Predictive Value of Plasma d-Dimer Levels for Cancer-related Stroke: A 3-Year Retrospective Study

Guo, Yi-Jen; Chang, Ming-Feng; Chen, Po‐Lin; Lee, Yu-Shan; Chang, Yeun‐Chung; Liao, Yi‐Chu

doi:10.1016/j.jstrokecerebrovasdis.2013.10.022

Cited by 52 publications

(68 citation statements)

References 23 publications

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“…4,18,19 There is still no consensus of its relative importance compared with classical risk factors 20 and the lack of specificity and sensitivity of coagulation markers, such as D-dimer levels, should be kept in mind. 7 The recent literature 5,7,8,19,21,22 significantly higher levels of D-dimers in cancer patients, especially in those with active malignancy 8,22 and metastatic disease. 7 In our study, D-dimers were higher in the cancer cohort and most patients had extensive or systemic disease, although these findings have to be interpreted with caution as the majority of patients did not have an evaluation of fibrin degradation products.…”

Section: Discussionmentioning

confidence: 99%

Acute Ischemic Stroke on Cancer Patients, a Distinct Etiology? A Case-Control Study

2015

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Discussion: In our case-control study two subsets of cancer patients were delineated. In a subgroup, cancer and stroke co-exist, sharing traditional vascular risk factors. In another subset of patients, stroke appears to be directly related to the presence of a malignancy, where hypercoagulopathy turns out to be a decisive mechanism. Conclusion:In clinical grounds, hypercoagulopathy as stroke etiology should prompt the physician to screen the patient for occult cancer.

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Section: Discussionmentioning

confidence: 99%

Acute Ischemic Stroke on Cancer Patients, a Distinct Etiology? A Case-Control Study

2015

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“…29 The peak concentrations are in the order of 50 mg/mL, [30][31][32][33][34] which is sufficient to induce only weak inhibition of aggregation and secretion to low concentrations of collagen. This inhibitory effect is readily overcome by moderate increases in the collagen concentration.…”

Section: Discussionmentioning

confidence: 99%

Fibrin and D-dimer bind to monomeric GPVI

et al. 2017

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Key Points• GPVI is the major signaling receptor for fibrin in human platelets; the GPVI binding site is located in the fibrin D-dimer region.• D-dimer blocks platelet aggregation by fibrin and collagen but not by a collagen-related peptide, suggesting a distinct binding epitope.Fibrin has recently been shown to activate platelets through the immunoglobulin receptor glycoprotein VI (GPVI). In the present study, we show that spreading of human platelets on fibrin is abolished in patients deficient in GPVI, confirming that fibrin activates human platelets through the immunoglobulin receptor. Using a series of proteolytic fragments, weshow that D-dimer, but not the E fragment of fibrin, binds to GPVI and that immobilized D-dimer induces platelet spreading through activation of Src and Syk tyrosine kinases. In contrast, when platelets are activated in suspension, soluble D-dimer inhibits platelet aggregation induced by fibrin and collagen, but not by a collagen-related peptide composed of a repeat GPO sequence or by thrombin. Using surface plasmon resonance, we demonstrate that fibrin binds selectively to monomeric GPVI with a K D of 302 nM, in contrast to collagen, which binds primarily to dimeric GPVI. These results establish GPVI as the major signaling receptor for fibrin in human platelets and provide evidence that fibrin binds to a distinct configuration of GPVI. This indicates that it may be possible to develop agents that selectively block the interaction of fibrin but not collagen with the immunoglobulin receptor. Such agents are required to establish whether selective targeting of either interaction has the potential to lead to development of an antithrombotic agent with a reduced effect on bleeding relative to current antiplatelet drugs.

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“…Certain biological markers such as increased C-reactive protein (CRP), an unspecific acute phase reactant, and elevated fibrinogen and D-dimer, signaling a hypercoagulable state, have been suggested to have predictive values for underlying cancer [12, 13]. Radiological findings such as multiple acute cerebral infarcts (MACI) and specific cancer-related stroke patterns on diffusion weighted imaging (DWI) have also been suggested [13-16]. …”

Section: Introductionmentioning

confidence: 99%

When to Screen Ischaemic Stroke Patients for Cancer

et al. 2018

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Background and Purpose: Ischemic stroke can be the first manifestation of cancer and it is therefore important to ascertain which stroke patients should be considered for cancer-diagnostic investigations. We aimed to determine the frequency of active cancer in patients with acute ischemic stroke and to compare clinical findings in stroke patients with active cancer to ischemic stroke patients with no history of cancer. Finally, we aimed to develop a predictive and feasible score for clinical use to uncover underlying malignancy. Methods: All ischemic stroke patients admitted to the stroke unit in the Department of Neurology, Haukeland University Hospital were consecutively included in the Norwegian Stroke Research Registry (NORSTROKE). Stroke etiology was determined by the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Data on cancer diagnoses was obtained from patients’ medical records and the Cancer Registry of Norway. Active cancer was defined as cancer diagnosis, metastasis of known cancer, recurrent cancer or receiving cancer treatment, all within 12 months before or after the index stroke. Based on variables independently associated with active cancer, a predictive score was developed using the area under the receiver operating characteristic (AUC-ROC) curves. Bayes’ theorem was used to calculate post-test probabilities of active cancer. Results: Of the 1,646 ischemic stroke patients included, 82 (5.0%) had active cancer. Increased D-dimer (OR = 1.1, 95% CI: 1.1–1.2, p = <0.001), lower Hb (OR = 0.6, 95% CI: 0.5–0.7, p = <0.001), smoking (OR = 2.2, 95% CI: 1.2–4.3, p = 0.02) and suffering a stroke of undetermined etiology (OR = 1.9, 95% CI: 1.1–3.3, p = 0.03) were factors independently associated with active cancer. These were included in the final predictive score which gave an AUC of 0.73 (95% CI: 0.65–0.81) in patients younger than 75 years of age. Assuming the prevalence of cancer to be 5%, the score shows that if a patient fulfills all 3 score points, the probability of active cancer is 53%. Conclusions: Active cancer was found in 5% of our ischemic stroke patients. We found that a clinical score comprising elevated D-dimer ≥3 mg/L, lower Hb ≤12.0 g/dL and previous or current smoking is feasible for predicting active cancer in ischemic stroke patients.

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Predictive Value of Plasma d-Dimer Levels for Cancer-related Stroke: A 3-Year Retrospective Study

Cited by 52 publications

References 23 publications

Acute Ischemic Stroke on Cancer Patients, a Distinct Etiology? A Case-Control Study

Acute Ischemic Stroke on Cancer Patients, a Distinct Etiology? A Case-Control Study

Fibrin and D-dimer bind to monomeric GPVI

When to Screen Ischaemic Stroke Patients for Cancer

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