thromboplastin and Intermittent-Claudication

Increased numbers of CD146-defined circulating endothelial cells (CECs), as are present in the peripheral blood of patients suffering acute coronary syndromes, imply injury to the endothelium. Endothelial damage can also be assessed by the measurement of plasma levels of von Willebrand factor (vWf). Increased levels of procoagulant plasma tissue factor (TF), arising from monocytes/macrophages and endothelial cells, is present in atherosclerosis. We hypothesised increased CECs in patients with ischaemic rest pain (IRP) of the lower limb due to peripheral atherosclerosis and comparable to that seen in patients with acute myocardial infarction (AMI), when compared to patients with intermittent claudication (IC) or healthy controls that would correlate with vWf and TF.. We recruited 20 patients in each of four groups: (i) IRP of the lower limb; (ii) AMI; (iii) 'stable' IC; and (iv) healthy controls. CD146-expressing CECs were measured by immumomagnetic separation and counting under a fluorescence microscope; plasma vWf and TF by ELISA.. In IRP, median (IQR) CEC levels were 3.5 (2.0-5.8) cells/ml, in IC were 1.1 (0.6-2.9) cells/ml, and in healthy controls were 1.0 (0.5-1.7) cells/ml (p<0.001). The levels of vWf (p=0.034) and TF (p=0.007) were also significantly different between the groups, with the highest levels in patients with IRP. Levels of CECs correlated with vWf (rs=0.4, p=0.002) and TF ( rs=0.296, p=0.021 ). In AMI, CEC levels were higher than those in IRP at 4.9 (3.6-8.4) cells/ml (p=0.0385).. This study demonstrates evidence of direct endothelial cell injury (i.e. raised CECs) in patients with IRP that correlated with vWf and TF, but that this is less severe than in AMI.

Topics: Aged; Analysis of Variance; Antigens, CD; Arteriosclerosis; CD146 Antigen; Endothelial Cells; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Female; Humans; Intermittent Claudication; Ischemia; Leg; Male; Membrane Glycoproteins; Middle Aged; Myocardial Infarction; Neural Cell Adhesion Molecules; Pain; Thromboplastin; von Willebrand Factor

Peripheral artery disease (PAD) and intermittent claudication are common in men aged over 55 years. Once the diagnosis has been made, very few patients suffer from a deterioration of the disease. Those that do deteriorate tend to do so due to thrombosis of an affected artery. It is apparent that the disruption in the vessel wall accounts for some of the cause of the thrombosis but blood constituents also play a role. We hypothesized that levels of soluble P-selectin (sP-sel, a marker of platelet activation), von Willebrand factor (vWf, an index of endothelial damage/dysfunction), tissue factor (TF, a coagulation protein involved in the 'extrinsic' coagulation pathway) and fibrinogen would be abnormally elevated in relation to disease severity and correlated with each other, and related to ethnicity, in a multiethnic population of patients with PAD. To test this hypothesis, we studied 234 patients (80% white, 7% Indo-Asian, 13% Afro-Caribbean) with confirmed PAD [ankle brachial pressure index (ABPI)< or =0.8] and 50 healthy controls. All of the indices studied were increased in patients over controls (p<0.05). None of the indices of the hypercoagulable state were significantly different between the three ethnic groups studied. Patients with ischaemic rest pain were shown to have higher levels of plasma fibrinogen (p<0.001) although none of the other prothrombotic markers were increased in this group. Furthermore, fibrinogen was higher in cases whose ABPI was below the median (<0.52) when compared to those less severely affected, with an inverse correlation between fibrinogen and ABPI (Spearman, r=-0.178, p=0.009). In conclusion, we found a prothrombotic state in patients with PAD with increased levels of markers of endothelial damage/dysfunction, platelet activation and thrombosis, which may contribute to the pathogenesis of this condition. However, disease severity was only related to plasma fibrinogen levels.

Topics: Aged; Arteries; Arteriosclerosis; Asian People; Biomarkers; Black People; Causality; Comorbidity; Endothelium, Vascular; Female; Fibrinogen; Humans; Intermittent Claudication; Male; P-Selectin; Peripheral Vascular Diseases; Risk Assessment; Risk Factors; Severity of Illness Index; Statistics as Topic; Thromboplastin; Thrombosis; United Kingdom; von Willebrand Factor; White People

In vitro studies suggest an association between raised levels of tissue factor and restenosis after coronary percutaneous transluminal angioplasty (PTA). This prospective, controlled study examined the association between plasma tissue factor concentrations and restenosis after femoropopliteal PTA.. Plasma samples from ten healthy controls and 36 patients with unilateral claudication undergoing femoropopliteal PTA were collected at baseline and, in the patients with claudication, at 24 h and 1, 3 and 6 months after PTA. Clinical assessment and arterial duplex imaging were performed before and at the same time points after PTA to identify restenosis. Plasma tissue factor was measured using a specific enzyme-linked immunosorbent assay.. Baseline plasma tissue factor concentrations were significantly higher in patients with claudication (median 3.4 (interquartile range (i.q.r.) 1.3-7.4) ng/ml) than in controls (median 1.2 (i.q.r. 0.5-1.8) ng/ml) (P < 0.050). Baseline tissue factor concentrations were significantly higher in the ten patients with claudication who developed restenosis after PTA (median 7.0 (i.q.r. 3.4-183.5) ng/ml) than in those who did not (median 1.7 (i.q.r. 1.3-7.2) ng/ml) (P < 0.050). In addition, plasma tissue factor levels increased significantly over time in the patients who developed restenosis after PTA.. High baseline and progressive increases in the plasma tissue factor concentration were useful predictors of restenosis after femoropopliteal angioplasty.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon; Case-Control Studies; Female; Femoral Artery; Humans; Intermittent Claudication; Male; Middle Aged; Popliteal Artery; Prospective Studies; Secondary Prevention; Thromboplastin; Treatment Outcome

Localized large vessel thrombosis in acute leukaemia is rare, haemorrhagic complications being more common.. We present a patient with acute promyelocytic leukaemia (APL) presenting with an acutely ischaemic lower limb. Large vessel thrombosis is a rare presentation of APL. We reviewed the literature on the coagulopathy of APL and discuss the pathology and current treatment options.. Disordered haemostasis is typical of acute promyelocytic leukaemia (FAB M3) and relates to the intrinsic properties of the blast cells as well as thrombocytopenia from bone marrow involvement. Expression of procoagulants, stimulation of cytokines and alterations in endothelial cell anticoagulant properties initiate a disseminated intravascular coagulation (DIC) resulting in the typical clinical and laboratory findings in APL. The promyelocytes are characterized by the balanced reciprocal translocation between chromosomes 15 and 17. All-trans-retinoic acid (ATRA) induces differentiation in these cells, revolutionizing the treatment of APL.. Unexpected limb ischaemia in a young, apparently healthy patient might be the presenting symptom of an underlying haematological disorder such as APL. A thorough haematological investigation should be performed prior to contemplating surgery. New treatment strategies based on knowledge of the molecular biology of APL has improved the prognosis of patients suffering from APL.

Topics: Amputation, Surgical; Antineoplastic Combined Chemotherapy Protocols; Arterial Occlusive Diseases; Cysteine Endopeptidases; Cytarabine; Daunorubicin; Female; Gangrene; Humans; Intermittent Claudication; Ischemia; Leg; Leukemia, Promyelocytic, Acute; Middle Aged; Neoplasm Proteins; Neoplastic Stem Cells; Popliteal Artery; Remission Induction; Smoking; Thioguanine; Thrombophilia; Thromboplastin; Thrombosis; Toes; Tretinoin