Stroke secondary to cancer-associated coagulopathy: a systematic review.
Stroke is the second most common neurological complication in cancer patients after metastases. Cancer-associated coagulopathy (CAC) is an important mechanism of ischemic stroke in this population. We systematically reviewed the epidemiological, clinical, radiological, and pathophysiological features of CAC-related stroke, as well as associated biomarkers and treatment strategies.
A systematic search of PubMed/MEDLINE, Scopus, Cochrane Library, and Embase (2000-2025) was performed according to PRISMA 2020 guidelines. Search terms included "stroke", "cancer", "hypercoagulability", "coagulopathy", "disseminated intravascular coagulation", and "non-bacterial or marantic thrombotic endocarditis". Studies published in English or Spanish were included, whereas case reports and review articles were excluded. Data were synthesized qualitatively.
Eighty-two studies met inclusion criteria. CAC-related stroke occurs predominantly within six months of cancer diagnosis and is strongly associated with advanced or metastatic disease and a high risk of early recurrence. Adenocarcinoma, particularly lung and pancreatic cancer, is the most frequently associated histological subtype. Proposed mechanisms include mucin-mediated platelet aggregation, tissue factor-driven coagulation, extracellular vesicles, and neutrophil extracellular trap formation, leading to thromboinflammation and platelet-rich thrombi. D-dimer is the biomarker most consistently associated with recurrence and mortality, while C-reactive protein, fibrinogen, CA-125, and transcranial Doppler microembolic signals show limited specificity. Characteristic imaging findings include multiple infarcts involving more than two vascular territories, particularly the 'three territories sign'. Low-molecular-weight heparin and direct oral anticoagulants are the most commonly used secondary prevention strategies. Thirty-day mortality rates range from 25 to 50%.
CAC-related stroke is a distinct and underrecognized entity characterized by specific biological and radiological features and poor outcomes. Earlier recognition and optimized antithrombotic strategies may improve prognosis.
A systematic search of PubMed/MEDLINE, Scopus, Cochrane Library, and Embase (2000-2025) was performed according to PRISMA 2020 guidelines. Search terms included "stroke", "cancer", "hypercoagulability", "coagulopathy", "disseminated intravascular coagulation", and "non-bacterial or marantic thrombotic endocarditis". Studies published in English or Spanish were included, whereas case reports and review articles were excluded. Data were synthesized qualitatively.
Eighty-two studies met inclusion criteria. CAC-related stroke occurs predominantly within six months of cancer diagnosis and is strongly associated with advanced or metastatic disease and a high risk of early recurrence. Adenocarcinoma, particularly lung and pancreatic cancer, is the most frequently associated histological subtype. Proposed mechanisms include mucin-mediated platelet aggregation, tissue factor-driven coagulation, extracellular vesicles, and neutrophil extracellular trap formation, leading to thromboinflammation and platelet-rich thrombi. D-dimer is the biomarker most consistently associated with recurrence and mortality, while C-reactive protein, fibrinogen, CA-125, and transcranial Doppler microembolic signals show limited specificity. Characteristic imaging findings include multiple infarcts involving more than two vascular territories, particularly the 'three territories sign'. Low-molecular-weight heparin and direct oral anticoagulants are the most commonly used secondary prevention strategies. Thirty-day mortality rates range from 25 to 50%.
CAC-related stroke is a distinct and underrecognized entity characterized by specific biological and radiological features and poor outcomes. Earlier recognition and optimized antithrombotic strategies may improve prognosis.
Authors
Jauregui Larrañaga Jauregui Larrañaga, Gómez Arteta Gómez Arteta, Marta Enguita Marta Enguita, Erro Aguirre Erro Aguirre
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