Platelets, coagulation, and fibrinolysis in sickle cell disease

Rb, Francis

doi:10.1097/00001721-199104000-00018

Cited by 125 publications

(89 citation statements)

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“…Finally, while the changes in red cell rigidity tested here would not normally influence behaviors, the experiments did support the concept that adhesion of small particles will be promoted by a narrowing of the red celldepleted layer and increase in normal force. Moreover, in conditions such as sickle cell disease, thrombosis is known to be increased (16) and abnormal red cell rigidity might contribute to platelet deposition. …”

Section: Discussionmentioning

confidence: 99%

Comparative rheology of the adhesion of platelets and leukocytes from flowing blood: why are platelets so small?

Watts

Barigou

Nash

2013

American Journal of Physiology-Heart and Circulatory Physiology

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Watts T, Barigou M, Nash GB. Comparative rheology of the adhesion of platelets and leukocytes from flowing blood: why are platelets so small? Am J Physiol Heart Circ Physiol 304: H1483-H1494, 2013. First published April 12, 2013 doi:10.1152/ajpheart.00881.2012.-We investigated rheological adaptation of leukocytes and platelets for their adhesive functions in inflammation and hemostasis, respectively. Adhesion and margination of leukocytes or platelets were quantified for blood perfused through capillaries coated with P-selectin or collagen, when flow rate, suspending phase viscosity, red cell aggregation, or rigidity was modified. Independent variation of shear rate and shear stress indicated that the ability of platelets to attach at higher levels than leukocytes was largely attributable to their smaller size, reducing their velocity before attachment, and, especially, drag after attachment. Increasing red cell aggregation increased the number of marginated and adhering leukocytes but inhibited platelet adhesion without effect on the number marginated. Increasing red cell rigidity tended to inhibit leukocyte adhesion but promote platelet adhesion. The effects on platelets may be explained by changes in the depth of the nearwall, red cell-depleted layer; broadening (or narrowing) this layer to greater (or less) than the platelet diameter would decrease (or increase) the normal force applied by red blood cells and make attachment less (or more) efficient. Thus different adhesive capabilities of leukocytes and platelets may arise from their differences in size, both directly because of influence on cell velocity and force experienced at the wall and indirectly through effects of size on margination in the bloodstream and interaction with the cell-free layer. In addition, red cell aggregation (of hitherto uncertain physiological significance) may be useful in promoting leukocyte adhesion in inflamed venules but inhibiting unwanted platelet deposition in veins. blood rheology; leukocyte adhesion; platelet adhesion; margination CIRCULATING LEUKOCYTES and platelets must adhere to the wall of blood vessels to carry out their protective functions in inflammation and hemostasis. Typically, leukocyte adhesion is restricted to postcapillary venules, where the wall shear rate (local velocity gradient) and wall shear stress (frictional drag on the wall) are low (ϳ100 s Ϫ1 and Ͻ1 Pa, respectively) (29, 38). Platelet adhesion is most important in the arterial circulation (with shear rate ϳ1,000 s Ϫ1 and stress Ͼ1 Pa) and, indeed, may be undesirable in slow-flowing veins at risk of thrombosis. Specialized, fast-acting receptors have evolved for the purpose of capture from flow: endothelial cell selectins bind sialylated, fucosylated glycoproteins on leukocytes, and von Willebrand factor (vWF) on collagen matrix binds the glycoprotein Ib complex on platelets (6, 54). The kinetics of these receptor pairs are quite similar (15), suggesting that attachment of the different cells in different regions must depend on their unequal ph...

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Section: Discussionmentioning

confidence: 99%

Comparative rheology of the adhesion of platelets and leukocytes from flowing blood: why are platelets so small?

Watts

Barigou

Nash

2013

American Journal of Physiology-Heart and Circulatory Physiology

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“…As a result of these findings, SCD is frequently referred to as a "hypercoagulable state." 6 Loss of normal membrane phospholipid asymmetry is present in a subpopulation of red blood cells (RBC) in SCD patients, occurring in mature cells, RNA-containing reticulocytes, and transferrin receptor-positive "stress" erythrocytes. 7,8 Normally, phosphatidylserine (PS) is found in the inner monolayer of the cell membrane, whereas choline-containing phospholipids such as phosphatidylcholine and sphingomyelin are located in the outer monolayer in the plasma membrane.…”

Section: Pathogenesismentioning

confidence: 99%

Hypercoagulability in Sickle Cell Disease: New Approaches to an Old Problem

Ataga¹,

Key²

2007

Hematology

185

168

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Patients with sickle cell disease (SCD) exhibit high plasma levels of markers of thrombin generation, depletion of natural anticoagulant proteins, abnormal activation of the fibrinolytic system, and increased tissue factor expression, even in the non-crisis steady state. In addition, platelets and other cellular elements are chronically activated in the non-crisis state. Despite an abundance of evidence for coagulation and platelet activation, it remains uncertain whether these changes contribute to the pathophysiology of SCD or are, rather, simple epiphenomena. With the occurrence of macrovascular thrombotic complications in SCD, as well as the recognition that soluble CD40 ligand is biologically active in SCD, coagulation and platelet activation may indeed play a role in SCD pathophysiology. Defining a role for hypercoagulability in SCD requires further understanding of its pathogenesis. Furthermore, the conduct of well-controlled clinical trials using anticoagulants and antiplatelet agents and using a variety of clinical endpoints is warranted.

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“…80,81 Sporadic cases of DVT, pulmonary embolism, portal vein thrombosis, aseptic necrosis of bone, leg ulcers, retinopathy, and miscarriage have also been reported. [82][83][84][85][86] Hemostatic abnormalities, including low protein C and protein S levels, and elevated plasma concentrations of TAT, F 1,2 , and D-dimer complexes have been found in sickle cell patients. 61,75,[87][88][89] In addition, chronic platelet activation was indicated by the elevated plasma levels of platelet factor 4 (PF4) and ␤-thromboglobulin (␤-TG) and the expression of P selectin and enhanced binding of annexin V to the SCD platelets.…”

Section: Similarity Of Thromboembolic Manifestations and Hemostatic Cmentioning

confidence: 99%

The hypercoagulable state in thalassemia

Eldor

Rachmilewitz

2002

Blood

440

376

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Thalassemia is a congenital hemolytic disorder caused by a partial or complete deficiency of ␣-or ␤-globin chain synthesis. Homozygous carriers of ␤-globin gene defects suffer from severe anemia and other serious complications from early childhood. The disease is treated by chronic blood transfusion. However, this can cause severe iron overload resulting in progressive organ failure. Some forms of ␣ thalassemia are also associated with a similar clinical picture. Despite the difficulties associated with treatment, standards of care for thalassemic patients have improved in recent years, resulting in almost doubling of the average life expectancy. As a consequence, additional previously undescribed, complications are now being recognized. In particular, profound hemostatic changes have been observed in patients with ␤-thalassemia major (␤-TM) and ␤-thalassemia intermedia (␤-TI) and also in patients with ␣ thalassemia (hemoglobin H disease). The presence of a higher than normal incidence of thromboembolic events, mainly in ␤-TI, and the existence of prothrombotic hemostatic anomalies in the majority of the patients, even from a very young age, have led to the recognition of the existence of a chronic hypercoagulable state in thalassemic patients. Despite the appearance of numerous publications on the frequent occurrence of thromboembolic complications in thalassemia, this complication has not been emphasized or comprehensively reviewed. This review summarizes the current literature and discusses possible mechanisms of the lifelong hypercoagulable state that exists in thalassemia. (Blood. 2002;99:36-43)

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Platelets, coagulation, and fibrinolysis in sickle cell disease

Cited by 125 publications

References 0 publications

Comparative rheology of the adhesion of platelets and leukocytes from flowing blood: why are platelets so small?

Comparative rheology of the adhesion of platelets and leukocytes from flowing blood: why are platelets so small?

Hypercoagulability in Sickle Cell Disease: New Approaches to an Old Problem

The hypercoagulable state in thalassemia

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