Haptoglobin degradation product as a novel serum biomarker for hematopoietic stem cell transplant-associated thrombotic microangiopathy

  • Meredith P. SchuhEmail author
  • Michael R. Bennett
  • Adam Lane
  • Sonata Jodele
  • Benjamin L. Laskin
  • Prasad Devarajan
Original Article



Hematopoietic stem cell transplant (HSCT)-associated thrombotic microangiopathy (TA-TMA) is a well-known complication of HSCT and carries high risk of morbidity and mortality. A lack of consistent non-invasive diagnostic criteria can delay diagnosis and lead to irreversible organ damage.


Serum samples of 100 patients that underwent HSCT at Cincinnati Children’s Hospital were serially collected. Unbiased proteomic profiling by SELDI-TOF-MS was performed on serum from TA-TMA patients at baseline (pre-HSCT), 2 weeks before TMA diagnosis (pre-TMA), and at clinical TMA diagnosis. Two proteins with mass to charge ratios of 12–13 kDa were consistently elevated at the 2 week pre-TMA time point by SELDI-TOF, compared to control samples. Potential peptides were isolated and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) on the Linear Trap Quadropole (LTQ). A MASCOT search identified haptoglobin fragments in the 12–17-kDa range. Western blot was performed to validate haptoglobin fragments as a potential biomarker.


Western blot of TA-TMA patients showed haptoglobin fragments at 12, 14, and 17 kDa that varied between baseline, pre-TMA, and TMA time points for each patient. By densitometric analysis, the 17-kDa fragment in the pre-TMA samples differed significantly from TMA diagnosis (p < 0.0001). There was no significant difference in the concentrations of the 12-kDa and 14-kDa fragments.


The 17-kDa haptoglobin degradation product may represent a novel early serum biomarker for TA-TMA that could potentially allow for earlier diagnosis and intervention.


Thrombotic microangiopathy Hematopoietic stem cell transplant Biomarker Haptoglobin 



This study was supported by NIH P50 DK096418.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

This was an analysis of a previously collected, prospective study that was approved by the institutional review board.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© IPNA 2018

Authors and Affiliations

  1. 1.Division of Nephrology and Hypertension, Cincinnati Children’s Hospital Medical CenterUniversity of CincinnatiCincinnatiUSA
  2. 2.Division of Bone Marrow Transplantation, Cincinnati Children’s Hospital Medical CenterUniversity of CincinnatiCincinnatiUSA
  3. 3.Division of Nephrology, The Children’s Hospital of Philadelphia and the Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA

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