Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the mechanisms involved in the persistent clinical complications of sickle cell disease have not yet been fully delineated, previous studies suggest that sickle cell (HbSS) patients have a disposition to generate more thrombin and plasma in vivo than normal subjects. The reasons for the impaired regulation of haemostasis in HbSS patients is poorly understood. We report studies evaluating the extent to which in vivo coagulation and fibrinolysis are altered in HbSS patients in steady state. The concentrations of total factor VII (F(VII)t), factor VII zymogen (F(VII)z), thrombin-antithrombin III (TAT), fibrinopeptide A(FPA), and fibrin D-dimer in plasmas of 50 normal controls (HbAA) and 45 HbSS steady state patients, were measured using sensitive and specific enzyme-linked immunoassays. The average plasma concentration of F(VII)t, in sickle cell plasma was significantly lower than that of the control subjects (0.70 +/- 0.19 U/ml versus 1.16 +/- 0.41 U/ml), whereas F(VII)z in the patients and controls were 0.47 +/- 0.15 U/ml and 1.15 +/- 0.33 U/ml respectively, P < 0.001. Both measures of factor VII suggest a higher factor VII turnover in sickle cell disease. The mean concentration of TAT in the plasma of HbSS patients were significantly higher than those of HbAA controls (371 +/- 44 pM versus 42 +/- 2 pM) (P < 0.001), a difference that is strongly indicative of higher rates of in vivo thrombin generation by HbSS patients. Plasmas of HbSS patients had significantly higher concentrations of FPA compared to those of the control subjects (12.85 +/- 1.96 ng/ml versus 4.22 +/- 0.37 ng/ml) (P < 0.001). The D-dimer levels were also higher in the HbSS than control plasmas (1029.6 +/- 58.6 ng/ml versus 224.3 +/- 27.6 g/ml) (P < 0.001), with the patients' values being indicative of enhanced fibrinolysis. These results strongly suggest accelerated in vivo coagulation and fibrinolysis in HbSS patients even during steady state. They are consistent with the hypothesis that haemostasis is less tightly regulated in the HbSS patients than in HbAA controls. The altered regulation of haemostasis may contribute to the initiation of vaso-occlusive processes associated with sickle cell painful episodes.
 ...
PMID:Plasma factor VII and thrombin-antithrombin III levels indicate increased tissue factor activity in sickle cell patients. 139 Feb 42

There is evidence for increased factor VII turnover and the associated increased thrombin generation and fibrinolytic activities in sickle cell disease (SCD) that may affect in vivo platelet and endothelial cell reactivity. We studied the release of specific eicosanoids that are indicative of in vivo platelet activation and endothelial cell injury. The circulating and urinary levels of 2,3-dinor thromboxane B2(2,3-dinor-TxB2),TxB2,PGI2 [as 6-keto-PGF1 alpha], and PGE2 were measured in 15HbSS patients, eight HbAA non-haemolytic anaemic individuals and 12 healthy HbAA controls using specific RIAs. The mean urinary 2,3-dinor-TxB2 in the HbSS patients was significantly higher than in both the healthy HbAA and the anaemic controls. 6-keto-PGF1 alpha was undetected in the urines of the healthy HbAA controls, but was measured insignificant amounts in the HbSS and the HbAA anaemic patients. The urinary concentrations of PGE2 and TxB2 in HbSS patients' samples were also significantly higher than those of both control groups (P < 0.05). PGE2 and TxB2 levels were below the detection limit in the plasmas of the HbAA subjects, but were measurable in the HbSS and HbAA anaemic plasmas. The plasma level of 6-keto-PGF1 alpha in the HbSS patients was also significantly higher than in the control groups. The data indicates a persistent inflammatory process in the HbSS patients, and is consistent with the hypothesis that there is platelet and endothelial cell activation in SCD.
 ...
PMID:Elevated urinary levels of thromboxane and prostacyclin metabolities in sickle cell disease reflects activated platelets in the circulation. 799

Several studies had assessed the rheological and haemostatic parameters in both sickle cell anaemia(HbSS) and haemoglobin AA(HbAA) subjects. The effect of the heterogeneous state on these parameters has not been fully determined. Our aim was to assess the haemorheological and haemostatic parameters and there relationship to body mass index in individuals with the sickle cell trait. Fifty eight males (41 HbAA and 17 HbAS) who were neither smokers nor drinkers were studied. Body mass index was calculated as weight in Kg divided by height in m(2), blood samples were analysed for haematocrit, erythrocyte sedimentation rate, platelets, fibrinogen and factor VII by standard methods. There were no significant differences in the levels of haemostatic and cardiovascular risk factors between the HbAA and HbAS individuals. Fibrinogen correlated positively with BMI (r=0.6014, p=0.0107), systolic blood pressure (r=0.4820, p=0.0570), diastolic blood pressure (r=0.4699, p=0.0570) in HbAS individuals. The body mass index also correlated positively with diastolic blood pressure (r=0.5182, p<0.05), and systolic blood pressure (r=0.6189, p<0.01). Positive associations were also found between fibrinogen and body mass index (r=0.5012, p=0.0008), and fibrinogen and haematocrit (r=0.3696, r=0.0174) respectively in HbAA subjects. We conclude that the lack of significant difference in both haemorheological and cardiovascular risk factors in HbAS and HbAA subjects has further supported the observation that HbAS is a benign condition under physiological settings. Also the positive associations of fibrinogen with other cardiovascular risk factors have further underscored the central role of fibrinogen as an independent risk factors in the development of cardiovascular diseases.
 ...
PMID:Haemostatic variables and their relationship to body mass index and blood pressure in adult Nigerians with the sickle cell trait. 1721 Oct 65