7 research outputs found
Platelet and Fibrin Deposition at the Damaged Vessel Wall: Cooperative Substrates for Neutrophil Adhesion Under Flow Conditions
At sites of vessel wall damage, the primary hemostatic reac-
tion involves platelet and fibrin deposition. At these sites,
circulating leukocytes marginate and become activated. Ad-
hered platelets can support leukocyte localization; however,
the role of fibrin in this respect is not known. We studied
the adhesion of human neutrophils (polymorphonuclear leukocytes
[PMNs]) to endothelial extracellular matrix (ECM)-
bound fibrin and platelets under flow conditions. ECM alone
did not show PMN adhesion. ECM-coated cover slips were
perfused with plasma to form a surface-bound fibrin network,
and/or with whole blood to allow platelet adhesion.
Unstimulated PMNs adhered to fibrin at moderate shear
stress (20 to 200 mPa). ECM-bound platelets induced rolling
adhesion and allowed more PMNs to adhere at higher shear
(320 mPa). ECM coated with both platelets and fibrin induced
more static and shear-resistant PMN adhesion. PMN
adhesion to fibrin alone but not to platelet/fibrin surfaces
was inhibited by soluble fibrinogen. Adhesion to fibrin alone
was inhibited by CD11b and CD18 blocking antibodies. Furthermore,
fibrin formed under flow conditions showed up to
threefold higher PMN adhesion compared with fibrin formed
under static conditions, due to structural differences. These
results indicate that circulating PMNs adhere to fibrin in an
integrin-dependent manner at moderate shear stresses.
However, at higher shear rates (Û200 mPa), additional mechanisms
(ie, activated platelets) are necessary for an interac-
tion of PMNs with a fibrin network
The role of preoperative iron deficiency in colorectal cancer patients: prevalence and treatment
Background: In preoperative blood management of colorectal cancer patients, intravenous iron therapy is increasingly used to treat anaemia and prevent red blood cell transfusions. However, while iron deficiency is the most common cause of anaemia, little is known about the prevalence and namely type of iron deficiency in this population, whereas both types of iron deficiency (i.e. absolute and functional iron deficiency) are recommended to be treated differently by international cancer guidelines. Objective: The aim of present study is to investigate the prevalence and namely type of iron deficiency in colorectal cancer patients, and to assess its clinical relevance. Methods: Preoperative iron status, clinical parameters (i.e. age, ASA classification, tumour location, tumour stage) and postoperative complications were retrospectively collected for all newly diagnosed colorectal cancer patients in our institution over a 3-year period. Results: Iron deficiency was observed in 163 (48.1%) of 339 patients. Of these iron-deficient patients, 3.7% had an isolated absolute iron deficiency (AID) and 15.3% a functional iron deficiency (FID), while the rest had a combination of AID and FID. Anaemia was present in 66.1% of iron-deficient patients. Iron deficiency was significantly associated with an increased postoperative complication rate (univariable OR 1.94, p = 0.03, multivariable OR 1.84, p = 0.07), with right-sided tumours (p < 0.001), high ASA classification (p = 0.002), advanced tumour stage (p = 0.01) and advanced age (p = 0.04). In comparing clinical parameters between patients with AID and FID, advanced age was significantly associated with FID (p = 0.03), and the presence of anaemia with AID (p = 0.02). Conclusion: In preoperative colorectal cancer patients, there is a high prevalence of iron deficiency, including a high percentage of patients with—a component of—functional iron deficiency, associated with the increased postoperative complication rate. As both types of iron deficiency require a different treatment strategy, our results illustrate the therapeutic potential of especially intravenous iron supplementation in patients with severe iron deficiency and stress the urgency of routinely monitoring preoperative iron status and differentiation between types of iron deficiency. As iron therapy may also be potentially harmful in respect to stimulation of tumour growth, future clinical trials assessing the long-term effect of iron therapy are necessary
Neutrophil Adhesion to Fibrinogen and Fibrin Under Flow Conditions Is Diminished by Activation and L-Selectin Shedding
The adhesion of neutrophils (polymorphonuclear leukocytes
[PMNs]) to immobilized fibrinogen/fibrin is mediated by
b2-integrins. However, the influence of physiologic flow con-
ditions on neutrophil adhesion to these surfaces is poorly
defined. In this report, the effect of flow and neutrophil acti-
vation on adhesion to immobilized fibrinogen and fibrin was
examined. For the evaluation of (the distribution of) neutro-
phil adhesion, real-time video-assisted microscopy and custom-
made software were used. Under flow conditions, ad-
herent neutrophils appeared to support the subsequent
margination of other neutrophils, thereby enhancing the ad-
herence of these cells to fibrin. Consequently, neutrophils
adhered in clusters, especially at higher shear stresses (eg,
cluster index 1.4 at shear 80 mPa). Preactivation of PMNs
with fMLP (10ĂŹ7 mol/L) or 4b-phorbol, 12-myristate, 13-ace-
tate (PMA; 100 ng/mL) resulted in approximately 50% inhibi-
tion of adhesion to fibrin and a more random distribution
(cluster index Ăš0.5). L-selectin antibodies or neuraminidase
treatment of PMNs also inhibited adhesion and clustering,
indicating a role for L-selectin. Under static conditions, no
clustering appeared and PMN activation with fMLP or PMA
caused threefold and sevenfold increased adhesion, respec-
tively. Under these conditions, anti-L-selectin antibodies or
neuraminidase did not affect adhesion. These results indi-
cate that, under flow conditions, adherent neutrophils support
adhesion of flowing neutrophils by L-selectin-mediated
cell-cell interactions. Preactivated neutrophils, with lowered
L-selectin expression, are less susceptible for this interac-
tion. By this mechanism, adhered leukocytes can modulate
the recruitment of leukocytes to the vessel wall at sites of
inflammation
Allogeneic cord blood transfusions for extremely preterm neonates: an extremely promising proof of concept
Thrombosis and Hemostasi
The association between haemorrhage and markers of endothelial insufficiency and inflammation in patients with hypoproliferative thrombocytopenia: a cohort study
In daily haematological practice, predicting bleeding in thrombocytopenic patients is difficult, and clinicians adhere to transfusion triggers to guide patients through the aplastic phase of chemotherapy. Platelet count is not the only determinant of bleeding and additional mechanisms for impending haemostasis are likely. Beside clot formation, platelets are essential for the maintenance of integrity of vascular beds. We therefore prospectively investigated associations between biomarkers for endothelial damage (urine albumin excretion) and inflammation (C-reactive protein) and bleeding (WHO grading) in 88 patients with 116 on-protocol episodes. We found an increase in grade 2 bleeding with a higher urine albumin/creatinine ratio one day after the measurement [odds ratio (OR) 1·24 for every doubling of the ratio, 95% CI 1·05–1·46, P-value 0·01] and a 29% increase in the odds of grade 2 bleeding for every doubling of serum C-reactive protein (CRP) (95% CI 1·04–1·60, P-value 0·02) after correction for morning platelet count. The 24 h post-transfusion corrected count increment (CCI24) showed a significant association with these biomarkers: increasing urine albumin/creatinine ratio and CRP were associated with lower CCI24. We report two inexpensive and easy-to-apply biomarkers that could be useful in designing a prediction model for bleeding risk in thrombocytopenic patients
Age of platelet concentrates and time to the next transfusion
BACKGROUND: Storage time of platelet (PLT) concentrates has been negatively associated with clinical efficacy outcomes. The aim of this study was to quantify the association between storage time of PLT concentrates and interval to the next PLT transfusion for different types of PLT components, stored for up to 7 days and transfused to transfusion-dependent hematooncology patients with thrombocytopenia. STUDY DESIGN AND METHODS: From a cohort of patients from 10 major Dutch hospitals, patients were selected whose transfusion patterns were compatible with PLT transfusion dependency due to hematooncologic disease. Mean time to the next transfusion and mean differences in time to the next transfusion for differen