Noon conference 6_27_2018

1. Noon conference
Kristy Barker MD, PGY-3+

2. Fever & rash
People presenting with fever & rash should be
divided into 2 categories:
1. Critically ill
2. Not critically ill

3. Fever & rash
Name as many causes of critical illness fever &
rash as you can.

4. Fever & rash
Critical illness fever & rash examples:
Hemorrhagic fever syndromes, meningococcemia, Rocky
Mountain spotted fever, toxic shock, Stevens-Johnson
syndrome, toxic epidermal necrolysis, and acute vasculitis.
From ACP Principles & Practice of Hospital Medicine, 2nd edition

5. Causes of Hemolytic Anemia
1. List as many examples of inherited hemolytic
anemias as you can.
1. List as many examples of acquired hemolytic
anemias as you can.

6. Causes of Hemolytic Anemia
1. List as many examples of inherited hemolytic anemias as
you can.
Congenital Hemolytic Anemias Examples
Defects in erythrocyte membrane Hereditary spherocytosis
Deficiency in erythrocyte metabolic
enzymes
G6PD deficiency
Defects in hemoglobin structure or
synthesis
Sickle cell disease, alpha & beta
thalassemia
This slide & next: from ACP MKSAP 17: Hematology and Oncology, page 27

7. Causes of Hemolytic Anemia
2. List as many examples of acquired hemolytic anemias as you
can.
Acquired Hemolytic Anemias Examples
Autoimmune hemolytic anemia Warm autoimmune hemolytic anemia, cold
agglutinin disease
Microangiopathic hemolytic anemia TTP, DIC
Paroxysmal nocturnal hemoglobinuria
Infectious, chemical, and physical agents Plasmodium, Babesia, Clostridium,
Bartonella, copper, thermal injury, venoms,
spider toxins

8. Summary Assessment

9. Summary Assessment
Younger middle-aged man from an endemic area with
recent tick exposure p/w acute fatigue, fever, and rash
with 2nd episode of anemia, AKI, and thrombocytopenia
separated by 3 years of good health, found to have B.
burgdorferi positivity.

10. Admission & early hospital course
- Admitted to hospital on azithromycin, atovaquone, and
doxycycline.
- Hospital day #3: develops sudden onset of expressive
aphasia, R pronator drift, inability to follow complex
commands
- CT angio of head/neck normal

11. Clinical Diagnosis

12. Clinical Diagnosis
Thrombotic thrombocytopenic purpura

13. TTP can be congenital or acquired
Congenital TTP is caused by mutations in
ADAMTS13

14. TTP can be congenital or acquired
- Acquired TTP is caused by autoantibodies to
ADAMTS13
- Can be primary (no known cause) or secondary

15. Causes of secondary TTP
1. Rheum (SLE, RA, Sjogrens)
2. Infectious (HIV, CMV)
3. Exposures/drugs (quinine, ticlodipine,
cyclosporine, gemcitabine)
4. Pregnancy

16. Causes of secondary TTP
A triggering event can cause expression of
ADAMTS13 deficiency/TTP to flare in association
with stress, similar to an autoimmune disease

18. TTP: Epidemiology
More common in young adults, women, black
patients

20. TTP: Clinical presentation
The entire pentad of fever, anemia,
thrombocytopenia, neuro sx and renal injury really
is seen in only 5% of patients
Thrombocytopenia & anemia in 100% of patients

21. TTP: History
Anemia: weakness, fatigue, jaundice
Thrombocytopenia:
bleeding/bruising/menorrhagia etc

22. TTP: History
End-organ ischemia:
Neuro (confusion, headaches, weakness, etc)
GI (abdominal pain, n/v/d)
Cardiac

23. TTP: History
? precipitating factors
- Infectious, EtOH, pregnancy, vaccination
- Drugs (ticlodipine, quinine, etc)
- Underlying rheum (SLE, RA, Sjogrens)

24. TTP: Exam
Gen: Fever
Skin: pallor, petechiae/purpura, jaundice
Neuro: confusion, paresis, aphasia, etc

25. TTP: Diagnosis
Prompt dx is important as is 90% fatal without tx
When to suspect: isolated MAHA, new neuro sx or
acute MI with unexplained MAHA, prior hx of TTP

26. TTP: Diagnosis
Initial dx is made clinically with supporting labs &
peripheral smear

27. TTP Prediction Tool: PLASMIC Score
Bendapudi PK, Hurwitz S, Fry A, et al. Derivation and external validation of the PLASMIC score for rapid assessment of adults with thrombotic
microangiopathies: a cohort study. Lancet Haematol 2017;4:e157-e164

28. TTP Prediction Tool: PLASMIC Score
Bendapudi PK, Hurwitz S, Fry A, et al. Derivation and external validation of the PLASMIC score for rapid assessment of adults with thrombotic
microangiopathies: a cohort study. Lancet Haematol 2017;4:e157-e164

29. TTP: Diagnosis
Confirmed by assay for ADAMTS13 activity,
ADAMTS13 inhibition, and Anti-ADAMTS13 Abs
ADAMTS13 activity level <10% highly suggestive
of TTP
Our patient had an activity level of <5%

30. TTP: Diagnosis
ADAMTS13 inhibition & Anti-ADAMTS13 Ab tests
are done to distinguish between inherited vs
acquired TTP
Acquired TTP should show + ADAMTS13 inhibitor
in mixing studies or anti-ADAMTS13 IgG Abs

31. TTP: Diagnosis
Our patient’s inhibition level was negative & Ab
assay was positive

32. TTP: Diagnosis
Genetic testing at the ADAMTS13 locus indicated
our patient had autosomal recessive (inherited)
TTP

33. Final Diagnosis
Combined inherited and acquired thrombotic
thrombocytopenic purpura

34. Treatment
Plasma exchange is standard of care for initial
management of acquired TTP
Continued daily until organ dysfx is resolved

35. Treatment
Adjunctive tx with glucocorticoids,
immunosuppressive doses
Goal is to decrease production of Anti-ADAMTS13
Abs

36. Our patient, conclusion
Plasma exchange #1: marked neuro improvement
Plasma exchange #2: headache resolved
Plasma exchange #3: platelet count normalized

37. Our patient, conclusion
Plasma exchange was stopped after 6 days with
rapid steroid taper
ADAMTS-13 activity rose to 62%

38. Our patient, conclusion
14 days after plasma exchange stopped, platelet
count drops again to 120K and ADAMTS13 level
drops to <5%
Receives plasma transfusions x 3 days with no
increase in platelet counts, so another exchange
was performed & platelet count rose to >200K

39. Our patient, conclusion
Because the patient had a early relapse, rituximab
tx x 4 weeks and achieved complete remission but
continued to have undetectable ADAMTS13
activity

40. Our patient, conclusion
Has been receiving infusions of FFP every 8-10
weeks without evidence of relapse

41. References
1. I grumpily used Dynamed
2. ACP MKSAP 17, Hematology/Oncology
3. ACP Principles & Practice of Hospital Medicine, 2nd Ed
4. Dhualiwal, G. et al. Case 36-2017: N Engl J Med 2017; 377:2074-2083
5. George, J. and Nester, C. Syndromes of Thrombotic Microangiopathy. N Engl J
Med 2014; 371: 654-666