Bri presented a case of a gentleman with multiple medical comorbidities with a recent lap chole presenting with confusion. His labs were significant for anemia, thrombocytopenia, elevated indirect bilirubin, elevated LDH, and undetectable haptoglobin. A smear revealed numerous schistocytes concerning for MAHA. ADAMTS13 levels were found to be very low, and the presence of an ADAMTS13 inhibitor was detected as well. This presentation is consistent with thrombotic thrombocytopenic purpura (TTP)!

Common differential for microangiopathic hemolytic anemia (MAHA):

• DIC
• HELLP/Eclampsia
• TTP/HUS, atypical HUS
• Mechanical heart valves
• Severe B12 deficiency

TTP

Epidemiology

• Rare, most often > 40 in adults, congenital ADAMTS13 deficiencies can be seen in kids (Upshaw-Schulman Syndrome, autosomal recessive)
• 2:1 female to male predominance

Pathophysiology

• Non-immune mediated platelet and RBC destruction due to mechanical shearing of platelets and RBC when they pass through platelet/fibrin deposits on small vessel walls in absence of ADAMTS13 activity.
• Further consumption of plts via formation of microthrombi in small arterioles/capillaries, brain/heart/kidneys are especially affected.
• ADAMTS13 cleaves VWF, preventing large multimer formation on vessel walls

J Evan Saldler. Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura. Blood 2008 112:11-18; doi: https://doi.org/10.1182/blood-2008-02-078170

Causes

• Idiopathic
• Drug-induced (Immunosuppressants, chemo)
• Pregnancy (preeclampsia/eclampsia)
• Hemorrhagic colitis
• HUS: more likely in kids, more commonly presents with AKI and in higher severity. Associated with E.coli O157:H7 infection and some strains of Shigella
• Atypical HUS: very similar to TTP but differnet pathophys (congenital complementary activation defect)

Presentation

• Pentad of FATRN: < 1/3, can be indolent (days to weeks of malaise)
  • Fever( 10%)
  • Anemia (100%)
  • Thrombocytopenia (100%)
  • Renal dysfunction, more common in HUS
  • Neuro (encephalopathy): More common in TTP (53%), less in HUS
• Triad that’s almost always present:
  • LDH elevation
  • Schistocytes
  • Thrombocytopenia
• Sx: Non-specific, encephalopathy, abd pain, N/V, diarrhea, arrhythmia.
• Exam: SICK compared to pts with ITP.

Diagnosis

• Thrombocytopenia
• E/O hemolysis: Anemia, polychromasia, elevated retic, reduced hepato, elevated LDH, elevated indirect bilirubin
• Fibrinogen is normal (although early DIC can also be relatively normal)
• PT/PTT are normal (vs elevated in DIC!)
• Low ADAMTS13 level (<10%) is highly specific for TTP
• ADAMTS13 inhibitor usually seen in adults, suggestive of autoimmune related deficiency of ADAMTS13. Generally responsive to immune suppression.

Management

• Emergent consultation with specialists, coordinate with MICU, Heme/Onc, and Renal! 
• FFP can be given to temporize things, fastest treatment option
• DO NOT TRANSFUSE PLATELETS
• 90% mortality without tx
• Emergent PLEX: reduces mortality to 20-30%, but those who survive the initial episode can have relapses 20-50% of the time.
  • Low ADAMTS13 activity and higher titers of ADAMTS13 inhibitor are associated with worse prognosis.
  • Plasma exchange usually continued until e/o dz activity has decreased (nrl plt, nrl LDH)
• Immune suppression with corticosteroids, rituximab can be considered in refractory cases.
• For HUS, tx is mainly supportive +/- dialysis but Eculizumab can be used.