User login
A Case Report on Bortezomib- Induced Hypotension: Rare Adverse Effect in Proteasome Inhibitor Therapy
Case Presentation
A 75-year-old man with chronic kidney disease, hypertension and diabetes mellitus presented with acute kidney injury (creatinine 5.2 from baseline 4.2) and a two-week history of increased urinary frequency. Labs revealed high anion gap metabolic acidosis, proteinuria, hematuria, pyuria, and acute on chronic anemia. He was diagnosed with kappa light chain nephropathy and multiple myeloma with 32% plasma cells on bone marrow biopsy. He began treatment with bortezomib, cyclophosphamide, and dexamethasone (Cy- BorD). Three days after cyclophosphamide and five days after bortezomib, the patient developed persistent hypotension with systolic BP in the 50s, unresponsive to fluids and Trendelenburg position. Due to end-stage renal disease with anuria, fluid resuscitation was limited. He required norepinephrine and was transferred to the ICU. Given instability, hemodialysis was deferred, and continuous renal replacement therapy was initiated. Shock evaluation included a CT abdomen showing enteritis versus ileus; however, infectious workup was negative. Cardiogenic shock was ruled out with a serial echocardiogram showing normal ejection fractions of 59-67% without significant valvular disease. The workup for adrenal insufficiency was negative. After the exclusion of other potential causes of shock, severe refractory hypotension was attributed to bortezomib toxicity.Hypotension is a known adverse effect of bortezomib. Orthostatic hypotension may occur in 8 to 9% of patients, and rarely, patients may experience heart failure, conduction disorders and arrhythmias, or cardiogenic shock. The pathologic mechanism of this toxicity is still poorly understood. Proposed mechanisms include direct endothelial toxicity as evidenced by thrombotic microangiopathy or impairment of sympathetic and parasympathetic nerve fibres. Most commonly, patients experience neurotoxicity, which may manifest as autonomic dysfunction or peripheral neuropathy. Cardiovascular complications are typically reversible. Our patient’s cardiac function remained within normal limits; therefore, his persistent hypotension was felt to be the result of direct toxicity from bortezomib rather than cardiogenic shock. Ultimately, blood pressure did improve, and vasopressors were discontinued. However, he continued to have orthostatic hypotension and continued to require supportive fludrocortisone, midodrine, and pyridostigmine. Goals of care have been discussed, and he wished to continue pursuing restorative care, with a plan for transition to carfilzomib versus daratumumab outpatient.
Case Presentation
A 75-year-old man with chronic kidney disease, hypertension and diabetes mellitus presented with acute kidney injury (creatinine 5.2 from baseline 4.2) and a two-week history of increased urinary frequency. Labs revealed high anion gap metabolic acidosis, proteinuria, hematuria, pyuria, and acute on chronic anemia. He was diagnosed with kappa light chain nephropathy and multiple myeloma with 32% plasma cells on bone marrow biopsy. He began treatment with bortezomib, cyclophosphamide, and dexamethasone (Cy- BorD). Three days after cyclophosphamide and five days after bortezomib, the patient developed persistent hypotension with systolic BP in the 50s, unresponsive to fluids and Trendelenburg position. Due to end-stage renal disease with anuria, fluid resuscitation was limited. He required norepinephrine and was transferred to the ICU. Given instability, hemodialysis was deferred, and continuous renal replacement therapy was initiated. Shock evaluation included a CT abdomen showing enteritis versus ileus; however, infectious workup was negative. Cardiogenic shock was ruled out with a serial echocardiogram showing normal ejection fractions of 59-67% without significant valvular disease. The workup for adrenal insufficiency was negative. After the exclusion of other potential causes of shock, severe refractory hypotension was attributed to bortezomib toxicity.Hypotension is a known adverse effect of bortezomib. Orthostatic hypotension may occur in 8 to 9% of patients, and rarely, patients may experience heart failure, conduction disorders and arrhythmias, or cardiogenic shock. The pathologic mechanism of this toxicity is still poorly understood. Proposed mechanisms include direct endothelial toxicity as evidenced by thrombotic microangiopathy or impairment of sympathetic and parasympathetic nerve fibres. Most commonly, patients experience neurotoxicity, which may manifest as autonomic dysfunction or peripheral neuropathy. Cardiovascular complications are typically reversible. Our patient’s cardiac function remained within normal limits; therefore, his persistent hypotension was felt to be the result of direct toxicity from bortezomib rather than cardiogenic shock. Ultimately, blood pressure did improve, and vasopressors were discontinued. However, he continued to have orthostatic hypotension and continued to require supportive fludrocortisone, midodrine, and pyridostigmine. Goals of care have been discussed, and he wished to continue pursuing restorative care, with a plan for transition to carfilzomib versus daratumumab outpatient.
Case Presentation
A 75-year-old man with chronic kidney disease, hypertension and diabetes mellitus presented with acute kidney injury (creatinine 5.2 from baseline 4.2) and a two-week history of increased urinary frequency. Labs revealed high anion gap metabolic acidosis, proteinuria, hematuria, pyuria, and acute on chronic anemia. He was diagnosed with kappa light chain nephropathy and multiple myeloma with 32% plasma cells on bone marrow biopsy. He began treatment with bortezomib, cyclophosphamide, and dexamethasone (Cy- BorD). Three days after cyclophosphamide and five days after bortezomib, the patient developed persistent hypotension with systolic BP in the 50s, unresponsive to fluids and Trendelenburg position. Due to end-stage renal disease with anuria, fluid resuscitation was limited. He required norepinephrine and was transferred to the ICU. Given instability, hemodialysis was deferred, and continuous renal replacement therapy was initiated. Shock evaluation included a CT abdomen showing enteritis versus ileus; however, infectious workup was negative. Cardiogenic shock was ruled out with a serial echocardiogram showing normal ejection fractions of 59-67% without significant valvular disease. The workup for adrenal insufficiency was negative. After the exclusion of other potential causes of shock, severe refractory hypotension was attributed to bortezomib toxicity.Hypotension is a known adverse effect of bortezomib. Orthostatic hypotension may occur in 8 to 9% of patients, and rarely, patients may experience heart failure, conduction disorders and arrhythmias, or cardiogenic shock. The pathologic mechanism of this toxicity is still poorly understood. Proposed mechanisms include direct endothelial toxicity as evidenced by thrombotic microangiopathy or impairment of sympathetic and parasympathetic nerve fibres. Most commonly, patients experience neurotoxicity, which may manifest as autonomic dysfunction or peripheral neuropathy. Cardiovascular complications are typically reversible. Our patient’s cardiac function remained within normal limits; therefore, his persistent hypotension was felt to be the result of direct toxicity from bortezomib rather than cardiogenic shock. Ultimately, blood pressure did improve, and vasopressors were discontinued. However, he continued to have orthostatic hypotension and continued to require supportive fludrocortisone, midodrine, and pyridostigmine. Goals of care have been discussed, and he wished to continue pursuing restorative care, with a plan for transition to carfilzomib versus daratumumab outpatient.
From Health to Hemolysis: A Unique Presentation of TTP in an Otherwise Well Individual
Background
Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening hematologic disorder that includes a combination of thrombocytopenia, microangiopathic hemolytic anemia, and neuropsychiatric symptoms. The pathogenesis of TTP is due to a deficiency of ADAMTS13. While early initiation of plasma exchange is vital for managing TTP, differentiating TTP from disseminated intravascular coagulation, hemolytic uremic syndrome, and heparin-induced thrombocytopenia is challenging. Standard of care includes plasma exchange and immunosuppressive agents. Relapse occurs in 36% of patients, and mortality rates range from 10% to 20%. Caplacizumab was approved in 2019 for the treatment of adults with acquired TTP in conjunction with the above therapies. Here we report a case of a 52- year-old patient treated with caplacizumab for TTP at our institution.
Case Presentation
A 52-year-old Jehovah’s Witness female with no prior hematologic history presented with one-day history of nausea and vomiting. While the patient did not initially present with neurologic changes, she did later become acutely confused, endorsing tactile hallucinations. Physical exam was notable for scattered ecchymoses on the upper extremities. Labs were notable for thrombocytopenia with a platelet count of 30,000, hemoglobin 13.6, and creatinine 1.5. There was evidence of hemolysis with elevated LDH, fibrinogen, undetectable haptoglobin, and schistocytes on peripheral smear. Her PLASMIC score on admission was 6. ADAMTS13 level was low at 0.5. The patient was initially on plasma exchange therapy and IV steroids, but with her degree of multiorgan dysfunction, treatment was escalated to caplacizumab and weekly rituximab. Platelet counts started to improve on hospital day four, and at the time of discharge, symptoms improved. Patient’s mental status returned to baseline and labs showed normalization of platelet count, hemoglobin, with improvement in kidney function.
Discussion
Early diagnosis and treatment of TTP is crucial for improving outcomes for patients. Here we show that treatment with caplacizumab is an effective adjunct therapy to steroids and plasmapheresis in patients with severe disease and multiorgan dysfuncition and is effective in rapidly improving hematologic abnormalities. While our patient was ultimately accepting of plasma exchange, caplacizumab could be considered as an off-label therapy in patients who are Jehovah’s witness patients and refuse treatment with plasma.
Background
Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening hematologic disorder that includes a combination of thrombocytopenia, microangiopathic hemolytic anemia, and neuropsychiatric symptoms. The pathogenesis of TTP is due to a deficiency of ADAMTS13. While early initiation of plasma exchange is vital for managing TTP, differentiating TTP from disseminated intravascular coagulation, hemolytic uremic syndrome, and heparin-induced thrombocytopenia is challenging. Standard of care includes plasma exchange and immunosuppressive agents. Relapse occurs in 36% of patients, and mortality rates range from 10% to 20%. Caplacizumab was approved in 2019 for the treatment of adults with acquired TTP in conjunction with the above therapies. Here we report a case of a 52- year-old patient treated with caplacizumab for TTP at our institution.
Case Presentation
A 52-year-old Jehovah’s Witness female with no prior hematologic history presented with one-day history of nausea and vomiting. While the patient did not initially present with neurologic changes, she did later become acutely confused, endorsing tactile hallucinations. Physical exam was notable for scattered ecchymoses on the upper extremities. Labs were notable for thrombocytopenia with a platelet count of 30,000, hemoglobin 13.6, and creatinine 1.5. There was evidence of hemolysis with elevated LDH, fibrinogen, undetectable haptoglobin, and schistocytes on peripheral smear. Her PLASMIC score on admission was 6. ADAMTS13 level was low at 0.5. The patient was initially on plasma exchange therapy and IV steroids, but with her degree of multiorgan dysfunction, treatment was escalated to caplacizumab and weekly rituximab. Platelet counts started to improve on hospital day four, and at the time of discharge, symptoms improved. Patient’s mental status returned to baseline and labs showed normalization of platelet count, hemoglobin, with improvement in kidney function.
Discussion
Early diagnosis and treatment of TTP is crucial for improving outcomes for patients. Here we show that treatment with caplacizumab is an effective adjunct therapy to steroids and plasmapheresis in patients with severe disease and multiorgan dysfuncition and is effective in rapidly improving hematologic abnormalities. While our patient was ultimately accepting of plasma exchange, caplacizumab could be considered as an off-label therapy in patients who are Jehovah’s witness patients and refuse treatment with plasma.
Background
Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening hematologic disorder that includes a combination of thrombocytopenia, microangiopathic hemolytic anemia, and neuropsychiatric symptoms. The pathogenesis of TTP is due to a deficiency of ADAMTS13. While early initiation of plasma exchange is vital for managing TTP, differentiating TTP from disseminated intravascular coagulation, hemolytic uremic syndrome, and heparin-induced thrombocytopenia is challenging. Standard of care includes plasma exchange and immunosuppressive agents. Relapse occurs in 36% of patients, and mortality rates range from 10% to 20%. Caplacizumab was approved in 2019 for the treatment of adults with acquired TTP in conjunction with the above therapies. Here we report a case of a 52- year-old patient treated with caplacizumab for TTP at our institution.
Case Presentation
A 52-year-old Jehovah’s Witness female with no prior hematologic history presented with one-day history of nausea and vomiting. While the patient did not initially present with neurologic changes, she did later become acutely confused, endorsing tactile hallucinations. Physical exam was notable for scattered ecchymoses on the upper extremities. Labs were notable for thrombocytopenia with a platelet count of 30,000, hemoglobin 13.6, and creatinine 1.5. There was evidence of hemolysis with elevated LDH, fibrinogen, undetectable haptoglobin, and schistocytes on peripheral smear. Her PLASMIC score on admission was 6. ADAMTS13 level was low at 0.5. The patient was initially on plasma exchange therapy and IV steroids, but with her degree of multiorgan dysfunction, treatment was escalated to caplacizumab and weekly rituximab. Platelet counts started to improve on hospital day four, and at the time of discharge, symptoms improved. Patient’s mental status returned to baseline and labs showed normalization of platelet count, hemoglobin, with improvement in kidney function.
Discussion
Early diagnosis and treatment of TTP is crucial for improving outcomes for patients. Here we show that treatment with caplacizumab is an effective adjunct therapy to steroids and plasmapheresis in patients with severe disease and multiorgan dysfuncition and is effective in rapidly improving hematologic abnormalities. While our patient was ultimately accepting of plasma exchange, caplacizumab could be considered as an off-label therapy in patients who are Jehovah’s witness patients and refuse treatment with plasma.