fibrinopeptide-a and Stroke

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

The association between hemostatic activation, stroke mechanism, and outcome is poorly defined. The Hemostatic System Activation Study (HAS) investigators measured serial levels of prothrombin fragment F1.2, a marker of thrombin generation, in patients enrolled in the Warfarin Aspirin Recurrent Stroke Study (WARSS).. HAS enrolled 631 of the 2,206 patients in WARSS. Strokes were subtyped according to inferred mechanism. Plasma was collected for F1.2 at randomization (within 30 days of stroke), 3 months, 12 months, and 18 months. The 3 to 6 month samples in aspirin-treated patients were used for the primary analysis.. The authors analyzed 3 to 6 month samples on 320 patients. Higher F1.2 levels were associated with older age, female sex, and hypertension. There was no difference between mean F1.2 levels in 56 cryptogenic (0.9 +/- 0.32 nmol/L) and 114 non-cryptogenic (1.13 +/- 0.74 nmol/L) patients or across specific stroke subtypes. There was an 8.8%/year (p = 0.006) increase in mean F1.2 levels. There was a trend toward higher risk of recurrent stroke or death as F1.2 levels increased in aspirin (RR: 1.30, 95% CI: 0.57 to 2.94, p = 0.53) and warfarin treated patients (RR: 1.68, 95% CI: 0.48 to 5.94, p = 0.42). F1.2 levels were reduced on average 70% in warfarin-treated patients in a dose-dependent fashion.. F1.2 levels did not appear to differ by stroke subtype, suggesting that factors other than underlying stroke pathophysiology influence thrombin generation in the post-acute stroke period. F1.2 levels were suppressed by warfarin in a dose-dependent fashion. Additional research is needed to determine the predictive value of F1.2 after stroke.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Biomarkers; Brain Infarction; Brain Ischemia; Cohort Studies; Comorbidity; Female; Fibrinopeptide A; Follow-Up Studies; Humans; International Normalized Ratio; Intracranial Thrombosis; Male; Middle Aged; Multicenter Studies as Topic; Peptide Fragments; Prothrombin; Randomized Controlled Trials as Topic; Recurrence; Stroke; Thrombin; Warfarin

Platelet aggregation and spontaneous thrombolytic activity were assessed in patients with non-insulin dependent diabetes and stroke using a shear-induced and agonist-induced platelet aggregation test. The Thrombotic Status Analyser (TSA), induces platelet-rich thrombus formation solely by shear forces, while whole blood platelet aggregometry measures platelet reactivity to different agonists. These tests were employed in the present study because in earlier studies they both demonstrated that platelet aggregability in healthy volunteers was unchanged with age. On the other hand, it is known that thrombolytic activity decreases with age in males, but not in females. In diabetic patients shear-induced platelet aggregability varied according to the stage of nephropathy but platelet aggregation to collagen was suppressed at all stages. Platelet reaction to shear stress was enhanced in stroke patients with haemorrhagic episodes but not in patients with lacunar infarction. In contrast, platelet reactivity to collagen was suppressed and changes in ADP-induced platelet aggregability were inconsistent. Suppressed thrombolysis was observed only in diabetes with minor renal defect. Fibrinogen was increased in diabetes with stage III and IV nephropathy. Fibrinopeptide A (FPA) and D-dimer were increased in stroke. Thus, the observed increase in fibrinogen, FPA and D-dimer is inconsistent with changes in platelet aggregability. Our present findings suggest that a shear-induced platelet aggregation test is superior to other tests such as agonist-induced platelet aggregation and thrombotic markers such as fibrinogen, FPA and D-dimer in detecting a prothrombotic state. It is concluded that elderly males may have a prothrombotic state not because of platelet hyper-aggregability but because of suppressed thrombolytic activity. On the other hand, a prothrombotic state in patients with non-insulin dependent diabetes and after stroke may be due to changes in age-independent platelet aggregability.

Topics: Adult; Age Factors; Aged; Antifibrinolytic Agents; Arteriosclerosis; Diabetes Mellitus, Type 2; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Humans; Male; Middle Aged; Platelet Aggregation; Platelet Function Tests; Stress, Mechanical; Stroke; Thrombophilia