, petechiae/bleeding
(accompanied by severe MAHA,
thrombocytopenia). 41% with neurologic sx
40-50% - one or recurrent episodes of gross
hematuria (w/ URI), less with microscopic hematuria
and mild proteinuria incidentally found on routine
exam, <10% with nephrotic syndrome vs.
glomerulonephritis (edema, HTN, renal insuff)
Diagnostics CBC, peripheral blood smear, high LDH/low
haptoglobin, Coags, Direct Coombs,
ADAMTS13 activity/inhibitor testing
UA, microscopy
Renal biopsy with MEST-C histologic scoring
Therapeutics Urgent plasma exchange + glucocorticoids BP control with ACEi/ARB (if proteinuria),
glucocorticoids, +/- immunosuppressive agents
Hi, I’m going to be presenting a case I saw in Dr. Patel’s clinic today.
Given that this patient presented with clear signs of hypertensive emergency, I wanted to review tx.
So, question 1…
Remember that in hypertensive urgency…. Reduction in BP is less defined, but generally with a goal of <160/<100 in SBP and DBP respectively. (not more than 25-30% in the first 2 hours)
To summarize our case thus far, Mr. R was diagnosed with kidney stones after an episode of hematuria one week prior to presentation. On 7/8, he awoke with HA/N/V and confusion. He presented to VMMC on 7/9 and was started on a nicardipine gtt, after which his BP was controlled with amlodipine 10, lisinopril 40mg with good effect. On 7/10, nephrology was consulted and recommended renal biopsy.
Question: As a Review from Aaron’s talk last thursday, what are the three reasons that biopsy recommended in this case? Urine protein> 500mg/day, elevated Cr, signifiant elevation in BP
Differential included TTP, which was important for us to consider since our patient presented with confusion, headache, thrombocytopenia, hemolytic anemia, acute renal failure
As a reminder, the pathophysiology of TTP: deficiency of adamts13 which normally cleaves vWF.
When not present, large multimers of vWF along the endothelial lining accumulate platelets and disturb blood flow.
On to the second question
You would expected elevated PT/PTT, however, it is not part of the pentad.
And so, because the treatment of TTP is urgent plasmapharesis, and the condition is fatal if not treated early
I wanted to look into how we would think about this pt, who came in with a complicated picture
In other words, is it TTP causing his AKI and hemolytic anemia/thrombocytopenia OR is this a primary kidney disease causing HTN and HTN-induced thrombotic microangiopathy?
If s/sx of TTP, would look at the degree of thrombocytopenia. If thrombocytopenia is severe – do an urgent plasma exchange
If thrombocytoepnia is only mild, and there severely elevated MAP, consider HTN associated TMA. Remember that the mechanism
damage to vascular wall disruption of endothelium plasma constituents enter vascular wall further damage
Back to the case… The results of the biopsy show IgA deposits in the glomerular mesangium.
Seeing Aaron’s talk was also very helpful to see that IgA nephropathy can present with great variety, and the presenting symptoms often tell us about prognosis.
Aaron discussed diagnosis and treatment, but I thought I would go into prognosis a bit since in medical school we learned about all these diseases, but don’t have good ways to counsel patients on them.
This patient specifically wanted to know about dialysis and whether he wiould eventually need a kidney transplant.
Strongest prognostic factor is magnitude of protein excretion.
In a largest ever prospective cohort study in 2011, they looked at the risk of death and dialysis at 10 and 20 years.
Aaron discussed diagnosis and treatment, but I thought I would go into prognosis a bit since in medical school we learned about all these diseases, but don’t have good ways to counsel patients on them.
This patient specifically wanted to know about dialysis and whether he wiould eventually need a kidney transplant.
Strongest prognostic factor is magnitude of protein excretion.
In a largest ever prospective cohort study in 2011, they looked at the risk of death and dialysis at 10 and 20 years.
One crucial note is that in TTP, patients often appear sicker given its nature, usually a much more severe level thrombocytopenia (median platelet count was 10)
Renal dysfunction and AKI is actually rare in TTP, despite being part of the pentad.