Cablivi (caplacizumab-yhdp) / Sanofi - LARVOL DELTA

Progression From Early Multiterritorial Punctate Infarcts to Massive Stroke in Fulminant Thrombotic Thrombocytopenic Purpura Despite Aggressive Therapy: A Therapeutic Dilemma in Initiating Antithrombotic Therapy. (PubMed, Cureus) - "Despite aggressive treatment with plasma exchange, corticosteroids, rituximab, cyclophosphamide, and caplacizumab, the patient's condition worsened, progressing to a large left middle cerebral artery ischemic stroke in addition to multifocal infarctions, seizures, encephalopathy, and ultimately, respiratory failure. This case highlights the diagnostic and therapeutic challenges of refractory TTP and underscores the devastating neurologic complications that can occur despite maximal medical therapy. It also raises important questions about the dilemma of whether or when to initiate antithrombotic therapy in the setting of severe thrombocytopenia and ongoing microvascular thrombosis."

Journal • Cardiovascular • CNS Disorders • Epilepsy • Hematological Disorders • Ischemic stroke • Pain • Renal Disease • Respiratory Diseases • Thrombocytopenia • Thrombocytopenic Purpura • Thrombosis

Evaluating caplacizumab's potential to mitigate thrombosis risk in aortic valve stenosis: a microfluidic and computational approach. (PubMed, Lab Chip) - "At an effective concentration (30 nM), caplacizumab reduced platelet coverage by up to 90% in high shear conditions (4500 s-1) and effectively mitigated shear gradient-dependent platelet aggregation across all stenotic conditions. These findings highlight caplacizumab's therapeutic potential for thrombosis prevention in patients with aortic valve stenosis, offering a foundation for personalized antithrombotic approaches that could potentially reduce thrombotic complications associated with the disease."

Journal • Cardiovascular • Hematological Disorders • Thrombosis

High anti-ADAMTS13 IgG levels after plasma exchange predict delayed ADAMTS13 normalization in immune-mediated thrombotic thrombocytopenic purpura. (PubMed, Thromb Haemost) - "The latter finding has important clinical implications, as it suggests that measuring post-TPE anti-ADAMTS13 IgG levels may help identify patients who need additional immunosuppressive treatment to avoid delayed ADAMTS13 normalization."

Journal • Hematological Disorders • Thrombocytopenic Purpura

Microangiopathic Anemia. (PubMed, Transfus Med Hemother) - "Meanwhile, caplacizumab - an anti-von Willebrand factor humanized single-variable-domain immunoglobulin fragment - is approved for the treatment of iTTP...Complement inhibition with C5 targeted treatment, such as eculizumab or ravulizumab, is approved for the treatment of cmTMA...Identifying TMA and defining the pathophysiology of TMA is urgently necessary in patients with thrombocytopenia and hemolytic anemia with or without obvious organ damage. ADAMTS13 testing is the most important specific test to classify TMA."

Journal • Review • Anemia • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • Infectious Disease • Nephrology • Oncology • Thrombocytopenia • Thrombocytopenic Purpura

Prognostic relevance of early clinical and laboratory findings in immune-mediated thrombotic thrombocytopenic purpura. (PubMed, Res Pract Thromb Haemost) - "Despite modern treatments, including therapeutic plasma exchange, immunosuppression, and rituximab, early mortality-often due to cardiac and neurologic events-remains a concern...No patient treated with caplacizumab died during the observation period. These findings suggest that early cardiac and neurologic symptoms may not be definitive predictors of iTTP-related death. Instead, extremely high lactate dehydrogenase levels indicated a worse prognosis, highlighting the need for targeted monitoring and interventions in high-risk cases."

Journal • Hematological Disorders • Thrombocytopenic Purpura

Caplacizumab for pediatric immune thrombotic thrombocytopenic Purpura: A scoping review of current evidence. (PubMed, Blood Rev) - "Caplacizumab was administered at 5 mg (17 %), 10 mg (75 %), or 11 mg (8 %), alongside plasma exchange (22 % received >10 sessions) and immunosuppression (97 % corticosteroids, 92 % rituximab). However, variability in dosing and limited data on long-term effects highlight the need for pediatric-specific guidelines and prospective studies. This review supports caplacizumab as a promising adjunct in childhood iTTP but calls for further research to optimize its use in this vulnerable population."

Journal • Review • Hematological Disorders • Pediatrics • Thrombocytopenic Purpura

Press Release: Q2: double-digit sales and solid business EPS growth. 2025 sales guidance is now high single-digit growth, at upper end of range (GlobeNewswire) - "ALTUVIIIO (hemophilia A) sales were €291 million of which 82% were in the US. Growth was driven by continued patient switches from older plasma-derived and recombinant factor medicines and to a lesser extent from non-factor treatments. Rest of World sales of €53 million benefited from the launch in Japan and supply sales to the collaborator Sobi. The hemophilia A franchise (ALTUVIIIO and Eloctate combined) sales were €356 million and increased by 41.1%, primarily driven by ALTUVIIIO’s strong performance of €291 million, while Eloctate contributed €65 million...Rezurock (chronic graft-versus-host disease, third line) sales were €132 million and increased by 21.1%, driven by launches gaining further momentum in Europe (sales of €14 million) and in Rest of World (sales of €11 million), including in China...Cablivi (acquired thrombotic thrombocytopenic purpura) sales were €69 million...Qfitlia (hemophilia A and B) sales were €1 million..."

Sales • Chronic Graft versus Host Disease • Hemophilia • Hemophilia A • Hemophilia B • Thrombocytopenic Purpura

Small but mighty: the versatility of nanobodies in modern medicine. (PubMed, Nanoscale Horiz) - "Despite challenges in manufacturing and regulatory approval, the approval of caplacizumab and ongoing clinical trials underscore the growing impact of nanobody therapeutics. With their versatility and potential for precision and personalized medicine, nanobody-based technologies drive innovation across biomedical research and next-generation therapies."

Journal • Review • CNS Disorders • Immunology • Infectious Disease • Oncology • Targeted Protein Degradation

[Translated article] Caplacizumab in acute thrombotic thrombocytopenic purpura refractory to standard treatment. (PubMed, Farm Hosp) - No abstract available

Journal • Hematological Disorders • Thrombocytopenic Purpura

Relapse and beyond: Navigating the long-term clinical impacts of immune thrombotic thrombocytopenic purpura. (PubMed, Transfus Apher Sci) - "While more recent advances in the use of immunotherapy (e.g. rituximab and caplacizumab) have significantly improved acute survival and short-term exacerbation/relapse prevention, long-term complications of the disease remain a concern for survivors. Providers should possess heightened awareness of long-term complications and atypical manifestations of relapse in survivors. We advocate for further research and observational cohort studies to formulate standardized guidelines for surveillance and intervention to mitigate the chronic burden of iTTP."

Journal • Review • Alzheimer's Disease • Cardiovascular • CNS Disorders • Cognitive Disorders • Depression • Hematological Disorders • Hypertension • Mood Disorders • Psychiatry • Rare Diseases • Thrombocytopenic Purpura

SARS-CoV-2 ORF7a activates the endothelium to release von Willebrand factor that promotes thrombosis. (PubMed, Res Pract Thromb Haemost) - "We demonstrate for the first time that SARS-CoV-2 ORF7a may be one of the pathogenic factors contributing to COVID-19-associated thrombosis by activating the vascular endothelium to release ultralarge VWF, which promotes platelet adhesion and agglutination, and thrombus formation. Thus, a strategy specifically targeting VWF-platelet interaction, such as recombinant a disintegrin and metalloprotease with thrombospondin type 1 repeats, 13 (ADAMTS-13) and/or caplacizumab, may be efficacious in reducing COVID-19-associated thrombosis and mortality."

Journal • Cardiovascular • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Thrombosis

Anti-ADAMTS13 Antibodies Trajectory is Associated With ADAMTS13 Recovery in Immune-Mediated TTP. (PubMed, Am J Hematol) - "Current triplet regimens associating therapeutic plasma exchange (TPE), immunosuppression with corticosteroids and rituximab, and caplacizumab have dramatically improved the outcome of immune-mediated thrombotic thrombocytopenic purpura (iTTP). These results highlight the possibility of intensifying immunosuppression in an early period post-TPE to shorten time to ADAMTS13 activity recovery. Close monitoring of anti-ADAMTS13 antibodies titer may guide immunomodulation strategies, including additional courses of B-cell depleting agents when appropriate."

Journal • Hematological Disorders • Immunology • Thrombocytopenic Purpura

Plasma exchange-free therapeutic management of immune-mediated thrombotic thrombocytopenic purpura (PubMed, Rinsho Ketsueki) - "Currently, a phase 3 clinical trial (MAYARI) is evaluating the efficacy of caplacizumab and immunosuppressive therapy without TPE in treating acute immune-mediated TTP. This trial aims to validate a simplified treatment paradigm, potentially transforming the management of TTP by offering safe and effective alternatives to TPE."

Journal • Hematological Disorders • Thrombocytopenic Purpura • Thrombosis

Thrombotic thrombocytopenic purpura: early diagnosis and effective treatment in 2025. (PubMed, Intensive Care Med) - "The discovery of ADAMTS13 and its deficiency has led to breakthroughs in diagnosis and differential diagnoses, and the development of targeted treatments, including therapeutic plasma exchange, caplacizumab (an anti-VWF nanobody), and recombinant ADAMTS13. It also serves as a tribute to the collaborative efforts that have shaped our understanding of this disease over the past century. By raising awareness and sharing best practices, this educational initiative aims to further improve outcomes for patients with TTP and foster continued progress in the field."

Journal • Acute Kidney Injury • Cardiovascular • Critical care • Hematological Disorders • Nephrology • Renal Disease • Thrombocytopenia • Thrombocytopenic Purpura • Thrombosis

2025 focused update of the 2020 ISTH guidelines for management of thrombotic thrombocytopenic purpura. (PubMed, J Thromb Haemost) - "For patients with iTTP, no change to 2020's recommendations. For patients with cTTP, the panel supports ADAMTS-13 replacement. Where accessible, recombinant ADAMTS-13 provides the most favorable balance of benefits and risks. Otherwise, fresh frozen plasma may still be effective. Shared decision-making should include the benefits, the potential harms, and the burden of care."

Clinical guideline • Journal • Cardiovascular • Hematological Disorders • Thrombocytopenic Purpura • Thrombosis

EASIX, A NEW TOOL TO PREDICT RESPONSE AND REFRACTORINESS IN IMMUNE THROMBOTIC THROMBOCYTOPENIC PURPURA? (EHA 2025) - "All received corticosteroids and plasma exchange (PE), with or without caplacizumab and/or rituximab. We propose EASIX as a possible marker for monitoring endothelial damage in iTTP. EASIX normalization by day 7, prior to ADAMTS13 recovery (day 21), may allow earlier monitoring of treatment responses. Additionally, clinical relapses triggered a significant increase in EASIX, while biochemical relapses and isolated ADAMTS13 decreases did not, suggesting that endothelial activation may not correlate with isolated ADAMTS13 declines."

IO biomarker • Acute Graft versus Host Disease • Anemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Myelodysplastic Syndrome • Oncology • Respiratory Diseases • Thrombocytopenia • Thrombocytopenic Purpura

AI-BASED RISK SCORE FOR THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP): ENHANCING DIAGNOSTIC ACCURACY AND TREATMENT OPTIMIZATION. (EHA 2025) - "ISTH guidelines also recommend to consider the treatment with caplacizumab, prior to the diagnostic confirmation, if there is a very high pretest probability of TTP (positive predictive value (PPV)>90%).Two risk scores (PLASMIC and French) are commonly used to assess pretest probability of TTP... This model provides a robust, data-driven approach for early risk stratification in TMA. By reliably excluding low-risk patients it allows detection of most TTP cases prior to ADAMTS13 testing (S=96.6%). In a subsequent step, the model accurately identifies high-risk patients with 95.7% PPV, exceeding the ISTH recommendations (>90%)."

Hematological Disorders • Thrombocytopenic Purpura

Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura: single centre experience (ISTH 2025) - "They were successfully treated with rituximab or cyclophosphamide. All these patients achieved clinical remission and received further administrations of caplacizumab."

Clinical • Acute Kidney Injury • Anemia • Hematological Disorders • Nephrology • Renal Disease • Thrombocytopenia • Thrombocytopenic Purpura

Recovery of ADAMTS13 activity in immune thrombotic thrombocytopenic purpura: a retrospective study (ISTH 2025) - "On the other hand, an additive effect was observed for time to recovery of ADAMTS13 activity which increased from the cases with low levels of anti-ADAMTS13 IgG and not treated with caplacizumab to those with high levels of anti-ADAMTS13 IgG and treated with caplacizumab (Figure 1B). Table or Figure Upload"

Retrospective data • Hematological Disorders • Thrombocytopenic Purpura

An atypical presentation of acquired thrombotic thrombocytopenia (ISTH 2025) - "The patient was treated with PEX for 5 days, prednisone and caplacizumab for 33 days. Metastatic prostate cancer was diagnosed, the patient was treated with hormonal castration, achieving biochemical remission (PSA 2ng/mL). There was no recurrence of aTTP."

Acute Kidney Injury • Anemia • Genito-urinary Cancer • Oncology • Prostate Cancer • Renal Disease • Solid Tumor • Thrombocytopenia • Thrombocytopenic Purpura • HP

Effectiveness of adjunctive caplacizumab treatment in immune thrombotic thrombocytopenic purpura (ISTH 2025) - "Contrary, it could lead to more frequent early relapse due to premature PEX suspension and use of rituximab. Newly diagnosed iTTP patients had significantly higher inhibitor levels compared to relapse episodes (63 vs 34 U/L, p=0.045), and shorter hospitalization (10 vs 12 days, p=0.03), probably due to more CAPLA patients (30% vs 18%). Table or Figure Upload"

Hematological Disorders • Thrombocytopenic Purpura

Von Willebrand factor/ADAMTS13 fluctuations during the immune TTP follow-up (ISTH 2025) - "These trends were also noted in a woman with exacerbation and relapse, but not in two patients treated with caplacizumab (Fig.1C). Table or Figure Upload"

Hematological Disorders • Thrombocytopenia • Thrombocytopenic Purpura

Management of immune TTP without plasma exchange: lessons learned from the Austrian experience (ISTH 2025) - "Methods Immunosuppression with steroids and rituximab was started upfront, and caplacizumab continued daily until ADAMTS13 increases >20%. Three patients had acute viral infections (cytomegalovirus, human immunodeficiency virus, hepatitis B), one had received 3 units of platelet concentrate before TTP was recognized and one had immune thrombocytopenia. Up to 3 sessions of TPE were required to normalize platelet counts."

Cardiovascular • Cytomegalovirus Infection • Hematological Disorders • Hepatitis B • Hepatology • Human Immunodeficiency Virus • Immune Thrombocytopenic Purpura • Infectious Disease • Inflammation • Thrombocytopenia • Thrombocytopenic Purpura

Clinical Response and Refractoriness in Immune Thrombotic Thrombocytopenic Purpura (ISTH 2025) - P | "The anti-VWF nanobody caplacizumab is effective in rapidly terminating fatal thrombotic microangiopathyDespite frontline use of caplacizumab, prolonged times to platelet count recovery are occasionally observed in clinical practice, potentially indicating refractory iTTP...Differential analysis of time to platelet count doubling and time to platelet count normalization in patients based on the presence of concomitant diseases demonstrates a clear effect on the latter outcome parameter (Figure 2). Table or Figure Upload"

Clinical • Cytomegalovirus Infection • Epstein-Barr Virus Infections • Immunology • Infectious Disease • Pneumonia • Respiratory Diseases • Thrombocytopenic Purpura • HP

Caplacizumab and immunosuppression without plasma exchange in thrombotic thrombocytopenic purpura (ISTH 2025) - No abstract available

Late-breaking abstract • Hematological Disorders • Thrombocytopenic Purpura