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Patients with cancer and acute ischemic stroke (AIS) face high rates of recurrent thromboembolism or death.To examine whether hematologic and embolic biomarkers soon after AIS are associated with subsequent adverse clinical outcomes.We prospectively enrolled 50 adults with active solid tumor cancer and AIS at two hospitals from 2016 to 2020. Blood was collected 72-120 h after stroke onset. A 30-min transcranial Doppler (TCD) microemboli detection study was performed. The exposure variables were hematologic markers of coagulation (D-dimer, thrombin-antithrombin), platelet (P-selectin), and endothelial activation (thrombomodulin, soluble intercellular adhesion molecule-1 [sICAM-1], soluble vascular cell adhesion molecule-1 [sVCAM-1]), and the presence of TCD microemboli. The primary outcome was a composite of recurrent arterial/venous thromboembolism or death. We used Cox regression to evaluate associations between biomarkers and subsequent outcomes.During an estimated median follow-up time of 48 days (IQR, 18-312), 43 (86%) participants developed recurrent thromboembolism or death, including 28 (56%) with recurrent thromboembolism, of which 13 were recurrent AIS (26%). In unadjusted analysis, D-dimer (HR 1.6; 95% CI 1.2-2.0), P-selectin (HR 1.9; 95% CI 1.4-2.7), sICAM-1 (HR 2.2; 95% CI 1.6-3.1), sVCAM-1 (HR 1.6; 95% CI 1.2-2.1), and microemboli (HR 2.2; 95% CI 1.1-4.5) were associated with the primary outcome, whereas thrombin-antithrombin and thrombomodulin were not. D-dimer was the only marker associated with recurrent AIS (HR 1.2; 95% CI 1.0-1.5). Results were generally consistent in analyses adjusted for important prognostic variables.Markers of hypercoagulability and embolic disease may be associated with adverse clinical outcomes in cancer-related stroke.

Introduction: We previously showed that patients with cancer and acute ischemic stroke (AIS) have higher markers of coagulation, platelet, and endothelial activation, and more circulating microemboli than patients with AIS and no cancer. Herein, we evaluate whether these markers are associated with clinical outcomes in patients with cancer and AIS. Methods: In the MOST-Cancer prospective study, we enrolled 50 adults with active solid-tumor cancer and AIS at 2 New York hospitals from 2016-2020. We collected blood from participants 72-120 hours after stroke onset. We performed a 30-minute transcranial Doppler (TCD) microemboli detection study a median of 4 days after stroke onset. The exposure variables were hematological markers of coagulation (D-dimer, thrombin-antithrombin), platelet (P-selectin), and endothelial activation (thrombomodulin, soluble intercellular adhesion molecule-1 [sICAM-1], soluble vascular cell adhesion molecule-1 [sVCAM-1]), and the presence of microemboli on TCD. The primary outcome was a composite of recurrent arterial or venous thromboembolism or death. The secondary outcome was recurrent AIS. We used Cox regression to evaluate individual associations between biomarkers and subsequent outcomes. Results: Median age was 69 years (IQR, 60-76) and 24 participants (48%) were women. The most common cancers were lung (28%) and pancreatic (22%); 86% of participants had distant metastases. During a mean follow-up of 278 days (SD, 367), 43 (86%) participants had the primary outcome of recurrent thromboembolism or death, including 28 (56%) who had recurrent thromboembolism, 13 who had recurrent AIS (26%), and 30 (60%) who died. D-dimer, P-selectin, sICAM-1, sVCAM-1, and microemboli were associated with the composite outcome (Table). Similar results were seen for recurrent AIS. Conclusion: Markers of hypercoagulability and embolic disease were associated with adverse clinical outcomes in cancer-related stroke.

The functional activity of von Willebrand factor (VWF) is most frequently measured by using the ristocetin cofactor assay (VWF:RCo). However, the method's drawbacks include unsatisfactory precision, sensitivity and availability of automated system applications. We have developed an alternative assay (INNOVANCE VWF Ac) that is based on the binding of VWF to recombinant glycoprotein Ib (GPIb). Two gain-of-function mutations were introduced into a GPIb fragment, allowing an assay format without ristocetin. Fully automated assay applications are available for the BCS/BCS XP systems and the Sysmex CS-2000i, Sysmex CA-7000, Sysmex CA-1500 and Sysmex CA-560 systems.The INNOVANCE VWF Ac assay measuring range extends from 4 to 600% VWF for all systems except the Sysmex CA-560 system. Within-device precision values were found to be between 2 and 7%. The limit of detection was below 2.2% VWF. In a study on the BCS XP system, a total number of 580 sample results yielded a correlation to the VWF:RCo assay of r equal to 0.99 (slope = 0.96). Very similar results were observed when von Willebrand disease samples type 1, 2A, 2B, 2M, 2N and 3 were investigated with the new assay and the VWF:RCo assay. The excellent performance data and comparability to VWF:RCo, together with the ease of use, led us to the conclusion that the ristocetin cofactor assay can be replaced by the new GPIb-binding assay to reliably diagnosing patients with von Willebrand disease.

Complement protein C1q is involved in many immunoregulatory functions, such as modulating T-cell proliferation and regulating dendritic cell (DC) differentiation and maturation. C1q has at least two multi-functional cell surface receptors, cC1qR and gC1qR. While these receptors ostensibly lack a direct conduit into intracellular elements, they are known to form docking/signaling complexes with transmembrane partners. DC-SIGN (dendritic cell-specific-ICAM-grabbing-non integrin) is a C-type lectin expressed on the surface of DCs and involved in T-cell activation and endocytosis. Because SIGN-R1, a C-type lectin related to DC-SIGN has been shown to bind directly to C1q, we investigated whether DC-SIGN also binds to C1q and if DC-SIGN may act as a transmembrane partner for gC1qR and/or cC1qR. Using flow cytometry, we found that DC-SIGN, gC1qR and cC1qR are all present on the surface of human immature DCs (iDC) grown in culture. While antigen-capture ELISA experiments using iDC lysates showed that C1q, gC1qR and cC1qR directly or indirectly associate with DC-SIGN, immunofluorescence microscopy revealed that C1q and gC1qR, but not cC1qR co-localize with DC-SIGN on the surface of iDCs. The data suggest that DC-SIGN and gC1qR may directly associate on the surface of iDCs and regulate DC differentiation in a stage specific manner. Since both gC1qR and DC-SIGN have been shown to bind HIV, it is possible that the two receptors may play a role in the pathogenesis of HIV-AIDS.