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Acquired thrombotic thrombocytopenic purpura (TTP) is an uncommon microangiopathic disorder that can have variable presentations and can be precipitated by a multitude of stressors to the body, most commonly sepsis. TTP is caused by a deficiency of ADAMTS13 leading to intravascular clotting causing thrombocytopenia and microangiopathic hemolytic anemia. TTP can be associated with various other pathologic conditions. One such rare association has been reported with diabetic ketoacidosis (DKA). Here, we present an even less appreciated presentation in association with DKA. A 62-year-old African American male with previously diagnosed prediabetes presented with DKA and developed hemodynamically significant bleeding. He was confirmed to have TTP that responded to plasmapheresis. TTP is a life-threatening illness if not treated urgently with plasmapheresis with or without rituximab. As acquired TTP most commonly occurs during stress on the body, it is important to treat the underlying stressor. Early identification and initiation of appropriate interventions are crucial to reducing mortality associated with TTP. Furthermore, we need to appreciate less commonly associated conditions such as DKA among patients.

Background: Immune-related adverse events (irAEs) are secondary reactions related to treatment with immune checkpoint inhibitors (ICIs). There have been six cases published reporting on an association between patients undergoing treatment with ICIs and the occurrence of acquired thrombotic thrombocytopenic purpura (TTP). Case report: We report a 61-year-old male receiving treatment with chemoimmunotherapy followed by pembrolizumab maintenance therapy for advanced non-small-cell lung cancer, presenting with bleeding symptoms, anemia, and thrombocytopenia. The patient received pembrolizumab seven times in total, in three-week cycles. Laboratory testing demonstrated hemolytic anemia, which, in combination with other findings, suggested thrombotic microangiopathy (TMA). PLASMIC scoring and specialized testing with ADAMTS13 activity and inhibitor confirmed a diagnosis of TTP. The patient was started on therapy with plasmapheresis and glucocorticoids, resulting in clinical improvement. The patient chose to leave the hospital under the care of home hospice and died approximately one month after being discharged. Conclusions: Of the six cases of ICI-induced TTP, only one other was treated with pembrolizumab to our knowledge to date. Our patient experienced an adverse reaction marked by thrombocytopenia and hematuria after drug exposure. With symptom improvement after ICI discontinuation and recurrence on readministration, a presumptive diagnosis of ICI-associated TTP was made. This case report and literature review emphasize the need for close observation of patients undergoing ICI therapy for potential rare irAEs. The further investigation aimed at the study of risk factors, disease severity, and treatment response to this form of secondary TTP is needed to guide treatment decisions.

Thrombotic thrombocytopenic purpura (TTP) is a rare but a potentially fatal condition. Although the majority of TTP cases are of unknown etiology, certain viral infections, malignancies, and medications have been linked to the acquired form of the illness. Regardless of the underlying etiology, TTP remains a great challenge diagnostically and therapeutically. TTP remains a very uncommon complication of HIV. We reviewed the current literature to better understand the relationship between HIV and TTP and address some of the major obstacles that may impede or delay the correct diagnosis. Here, we present a case of a 28-year-old male with complaints of light-headedness, fatigue, and gingival bleeding. He was found to have severe anemia and thrombocytopenia. He tested positive for the HIV and was then diagnosed with TTP. Despite needing endotracheal intubation for airway protection, he clinically improved with packed red blood cells, plasmapheresis, and highly active antiretroviral therapy.

Thrombotic thrombocytopenic purpura (TTP) is thrombotic microangiopathy that is universally fatal if not promptly recognized and treated. Standard treatment includes plasma exchange (PLEX) therapy and immunosuppression. We present a case of an 80 years old African American male with a past medical history significant for essential hypertension, chronic obstructive pulmonary disease, and a recent TTP diagnosis for which he was treated with PLEX, glucocorticoids, and rituximab. The patient presented with complaints of shortness of breath of four days duration. He was hypoxemic on presentation; other vital signs were within normal limits. The basic metabolic panel and complete blood count were unremarkable. A computed tomography (CT) of the chest with contrast showed right lower lobe segmental and subsegmental pulmonary emboli. He was initiated on intravenous heparin therapy. During hospitalization, he had progressive clinical deterioration with progressive hypoxemia. A repeat CT scan demonstrated bilateral pulmonary infiltrates. The patient underwent bronchoscopy due to concerns of opportunistic infections in view of his recent immunosuppressive treatment. Bronchoalveolar lavage revealed cytomegalovirus (CMV), and the patient was initiated on ganciclovir. CMV pneumonia has been reported after rituximab therapy in patients with lymphomas and lymphoproliferative disorders. To our knowledge, this is the first case of CMV pneumonia after rituximab therapy in a patient with TTP.

Acquired thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy with varied etiology and manifestations. It is uncommon for acute pancreatitis to trigger TTP. A 59-year-old man hospitalized with acute pancreatitis developed fever, acute kidney injury, thrombocytopenia, and microangiopathic hemolytic anemia (MAHA) on his second day in the hospital. Based on clinical suspicion and a high PLASMIC score indicating a severe deficiency in ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type 1 motif no. 13) activity, a presumptive diagnosis of TTP was made. He was treated with plasmapheresis with improvement in his hemoglobin and platelet count. Severely deficient ADAMTS13 activity causing accumulation of large von Willebrand factor (VWF) multimers and subsequent formation of platelet rich microthrombi are thought to be the mechanisms of development of TTP. Proinflammatory mediators released during the systemic inflammatory response seen in acute pancreatitis can promote VWF activity and inhibit ADAMTS13 activity. Diffuse endothelial injury as a result of the inhibition of vascular endothelial growth factor (VEGF)-mediated endothelial protection as well as production of excessive reactive oxygen species during an episode of acute pancreatitis also contributes to the pathogenesis of TTP. Thrombocytopenia and MAHA in a systemic inflammatory state should raise the suspicion for TTP. The PLASMIC score can further aid in the diagnosis and early initiation of plasmapheresis, which is key to the outcome.

Thrombotic thrombocytopenic purpura (TTP) is usually defined as microangiopathy characterized by low platelet count and low red blood cell count, i.e., hemolytic anemia. It can either be acquired or immune-mediated. TTP requires quick diagnostic identification and emergent management. According to the evidence-based guidelines, the recommended therapy is plasma exchange and immunosuppression. Caplacizumab is used alongside the standard recommended therapy. Caplacizumab is a monoclonal antibody (Mab) that binds to von Willebrand factor (VWF). This prevents A1 VWF to bind platelet glycoprotein 1b receptor. The recommended dosage for this drug is 10mg. At the start, 10mg intravenous (IV) dose is given before plasma exchange, followed by daily 10mg subcutaneous (SC) dose after plasma exchange. Moreover, the SC dose is continued even after the daily plasma exchange is stopped. This review aims to consolidate findings related to the efficacy of this recently approved drug.

Acquired thrombotic thrombocytopenic purpura is a combination of thrombocytopenia with microangiopathic hemolytic anemia. A 62-year-old female was transferred from an outside hospital for rapidly worsening mental status and severe thrombocytopenia. Laboratory studies were significant for reduced hemoglobin and platelet count along with raised blood urea nitrogen, creatinine, and serum lactate dehydrogenase levels. Peripheral smear showed numerous schistocytes and further testing showed low ADAMTS13 activity, high ADAMTS13 inhibitor, and positive hepatitis C virus antibody with a high hepatitis C virus ribonucleic acid (RNA) load. The patient was diagnosed with acquired thrombotic thrombocytopenic purpura and started on plasma exchange and steroids. Since no response was achieved until day four of treatment, weekly rituximab was initiated. After the initial two doses of rituximab, she showed significant improvement clinically. ADAMTS13 levels returned back to normal. Cyclosporine was added, following which platelet counts were normalized. Cyclosporine was discontinued, plasma exchange and steroids were slowly tapered off. Follow-up visits showed that the patient is off treatment and continues to be in remission and on regular treatment for hepatitis C. Acquired thrombotic thrombocytopenic purpura is a hematological emergency. Our patient remained refractory to standard therapies and required rituximab and immunosuppressive agents like cyclosporine. We describe the association of active hepatitis C with acquired thrombotic thrombocytopenic purpura that was refractory to plasma exchange, high dose steroids and rituximab. As per our knowledge, this is the first case in the literature to describe a possible association between active hepatitis C and acquired thrombotic thrombocytopenic purpura.