31-year-old female, with a history of controlled SLE, presents to your office with a 2 week history of headache, weakness, dizziness, and nausea.  She also reports a new rash on her legs that is non-pruritic.  She denies any recent illnesses, sick contacts, vomiting, abdominal pain, cough, or shortness of breath.  She has been taking hydroxychlorquine for her SLE and has had little complications from this disease.

Vital Signs

BP-131/72, HR-116, RR-15, O2-100%, T-101.2 F

Physical Exam

General – Mild distress

Skin

HEENT

Neck – Supple, no LAD

Pulmonary – CTA without adventitial breath sounds

CV – Tachycardic without M/G/R

Abdomen – S/NT/ND

PV – 2+ throughout

Neurologic – 5/5 strength throughout, 2+ reflexes throughout

Psychiatric – A&Ox3

Laboratory Screening

Answer

1. This patient has thrombotic thrombocytopenia purpura (TTP), which is a thrombotic microangioapathy caused by severely reduced activity of the von Willebrand factor-cleaving protease ADAMTS13 and small-vessel platelet-rich thrombi.  Classically it is associated with a pentad of symptoms (but current research only shows 5% of patients with all five):
   1. Hemolytic anemia
      1. Low H/H and high LDH
   2. Thrombocytopenia
      1. <150,000
   3. Neurologic symptoms
      1. Confusion, headache, focal deficits
   4. Fever
   5. Acute Kidney Injury
      1. Elevated creatinine
2. Addition findings in this patient that support the diagnosis are:
   1. Purpuric rash from small-vessell thrombosis
   2. Scleral icterus from elevated indirect bilirubin from hemolysis
3. Additional laboratory studies to help with the diagnosis of TTP are:
   1. Hemolysis labs
      1. Serum haptoglobin
         1. Often elevated
      2. Direct antiglobulin (Coombs) test (DAT)
         1. Often negative
   2. Fibrinogen and D-Dimer
      1. Evaluate for DIC as severely ill patient can progress to this very quickly
   3. ADAMTS13 activity and inhibitor testing
      1. Gold standard and confirmatory test of choice

References

1. George JN, Nester CM. Syndromes of thrombotic microangiopathy. The New England Journal of Medicine. 2014;371(7):654-66. [pubmed]
2. George JN. How I treat patients with thrombotic thrombocytopenic purpura: 2010. Blood. 2010;116(20):4060-9.  [pubmed]
3. Griffin D, Al-Nouri ZL, Muthurajah D. First symptoms in patients with thrombotic thrombocytopenic purpura: what are they and when do they occur? Transfusion. 2013;53(1):235-7.  [pubmed]