A 73 y/o F was admitted with new onset seizure and altered mental status. PMH was significant for HTN and recently diagnosed multiple myeloma (MM). She had received bortezomib 4 days prior to admission, as part of chemotherapy regimen consisting of bortezomib and dexamethasone. On exam she was drowsy with stable vital signs, no neck stiffness, and few scattered bruises on skin. Rest of the neurological and other systemic exam was normal. Labs revealed Hb of 6.6, platelet count 17, WBC 16 with left shift, peripheral smear showed numerous schistocytes, LDH was 1349, and haptoglobin 6. A clinical diagnosis of TTP was made and patient was started on plasmapheresis. Patient received 5 consecutive days of plasma exchange, and showed a remarkable clinical improvement. She had complete resolution of AMS and no recurrence of seizures. Her labs steadily improved to Hb of 11.4, Platelet count 190, LDH 230 (on day 6)
TTP is a rare life threatening disorder, defined by the “classic pentad” of thrombocytopenia, micro angiopathic hemolytic anemia, neurologic symptoms, renal failure and fever. A variety of underlying causes including medications have been identified in the pathogenesis of TTP. The pathogenesis of TTP has been very well elucidated. Most cases of acquired idiopathic TTP are caused by severe deficiency of von Willebrand factor (vWF) cleaving metalloprotease, (ADAMTS13). This leads to accumulation of ultra large vWF multimers (ULvWF), which can attach to platelets and cause platelet aggregation and thrombi in multiple organs, which is the hallmark of TTP. Our patient also had low ADAMTS 13 activity < 5%, and high antibody level of 87 units (normal <18units).
Plasma exchange successfully removes the circulating autoantibody and the ULvWF multimers and replaces the missing ADAMTS13 protease activity.
Bortezomib is a proteasome inhibitor used in the treatment of MM. The underlying mechanism of bortezomib induced micro angiopathy may be related to direct microvascular toxicity initiated by endothelial injury. Interestingly bortezomib and related class of drugs are known to decrease the transcription of vascular endothelial growth factor (VEGF). This may also be playing a role in pathogenesis in TTP in this scenario.
Our patient had TTP associated with bortezomib, which was successfully treated by plasma exchange. To our knowledge this is the fourth reported case of bortezomib induced TTP in the medical literature.
We consider that knowing this possible association can help in early recognition and treatment planning. This is relevant considering the fact that bortezomib and other proteasome inhibitors are being increasingly used for MM treatment.
1.Diagnose TTP clinically and understand the pathogenesis.
2. Recognize bortezomib as a potential cause of TTP.
To cite this abstract:Nath R, Ganipisetti V, Parikh M, Meenakshisundaram C, Mahmutoglu D, Raj R. Bortezomib Associated Ttp. Abstract published at Hospital Medicine 2015, March 29-April 1, National Harbor, Md. Abstract 629. Journal of Hospital Medicine. 2015; 10 (suppl 2). https://www.shmabstracts.com/abstract/bortezomib-associated-ttp/. Accessed April 2, 2020.