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

Because of the high prevalence of thrombotic complications in patients with sickle cell anemia (SCA), we investigated platelet function in patients with sickle hemoglobinopathies. Platelet aggregation induced by epinephrine, ADP, and collagen, except for absent secondary wave in 3 of 10 patients with SCA, was qualitatively normal. However, ristocetin-induced platelet aggregation (RIPA) with a final concentration 1.12 mg/ml was markedly abnormal-absent or virtually absent in 9 of 10 patients with SCA, 3 of 3 patients with hemoglobin S-C disease, and 2 of 3 patients with sickle trait. All 8 controls used in these experiments repeatedly demonstrated normal RIPA. Addition of normal plasma failed to correct abnormal RIPA in sickle hemoglobinopathy patients. All patients demonstrated normal RIPA with a ristocetin dose of 2.24 mg/ml and aggregated with bovine fibrinogen. Recombinant mixing experiments demonstrated that washed SCA platelets support RIPA (1.12 mg/ml) when resuspended in normal plasma or high dilutions of SCA plasma, but not in undiluted SCA plasma. Washed normal platelets do not support RIPA (1.12 mg/ml) when resuspended in SCA plasma. These findings suggest the presence of a plasma inhibitor of RIPA in patients with sickle hemoglobinopathies.
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PMID:A plasma inhibitor of ristocetin-induced platelet aggregation in patients with sickle hemoglobinopathies. 59 69

The statistical relationships among the glycolytic intermediates (GI)) of the Embden-Meyerhof pathway, adenine nucleotides (ANs) and various hematological measures were estimated for 34 sickle cell anemia patients. Heterogeneity in linear and quadratic regressions of hemoglobin and hematocrit, both singly and jointly, on the GI and AN variables implied 1) that any single formula to standardize optical density measures of the GIs and ANs on a per gram hemoglobin or per liter cell water basis would not uniformly remove hemoglobin and hematocrit effects: 2) that ignoring significant hematological effects could bias the estimates of correlation among GIs and ANs; and 3) that hemoglobin and hematocrit measures do not reflect the same source of variability. The correlations among the GIs and ANs, after adjustment for hematological variability, were analyzed by path analysis to determine which of five proposed path models for cause and effect relationships were compatible with the data. AMP had a greater influence on ADP (coefficient of determination (CD) = 23%) than all the GIs together, while G6P and ADP influenced ATP variability the most (CD = 33% and 12%). The contributions of unknown factors to ADP and ATP variability were large for all models (CD = 56--77%) possibly due to stress of sickle cell disease. The path model with AMP and the four GIs (G6P, F6P, FDP, DHAP) influencing ADP variation, and the same GIs and ADP influencing ATP was the model most compatible with the data.
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PMID:A path analysis of the causal relationships between red cell glycolytic intermediates, ADP and ATP in sickle cell anemia. 59 96

Platelet activation at sites of enmeshed sickled red cells in the microcirculation may contribute to platelet plug formation and microinfarction in sickle cell anemia. To test this hypothesis platelets from 116 sickle cell anemia patients free of crisis, 32 patients with crisis, 16 convalescents within 1 week of crisis, and 180 normal controls were studied. Platelets store 90% of their ADP in dense secretory granules. During activation ADP is secreted and permanently lost from the cell. This leads to a decrease in cellular ADP concentration and a sharp rise in the ATP/ADP ratio. ATP and ADP were ethanol-extracted from platelet-rich plasma, measured in the luciferase-luciferin assay and expressed in nmoles per 10(8) cells. No adenine nucleotide differences were found in platelets from patients free of crisis compared with normal controls. The ADP concentration of platelets from patients in crisis was significantly lowered, indicating that in vivo platelet secretion of ADP had occurred. Total and released ADP was decreased from 2.69 to 1.66, and from 1.90 to 1.21 respectively, and the total ATP/ADP ratio was increased from 1.85 to 2.84 (P less than 0.001). ADP stores in platelets from convalescents were significantly different from sickle controls (P less than 0.001) but were less abnormal than ADP stores in platelets from crisis patients (P less than 0.01), indicating recovery. Total and released ADP was decreased to 1.97 and 1.31 respectively, and the ATP/ADP ratio was increased to 2.38. Platelets from patients in crisis were able to release their remaining granular ADP in response to thrombin as effectively as normal platelets. Thus significant platelet activation with ADP release occurs during acute sickle pain crisis. This might contribute to platelet plug formation and microvascular obstruction.
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PMID:Platelet activation during pain crisis in sickle cell anemia patients. 274 22

Measurements of the coagulation system were carried out in children with sickle cell disease (SCD) in both steady state and on the 1st day of painful crisis and were compared to age- and sex-matched healthy controls. No significant differences were found in prothrombin time, partial thromboplastin time, thrombin time, reptilase time, plasma fibrinogen, antithrombin III, factor VIII:C, ristocetin-cofactor (Ri-Cof) and platelet aggregation responses to ADP, collagen and adrenaline. Abnormal aggregation responses to ristocetin were noted in all patients with SCD when compared to controls. Daily measurements during the first 4 days of painful crisis showed significant elevation of fibrinogen and Ri-Cof and enhancement of aggregation to ADP and adrenaline by the 3rd day of crisis. It was concluded that the changes noted, rather than being primarily responsible for the onset of crisis, can only be secondary changes arising from the aetiological factors of crisis, i.e. stasis and acute-phase proteins.
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PMID:Coagulation changes in sickle cell disease in early childhood. 311 56

Although numerous studies have provided indirect evidence for enhanced platelet activity in sickle cell anaemia, little attention has been directed to examination of platelet alpha and dense granule release in the sickling disorders. We simultaneously measured by radioimmunoassay plasma levels of the alpha granule constituents beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) in 43 children with sickle cell anaemia in steady state and 24 patients during severe vaso-occlusive crisis. beta-TG levels during steady state (50 +/- 3.6 ng/ml, mean +/- SEM) were greater (P less than 0.001) than in normal controls (36 +/- 1.6), but there was no additional significant rise during crisis (55 +/- 5.9). PF4 levels were similar (P = 0.12) in both steady state (10 +/- 1.2 ng/ml) and crisis (9.3 +/- 2.3) to those of normal controls (6.0 +/- 0.8). The similarity of beta-TG/PF4 ratios in normal and sickle cell anaemia patients as well as the positive correlation (P less than 0.05) between platelet count and beta-TG and PF4 suggested that an artefactual in vitro platelet activation was responsible for some of the observed increased beta-TG and PF4 levels. Further evidence against enhanced platelet activity in these sickle cell patients included normal intraplatelet content of the dense granule constituent 5-HT and a normal ATP/ADP ratio. From this data we conclude that platelet activation in children with sickle cell anaemia appears minimal.
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PMID:Evidence against enhanced platelet activity in sickle cell anaemia. 622 55

Previous reports have given conflicting conclusions of the role platelets may play in initiating vaso-occlusive sickle cell crisis. Seven patients homozygous for sickle cell hemoglobin, and seven age, race and sex matched controls were each studied on at least two occasions in a six week period of normal health. The number of platelets circulating as aggregates, the plasma concentration of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF-4) were significantly elevated compared with controls. These findings were confirmed with a second series of fourteen patients and nine controls. Patient's platelets in plasma adjusted for both platelet number and citrate concentration aggregated more in response to low concentrations (0.4 and 1 microM) but less to higher concentrations (4 and 20 microM) of ADP and needed significantly more prostacyclin (PGI2) to inhibit ADP induced aggregation than did platelets from control subjects. There was no significant difference in plasma concentration of fibrinopeptide A and thromboxane (Tx)B2, nor in the platelet generation of TxB2 and release of serotonin and beta TG induced by aggregating agents. Thus, the platelets of patients with sickle cell anemia in the steady state are readily activated and respond in vivo by increased formation of aggregates and release of beta TG and PF-4.
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PMID:Platelet activation during steady state sickle cell disease. 622 76

In vitro platelet aggregation responses to epinephrine and ADP were significantly lower in patients with sickle cell disease when compared to age- and sex-matched normal subjects. Platelet aggregation responses were reduced in all patients regardless of clinical status. Measurement of circulating platelet aggregates showed normal values in patients with sickle cell disease in steady state or with infection alone, but a significant increase in others with acute vaso-occlusive crises. Recovery from vaso-occlusion was associated with a decline in circulating platelet aggregates. This study suggests that in vivo platelet activation may result in "tired" platelets which are refractory to epinephrine and ADP stimulation in vitro.
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PMID:Abnormalities of platelet aggregation in sickle cell disease. 735 81

From July 1990 to January 1991 we studied platelet functions in 55 indigenous Kenyan patients (23 males and 32 females) with sickle cell anaemia (SCA) in steady state (SCASS) and in 20 (11 males and 9 females) SCA patients in vaso-occlusive sickle cell crisis (VSCC). A control group of 50 healthy (23 males and 27 females) individuals matched for age and sex was also studied. Platelet aggregation time to ADP in SCASS (57.2 +/- 39.1) and in VSCC (31 +/- 11.1) were more prolonged (p < 0.05) compared to controls (12.7 +/- 5.2). It was also significantly more prolonged (p < 0.05) in VSCC than in SCASS. Platelet adhesiveness time was 31.1 +/- 13.7 seconds in SCASS, 30.9 +/- 11.1 in VSCC, and 37.7 +/- 13.0 in controls and was significantly lower in both SCA groups (p < 0.05) but there was no significant difference between the two SCA groups themselves. Clot retraction was 52.8 +/- 6.9 in SCASS, 53.6 +/- 10.7 in VSCC, and 45.9 +/- 8 in controls and was significantly higher in both SCA groups than in controls (p < 0.05). There was no significant difference between the two SCA groups themselves. We conclude that platelet function is deranged in indigenous Kenyan patients with SCA.
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PMID:Platelet function in patients with sickle cell anaemia in Nairobi. 899 Dec 34

We evaluated the utility of the PFA-100 platelet function analyzer in identifying disorders in platelet function and/or von Willebrand factor (vWF) in patients with various systemic disorders being followed at a tertiary care center. Closure times were determined with collagen/ ADP (CADP) and collagen/epinephrine (CEPI) cartridges for 305 patients, and abnormal results were further evaluated with platelet aggregometry and vWF analysis. Prolonged CADP and/or CEPI closure times were identified in 114 patients (37.3%), but most were isolated prolonged CEPI closure times predominantly due to aspirin therapy (79 patients). Prolonged CADP closure times were most frequently due to qualitative platelet defects and/or decreased vWF levels. Prolonged CADP closure times were encountered most frequently in patients with sickle cell disease and were associated with a decreased hematocrit. This study demonstrated that the PFA-100 analyzer can accurately assess vWF-dependent platelet function and detect other platelet defects under high shear stress in complex patient populations.
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PMID:Assessment of primary hemostasis by PFA-100 analysis in a tertiary care center. 1092 77

Several lines of evidence point to the potential role of nitric oxide (NO) in the pathophysiology, as well as in the therapy, of sickle cell disease (SCD). In this study, we compared the effects of NO on platelets from normal individuals and from patients with SCD. Three NO donors were used to deliver NO to platelets: sodium 2-(N, N-diethylamino)-diazenolate-2-oxide (DEANO), S-nitrosocysteine (CysNO) and sodium trioxdintrate (OXINO or Angeli's salt). ADP-induced platelet aggregation, CD62P expression, PAC-1 binding and calcium elevation were evaluated in paired studies of normal and SCD subjects. DEANO significantly reduced aggregation in SCD platelets compared with normal platelets. DEANO similarly reduced the extent of CD62P expression in SCD platelets. All NO donors reduced PAC-1 binding, but there were no significant differences between platelets from normal or SCD subjects. Calcium elevation, as induced by ADP, was not altered by the presence of NO donors. However, when platelets were stimulated with thrombin, there was an increased initial response of SCD platelets compared with normal platelets. Taken together, these data suggest that the mode of NO delivery to platelets may produce various physiological responses and the optimization of NO delivery may contribute to reducing platelet aggregation in sickle cell disease.
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PMID:Biological action of nitric oxide donor compounds on platelets from patients with sickle cell disease. 1129 5


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