CASE DISCUSSION

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CASE DISCUSSION

• ??? ???

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BASIC DATA

• Mrs. ?
• Age 33
• Gender female
• Room 4B1 03
• Chart No. 5167098
• Chief Problem Dyspnea for 1.5 months

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BRIEF HISTORY

• Mrs. ?, a 33 y/o woman, denied any systemic
  disease
• G3P3, all healthy
• Dyspnea since GA 28 wks
• Dyspnea aggravated after C/S
• Palpitation was also noticed
• 04/26, to Cathay General Hospital

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BRIEF HISTORY

• 04/26 at Cathay General Hospital
• RBC 3.6 M, PLT 48 K, AST/ALT 188/199
• Fragmented RBC in peripheral blood
• LDH 1230, FDP-DD 749
• CK/CK-MB 686/18.1
• U/A gross hematuria, proteinuria 3
• bilirubin 3, WBC gt120
• Autoimmune study no obvious positive finding

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BRIEF HISTORY

• At Cathay General Hospital
• HELLP syndrome or pulmonary hypertension was
  suspected.
• Given with O2, Viagra, Herbesser, and then the
  condition improved.
• Deterioration again on 2007/05/08, persistence of
  low platelet
• Delirium once on 2007/05/18
• Transfer to our ICU on 2007/05/29

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BRIEF HISTORY

• In our ICU
• Initial presentation drowsy consciousness
• Vital sign 36.8/114/20, BP 132/85
• Non-rebreathing mask, FiO2 80, SpO2 97
• PE NE Within normal limits
• No arthralgia, no mucosal ulcer, no malar rash
• No purpura, no ecchymosis, no hypertension
• No gangrenes on extremities, no fever
• No edema on lower legs

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BRIEF HISTORY

• CXR (2007/05/29)
• Cardiomegaly and bulging pulmonary conus ,
• increased bilateral lung marking and
  engorged pulmonary arteries.
• Cardiac echo (2007/04/26)
• Dilated RA RV, LVEF 71, moderate to severe TR,
  pericardial effusion, pulmonary hypertension.

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BRIEF HISTORY

• Chest CT (2007/04/26)
• Dilated RA RV with RVH, pulmonary trunk larger
  than aortic root, pleural effusion, small LAP (lt
  1 cm) at bilateral axillary region.
• Lung perfusion scan (2007/06/01)
• Little possibility of pulmonary emboli
• Nuclear medicine study (2007/06/05)
• LVEF 58

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BRIEF HISTORY

• Lab data
• RBC 2.5 M, Hb 8.7, WBC 7.2 K, PLT 15 K
• Reticulocyte 7.96
• AST/ALT 25/29, BUN/CRE 29.2/0.7
• BIL (T/D) 1.95/0.7
• Iron 54, TIBC 296, Ferritin 112
• DIC profile 3P 1, FDP 5.3, D-Dimer 1.16
• LDH 1476, BNP 1154, CRP 0.48

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BRIEF HISTORY

• Autoimmune study (06/04)
• Anti-Jo1, anti RNP, anti SS-A, anti SS-B (-)
• Anti scl-70, anti SM (-)
• ANA 140, centromere type
• C3 64.5, C4 5.9, IgM IgG?(slightly)
• Coombs' Test Direct, positive, 1, weak
• RA factor lt20
• ADAMTS-13 normal
• Anti-cardiolipin antibody pending

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BRIEF HISTORY

• After consultation with hematologists and
  rheumatologists
• Thrombotic thrombocytopenic purpura (TTP) was
  suspected
• Pulmonary hypertension, unknown cause
• Should rule out autoimmune hemolytic anemia
  (AIHA), which may be secondary to SLE or
  Sjögren's syndrome .
• Should also rule out antiphospholipid syndrome
• No obvious evidence of SLE

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CURRENT MANAGEMENT

• Plasma exchange, FFP 27 U QD
• Flolan (epoprostenol) 500meq QD
• Viagra (sildenafil citrate) 0.25 BID

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FOLLOW-UP DATA
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SUMMARY

• This is a 33 y/o female with progressively severe
  dyspnea after giving birth to her third child. It
  was accompanied by thrombo- cytopenia, anemia,
  gross hematuria, elevated LDH, pulmonary
  hypertension, and right heart failure. Her
  immunological studies and DIC profiles were of
  little contribution. Under the impression of TTP,
  plasma exchange was performed for 13 days.
  However, the benefit of this management is
  limited.

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THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP)
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INTRODUCTION

• TTP syndrome characterized by microangiopathic
  hemolytic anemia (MAHA) and platelet aggregation.
• Platelet microthrombi form in the
  microcirculation throughout the body causing
  partial occlusion of vessels.
• Organ ischemia, thrombocytopenia, and erythrocyte
  fragmentation (ie, schistocytes) occur.

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INTRODUCTION

• The thrombi partially occlude the vascular lumina
  with overlying proliferative endothelial cells.
• The endothelia of the kidneys, brain, heart,
  pancreas, spleen, and adrenal glands are
  particularly vulnerable to TTP.
• The liver, lungs, gastrointestinal tract,
  gallbladder, skeletal muscles, retina, pituitary
  gland, ovaries, uterus, and testes are also
  affected to a lesser extent.
• Deep vein thrombosis can also occur.
• No inflammatory changes occur.

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INTRODUCTION

• Prevalence gt 3.7/1,000,000 (US)
• Age of onset 35 (median age), 4049 (in average)
• Sex female-to-male ratio of 32
• Mortality/Morbidity
• Untreated mortality rate is approximately 95
• Early diagnosis survival rate is 80-90

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ETIOLOGY OF TTP

• Primary/idiopathic TTP 80
• Decreased activity or amount of ADAMTS-13 (80)
• Persistence of ULVWF and abnormal platelet
  aggregation and microthrombi formation
• Genetic or acquired (existence of antibody)

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ETIOLOGY OF TTP

• Secondary TTP 20
• Drugs anti-platelet drug, eg. clopidogrel
  (Plavix)
• Pregnancy TTP can develop at any time during
  pregnancy even after the birth.
• Infections eg. HIV
• Systemic lupus erythematosus (SLE)
• Malignancy cancer of any type may be complicated
  by TTP

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CLINICAL PRESENTATION

• Fever (60)
• Purpura Nonpalpable small purpuric spots or
  petechiae occur with thrombocytopenia (platelet
  count lt 50 K/µL).
• Anemia, hemoglobin levels less than 10 g/dL
• Altered mental status (36)
• Abdominal pain (24)
• Renal changes (88) with gross hematuria (15)
• Heart failure, arrhythmias

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LAB STUDIES

• Thrombocytopenia and anemia
• Fragmented RBCs (schistocytes)
• LDH level gt 1000 mg/dL
• Indirect bilirubin level Elevated
• Reticulocyte count Elevated
• PT/aPTT Normal
• DIC panel (fibrinogen, D-dimer) usually normal
• Urinalysis Proteinuria and microscopic hematuria

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TREAMENT FOR TTP

• Plasma exchange with FFP standard method
• Steroid of no proven additional benefit
• Antiplatelet agents controversial
• Splenectomy is performed occasionally to treat
  patients who do not respond to plasma exchange.
  Some patients benefit from splenectomy. The
  response may be due to the removal of the site of
  sequestration of the RBCs and platelets. Another
  possibility is that the spleen is a major site of
  microvascular occlusive lesions in severe TTP.

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TREAMENT FOR TTP

• Vincristine, a second-line therapy with an un-
  known mechanism of action and with unproven
  benefit
• Supportive care, anticonvulsants,
  platelet-depleted packed RBCs
• Platelet transfusion is contraindicated because
  it is associated with rapid deterioration!

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CONCLUSION

• Thrombotic thrombocytopenic purpura is a rare
  condition associated with abnormal aggregation of
  platelets, intravascular destruction of RBCs, and
  the formation of microthrombi. The patient can
  present with some or all of the characteristics
  of the classic pentad including thrombocytopenia,
  fever, renal changes with gross hematuria,
  neurologic deficit, and hematologic changes. Some
  patients may exhibit dysfunction of ADAMTS-13. If
  treated early with plasma exchange, the prognosis
  is good.

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DISCUSSION
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REVIEW OF THIS CASE
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REVIEW OF THIS CASE
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DISCUSSION

• Poor response to plasma exchange. Poor responder?
  Not yet responsive? Wrong diagnosis?
• Obvious pulmonary hypertension while lung
  perfusion scan relatively normal. Pitfalls of
  perfusion scan? Causes of pulmonary hypertension?
• If TTP, the relationship between TTP and
  pulmonary hypertension? Single etiology, or two
  combined disease?

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TAKE HOME MESSAGE

• Thrombotic thrombocytopenic purpura (TTP)
• Platelet over aggregation
• Platelet?, hemolytic anemia, LDH elevation
• Diffused microthrombi formation and occlusion of
  vessels
• Multiple organ involvement, eg. kidneys, brain,
  heart, liver, lungs, gastrointestinal tract, etc.
• Standard treatment plasma exchange

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THANK YOU VERY MUCH FOR YOUR ATTENTION!HAVE A
GOOD DAY!