Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This report details the results of studies performed in nine patients with homozygous beta-thalassemia evaluating platelet function and prostaglandin formation. Platelet malonyldialdehyde (MDA) formation in the presence of N-ethyl maleimide (NEM 1 mM) or thrombin (0.5 u/ml) was used as an indicator of platelet prostaglandin synthesis. The data on the nine patients revealed two distinct subgroups of patients. Six of nine thalassemics, demonstrated platelet abnormalities. Their mean bleeding time was 7.5 +/- 2.5 min (1 SD), significantly prolonged (P less than 0.005) when compared to a value of 3.5 +/- 1.0 min in normal controls. MDA formation in the presence of NEM was significantly decreased (P less than 0.005) to 2.41 +/- 0.49 (1 SD) when compared to a control value of 3.24 +/- 0.33 nmoles MDA/10(9) platelets. Similarly, the mean value for thrombin induced MDA was 0.98 +/- 0.18 nmoles which was decreased (P less than 0.02) when compared to a value of 1.26 +/- 0.2 in the controls. Platelet aggregations with adenosine diphosphate (ADP), epinephrine, and collagen were abnormal in all six patients. However, when platelets from these patients were mixed with platelets from donors who had ingested aspirin 2-8 hr before donation mutual correction and secondary irreversible aggregation of the mixture resulted. No mutual correction was observed when the thalassemic platelets were preincubated with aspirin in vitro before mixing with platelets from donors who had recently ingested aspirin. Although the total amount of platelet malonyldialdehyde formed by the thalassemic platelets in response to NEM and thrombin was decreased when compared to normal controls, this reduction was not the cause of the platelet aggregation abnormalities. This appears to be so because the amount of MDA, and, thus, prostaglandin endoperoxides synthesized by these platelets in response to external stimuli was sufficient to cause irreversible aggregation of platelets from donors who had recently ingested aspirin, and were, therefore, unable to synthesize their own endogenous platelet endoperoxides. In the remaining three patients, bleeding times, platelet aggregation, and MDA formation was normal. No correlation was observed between the platelet abnormalities noted and the magnitude of iron overload, presence of fibrin degradation products, liver function abnormalities, or the use of iron chelators in the individual patient. Family studies were normal. Although the platelet dysfunction does not appear to be of major significance in the usual patient with thalassemia major under normal circumstances, antiplatelet aggregating agents should be used with caution. Aspirin inhibits platelet endoperoxide and prostaglandin formation and this effect may potentiate the platelet dysfunction present in some patients with thalassemia major.
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PMID:Platelet dysfunction in homozygous beta-thalassemia. 52 94

Simultaneous platelet and fibrinogen survival with 75Se selenomethionine was determined in eight patients with acute infectious hepatitis of intermediate severity. Fibrinogen survival alone was estimated in another nine patients, seven of whom were receiving heparin treatment. Platelet survival was found to be normal (7-9 days) in seven of the 8 patients; it was reduced 4,6 days) only in one patient, who was also affected by measles. Fibrinogen survival was markedly reduced (1-3.7 days) and fibrinogen turnover sharply increased (0.59-2.80 mg/ml/day) in all but one patient, who had thalassaemia major, with normal fibrinogen survival and fibrinogen turnover. Heparin treatment did not affect either platelet survival or fibrinogen turnover. In all patients the coagulation defect was mild and no sign of disseminated intravascular coagulation or of increased fibrinolytic activity could be demonstrated by routine tests. These results are consistent with the hypothesis that in acute infectious hepatitis the decreased survival and increased turnover of fibrinogen might be due to a pathological pathway of defibrination in dependent of thrombin of plasmin.
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PMID:Platelet and fibrinogen survival with 75Se selenomethionine in acute infectious hepatitis. 115 8

Fifty-two patients with sickle-cell (SC) disease (48 with SC-beta-thalassaemia and 4 with homozygous SC-anaemia) were studied as regards blood coagulation and fibrinolysis. It was found that the thrombin and the reptilase times of the patients' plasma were significantly shorter than normal. The mean values of platelet count, fibrinogen level and factor VIII activity of patients with SC disease were higher than normal; however, in the group of patients transfused, with less than 50% haemoglobin S (HbS), the fibrinogen level and the factor VIII activity were significantly lower compared to the other patients. Antithrombin-III (At-III) activity was normal in all. The fibrinolytic activity was normal in patients with asymptomatic SC disease, but reduced in patients on painful crises. Plasminogen and fibrinogen/fibrin degradation product (FDP) levels were normal in all patients. Two patients on painful crises with complications had additional abnormal findings, namely prolonged prothrombin time, reduced At-III level and elevated FDP.
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PMID:Hypercoagulability and hypofibrinolysis in sickle-cell disease. 120 41

We asked the question, "Can thalassemic erythrocytes play some role in alteration of the hemostatic system?", because clinical examination of thalassemic patients shows symptoms and signs related to alterations in hemostatic and circulatory systems, and thalassemic erythrocytes are different from normal erythrocytes. We obtained one of the answers to the question: The erythrocytes of postsplenectomized patients of beta-thalassemia/HbE disease could stimulate their own platelets to aggregate spontaneously. To know the role of erythrocytes in platelet aggregation, we wanted to examine the effect of thalassemic erythrocytes on the coagulation system by focusing of PF3-like activity of erythrocytes, because PF3-like activity of the ghosts of erythrocytes had been reported. For the study, we tried to develop a technique that was accurate and sensitive enough to detect PF3-like activity of blood. The system we developed was the following: 1) We activated the intrinsic coagulation pathway of commercial standard plasma by ellagic acid. 2) CaCl2, a fixed amount of PF 3 and synthetic thrombin inhibitor MD 805 were added to the reaction mixture. 3) At a fixed time, thrombin activity in the mixture was measured by using S-2238 as a substrate. At full activation of the contact system by ellagic acid, the amount of thrombin formed in a certain time depended on the amount of PF3-like substances such as cephalin, freeze-thawed platelets or ghosts of erythrocytes added to the test system, indicating that PF3-like activity of those substances can be measured by the activity of thrombin generated in a fixed time.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Development of a new method for detection of platelet factor 3 like activity. 129 93

A syndrome of intracranial hemorrhage with gross prolongation of the prothrombin and partial thromboplastin times, with normal thrombin time, fibrinogen concentrations, and coagulation factor assays is described in four children with homozygous beta-thalassemia. Mixing experiments and plasma thromboplastin inhibition tests revealed a persistent abnormality which was consistent with the presence of a circulatory prothrombinase inhibitor. The origin of this previously unreported inhibitor in thalassemia remains speculative.
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PMID:Intracranial hemorrhage and circulating coagulation inhibitor in beta-thalassemia major. 729 41

Low plasma heparin cofactor II (HCII) levels are associated with a thrombotic tendency, and we have previously shown these to be decreased in a variety of haemolytic conditions. The risk of thrombosis is recognized to be increased in both thalassaemia major (TM) and intermedia (TI), although the exact mechanisms are poorly understood. HCII levels have therefore been compared in 20 untransfused patients with TI and 20 regularly transfused TM patients to determine the influence of transfusion on HCII. Additionally, untransfused TI patients have been commenced on regular red cell transfusion and the effects on correction of low HCII levels investigated. HCII levels were significantly lower in the untransfused TI patients (mean 0.56 +/- 0.06 U/ml) compared to TM patients (mean 0.85 +/- 0.1 U/ml; P < 0.001). Levels in TI were significantly less than in healthy age-matched controls (P < 0.001) and correlated with Hb values (r = 0.8), whereas levels in TM were at the lower end of the normal range. ATIII values were within the normal reference range in both TI and TM, and HCII antigen showed a parallel reduction to HCII activity, indicating that reduction in HCII is not a consequence of increased thrombin consumption. Three patients with TI were commenced prospectively on hypertransfusion programmes which resulted in a slow normalization of their levels taking 2-3 months. These findings support a hypothesis that the low HCII levels are related to increased red cell turnover and can be normalized once this turnover has been suppressed by hypertransfusion. The thrombotic risk to patients with low HCII levels in the presence of haemolysis might in principle be decreased by such transfusion regimes.
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PMID:Low plasma heparin cofactor II levels in thalassaemia syndromes are corrected by chronic blood transfusion. 778 97

Platelet factor 3 (PF3) is a platelet membrane component that plays an important role in the activation of the coagulation mechanism. Whenever platelet activation occurred, PF3 is released and participates in thrombin formation. Erythrocyte membrane fraction has also some PF3 like activity, and in abnormal erythrocyte membrane disorders, eg thalassemia, some of the membrane fraction accelerates platelet activation by increasing the PF3 activity. Formerly it was difficult to measure the PF3 activity in plasma. Recently a sensitive chromogenic test to determine the PF3 activity, which could detect the changes in PF3 activity with time, was introduced. This study was done to observe the effect of abnormal erythrocyte on platelet activation. The results obtained using the chromogenic method are the following: whole blood taken from normal subjects showed OD 0.11 +/- 0.06 at 0 minutes after blood collection and then increased significantly (p < 0.01) to 0.21 +/- 0.10 after 90 minutes, while the platelet count did not differ significantly (p > 0.05). Those results showed that there were some platelet activation after 90 minutes as seen by the increased PF3 activity, with no significant change in platelet counts. In beta-thalassemic trait subjects the PF3 activity in whole blood at 0 minutes did not differ significantly compared to the normal subjects, but after 90 minutes it was significantly higher (p < 0.01), OD 0.52 +/- 0.35. However the PF3 in platelet rich plasma at 90 minutes did not increase. The platelet count after 90 minutes was significantly decreased (p < 0.01) This result suggest that the increase in PF3 activity was caused by the role of the abnormal erythrocytes.
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PMID:PF3 activity in normal subjects and beta-thalassemia trait. 788 79

Proteins C and S are vitamin K-dependent proteins with an essential anti-coagulant function. Protein C exists in an inactive form and is activated by a thrombin-thrombomodulin complex. Protein S combines with protein C and forms a stoichiometric complex which regulates coagulation in the presence of calcium. As patients with sickle cell disease (SCD) bear a high risk of developing thrombo-embolic disorders, we studied the coagulation derangement in 100 patients and 40 normal age- and sex-matched controls. The patients were clinically assessed and classified into sickle cell homozygotes (Hb SS), Hb S heterozygotes (Hb AS) and double heterozygotes for Hb S/beta 0-thalassaemia based on haematological parameters, red cell indices, Hb A2 and F levels and genetic studies. The proteins C and S were estimated and related to the type of the gene defect. The results showed significantly reduced levels of proteins C and S in SCD patients with the highest prevalence of deficiency in patients with a severe disease and frequent episodes of crisis. However, no significant differences were encountered in the level of proteins C and S in the same patients during the steady state and during episodes of crisis. It was concluded that the lower protein C and S levels in SCD is either due to decreased production or increased consumption though this reduction does not seem to play a role in producing thrombo-embolic disorders.
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PMID:Blood proteins C and S in sickle cell disease. 829 68

Thrombotic events are known to be increased in patients with sickle cell syndromes and a variety of abnormalities of coagulation or endothelial function have been described, although the relevance of these findings either to the pathogenesis of vaso-occlusive phenomena or the risk of thrombosis are unclear. Heparin cofactor II (HCII) and antithrombin III are circulating inhibitors of thrombin and low plasma levels have been associated with an increased risk of thrombosis in otherwise healthy individuals. We describe for the first time abnormally low plasma levels of HCII in patients with sickle cell syndromes. 45 adult patients with sickle cell syndromes (31 SS, 10 SC, 4 S beta Thal) were compared with 61 age matched control patients for HCII in plasma. There was a highly significant reduction in HCII in SS patients irrespective of crisis or transfusion state 0.68 +/- 0.15 U/ml (mean +/- SD) compared with controls 1.00 +/- 0.19 U/ml (P < 0.001). HCII antigen was also significantly reduced (0.53 +/- 0.19 U/ml) compared with controls (1.02 +/- 0.23 U/ml, P < 0.0001). By contrast there was no reduction in antithrombin III in this group. HCII (0.63 +/- 0.13 U/ml, P < 0.001) and HCII antigen (0.54 +/- 0.08 U/ml, P < 0.001) are also significantly reduced in SC patients HCII levels increased towards control values during sickle cell crises, in patients taking the contraceptive pill, or with regular blood transfusion; however, plasma HCII concentrations were not increased acutely by exchange transfusion. HCII was also decreased in thalassaemia intermedia and pyruvate kinase deficiency, suggesting that intravascular haemolysis may be the cause of reduced HCII levels.
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PMID:Sickle cell disorders and chronic intravascular haemolysis are associated with low plasma heparin cofactor II. 848 52

Several clinical and laboratory findings suggest the presence of a chronic hypercoagulable state in patients with beta-thalassaemia major (TM). We have previously shown that isolated TM red blood cells (RBC) strongly enhance prothrombin activation, suggesting an increased membrane exposure of procoagulant phospholipids (i.e. phosphatidylserine). In this study we quantitated the procoagulant activity of RBC in TM and thalassaemia intermedia (TI) patients. We also determined the fraction of activated platelets expressing p-selectin (CD62p) or CD63 in these subjects. Both assays were performed by dual-colour flow cytometry. A significantly (P < 0.01) higher fraction of FITC-annexin V-labelled RBC was found in TM and TI patients, compared to the controls. A highly significant correlation (P < 0.001) was found in TM patients between the number of RBC-bound annexin V molecules and the fraction of CD62p (p-selectin) or CD63-positive platelets. This association between annexin V binding to TM RBC and the expression of platelet activation markers was also found in individual TM patients over time. Thus, the procoagulant surface of TM RBC may accelerate thrombin generation in vivo which, in turn, triggers platelet activation.
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PMID:In-vivo platelet activation correlates with red cell anionic phospholipid exposure in patients with beta-thalassaemia major. 923 63


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