174 M. KÖKSAL ET AL.
several organs. The underlying mechanism is a dysbal-
ance between von Willebrand factor (vWf) and von
Willebrand processing factor. [5] A local increase in vWf
is seen in classic haemolytic uremic syndrome (HUS), or
hamburger disease, where thrombi are mainly formed in
the kidney, resulting in renal failure and minimal sys-
temic symptoms. In familiar thrombotic thrombocyto-
penic purpura (TTP) the processing factor ADAMTS13
is decreased and systemic symptoms prevail. Between
these two ends of the spectrum there is a range of clinical
presentations. Cause, genetic make-up of the patient and
many other factors determine the presenting symptoms.
Causes are mainly infectious diseases and medication
related. The therapy is based on supply of vWf process-
ing factor by FFP. To supply enough FFP plasma ex-
change is required. In this patient MMC is the most
probable cause. [6] Our patient presented with haemo-
lytic anaemia, thrombocytopenia, renal failure and som-
nolence. The later developing sick sinus can also be due
to micro infarction of the heart. After excluding sepsis,
immune mediated hemolysis, and disseminated in-
travascular coagulation the diagnosis atypical HUS was
made. [6] MMC induced TMA has been described after
intravenous dosing. [4 ,7-9] It has been sugg ested that the
chance of developing TMA is related to the cumulative
dose. Below 36mg/m2 MMC no TMA is seen. [10] The
mechanism is not clear although direct endothelial dam-
age has been suggested. [4,7,11] MMC induced TMA
has never been described after a single HIPEC procedure.
We have no serum levels of MMC but considerable ab-
sorption is possible because of the large wound surface
created by the extensive surgery. However, systemic
toxicity was limited because no toxic leucopenia oc-
curred. MMC induced TMA is considered a late compli-
cation because toxicity has mainly been described after
repeated doses reaching the cumulative dose after weeks
or months. Our patient received more than the suggested
maximal dose in a single gift presuming that limited ab-
sorption from the abdomen would occur. Our patient
shows several other unique features. TMA occurred im-
mediately after a single intraperitoneal dose and re-
sponded well to th erapy. [6]
Patients treated with HIPEC are prone to surgical
complications and to systemic toxicity of the chemo-
therapy. [3] Both have many symptoms in common with
TMA syndrome. Subscribing these symptoms to toxicity
or complications is imminen t and a potentially lethal but,
when recognized, treatable disease can easily be missed.
2. References
[1] D. Baratti, S. Kusamura, D. Nonaka, M. Langer, S. An-
dreola, M. Favaro, et al., “Pseudomyxoma Peritonei:
Clinical Pathological And Biological Prognostic Factors
In Patients Treated With Cytoreductive Surgery And
Hyperthermic Intraperitoneal Chemotherapy (HIPEC),”
Annals of Surgical Oncology, Vol. 15, No. 2, 2008, pp.
526-534. doi:10.1245/s10434-007-9691-2
[2] T. Yan, M. Deraco, D. Baratti, S. Kusamura, D. Elias, O.
Glehen, et al., “Cytoreductive Surgery and Hyperthermic
Intraperitoneal Chemotherapy for Malignant Peritoneal
Mesothelioma: Multi-Institutional Experience,” Journal
of Clinical Oncology, Vol. 27, No. 36, 2009, pp. 6237-6242.
doi:10.1200/jco.2009.23.9640
[3] T. Chua, T. Yan, A. Saxena and D. Morris, “Should the
Treatment of Peritoneal Carcinomatosis by Cytoreductive
Surgery and Hyperthermic Intraperitoneal Chemotherapy
Still Be Regarded as a Highly Morbid Procedure?: A Sys-
tematic Review Of Morbidity And Mortality,” Annals of
Surgery, Vol. 249, No. 6, 2009, pp. 900-907.
doi:10.1097/SLA.0b013e3181a45d86
[4] P. J. Medina, J. M. Sipols and J. N. George, “Drug-Asso-
Ciated Thrombotic Thrombocytopenic Purpura-Hemoly-
tic Uremic Syndrome,” Current Opinion in Hematology,
Vol. 8, No. 5, 2001, pp. 286-293.
doi:10.1097/00062752-200109000-00004
[5] X. L. Zheng and J. E. Sadler, “Pathogenesis of Throm-
botic Microangiopathies,” Annual Review of Pathology,
Vol. 3, 2008, pp. 249-277.
doi:10.1146/annurev.pathmechdis.3.121806.154311
[6] C. M. Taylor, S. Machin, S. J. Wigmore and T. H. Good-
ship, “Clinical Practice Guidelines for the Management of
Atypical Haemolytic Uraemic Syndrome in the United
Kingdom,” British Journal of Haematology , Vol. 148, No.
1, 2010, pp. 37-47.doi:10.1111/j.1365-2141.2009.07916.x
[7] A. Zakarija and C. Bennett, “Drug-Induced Thrombotic
Microangiopathy,” Seminars in Thrombosis and Hemo-
stasis, Vol. 31, No. 6, 2005, pp. 681-690.
doi:10.1055/s-2005-925474
[8] D. C. Doll, R. B. Weiss and B. F. Issell, “Mitomycin: Ten
Years After Approval For Marketing,” Journal of Clini-
cal Oncology, Vol. 3, No. 2, 1985, pp. 276-286.
[9] J. B. Lesesne, N. Rothschild, B. Erickson, S. Korec, R.
Sisk, J. Keller, et al., “Cancer-Associated Hemolytic-Ure-
mic Syndrome: Analysis Of 85 Cases From A National
Registry,” Journal of Clinical Oncology, Vol. 7, No. 6,
1989, pp. 781-789.
[10] N. Ntukidem, C. Arce-Lara, G. A. Otterson, E. Kraut, S.
Cataland and T. Bekaii-Saab, “Capped-Dose Mitomycin
C: A Pooled Safety Analysis From Three Prospective
Clinical Trials,” Cancer Chemotherapy and Pharmacol-
ogy, Vol. 65, No. 2, 2010, pp. 319-324.
doi:10.1007/s00280-009-1036-3
[11] R. Shah, E. Beem, L. Sautina, S. I. Zharikov and M. S.
Segal, “Mitomycin- and Calcineurin-Associated HUS,
Endothelial Dysfunction and Endothelial Repair: A New
Paradigm For The Puzzle?,” Nephrology Dialysis Trans-
plantation, Vol. 22, No. 2, 2007, pp. 617-620.
doi:10.1093/ndt/gfl586
Copyright © 2011 SciRes. SS