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)

The most important side effects of oral contraceptives (OCs) and their incidence, together with advice and monitoring of the patient at risk, are pointed out. There is a mild increase in blood pressure in longterm contraceptive use caused by increased angiotensinogen production by the liver. It is significant only for women with a history of familial hypertension, diabetes mellitus, or pre-eclampsia. Smoking increases this risk. Urinary tract infections are 25-50% more frequent in pill users. Glucose tolerance is slightly decreased. Contraceptives' diabetogenic effect is higher in women with hereditary tendency for diabetes, latent diabetes, and/or obesity. They are contraindicated in latent diabetes. Findings are contradictory in their effects on cholesterol and triglyceride serum level, but the pill is contraindicated in lipid metabolism disorders. There is an increased incidence in cholecystitis and cholelithiasis in pill-users (70-80 additional cases/100,000 user years). Liver diseases, intrahepatic cholestasis, occur rarely and benign liver tumors have not conclusively been proved to be caused by the pill. A variety of laboratory findings have been related to contraceptive use and drug interactions occur with barbiturates, rifampicin, hydantoin, and phenylbutazone. Blood coagulation is increased, partially by increased production of various blood coagulation factors; but more importantly, by a decreased synthesis of antithrombin III, a natural protective mechanism against intravascular coagulation. This increases thrombosis risk. Risk doubles with simultaneous cigarette smoking. Various epidemiological studies indicate a 5-10 fold increase in thromboembolism and thrombophlebitis, deep vein thrombosis, and pulmonary embolism. There is a correlation between contraceptive use and cerebrovascular disorders and myocardial infarction. This risk increases with age and years of pill use. The pill is contraindicated with symptoms of thrombophlebitis and thromboembolism, sickle cell anemia, proposed surgery, and longterm immobilization. Overall risk factors are not too high. Recommendations for rational pill use related to age are given and further contraindications are mentioned.
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PMID:[Adverse effects of oral contraceptives]. 55 52

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.
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PMID:Plasma factor VII and thrombin-antithrombin III levels indicate increased tissue factor activity in sickle cell patients. 139 Feb 42

A prospective study of Nigerian children with sickle cell disease was undertaken to determine serum levels of antithrombin III (AT-III) and compare these with normal controls. Mean serum AT-III was significantly lower in patients than in controls (14.51 +/- 4.84 mg/dl and 17.75 +/- 5.92 mg/dl) respectively. Seven of the 49 sickle cell patients had AT-III levels below 50% of normal values. Mean platelet counts were significantly higher in sicklers than in normal controls. AT-III deficiency may predispose to thrombotic complications in children with sickle cell disease.
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PMID:Anti-thrombin III deficiency in Nigerian children with sickle cell disease. Possible role in the cerebral syndrome. 149 20

More than a dozen primary hematologic disorders have been associated with ischemic stroke. Inherited deficiencies of antithrombin III, protein C, and protein S have been linked with stroke in case reports; optimal screening requires functional as well as antigenic assays. Antiphospholipid antibodies and lupus anticoagulants are the most frequently identified acquired states associated with ischemic stroke. Polycythemia vera, sickle cell anemia, sickle-C disease, and essential thrombocythemia are the major disorders of formed blood elements causing stroke. Special, step-wise screening for occult prothrombotic entities in stroke patients is recommended for young persons with stroke of uncertain cause, for those with prior venous thrombosis, for those with a family history of unusual thrombosis, and for those with no other explanation for recurrent stroke. Acquired, perhaps transient, abnormalities of platelets, coagulation inhibition, and fibrinolysis may contribute importantly to brain ischemia in synergy with other mechanisms, but at present these remain ill-defined. The contribution of prothrombotic diatheses to stroke is probably underrecognized and warrants further investigation.
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PMID:Hematologic disorders and ischemic stroke. A selective review. 186 63

Restriction site polymorphisms are normal inherited variations in DNA that can be readily detected by restriction endonuclease analysis. Currently, 17 such polymorphisms are recognized within a 60 kb (kilobase) stretch of DNA which includes the beta-globin gene complex. Because of their proximity to the beta-globin gene, often these restriction site polymorphisms can be used to predict inheritance of beta-globin variants that produce disease. For example, restriction site polymorphisms can be used for prenatal diagnosis for the large majority of couples at risk of having a child with beta-thalassemia. When each member of such a couple is heterozygous at one or more of these 17 sites, family studies are usually successful in determining which forms of the polymorphism are co-inherited with the beta-thalassemia genes in that particular family. Subsequently, study of fetal DNA isolated from amniocytes obtained by midtrimester amniocentesis or from chorionic villi obtained by first trimester chorion biopsy will reveal which DNA polymorphisms that fetus has inherited. By deductive reasoning one can then predict which beta-globin genes it has co-inherited. Because of the general nature of these polymorphisms, which are related to the beta-globin gene and its variants only because of their proximity on chromosome 11, they are potentially useful in the prenatal diagnosis of any beta-chain hemoglobinopathy. Some hemoglobinopathies (including alpha-thalassemia, sickle cell anemia, and some cases of beta-thalassemia) can be detected directly by DNA analysis. In these cases in utero diagnosis does not need to rely on restriction site polymorphisms, which require preliminary family studies and are not applicable in all at risk pregnancies. Recently, genetic probes, which are necessary for detecting restriction site polymorphisms, have been isolated for sequences of several genes whose protein products are important in blood coagulation. These include probes for all three genes whose polypeptide products combine to form the fibrinogen molecule as well as probes for the prothrombin, Factor IX, Factor VIII, and antithrombin III genes. Defects in these genes are expected to be the causes of afibrinogenemia, prothrombin deficiency, hemophilia B, hemophilia A, and antithrombin III deficiency, respectively. From experience with other genes, it is expected that restriction site polymorphisms within and/or flanking these genes will be found.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Prenatal diagnosis of hemoglobinopathies by DNA analysis. 299 37

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

Seventeen parameters of coagulation and fibrinolysis were measured in 33 patients with sickle cell disease; 30 were tested in steady state (SS) and 19 in crisis (Cr). There were 16 patients in both groups. The same parameters were measured in 16 controls of similar ethnic origin (Black controls; BC) and 20 Caucasian controls (CC), all with HbA only. Highly significant differences (P < 0.001) between Black and Caucasian control groups were noted for: fibrinogen, fibrinopeptide-A (FPA), beta-thromboglobulin (beta TG) and D-dimer. Significant differences (P < 0.03) in plasminogen activator inhibitor (PAI) and functional antithrombin III levels were also noted. Results of the sickle cell patients were therefore compared with those of the Black controls. Sickle cell patients in SS had raised v Wf compared with BC, which increased further during Cr (P = 0.001), but showed no significant increase in fibrinogen. Functional protein C was reduced in SS (P = 0.004) but with no further fall in Cr, while free protein S was normal in SS but reduced in Cr (P = 0.02). Total protein S and ATIII were normal in SS and Cr. FPA and beta TG were not significantly raised in SS or Cr compared with BC. There were, however, highly significant increases in D-dimer and thrombin-antithrombin complexes (TAT) in both SS and Cr compared with BC (P < 0.001 for SS and Cr vs BC). Thus significant activation of coagulation with consequent increase in fibrinolysis occurs during both the sickle cell crisis and in the steady state.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in coagulation and fibrinolysis in patients with sickle cell disease compared with healthy black controls. 760 84

Recent studies suggest that increased activity of the coagulation system, measured with sensitive assays for activation markers, may be important in the pathogenesis of vascular occlusion in sickle cell disease (SCD). Since most of these studies were carried out in adult patients and SCD is an inherited disorder with severe morbidity even in childhood, we decided to determine the activity of the coagulation system in children with SCD. In a prospective study markers of thrombin generation as well as coagulation inhibitors were investigated in 16 homozygous SCD patients and 16 age-matched control children. Significantly increased plasma concentrations of the prothrombin fragment F1+2 and of thrombin-antithrombin III (TAT) complexes were found in SCD patients. The levels of protein C activity and total and free protein S were significantly reduced in SCD patients as compared with control values. Plasma AT III levels were not different in the two groups. We conclude that, in children with SCD, evidence of enhanced thrombin generation is present, which may in part be due to reduced levels of the inhibitors proteins C and S. The clinical relevance of this coagulation imbalance has to be demonstrated.
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PMID:Enhanced thrombin generation in children with sickle cell disease. 819 93

In sickle cell disease (SCD), vaso-occlusion is a complex process involving cellular, vascular and humoral factors and possibly thrombotic events. We studied three physiological inhibitors of the coagulation system, antithrombin III (AT III), protein C (PC) and protein S (PS), in three groups of subjects: 27 homozygous patients observed either in crisis or in a steady state, 23 heterozygous patients and 30 healthy subjects. PS study included the measurement of total and free PS antigen, PS activity and C4bBP antigen. In heterozygous subjects the results were similar to those of controls, but in homozygous subjects abnormalities of PS and to a lesser extent PC were observed. Values of PC were extremely variable with 10 cases lower than the normal range (2 SD of the mean) and 17 others within this range. In all cases total PS antigen was slightly reduced (77 +/- 18%, M +/- SD) with a more marked decrease of free antigen (59 +/- 17%) and normal values of C4bBP. Levels of PS activity were greatly reduced and lower than those of free antigen with a mean ratio of PS activity to free antigen of 0.6. These abnormalities were associated with significantly high concentrations of fibrinogen D-dimers. PS deficiency in SCD may be at least partly due to adsorption of free PS to aminophospholipids abnormally expressed on sickle cells membranes, microvesicles and activated platelets, while the discrepancy between PS activity and free antigen could reflect proteolytic inactivation of PS by traces of thrombin.
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PMID:Decreased protein S activity in sickle cell disease. 841 63

Despite important new diagnostic laboratory and imaging technologies, the cause of brain infarction remains unexplained in 20% to 40% of subjects. Most stroke patients do not require extensive evaluations of coagulation, but hypercoagulability may account for a significant proportion of unexplained strokes. Hemostatic abnormalities associated with stroke may be broadly classified as familial or acquired. Principal among the familial thrombotic coagulopathies are deficiencies in concentration or function in protein-C, protein-S, and antithrombin III, but other hereditary abnormalities include sickle cell disease, homocystinuria, and dysfibrinogenemia. The acquired disorders of hemostasis associated with stroke probably constitute a larger proportion of the important stroke-related coagulopathies. In particular, the aPL antibody syndrome is now strongly associated with thrombotic events including stroke, although neither the mechanism of thrombosis nor effective therapies for this syndrome have been clearly elucidated. Many of the acquired hemostatic abnormalities exist within a special clinical setting such as with malignancy or with myeloproliferative diseases, nephrotic syndrome, and liver disease. Presumably many of these share common pathways of coagulation activation or dysfunction with the inherited disorders. Most of the hemostatic disorders in stroke are associated with dysfunction of vascular endothelium and abnormalities of or interference with the natural anticoagulant proteins: protein-C, protein-S, and antithrombin III. Improved understanding of these relationships should lead to better diagnosis and treatment for people at risk of stroke.
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PMID:Abnormalities of hemostasis in ischemic stroke. 841 25


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