Is it TTP or aHUS?

The clinical presentation of acquired/immune-mediated thrombotic thrombocytopenic purpura (aTTP/iTTP) can be strikingly similar to that of atypical hemolytic uremic syndrome (aHUS), which is why diagnosis can often be complicated. The creatinine levels, platelet count, and ADAMTS13 levels may guide toward distinguishing one from the other.1,2

Less than symbol

Indicators of aTTP/iTTP3,4

  • Creatinine <2.25 mg/dL
  • Platelet count <30 × 109/L
  • ADAMTS13 activity <10%
Greater than symbol

Indicators of aHUS/CM-HUS3,4

  • Creatinine ≥2.25 mg/dL
  • Platelet count >30 ×109/L
  • ADAMTS13 activity ≥10%

Differentiating TTP from HUS is crucial in order to start an appropriate therapy2

The following chart can help guide diagnosis to quickly differentiate patients with TTP in need of emergency care.

Flowchart for differentiating TTP from HUS and other TMAs

Adapted from: Kremer Hovinga JA et al. Nat Rev Dis Primers. 2017;3:17020.

Biopsies can be useful in differentiating aTTP/iTTP from aHUS in difficult cases5

Biopsies can be useful in difficult diagnostic situations. Sampling of any accessible, highly vascular site may help inform the differential diagnosis of a TMA, based on pathologic distinctions between aTTP/iTTP and aHUS.

Icon of platelets with vWF

Biopsy sample of any accessible, highly vascular site shows the following:

  • Microthrombi appear as “white clots” composed of platelets and vWF, with only small amounts of fibrin
  • Vascular or perivascular inflammatory cell infiltrations are minimal or absent
Icon of platelets with fibrin

Biopsy sample of any accessible, highly vascular site shows the following:

  • Microthrombi appear as “red clots,” predominated by fibrin
  • An inflammatory infiltrate may be seen together with deposits of C5b-9

The ISTH TTP Guidelines provide support for diagnosing and treating aTTP/iTTP quickly

Guidelines checkmarks

ISTH Guideline recommendations*

Day 1 icon

Choose CABLIVI on day 1 in combination with PEX and immunosuppressive therapy

Who should not start CABLIVI?

  • CABLIVI is contraindicated in patients with a previous severe hypersensitivity reaction to caplacizumab-yhdp or to any of its excipients
  • Withhold CABLIVI treatment 7 days prior to elective surgery, dental procedures, or other invasive interventions

*A conditional recommendation defined as desirable effects of the recommendation probably outweighing the undesirable effects. Assumes timely access to ADAMTS13 testing and clinical diagnosis based on high likelihood of aTTP/iTTP. In de novo patients where no reasonable access to ADAMTS13 activity testing is available, the Guidelines do not recommend CABLIVI; however, treatment of a patient previously diagnosed with aTTP/iTTP could be safely undertaken on clinical grounds without the need for a confirmatory ADAMTS13 test.6

ADAMTS13=a disintegrin and metalloproteinase with a thrombospondin type 1 motif, 13; CM-HUS=complement-mediated hemolytic uremic syndrome; HUS=hemolytic uremic syndrome; ISTH=International Society on Thrombosis and Haemostasis; PEX=plasma exchange; TMA=thrombotic microangiopathy; TTP=thrombotic thrombocytopenic purpura; vWF=von Willebrand factor.