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Duodenal Thrombotic Thrombocytopenic Purpura
Image of the Month Duodenal Thrombotic Thrombocytopenic Purpura DAVID J. OWENS and BARBARA JUNG Division of Gastroenterology, University of California, San Diego, San Diego, California
A
28-year-old woman with history of acute myelogenous leukemia for which she underwent allogeneic transplantation 2 years prior presented to our hospital with abdominal pain, nausea, and vomiting for 5 days. On examination, the patient was tachycardic but with otherwise stable vital signs. She displayed mild tenderness to palpation in the epigastrium but without guarding or rebound. Laboratory testing revealed anemia (hemoglobin, 7.3g/dL) and thrombocytopenia (platelets, 35,000). Her creatinine was 1.4 from 1.2 previously, and her lactate dehydrogenase level was elevated at 572 IU/L. Her peripheral smear was notable for fragmented red cells. A computed tomography scan showed abnormal thickening of the distal duodenum (Figure A). An esophagogastroduodenoscopy was performed showing multiple large, ulcerated, polypoid masses located in the distal duodenum (Figure B). Biopsies of these lesions revealed thrombotic microangiopathy (TMA) consistent with thrombotic thrombocytopenic purpura (TTP). TMA is a pathologic term describing microvascular thrombosis with fibrinoid necrosis of the vessel wall. TMA is the characteristic pathologic finding associated with TTP and hemolytic uremic syndrome.1 The classic clinical findings associated with TTP are hemolytic anemia, thrombocytopenia, neurologic deficits, renal dysfunction, and fever. Given the clinical picture and pathologic findings, our patient was diagnosed with TTP. TTP after allogeneic stem cell transplant occurs in approximately 5%–15% of all transplants with a mortality of 50% and is not associated with a deficiency in ADAMTS-13.2 ADAMTS-13 is a metalloproteinase in plasma that specifically
cleaves the A2 domain of von Willebrand factor (vWF) to regulate circulating vWF, a factor critical to hemostasis. Risk factors associated with TMA include graft-versus-host disease, older age, female sex, unrelated donor or mismatched donor, tacrolimus, sirolimus, and total body irradiation. Intestinal involvement is relatively uncommon and is usually discovered at autopsy. Fortunately for our patient, she responded well to conservative therapy that included a rapid tacrolimus taper and cessation of sirolimus. On hospital day 8 the patient’s platelet count and hemoglobin reached nadir, and she was discharged without significant abdominal pain. References 1. George JN, Selby GB. Thrombotic microangiopathy after allogeneic bone marrow transplantation: a pathologic abnormality associated with diverse clinical syndromes. Bone Marrow Tranplant 2004;33: 1073–1074. 2. Shimoni A, Yeshuran M, Hardan I, et al. Thrombotic microangiopathy after allogeneic stem cell transplantation in the era of reducedintensity conditioning: the incidence is not reduced. Biol Blood Marrow Transplant 2004;10:484 – 493.
© 2007 by the AGA Institute
1542-3565/07/$32.00 doi:10.1016/j.cgh.2006.12.016 CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2007;5:e15
A
28-year-old woman with history of acute myelogenous leukemia for which she underwent allogeneic transplantation 2 years prior presented to our hospital with abdominal pain, nausea, and vomiting for 5 days. On examination, the patient was tachycardic but with otherwise stable vital signs. She displayed mild tenderness to palpation in the epigastrium but without guarding or rebound. Laboratory testing revealed anemia (hemoglobin, 7.3g/dL) and thrombocytopenia (platelets, 35,000). Her creatinine was 1.4 from 1.2 previously, and her lactate dehydrogenase level was elevated at 572 IU/L. Her peripheral smear was notable for fragmented red cells. A computed tomography scan showed abnormal thickening of the distal duodenum (Figure A). An esophagogastroduodenoscopy was performed showing multiple large, ulcerated, polypoid masses located in the distal duodenum (Figure B). Biopsies of these lesions revealed thrombotic microangiopathy (TMA) consistent with thrombotic thrombocytopenic purpura (TTP). TMA is a pathologic term describing microvascular thrombosis with fibrinoid necrosis of the vessel wall. TMA is the characteristic pathologic finding associated with TTP and hemolytic uremic syndrome.1 The classic clinical findings associated with TTP are hemolytic anemia, thrombocytopenia, neurologic deficits, renal dysfunction, and fever. Given the clinical picture and pathologic findings, our patient was diagnosed with TTP. TTP after allogeneic stem cell transplant occurs in approximately 5%–15% of all transplants with a mortality of 50% and is not associated with a deficiency in ADAMTS-13.2 ADAMTS-13 is a metalloproteinase in plasma that specifically
cleaves the A2 domain of von Willebrand factor (vWF) to regulate circulating vWF, a factor critical to hemostasis. Risk factors associated with TMA include graft-versus-host disease, older age, female sex, unrelated donor or mismatched donor, tacrolimus, sirolimus, and total body irradiation. Intestinal involvement is relatively uncommon and is usually discovered at autopsy. Fortunately for our patient, she responded well to conservative therapy that included a rapid tacrolimus taper and cessation of sirolimus. On hospital day 8 the patient’s platelet count and hemoglobin reached nadir, and she was discharged without significant abdominal pain. References 1. George JN, Selby GB. Thrombotic microangiopathy after allogeneic bone marrow transplantation: a pathologic abnormality associated with diverse clinical syndromes. Bone Marrow Tranplant 2004;33: 1073–1074. 2. Shimoni A, Yeshuran M, Hardan I, et al. Thrombotic microangiopathy after allogeneic stem cell transplantation in the era of reducedintensity conditioning: the incidence is not reduced. Biol Blood Marrow Transplant 2004;10:484 – 493.
© 2007 by the AGA Institute
1542-3565/07/$32.00 doi:10.1016/j.cgh.2006.12.016 CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2007;5:e15