fibrinopeptide-a and Anemia--Sickle-Cell

To determine the plasma concentration of fibrinolytic protein (D-dimer) and Fibrinopeptide A(FPA) in sickle cell anaemia (SCA) patients in steady state and vaso-occlusive crisis(VOC) for the purpose of determining their clinical value in assessing/or predicting the onset of VOC Subjects and Methods: A total of 25 (14 Males: 11Females) HbSS subjects in VOC , 24 (13M:11F) HbSS subjects in steady state between the ages of 10-40 years old and 30 (17M:13F) healthy HbAA volunteers, of the same age and sex with the subjects were recruited for the study. Haematological parameters{Haemoglobin (Hb), Haematocrit(HCT), White blood cell count(WBC) and Platelets(Plt)}, prothrombin time(PT), activated partial thromboplastin time(APTT), plasma concentrations of D-dimer and FPA were determined.. Haemoglobin concentration of 6.22±1.75 g/dl and HCT of 18.45±6.43% for SCA subjects in VOC; Hb of 7.42±1.36 g/dl and HCT of 22.83 ±4.68% in steady state were significantly decreased(p <0.01) compared with Hb(13.0±1.04 g/dl and HCT( 41.09±3.50%) for HbAA controls. However, plasma FPA of 680.99 ± 411.37 ng/ml, WBC of 19.44±14.88 x109/L, Plt of 292.72±148.57 x109/L, APTT of 52.24±5.34sec. for SCA subjects in VOC and Plasma FPA of 449.67 ± 310.01 ng/ml, WBC of 11.84±7.67 x109/L, Plt of 292.72±148.57 x109/L, APTT of 47.76±4.80secs in steady state were significantly increased when compared with FPA(163.52 ± 86.26ng/ml), WBC(5.15±1.24 x109/L), Plt(173.44±59.90 x109/ L), APTT( 37.75±1.41secs) for HbAA controls.. Fibrinolysis is not significantly increased in SCA either in the steady state or during VOC. Fibrinopeptide A assay appears to be of value in the assessment of VOC in sickle cell anaemia.

Topics: Adolescent; Adult; Anemia, Sickle Cell; Biomarkers; Case-Control Studies; Child; Female; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Hemoglobins; Humans; Male; Partial Thromboplastin Time; Prothrombin Time; Young Adult

Sickle cell disease (SCD) is a group of genetic disorders characterized by the production of the abnormal hemoglobin S (HbS). Sickle cell anemia (SCA) is the most common type of SCD and represents the homozygous form, in which the individual inherits a double dose of the abnormal gene that codes for hemoglobin S. This study was done to detect cases of silent and clinically overt strokes in children with sickle cell anemia (SCA) and examine predisposing factors for stroke development. The study included 20 children with clinically and hematologically confirmed SCA and 10 controls. They were divided into two groups, group I; included 10 steady state cases and group II; included 10 cases with thrombotic crisis. All subjects were subjected to full clinical examination, measurements of plasma level of: fibrinopeptid A (FPA), thrombin-antithrombin III (TAT), fibrin degradation product (D-dimer) and serum level of platelet endothelial cell adhesion molecule-1 (PECAM-1), and analysis of the ACE gene polymorphism by polymerase chain reaction (PCR). Patients were further subjected to Brain computed axial tomography (CT) scan and/or magnetic resonance imaging (MRI) as well as electro-encephalographic studies (EEG). Silent ischemic brain infarction as evidenced by CT scan and/or MRI was present in one patient in group I (10%) and one patient in group II (10%). On the other hand, two patients in group II (20%) showed clinically overt strokes. Thus, 4 children had silent or clinically overt stroke and the remaining 16 were non-stroke cases. Laboratory results showed that the levels of FPA, TAT, D-dimer and PECAM-1 were significantly elevated in SCA patients both in the steady and crisis states as compared to control, with more evident significant elevation in group II (thrombotic crisis) as compared to group I (steady state). The stroke group showed significant elevation; FPA, TAT, D-dimer and PECAM-1 as compared with non-stroke group. The PCR results showed that the frequencies of both DD genotype and D allele of ACE gene in the thrombotic crisis are significantly higher than in the control group and that all stroke children are of DD genotype. In conclusion, significant increase in FPA, TAT, D-dimer and PECAM-1 levels as well as the presence of ACE D allele of the ACE gene are significant predisposing factors for stroke in children with SCA. Regular follow-up by thorough neurological examination and neuro-imaging studies for early detection of silent brain infarction

Topics: Anemia, Sickle Cell; Antithrombin III; Causality; Child; Child, Preschool; Egypt; Female; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Gene Frequency; Genotype; Hemostasis; Humans; Male; Peptide Hydrolases; Peptidyl-Dipeptidase A; Platelet Endothelial Cell Adhesion Molecule-1; Polymorphism, Genetic; Risk Factors; Stroke

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.

Topics: Adult; Anemia, Sickle Cell; Antithrombin III; Factor VII; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Hemostasis; Humans; Peptide Hydrolases; Thromboplastin

Platelet function was investigated in 37 patients with sickle cell disease during steady state. The measurement of platelet aggregation in whole blood, demonstrating interaction of sickle cells and platelets, showed increased activity in patients compared to controls. In contrast, by classical platelet aggregation in platelet-rich plasma (PRP) we observed decreased platelet aggregation in sickle cell patients. Aggregation of washed platelets appeared identical in patients and controls beta thromboglobulin (beta TG) and platelet factor 4 (PF4) as well as fibrinopeptide A (FPA) plasma levels were increased in patients with sickle cell disease. These results suggest that in sickle cell patients there is in vivo platelet stimulation, which may therefore appear "exhausted" in patients plasma during in vitro studies, and also a possible role of coagulation in the pathophysiology of sickle cell disease as supported by high levels of FPA.

Topics: Adenosine Triphosphate; Adolescent; Adult; Anemia, Sickle Cell; beta-Thromboglobulin; Blood Platelets; Child; Child, Preschool; Fibrinopeptide A; Humans; Platelet Aggregation; Platelet Factor 4; Thrombin

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.

Topics: Adenosine Diphosphate; Adolescent; Adult; Anemia, Sickle Cell; beta-Thromboglobulin; Blood Platelets; Epoprostenol; Female; Fibrinopeptide A; Hematocrit; Humans; Male; Platelet Aggregation; Platelet Count; Platelet Factor 4; Thromboxane B2

Topics: Anemia, Sickle Cell; Disseminated Intravascular Coagulation; Female; Fibrinogen; Fibrinopeptide A; Humans; Kidney Failure, Chronic; Male; Malingering; Pain