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.
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.
Unintended Interruption of Caplacizumab Therapy Can Compromise Outcomes in Immune-Mediated Thrombotic Thrombocytopenic Purpura: Lessons from Two Clinical Cases
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.
Immune thrombotic thrombocytopenic purpura (iTTP) is a life-threatening thrombotic microangiopathy that can have acute neurological symptoms and resemble ischemic stroke. A 27-year-old Pakistani man was transported by ambulance after being found unconscious, unable to speak, and unable to move his right side, which was suspected to be a stroke. He had been unwell for two weeks, was clinically jaundiced, and had a possible seizure during the previous week. Urgent plain computed tomography (CT) and CT angiography of the brain were called and revealed no acute abnormality and no obvious large vessel occlusion. There was no evidence of acute infarction on magnetic resonance imaging. His National Institutes of Health Stroke Scale (NIHSS) score was 15/42, which is a moderate stroke. Laboratory studies showed hemoglobin 6.0 g/dL, platelet count 3x109/L, schistocytes on peripheral smear, lactate dehydrogenase 2139 U/L, haptoglobin <0.01 g/L, reticulocytosis, and mainly indirect hyperbilirubinemia. The clinical features were compatible with iTTP complicated with neurological involvement. The patient was treated with therapeutic plasma exchange daily, high-dose methylprednisolone, and rituximab. Platelets rose steadily to 199x109/L on day 8, bilirubin levels dropped to 14.2 µmol/L, and lactate dehydrogenase levels dropped to 259 U/L at discharge. Neurological recovery was quick, with resolution of the right-sided weakness by the fourth hospital day and an NIHSS score of 0. This case highlights that in young patients with stroke-like presentation, severe thrombocytopenia, and microangiopathic hemolytic anemia, prompt plasma exchange and immunosuppression can be lifesaving and should be considered in iTTP.
Primary immune thrombocytopenia (ITP) is an autoimmune mediated thrombocytopenia with destruction and impaired production of platelets. Though life-threatening bleeding can occur in ITP, bleeding symptoms are often mild relative to platelet count. ITP is also associated with an increased thromboembolic risk. Variations in platelet function may contribute to the bleeding and thrombotic phenotype of ITP. Vitamin D (VD) deficiency (VDD) has been linked to enhanced platelet function in healthy individuals and patients receiving dual antiplatelet therapy. As VDD is associated with several autoimmune diseases including ITP, we aimed to investigate the influence of serum VD levels on platelet function in ITP. We assessed P-selectin and activated GPIIb/IIIa expression in naïve and stimulated platelets, soluble P-selectin levels, bleeding severity, and mean platelet volume in 79 primary ITP patients from the Vienna ITP Biobank but found no association with VD levels. Thus, low VD levels do not correlate with enhanced platelet function in ITP. Further, bleeding was not associated with VD, adjusting for platelet count. In summary, VD does not seem to be the primary driver of platelet function in ITP.