血栓性血小板減少性紫斑病

Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening complication of transcatheter aortic valve replacement (TAVR). Because early thrombocytopenia after TAVR is common and usually benign, iTTP may be overlooked. An 87-year-old man underwent successful transaxillary TAVR. His platelet count fell from 210 to 16×10³/µL within 72 hours, with hemoglobin declining from 9.5 to 6.8 g/dL. There were no bleeding, neurological, or renal manifestations. Laboratory findings were consistent with microangiopathic hemolytic anemia, and ADAMTS13 activity was <1% (French score 3), confirming iTTP. Treatment with plasma exchange, corticosteroids, caplacizumab, and rituximab led to rapid platelet recovery. The diagnosis of iTTP should be considered in patients presenting with unexplained thrombocytopenia and hemolysis after TAVR, even when asymptomatic. Early recognition and prompt initiation of therapy are essential to improve outcomes.

Atypical hemolytic uremic syndrome (aHUS) is a rare disorder that affects individuals of any age. It is caused by genetic abnormalities of the alternative complement pathway, arising from inherited or de novo mutations, or from acquired factors such as autoantibodies against complement proteins, including complement factor H. Clinically, aHUS is characterized by the classic triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. However, its clinical presentation may be difficult to distinguish from typical hemolytic uremic syndrome and thrombotic thrombocytopenic purpura. aHUS is driven by uncontrolled activation of the alternative complement pathway, leading to endothelial injury and microvascular thrombosis. Atypical HUS may also occur after kidney transplantation, either as recurrence of the native disease or as de novo post-transplant thrombotic microangiopathy. The diagnosis of post-transplant aHUS relies on the presence of the above-mentioned classic triad and the exclusion of secondary causes such as thrombotic thrombocytopenic purpura and Shiga toxin-associated HUS. The pathophysiology is similar, involving either genetic mutations affecting complement proteins or acquired dysregulation due to autoantibodies. Historically, plasma exchange was used to replace dysfunctional complement regulators and remove circulating autoantibodies, with variable success. After transplantation, the disorder may either recur or develop de novo. In the past, plasmapheresis was considered beneficial. More recently, the availability of eculizumab, an anti-C5 monoclonal antibody that inhibits terminal complement activation, has become the treatment of choice, either as monotherapy or with plasma exchange. However, uncertainties remain regarding the optimal duration and dosing of long-term therapy, particularly in transplant recipients.

Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening hematologic disorder characterized by widespread microvascular thrombosis. Classic clinical features include: fever, microangiopathic hemolytic anemia, thrombocytopenia, renal dysfunction, and neurologic abnormalities, such as altered mental status, confusion, or coma. Prompt recognition and initiation of plasma exchange therapy in the emergency department (ED) are essential for patient survival. We report a case of a 40-year-old female who presented to the ED with a vague complaint of joint pain and no remarkable findings on physical examination. Despite the absence of hallmark features, further evaluation revealed a diagnosis of TTP. This case underscores the diagnostic challenge posed by atypical TTP presentations and highlights the importance of maintaining a high index of suspicion, even in the absence of classic clinical signs.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening thrombotic microangiopathy caused by severe ADAMTS13 deficiency due to anti-ADAMTS13 autoantibodies. The resulting persistence of ultra-large von Willebrand factor (VWF) multimers promotes uncontrolled platelet adhesion and aggregation in the microcirculation, leading to thrombocytopenia, microangiopathic hemolytic anemia, and ischemic organ injury. Therapeutic plasma exchange (TPE) has transformed the prognosis of iTTP by removing circulating autoantibodies and replenishing functional ADAMTS13, and it remains a life-saving intervention in acute disease. However, TPE is invasive, resource-intensive, dependent on central venous access and plasma availability, and associated with catheter-related, hemodynamic, metabolic, infectious, and plasma-related adverse events. The therapeutic landscape has changed substantially with the incorporation of immunosuppression and the anti-VWF nanobody caplacizumab. Caplacizumab rapidly blocks VWF-platelet interactions at the effector level, whereas corticosteroids and B-cell-directed therapy target the autoimmune basis of iTTP. Triple therapy with TPE, immunosuppression, and caplacizumab accelerates platelet recovery and reduces unfavorable outcomes. At the same time, accumulating observational evidence and early prospective data suggest that selected patients may achieve remission with caplacizumab plus immunosuppression without routine first-line TPE. This perspective review critically re-evaluates the role of TPE in contemporary iTTP management. We propose that TPE should no longer be viewed exclusively as an obligatory universal first-line intervention, but rather as a contextualized component of individualized, response-adapted care. TPE remains indispensable for severe, unstable, or refractory disease and must be immediately available when TPE-free treatment is attempted. Safe implementation of TPE-free strategies requires experienced centers, rapid ADAMTS13 testing, immediate access to caplacizumab and immunosuppression, careful patient selection, and close clinical and laboratory monitoring. Defining which patients can be treated safely without TPE is a central challenge for future trials and guideline development.

Background: Caplacizumab is a cornerstone in the management of immune-mediated thrombotic thrombocytopenic purpura (iTTP), in combination with plasma exchange (PEX) and immunosuppression. Pivotal trials and real-world data have demonstrated faster platelet count recovery and improved remission rates. Nevertheless, a subset of patients still experiences exacerbations or delayed response. Observational evidence suggests that unintended treatment interruptions may contribute to these unfavorable outcomes. Methods: We report on two patients with iTTP treated with caplacizumab and immunosuppression; PEX was used in Case 1 and as escalation therapy in Case 2. Laboratory parameters including platelet count, lactate dehydrogenase (LDH), ADAMTS13 activity, and anti-ADAMTS13 autoantibodies were monitored. Results: In the first case, a 29-year-old female experienced an exacerbation and ischemic complications after two individual caplacizumab doses were unintentionally missed on days 12 and 14. Subsequent continuous administration led to stabilization and recovery. In the second case, a 42-year-old male presented with hemolytic anemia, thrombocytopenia, and ADAMTS13 activity of 1% and was initially treated with prednisolone and caplacizumab without PEX. Two individual caplacizumab doses were unintentionally missed on days 3 and 5 and were followed by delayed treatment response and microembolic infarcts. Treatment escalation to PEX and rituximab and reinitiation of continuous caplacizumab administration led to clinical stabilization. Conclusions: Even brief interruptions of caplacizumab therapy may compromise outcomes in iTTP. Continuous administration and secured availability, together with serial monitoring of ADAMTS13 activity to guide treatment duration and discontinuation, are essential to improve patient care.