Anaplasmosis as a Mimicker of TTP/HUS - American College of ...

TTP or not TTP?
Joshua Barocas , MD
Saurabh Rajguru, MD
The University of Wisconsin Hospital and Clinics

Case Presentation
HPI: A 59 y/o male with CAD presents with two days of
confusion, fevers, unsteady gait and non-bloody diarrhea. He
denies any sick contacts, N/V or abdominal pain.

Case Presentation
PMH:
CAD s/p 4v CABG
HTN
HL
Rheumatic fever as a child
FH:
Non-contributory
SH:
Smokes 2-3 cigarettes/day
Drinks 1 glass of wine/wk
Lives in Northern WI with his wife
Allergies:
Niacin
Medications:
Amiodarone
Baby ASA
Lisinopril
Metroprolol
Ezetemibe
Rosuvastatin

Physical Exam
• Vitals: T-100.4, BP-82/48, P-78, RR-16, SpO2-97% on RA
• Gen: awake, alert, some slurring of speech
• HEENT: ncat, eomi, anicteric, dry oral mucosa, no pharyngeal
erythema/exudate
• CV: rrr, nl s1s2, no s3/s4, no m/r/g
• Lungs: ctab, no w/r/r
• Abd: soft, nd, nd, no HSM, normal bowel sounds, no
rebound/guarding
• Ext: warm, no c/c/e
• Skin: no rashes, bruises, ecchymoses or petechiae
• Neuro: CN III-XII grossly intact, 5/5 UE/LE strength b/l,
downgoing Babinski, no clonus

Laboratory Assessment
MCV-90.4
14.6
127
93
54
89% PMNs
5.4
42.4
35
4.5
22
4.3
133
6 hrs later
3.8
11.5
33.8
21
131
3.9
102
18
57
4.0
124
*Review of peripheral smear revealed very few schistocytes and occasional Burr cells

Laboratory Assessment
• Tbili-0.9
• AST-181
• ALT-90
• Alk Phos-97
• LDH-619
• D-dimer >3.2
• ADAMSTS13 activity-pending
• von Willebrand factor cleaving protease
• Function to degrade unusually large von Willebrand factor (ULVWF).
• Deficiency leads to accumulation of ULVWF, platelet aggregation, and
subsequent thrombi formation
• Activity level decreased in TTP

Over the next 48 hrs…
• He was given IVF, started on empiric antibiotics
(vancomycin, zosyn, ciprofloxacin) and transferred to the
ICU for urgent plasma exchange
• His mental status began to improve somewhat, even before
plasma exchange , and his haptoglobin returned normal
(135), so a search for other causes of renal failure,
thrombocytopenia and mental status changes was begun

Over the next 48 hrs…
• Now that he was more lucid, further history was obtained:
• revealed that he was bitten a number of times by ticks (most
recently a week before presentation)
• He was started empirically on doxycycline
• Testing for ehrlichia, anaplasma and lyme disease returned
positive for A. phagocytophilum DNA

Case Summary
59 y/o male presents with acute onset thrombocytopenia, renal
failure, fever, altered mental status, and recent tick bites
found to have anaplasmosis

Differential of TTP Mimickers
• Malignant HTN
• Systemic Malignancies
• SLE
• Drugs
– Heparin
– Haldol
– Phenytoin
– Quinine
• DIC
• Systemic Infections
– Anaplasma/Ehrlichia
– Lyme Disease
– Aspergillus fumigatus
– Rickettsia rickettsii
– E. faecalis
– CMV
– Hepatitis A
– Group A strep
– Candida
– S. aureus
– Blastomyces
– Cryptococcus
– HIV
Booth KK, Terrell DR, Vesely SK, George JN. Systemic infections mimicking thrombotic thrombocytopenic purpura.
Am. J. Hematol. 2011;86(9):743-751.
Modi KS, Dahl DC, Berkseth RO, Schut R, Greeno E. Human Granulocytic Ehrlichiosis Presenting with Acute Renal
Failure and Mimicking Thrombotic Thrombocytopenic Purpura. Am. J. Nephrology. 1999; 19:677-681.

TTP/HUS vs. Anaplasmosis
TTP/HUS
• Fever
• AMS/HA
• AKI
• Thrombocytopenia
• MAHA
• Diarrhea
Anaplasmosis
• Fever
• AMS/HA
• AKI
• Thrombocytopenia
• Leukopenia
• Myalgias/arthralgias

Initial Management
• TTP suspected
• Plasma exchange
• Look for other causes
• Tick borne illness
suspected
• Doxycycline 100mg BID
OR
• Rifampin if allergy or
pregnant OR
• Ciprofloxacin
Booth KK, Terrell DR, Vesely SK, George JN. Systemic infections mimicking thrombotic thrombocytopenic purpura. Am.
J. Hematol. 2011;86(9):743-751
Rock GA, Shumak KH, Buskard NA, et al. Comparison of plasma exchange with plasma infusion in the treatment of
thrombotic thrombocytopenic purpura. New Eng J Med 1991;325:393–397
Clark WF, Garg AX, Blake PG, et al. Effect of awareness of a randomized controlled trial on use of experimental
therapy. JAMA. 2003: 290: 1351-1355
George JN. How I treat patients with thrombotic thrombocytopenic purpura—2010. Blood. 2010;116:4060–4069.
Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of lyme disease,
human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of
America. Clin. Infect. Dis. 2006;43(9):1089-1134
Woldehiwet Z. In-vitro studies on the susceptibility of ovine strains of Anaplasma phagocytophilum to antimicrobial
agents and to immune serum. J. Comp. Pathol. 2010;143(2-3):94-100

What to order
• SMEAR (evidence of morulae in PMNs)
• Anaplasma/Ehrlichia:
– Serology using indirect flourescent antibody to HME and HGA
– PCR for HME and HGA
– Tissue staining
• Babesia
– Specific Babesia smear
– DNA PCR
• Lyme
– ELISA for IgM and IgG
– Western blot

Epidemiology of Anaplasmosis
• Seroprevalence of 14.9% among healthy residents from
northwestern Wisconsin who had no h/o a tick bite
• Highest annual avg HGA incidence rates:
• CT (15.9/million), WI (8.8/million), MN (3.9/million), NY
State (2.7/million)
• However, rates as high as 650/million reported in some NW WI counties
Bakken JS, Dumler S. Human Granulocytic Anaplasmosis, Infect Dis Clin N Am. 2008; 22, 433-448.
Belongia EA et al. Population-Based Incidence of Human Granulocytic Ehrlichiosis in Northwestern
Wisconsin, 1997-1999, J of Inf Dis. 2001; 184 (11), 1470-1474.

No.
No. in parenthesis is mean annual cases/100,000
Belongia E A et al. J Infect Dis. 2001;184:1470-1474
© 2001 by the Infectious Diseases Society of America
Belongia EA et al. Population-Based Incidence of Human Granulocytic Ehrlichiosis in Northwestern
Wisconsin, 1997-1999, J of Inf Dis. 2001; 184 (11), 1470-1474.

New Ehrlichia Species

New Ehrlichia Species
• Close relative of E. muris that was prevalent
throughout Minnesota and Wisconsin.
• Clinically similar to the other forms of Ehrlichia and
anaplasma
• Causes fever, malaise, headache, lymphopenia,
thrombocytopenia, and elevated liver-enzymes
• Highly susceptible to doxycycline
• Not yet part of the routine send out PCR for ehrlichia
and anaplasma.
• Need to treat in our area if high clinical suspicion for
tick borne illness even in the face of a negative PCR.
Pritt BS, Sloan LM, Johnson DKH, et al. Emergence of a new pathogenic Ehrlichia species, Wisconsin and
Minnesota, 2009. N. Engl. J. Med. 2011;365(5):422-429

Back to our patient…
• His mental status improved before initiation of
plasmapheresis and is likely attributable to the empiric
antibiotics he received on presentation (zosyn, ciprofloxacin)
and IVF
• After initiation of doxycycline, he improved rapidly and left
the ICU after two days
• His ADAMSTS13 activity returned at 70% (nl >67%)
further proving he did not have TTP
• He was seen by his PCP two weeks after discharge at which
point his plts-332 and Cr-3

Conclusions
• Anaplasmosis can present with thrombocytopenia, fever,
AMS, AKI, and anemia.
• It can be indistinguishable from TTP
• Early doxycycline is the mainstay of treatment. If TTP is still
strongly considered, early plasma exchange is indicated.
• New species of tick borne illness continue to emerge so
clinical suspicion is paramount

References
• Booth KK, Terrell DR, Vesely SK, George JN. Systemic infections mimicking thrombotic thrombocytopenic purpura. Am. J.
Hematol. 2011;86(9):743-751.
• Clark WF, Garg AX, Blake PG, et al. Effect of awareness of a randomized controlled trial on use of experimental therapy. JAMA.
2003: 290: 1351-1355
• George JN. How I treat patients with thrombotic thrombocytopenic purpura—2010. Blood. 2010;116:4060–4069.
• Modi KS, Dahl DC, Berkseth RO, Schut R, Greeno E. Human Granulocytic Ehrlichiosis Presenting with Acute Renal Failure and
Mimicking Thrombotic Thrombocytopenic Purpura. Am. J. Nephrology. 1999; 19:677-681.
• Rock GA, Shumak KH, Buskard NA, et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic
thrombocytopenic purpura. New Eng J Med 1991;325:393–397
• Pritt BS, Sloan LM, Johnson DKH, et al. Emergence of a new pathogenic Ehrlichia species, Wisconsin and Minnesota, 2009. N.
Engl. J. Med. 2011;365(5):422-429
• Woldehiwet Z. In-vitro studies on the susceptibility of ovine strains of Anaplasma phagocytophilum to antimicrobial agents and
to immune serum. J. Comp. Pathol. 2010;143(2-3):94-100
• Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of lyme disease, human
granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin. Infect.
Dis. 2006;43(9):1089-1134
• Bakken JS, Dumler S. Human Granulocytic Anaplasmosis, Infect Dis Clin N Am. 2008; 22, 433-448.
• Belongia EA, Gale CM et al. Population-Based Incidence of Human Granulocytic Ehrlichiosis in Northwestern Wisconsin, 1997-1999, J of Inf
Dis. 2001; 184 (11), 1470-1474.

Acknowledgements
• American College of Physicians
• Dr. Bennett Vogelman
• Dr. Matthew Crowe

Questions?