Bone marrow transplant-associated thrombotic microangiopathy without peripheral blood schistocytes: a case report and review of the literature

Abstract

BackgroundBone marrow transplant-associated thrombotic microangiopathy (TA-TMA) is a relatively frequent but under-recognized and under-treated hematopoietic stem cell transplant (HSCT) complication that leads to significant post-transplant morbidity and mortality. Classic TMA-defining laboratory abnormalities appear at different times in the course of TA-TMA development, with schistocytes often appearing later in the disease course. In some severe TMA cases, schistocytes may be absent due to increased endothelial permeability. Unfortunately, many clinicians continue to perceive the presence of schistocytes as an absolute requirement for TA-TMA diagnosis, which leads to delayed recognition and treatment of this potentially fatal transplant complication.MethodsPatient chart review and PubMed literature search using the term, “transplant-associated thrombotic microangiopathy”.Case presentationA 54-year-old male IgG kappa multiple myeloma underwent a reduced intensity allogeneic HSCT from a 9/10 HLA-matched unrelated donor after conditioning with fludarabine and melphalan. On day + 27, the patient developed acute kidney injury followed by repeated episodes of diarrhea and gastrointestinal bleeding attributed to graft versus host disease (GVHD) and cytomegalovirus (CMV) colitis. Repeated colonic biopsies suggested CMV infection and GVHD. Despite appropriate treatment with antiviral therapy and immunosuppressants, the patient’s condition continued to deteriorate. He experienced concomitant anemia and thrombocytopenia as well as elevated lactate dehydrogenase and low haptoglobin levels, but a TA-TMA diagnosis was not made due to an absence of schistocytes on peripheral smear. The patient expired secondary to uncontrolled gastrointestinal bleeding. A post-mortem analysis of the resection specimen revealed extensive TMA involving numerous arteries and arterioles in the ileal and colonic submucosa as well as in the muscularis propria and deep lamina propria of the mucosa.ConclusionsTA-TMA can occur in the absence of peripheral blood schistocytes. Our experience underscores the importance of considering the diagnosis of intestinal TA-TMA in patients with refractory post-transplant diarrhea and GI bleeding, even if all classic features are not present.

Transplant-Associated Thrombotic Microangiopathy in Pediatric Hematopoietic Cell Transplant Recipients: A Practical Approach to Diagnosis and Management

“…The presence of schistocytes on a peripheral blood smear should be the pathognomonic marker of TA-TMA, but because this is a subjective test requiring interpretation from a skilled microscopist, at many institutions it may be of very limited utility and therefore should not be relied upon to verify the diagnosis of TA-TMA (24). There is also the possibility that high vascular permeability leads to extravasation of the fragmented erythrocytes so that they are no longer in active circulation (19).…”

Acute Complications in Stem Cell Transplantation

“…Lastly, they pointed out that schistocytes are evident later in the course of the disease. The description of cases with histopathological evidence of TMA, without any schistocytes on smear, refutes the norm that they are sine-qua-non in TMA (Wirtschafter et al 2018;Murphree et al 2019). It has been hypothesized that this might be due to increased vascular permeability and extravasation of RBCs into tissues.…”

Acute liver failure with thrombotic microangiopathy due to sodium valproate toxicity: A case report

“…However, no fragmented erythrocytes were observed on the peripheral blood smear either before or after PE. Cases of TMA without the presence of fragmented erythrocytes on the peripheral blood smear have been reported previously[ 21 , 22 ]. This patient responded to PE and methylprednisolone.…”