DEFECTIVE FIBRINOLYSIS IN SICKLE CELL DISEASE

1987 ◽  
Author(s):  
P Glas-Greenwalt ◽  
J Palascak ◽  
R Gruppo ◽  
D Stroop ◽  
V Pollak
Keyword(s):  
Sickle Cell Disease ◽  
Plasminogen Activator ◽  
Sickle Cell ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Cell Disease ◽  
Normal Range ◽  
Clearing System ◽  
Functionally Impaired ◽  
Predominant Factor

Vasocclusive crises (VOC) cause significant morbidity and mortality in sickle cell disease (SCD). Although sickling is thought to be the predominant factor in VOC, investigators have examined the possible role of the hemostatic mechanism in the process. The data are, however, inconsistent. We studied, functionally with the fibrin plate method, the fibrinolytic system in 36 adults in the steady state and in 8 children, 7 of whom suffered from painful crises. Values in 240 normal blood donors were: tissue-type plasminogen activator activity (t-PA); 3-25 activator units/ml, corresponding to 0.04 to 0.4 ng/ml; plasminogen activator inhibitor (PA-I): 649-885 inhibitor units/ml; and α2-antiplasmin (α2-AP) : 718-970 inhibitor units/ml. In patients with sickle cell disease t-PA levels were below the normal range in 24/44. PA-I and α2-AP levels were elevated in 35/44 and 23/44 respectively. The prevalence was similar in patients in crises and quiescent. Functionally impaired t-PA was associated with either low, normal or high t-PA antigen levels measured immunologically with an ELISA technique (normal range: 3-6 ng/ml). This indicates various degrees of endothelial dysfunction, ranging from impaired synthesis to functionally defective protein to complex formation with PA-I. Fibrin has been implicated in the intravascular sludging of sickle cells. It is suggested that a defective fibrin-clearing system contributes to the syndrome of SCD.

Impaired Fibrinolysis in Sickle Cell Disease

1970 ◽  
Vol 24 (01/02) ◽  
pp. 010-016 ◽  
Author(s):  
D Green ◽  
H. C Kwaan ◽  
G Ruiz
Keyword(s):  
Sickle Cell Disease ◽  
Factor Viii ◽  
Plasminogen Activator ◽  
Sickle Cell ◽  
Fibrinolytic Activity ◽  
Endothelial Damage ◽  
Cell Disease ◽  
Clotting Factors ◽  
Platelet Counts

SummaryCoagulation studies were performed in 52 patients with sickle cell disease during asymptomatic periods and during episodes of crisis and infection. Platelet counts averaged 473,000, 469,000, and 461,000 per mm3 in these 3 groups, and factor VIII concentrations were elevated in all. Fibrinogen was increased to the same extent in both sickle cell and non-sickle cell patients with infection. Fibrinolytic activity, as measured by euglobulin lysis times and zones of lysis on fibrin plates, was markedly reduced during periods of infection in sickle cell patients but not in non-sickle patients. Impairment of fibrinolysis in most patients was not on the basis of overutilization or consumption, since no decrease in the levels of clotting factors or plasminogen was observed. It was suggested that generalized intravascular sickling in these patients may have caused widespread endothelial damage, resulting in decreased production of plasminogen activator.In addition, several sickle cell patients with infection were found to possess elevated levels of an inhibitor directed against urokinase.

scholarly journals Elevated Plasma Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) in Sickle Cell Disease - a Marker of Chronic Kidney Disease

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 968-968
Author(s):  
Nowah Kokou Apeadoufia Afangbedji ◽  
James G. Taylor ◽  
Sergei Nekhai ◽  
Marina Jerebtsova
Keyword(s):  
Chronic Kidney Disease ◽  
Sickle Cell Disease ◽  
Kidney Disease ◽  
Renal Disease ◽  
Plasminogen Activator ◽  
Sickle Cell ◽  
Cell Disease ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Plasminogen Activator Receptor

Abstract Background: Sickle cell nephropathy (SCN) is one of the most common complications of SCD, leading in most cases to chronic kidney disease (CKD) and end-stage renal disease (ESRD). Despite the high prevalence of CKD in sickle cell disease (SCD) patients, there remains a poor understanding of the pathophysiological mechanism of SCN and a lack of biomarkers for early detection of SCD-associated CKD. Soluble urokinase-type plasminogen activator receptor (suPAR) is an emerging biomarker of CKD. suPAR is a member of the fibrinolytic system, which is dysregulated in SCD patients. Objective: To evaluate suPAR as a biomarker of SCD-associated nephropathy and identify plasma proteases responsible for its increase in SCD. Methods: The study was approved by Howard University review board (IRB) and all subjects provided written inform consent prior to the sample collection. Whole blood and urine samples were collected from 77 SCD patients and 10 healthy individuals, and plasma was isolated. Levels of creatinine and cystatin C in plasma and albumin and creatinine in urine were measured by ELISA. eGFR was calculated using CKD-EPI creatinine-cystatin equation, and CKD stages were assigned. Plasma suPAR was measured by ELISA and was correlated with CKD stages. The activities of candidates uPAR proteases: Neutrophile elastase (NE), urokinase-type plasminogen activator (uPA) and plasmin in plasma samples from SCD patients were measured and compared to healthy participants. Results: The average age of SCD patients was 42.5 years (range 18-67 years). Most patients had HbSS genotype (67.5%),19.5% of patients were HbSC (hemoglobin C sickle cell compound heterozygous), and 13% had HbS β-thalassemia. More than half (53.2 %) were females. We observed an increased level of plasma suPAR (>3ng/ml) in more than 60% of SCA patients without renal disease, representing a risk factor for CKD progression. Plasma suPAR levels further increased in the patients with CKD and positively correlated with stages of CKD (r=0.419, R2=0.1696). Analysis of plasma proteases that cleaved uPAR producing soluble peptides (suPAR) demonstrated increased urokinase-type plasminogen activator (uPA) activity without significant changes in neutrophile elastase. Conclusion: This study validated plasma suPAR as a potential marker of CKD in SCD patients and identified plasma uPA as a uPAR protease that may increase circulating suPAR in SCD. Future longitudinal analysis of suPAR levels in patients with SCA is needed. Acknowledgments: We thank Drs. Namita Kumari and Xiaomei Niu for their help in samples identification. This work was supported by NIH Research Grants 1R01HL125005-06A1, 5U54MD007597, 1P30AI117970-06,1UM1AI26617, and 1SC1HL150685. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Paracentral Acute Middle Maculopathy as a Presenting Sign of CRAO in Sickle Cell Disease Treated with Tissue Plasminogen Activator

2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Michael R Chua ◽  
Jerome V Giovinazzo ◽  
Richard I Kaplan ◽  
Thomas Connor ◽  
Christopher Kellner ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Sickle Cell ◽  
Cell Disease ◽  
Tissue Plasminogen

scholarly journals Red blood cells modulate structure and dynamics of venous clot formation in sickle cell disease

Blood ◽  
2019 ◽  
Vol 133 (23) ◽  
pp. 2529-2541 ◽  
Author(s):  
Camille Faes ◽  
Anton Ilich ◽  
Amandine Sotiaux ◽  
Erica M. Sparkenbaugh ◽  
Michael W. Henderson ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Sickle Cell Disease ◽  
Plasminogen Activator ◽  
Sickle Cell ◽  
Whole Blood ◽  
Blood Cells ◽  
Cell Disease ◽  
Increased Risk ◽  
Blood Clots ◽  
Tissue Plasminogen

Abstract Sickle cell disease (SCD) is associated with chronic activation of coagulation and an increased risk of venous thromboembolism. Erythrocyte sickling, the primary pathologic event in SCD, results in dramatic morphological changes in red blood cells (RBCs) because of polymerization of the abnormal hemoglobin. We used a mouse model of SCD and blood samples from sickle patients to determine if these changes affect the structure, properties, and dynamics of sickle clot formation. Sickling of RBCs and a significant increase in fibrin deposition were observed in venous thrombi formed in sickle mice. During ex vivo clot contraction, the number of RBCs extruded from sickle whole blood clots was significantly reduced compared with the number released from sickle cell trait and nonsickle clots in both mice and humans. Entrapment of sickled RBCs was largely factor XIIIa–independent and entirely mediated by the platelet-free cellular fraction of sickle blood. Inhibition of phosphatidylserine, but not administration of antisickling compounds, increased the number of RBCs released from sickle clots. Interestingly, whole blood, but not plasma clots from SCD patients, was more resistant to fibrinolysis, indicating that the cellular fraction of blood mediates resistance to tissue plasminogen activator. Sickle trait whole blood clots demonstrated an intermediate phenotype in response to tissue plasminogen activator. RBC exchange in SCD patients had a long-lasting effect on normalizing whole blood clot contraction. Furthermore, RBC exchange transiently reversed resistance of whole blood sickle clots to fibrinolysis, in part by decreasing platelet-derived PAI-1. These properties of sickle clots may explain the increased risk of venous thromboembolism observed in SCD.

scholarly journals Serum Calcium, Parathyroid Hormone, and Vitamin D Status in Children and Young Adults with Sickle Cell Disease

1993 ◽  
Vol 30 (1) ◽  
pp. 45-51 ◽  
Author(s):  
S Mohammed ◽  
S Addae ◽  
S Suleiman ◽  
F Adzaku ◽  
S Annobil ◽  
...  
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Serum Calcium ◽  
Inverse Correlation ◽  
Cell Disease ◽  
Normal Range ◽  
Hydroxyvitamin D ◽  
Significant Difference

The concentrations of serum calcium, parathyroid hormone (PTH), 25 Hydroxyvitamin D (25OHD), and 1,25 Dihydroxyvitamin D (1,25(OH)2D) were determined in 99 Saudi patients with sickle cell disease and in 104 matching healthy controls. Serum calcium and 25OHD were significantly lower in the patients, with 14% and 12% of them had serum calcium and 25OHD concentrations, respectively, below the normal range. PTH was significantly higher in the patients, with 31% having values above the normal range. There was no significant difference between patients and controls in regard to 1,25(OH)2D. There was a significant inverse correlation of 25OHD with PTH and a direct correlation of PTH with 1,25(OH)2D. Dietary intake of calcium and vitamin D was adequate in both patients and controls. The results indicate that sickle cell patients have hypocalcaemic tendency associated with supranormal PTH, and imply impaired intestinal absorption of calcium and vitamin D leading to a disturbed calcium metabolism which might contribute to the skeletal changes seen in sickle cell disease.

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