Author details

Klara Gadó<sup>1</sup> \* and Gyula Domján<sup>2</sup>

\*Address all correspondence to: gadok@freemail.hu

1 Faculty of Health Sciences, Department of Clinical Studies, Semmelweis University of Medicine, Budapest, Hungary

2 Faculty of Medicine, 1st Department of Medicine, Semmelweis University of Medicine, Budapest, Hungary

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**Chapter 5**

**Provisional chapter**

**Interferon-Induced Thrombotic Microangiopathy**

**Interferon-Induced Thrombotic Microangiopathy**

DOI: 10.5772/intechopen.74226

Interferon (IFN) is an effective therapy for multiple disorders. An infrequently reported side effect is thrombotic microangiopathy (TMA): thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). We published the first comprehensive review analyzing this association with the following observations: (1) there was a higher incidence of IFN-induced TMA in myeloproliferative disorders (chronic myelogenous leukemia (CML)) than that in nonmalignant disorders (multiple sclerosis (MS), chronic hepatitis C virus infection (HCV)); (2) mean age at diagnosis was 47 years; (3) there was rare association with hairy cell leukemia (HCL), Sezary syndrome (one case each) and no cases reported for polycythemia vera (PV); (4) sex distribution was balanced (exception of higher prevalence in females for MS); (5) TMA was insidious in onset with long incubation periods (average treatment duration 40.4 months); (6) comparative analysis of mean time (months) to onset of TMA ensuing cumulative IFN exposure was: MS 68.6 vs. CML 35.5 vs. HCV 30.4; (7) confirmed TTP (low ADAMTS 13 levels) was associated with the presence of an inhibitor; (8) outcome analysis revealed complete remission in 27 (40%), persistent chronic kidney disease in 28 (42%) and fatality in 12 patients (18%); (9)

corticosteroids, plasma exchange (PEX) and rituximab are effective therapies.

**Keywords:** thrombocytopenia, interferon, thrombotic microangiopathy (TMA), thrombotic thrombocytopenia purpura (TTP), myeloproliferative disorder, HCV

Thrombocytopenia is a common side effect of IFN treatment. TMA is a distinct clinical entity with potentially fatal consequences without precise and expeditious intervention. Classic clinical presentation includes a triad of anemia, thrombocytopenia, and evidence of microangiopathic hemolysis on the peripheral blood smear. The quintessential pathologic feature is the development of microvascular thrombi affecting small or larger vessels with variable

> © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2018 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Ajay Kundra, Mirela Andrei and Jen Chin Wang

Ajay Kundra, Mirela Andrei and Jen Chin Wang

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.74226

**Abstract**

**1. Introduction**

#### **Interferon-Induced Thrombotic Microangiopathy Interferon-Induced Thrombotic Microangiopathy**

DOI: 10.5772/intechopen.74226

Ajay Kundra, Mirela Andrei and Jen Chin Wang Ajay Kundra, Mirela Andrei and Jen Chin Wang

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.74226

#### **Abstract**

Interferon (IFN) is an effective therapy for multiple disorders. An infrequently reported side effect is thrombotic microangiopathy (TMA): thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). We published the first comprehensive review analyzing this association with the following observations: (1) there was a higher incidence of IFN-induced TMA in myeloproliferative disorders (chronic myelogenous leukemia (CML)) than that in nonmalignant disorders (multiple sclerosis (MS), chronic hepatitis C virus infection (HCV)); (2) mean age at diagnosis was 47 years; (3) there was rare association with hairy cell leukemia (HCL), Sezary syndrome (one case each) and no cases reported for polycythemia vera (PV); (4) sex distribution was balanced (exception of higher prevalence in females for MS); (5) TMA was insidious in onset with long incubation periods (average treatment duration 40.4 months); (6) comparative analysis of mean time (months) to onset of TMA ensuing cumulative IFN exposure was: MS 68.6 vs. CML 35.5 vs. HCV 30.4; (7) confirmed TTP (low ADAMTS 13 levels) was associated with the presence of an inhibitor; (8) outcome analysis revealed complete remission in 27 (40%), persistent chronic kidney disease in 28 (42%) and fatality in 12 patients (18%); (9) corticosteroids, plasma exchange (PEX) and rituximab are effective therapies.

**Keywords:** thrombocytopenia, interferon, thrombotic microangiopathy (TMA), thrombotic thrombocytopenia purpura (TTP), myeloproliferative disorder, HCV
