KEEP CALM AND PLEX ON? N OV EM BER 3 , 2 0 1 7 DR. M I CH ELA - - PowerPoint PPT Presentation

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KEEP CALM AND PLEX ON? N OV EM BER 3 , 2 0 1 7 DR. M I CH ELA - - PowerPoint PPT Presentation

Aug 21, 2023 197 likes •420 views

KEEP CALM AND PLEX ON? N OV EM BER 3 , 2 0 1 7 DR. M I CH ELA FEBBRARO, PGY 3 I N T ERN AL M EDI CI N E, N OSM DR. SI RAJ M I T H OOWAN I , PGY 5 H EM AT OLOGY, M CM AST ER DR. K I M LEGAU LT, DI V I SI ON OF RH EU M AT OLOGY, M CM AST

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SLIDE 1

KEEP CALM AND… PLEX ON?

N OV EM BER 3 , 2 0 1 7

  • DR. M I CH ELA FEBBRARO, PGY 3 I N T ERN AL M EDI CI N E, N OSM
  • DR. SI RAJ M I T H OOWAN I , PGY 5 H EM AT OLOGY, M CM AST ER
  • DR. K I M LEGAU LT, DI V I SI ON OF RH EU M AT OLOGY, M CM AST ER
  • DR. ALI I QBAL, DI V I SI ON OF N EPH ROLOGY, M CM AST ER
  • DR. AZ I M GAN GJ I , DI V I SI ON OF N EPH ROLOGY, M CM AST ER
  • DR. DEBORAH SI EGAL, DI V I SI ON OF H EM AT OLOGY, M CM AST ER

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SLIDE 2

CASE

An 18 year old Hispanic male with a history of Raynaud’s phenomenon was admitted with:

  • Acute left leg deep vein thrombosis
  • Hypertension
  • Acute kidney injury
  • Creatinine: 127 micromol/L (normal: 61 – 97 micromol/L)
  • Urinalysis demonstrating 2+ blood and 3+ protein.

One week earlier, he was admitted for splenic laceration and left-sided pleural effusion attributed to recreational trauma.

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SLIDE 3

CASE

Auto-immune work up:

  • Positive ANA: titre > 1:640, speckled pattern
  • Positive anti-dsDNA: 8 IU/mL (negative ≤ 4 IU/mL)
  • Positive anti-Smith antibody: > 8 AI (normal < 1 AI)
  • Positive anti-RNP antibody: > 8 AI (normal < 1 AI)
  • Low C3: 0.48 g/L (normal: 0.79 - 1.52 g/L)
  • Low C4: 0.12 g/L (normal: 0.16 – 0.38 g/L)
  • Negative anti-cardiolipin antibody
  • Negative non-specific inhibitor

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SLIDE 4

CASE

A renal biopsy demonstrated class IV lupus nephritis. Immunosuppression for SLE was initiated with:

  • Mycophenolate mofetil 750mg QID
  • Hydroxychloroquine 200mg daily
  • Prednisone 70 mg daily (dosed at 1 mg/kg)

DVT was managed:

  • Initially with Apixaban
  • Switched to Warfarin given kidney function

Hypertension was managed with:

  • Ramipril
  • Furosemide

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SLIDE 5

CASE – ONE MONTH LATER

Patient was transferred to our tertiary care hospital following 5 days in a regional hospital with:

  • Worsening kidney function:
  • Creatinine: 384 micromol/L (normal: 61 – 97 micromol/L)
  • Anemia
  • Hemoglobin: 88 g/L (normal: 130 – 180 g/L)
  • Thrombocytopenia
  • Platelets: 42 x 10^9/L (normal: 150 – 400 x 10^9/L)
  • Evidence of hemolysis
  • Reticulocytes: 217 x 10^9/L (normal: 10 – 86 x 10^9/L)
  • LDH: 591 U/L (normal: 130 – 250 U/L)
  • Low Haptoglobin
  • Moderate schistocytes on blood film

The patient was diagnosed with thrombotic thrombocytopenic purpura and daily plasma exchange (PLEX) was initiated.

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SLIDE 6

THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP)

  • Initially described as a pentad of clinical features:
  • Microangiopathic hemolytic anemia (MAHA)
  • Thrombocytopenia
  • Neurologic abnormalities
  • Renal abnormalities
  • Fever
  • Fatal in 90% of patients prior to the availability of effective

treatment

George JN. NEJM 2006. 354(18): 1927 Vesely SK, et al. Blood 2003; 102(1): 60

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SLIDE 7

THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP)

  • Initially described as a pentad of clinical features:
  • Microangiopathic hemolytic anemia (MAHA)
  • Thrombocytopenia
  • Neurologic abnormalities
  • Renal abnormalities
  • Fever
  • Fatal in 90% of patients prior to the availability of effective

treatment Early initiation of treatment has brought the mortality rate to < 20%

George JN. NEJM 2006. 354(18): 1927 Vesely SK, et al. Blood 2003; 102(1): 60

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SLIDE 8

HEMOGLOBIN AND PLATELET TREND FOLLOWING PLEX INITIATION

20 40 60 80 100 120 1 2 2 4 5 Hemoglobin (g/L) Platelet Count (10^9/L)

Day of Admission

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SLIDE 9

CASE

Hematology, Nephrology and Rheumatology services concluded that the most likely diagnosis was lupus- associated thrombotic microangiopathy (TMA).

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SLIDE 10

CASE

Hematology, Nephrology and Rheumatology services concluded that the most likely diagnosis was lupus- associated thrombotic microangiopathy (TMA). Conclusion based on:

  • Poor response to daily PLEX after 5 days
  • Normal ADAMTS-13 level
  • Positive autoimmune workup
  • Negative antiphospholipid antibody testing

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SLIDE 11

DIFFERENTIAL DIAGNOSIS OF THROMBOCYTOPENIA AND MAHA

  • Autoimmune hemolytic anemia/Evans syndrome
  • Disseminated intravascular coagulation
  • Pregnancy associated (eg. HELLP, eclampsia, HUS)
  • Drugs
  • Malignant hypertension
  • Viral Infections (eg. CMV, adenovirus, HSV)
  • Bacterial Infections (eg. pneumococcus, meningococcus)
  • Autoimmune disease (eg. lupus nephritis, scleroderma)
  • Vasculitis
  • Shiga toxin associated hemolytic uremic syndrome
  • Complement mediated hemolytic uremic syndrome
  • Malignancy
  • Catastrophic antiphospholipid syndrome

Scully M, et al. BJH 2012; 158: 323

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SLIDE 12

CASE - TREATMENT

The patient was treated with:

  • Cyclophosphamide 500mg IV q14 days
  • Prednisone daily
  • PLEX

The TMA resolved and hematologic parameters gradually normalized.

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SLIDE 13

HEMOGLOBIN AND PLATELET TREND THROUGHOUT ADMISSION

50 100 150 200 250 300 350 400 450 1 5 10 15 20 25 Hemoglobin (g/L) Platelets (10^9/L)

Day of Admission

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SLIDE 14

HEMOGLOBIN AND PLATELET TREND THROUGHOUT ADMISSION

50 100 150 200 250 300 350 400 450 1 5 10 15 20 25 Hemoglobin (g/L) Platelets (10^9/L)

Day of Admission

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SLIDE 15

LUPUS ASSOCIATED TMA

  • Unexplained MAHA and thrombocytopenia in a patient

meeting diagnostic criteria for SLE

  • May also have acute renal failure, fever, and neurologic

deterioration

  • Not associated with a severe reduction in ADAMTS13

activity

  • Early initiation of plasma exchange with additional therapy

has the potential to be curative

Blum D, et al. World J Nephrol 2015; 4(5): 528

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SLIDE 16

CASE - RESOLUTION

In hospital complications included:

  • Hypertension
  • Seizure secondary to posterior reversible

leukoencephalopathy syndrome (PRES)

  • Severe volume overload

Three further doses of IV cyclophosphamide have been administered as an outpatient. On follow-up, the patient continues to have stable hematologic parameters with no evidence of recurrent TMA

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SLIDE 17

TAKE HOME MESSAGES

  • TMA is a rare and potentially fatal manifestation of SLE
  • Distinguishing SLE-associated TMA from other TMAs is

important in order to administer SLE-specific therapy

  • Unlike TTP, the role of PLEX is less clear in the treatment of

SLE-associated TMA

  • Mortality benefit with and without PLEX has not been studied

in the context of SLE-associated TMA

  • Treatment is primarily directed at the underlying SLE with

immunomodulator agents

  • There may be a delay to peak response with

immunomodulator agents when treating severe manifestations of SLE

  • Inter-specialty collaboration is important in order to diagnose

and manage a rare condition

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SLIDE 18

SPECIAL THANKS TO:

  • Dr. Deborah Siegal, Division of Hematology, McMaster
  • Dr. Kimberly Legault, Division of Rheumatology, McMaster
  • Dr. Siraj Mithoowani, PGY5 Hematology, McMaster
  • Dr. Ali Iqbal, Division of Nephrology, McMaster
  • Dr. Azim Gangji, Division of Nephrology, McMaster

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SLIDE 19

THANK YOU

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SLIDE 20

LUPUS ASSOCIATED TMA

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