Hanan Azzam

The condensed MCMDM-1 VWD bleeding questionnaire as a predictor of bleeding disorders in women with unexplained menorrhagia.

Menorrhagia is a common clinical problem and is unexplained in more than 50% of women. Many studies have suggested that underlying bleeding disorders are prevalent in menorrhagic women. However, the assessment and quantifying of hemorrhagic symptoms are still limited and not widely used. Thirty women aged 11–31 years with a clinical diagnosis of unexplained menorrhagia were investigated to assess the diagnostic utility of the condensed MCMDM-1VWD bleeding questionnaire as a predictive of bleeding disorders in these women. In addition to administration of the questionnaire, comprehensive hemostatic testing was performed to all women. The incidence of inherited bleeding disorders among this group was 66.6% (20/30). Eight patients had von Willebrand disease (VWD) and seven had possible Glanzmanns thrombasthenia. Rare bleeding disorders including hemophilia A carrier, Afibrinogenemia, Factor V deficiency and combined factor V and factor VIII deficiency were also identified. The receiver operator characteristic analysis of the condensed MCMDM-1 VWD bleeding questionnaire in menorrhagic women showed that the cutoff, sensitivity, specificity, positive and negative predictive values were 3.5, 85, 90, 89 and 86%, respectively. Bleeding score was strongly correlated to bleeding time in women with possible Glanzmanns thrombasthenia. In VWD, a significant inverse correlation between the bleeding score and the VW factor levels was detected with a significant increase of bleeding score in type III VWD compared with type I. Bleeding disorders are common in women with unexplained menorrhagia and the condensed MCMDM-1VWD bleeding questionnaire can distinguish between menorrhagic women with and without bleeding disorders and help assess their severity.

Predictability of Vitreous Detachment Following Intravitreal Plasmin Injection in Diabetic Macular Edema Associated with Vitreomacular Traction

Purpose: To assess preoperative factors associated with postoperative posterior vitreous detachment (PVD) following intravitreal autologous plasmin injection in diabetic macular edema associated with vitreomacular traction. Methods: Twenty-five eyes with diabetic macular edema associated with vitreomacular traction as documented with optical coherence tomography were included. Approximately 0.2 IU/0.2 ml of autologous plasmin was injected intravitreally. Condition of the posterior vitreous face (degree of detachment, thickness, reflectivity, and diameter of attached vitreous base) was evaluated preoperatively and postoperatively up to 3 months. Results: PVD was achieved in ten eyes (41.7%). There was a significant difference (P = 0.03) in mean posterior vitreous face thickness between the eyes with PVD and the eyes with failed PVD. There was a significant correlation between PVD and both posterior vitreous face thickness (P < 0.03%) and degree of posterior vitreous face reflectivity (P = 0.002). Conclusion: In diabetic eyes with vitreomacular traction, the prediction of PVD after plasmin injection is governed by the condition of posterior vitreous face; mainly posterior vitreous face thickness and reflectivity. Eyes with thinner, less reflective posterior vitreous face are more likely to develop PVD.

Elevated platelet microparticle levels in valvular atrial fibrillation

Abstract Platelet activation occurs in peripheral blood of patients with rheumatic mitral stenosis (MS) and atrial fibrillation (AF) and could be related to abnormal thrombogenesis. However, the plasma level of platelet microparticles (PMPs), a marker of platelet activation, in patients with valvular AF remains unresolved. We performed a case control study of 20 patients with chronic rheumatic MS and chronic long AF and 10 healthy volunteers who were in sinus rhythm. Peripheral plasma levels of PMP were assessed by quantifying CD41-positive microparticles by flow cytometry. The mitral valve area was calculated by means of the Doppler pressure half-time method. The levels of circulating PMP were elevated significantly in valvular AF patients when compared with controls (12·36±5·51 × 105/ml versus 7·56±0·86 × 105/ml, P=0·011). Correlation analysis demonstrated that there was a significantly direct relationship between the severity of MS and PMP levels (r=−0·507, P=0·004). We conclude that in patients with rheumatic MS and AF, there is evidence of platelet activation detected by high PMP levels which have a significantly direct relationship with the severity of MS.

Atherosclerotic Effects of Long-Term Old and New Antiepileptic Drugs Monotherapy A Cross-Sectional Comparative Study

This work aimed to evaluate the metabolic and atherogenic effects of long-term antiepileptic drugs in a group of Egyptian epileptic patients. Sixty-nine epileptic patients on antiepileptic drug monotherapy for at least 2 years and 34 control subjects were recruited in this study. Patients were divided into 5 subgroups according to antiepileptic drugs used (valproate, carbamazepine, lamotrigine, topiramate, and levetiracetam). Fasting lipid profile (total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol), lipoprotein(a), homocysteine, free thyroxine, thyroid-stimulating hormone, and common carotid artery intima-media thickness were measured for all subjects. Significant higher mean values of low-density lipoprotein cholesterol, low-density lipoprotein / high-density lipoprotein ratio, lipoprotein(a), homocysteine, significantly lower mean value of high-density lipoprotein cholesterol, and significantly larger diameter of common carotid artery intima-media thickness were observed in each drug-treated group versus control group. Our study supports that long-term monotherapy treatment with valproate, carbamazepine, lamotrigine, and topiramate had altered markers of vascular risk that might enhance atherosclerosis, whereas levetiracetam exerted minimal effect.

Reverse hybridization StripAssay detection of β-thalassemia mutations in northeast Egypt

Abstract Aim: β-Thalassemias are widely distributed in Mediterranean and Middle Eastern countries. Reverse hybridization StripAssay method is reported to be rapid, simple, reproducible and less expensive. The aim of this study is to evaluate reverse hybridization StripAssay method for detection of β-thalassemia mutations in Egyptian children. Subjects and methods: Forty children with β-thalassemia major with mean age of 10·33±4·75 years were recruited consecutively from outpatient Hematology Clinic of Mansoura University Childrens Hospital. Mutation analysis was performed by the β-Globin StripAssay MED. Results: The most frequent mutant alleles detected were; IVS 1·110, IVS 1·1 and IVS 1·6 accounting for 33·75, 27·5 and 18·75% respectively. The detection rate of the used method in our population was 90%. Conclusion: β-globin StripAssay is a fast, easy-to-perform and reliable method for genetic screening of β-thalassemia patients in Egypt. IVS 1·110, IVS 1·1 and IVS 1·6 are the most frequent mutant alleles with poor phenotype/genotype correlation.

Association of Hemostatic Gene Polymorphisms With Early-Onset Ischemic Heart Disease in Egyptian Patients

The association between hereditary thrombophilia and venous thrombosis is well established but controversial data exist with respect to arterial thrombosis. We performed a pilot study on 31 patients with acute myocardial infarction (AMI), 21 patients with unstable angina (UA), and 20 healthy volunteers to investigate the role of various hemostatic gene polymorphisms in young Egyptian patients, who survived their first ischemic heart disease (IHD). Thrombophilic gene polymorphisms were tested using multiplex polymerase chain reaction and reverse-hybridization technique. We showed an increased risk of AMI with factor V (FV) Leiden and prothrombin G20210A heterozygosity. The increased risks of UA was associated with GA and A allele of fibrinogen β-455G→A polymorphism. Conversely, factor XIII (FXIII) Val34Leu GT and T allele were protective in the UA group. Nevertheless, the prevalence of FV H1299R, plasminogen activator inhibitor 1 4G/5G, glycoprotein IIIa C1565T, 5,10-methylenetetrahydrofolate reductase C677T, and A1298C mutations did not differ between patients with IHD and controls. The data have clinical implications regarding screening and thromboprophylaxis in high-risk individuals younger than 40 years.

Upregulation of CD40/CD40L system in rheumatic mitral stenosis with or without atrial fibrillation.

Platelet activation occurs in peripheral blood of patients with rheumatic mitral stenosis (MS) and atrial fibrillation (AF) and could be related to abnormal thrombogenesis. The CD40/CD40 ligand (CD40L) which reflects platelet activation, mediate a central role in thrombotic diseases. However, the role of CD40/CD40L system in rheumatic MS with or without AF remains unclear. Expressions of CD40 on monocytes and CD40L on platelets were determined by whole blood flow cytometry and serum levels of soluble CD40L were measured by enzyme-linked immunosorbent assay in group 1 (19 patients with MS) and group 2 (20 patients with MS and AF) compared to group 3 (10 controls). Patients with groups 1 and 2 had a significant increase in expression of CD40 on monocytes (P1 and P2 = 0.000) and serum levels of sCD40L (P1 = 0.014 and P2 = 0.033, respectively), but nonsignificant increase in expression of CD40L on platelets (P1 = 0.109 and P2 = 0.060, respectively) as compared to controls. There were no significant difference in all the parameters in group 1 compared to group 2. Correlation analysis demonstrated that there was a significant direct relationship between the severity of MS and serum levels of sCD40L (r = −0.469, p = 0.043). In conclusion, rheumatic MS patients with or without AF had upregulation of the CD40/CD40L system as well as elevated sCD40L levels. The levels of sCD40L had a significantly direct relationship with the severity of MS and it was the stenotic mitral valve, not AF, that had a significant impact on platelet activation.

The utility of International Society on Thrombosis and Haemostasis-Bleeding Assessment Tool and other bleeding questionnaires in assessing the bleeding phenotype in two platelet function defects.

The main objective of this study is to investigate the utility of International Society on Thrombosis and Haemostasis-Bleeding Assessment Tool (ISTH-BAT) in comparison with the condensed form of Molecular and Clinical Markers for the Diagnosis and Management of type 1 and WHO BATs, in assessing bleeding in two well known and clinically significant platelet function defects. Thirty-eight patients previously diagnosed with Glanzmanns thrombasthenia and 10 with Bernard–Soulier syndrome (BSS) were analyzed. Bleeding scores were significantly higher than that of controls using both electronic bleeding questionnaire (eBQ) and ISTH-BAT with no significant difference between both tools. ISTH-BAT had a sensitivity, specificity, positive predictive value and negative predictive value of 100%, 76.2%, 0.9 and 1. This was closely similar to eBQ. Both ISTH-BAT and eBQ are efficient in BSS and Glanzmanns thrombasthenia. However, given the ISTH recommendation, ISTH-BAT should be adopted. Larger study including other platelet defects will enhance its utility and support the integration of bleeding scores with standardized laboratory testing to allow for a universal diagnostic approach to patients with suspected bleeding disorders.

Clinical and biochemical aspirin resistance in patients with recurrent cerebral ischemia

BACKGROUND AND AIM Stroke recurrence is an important public health concern. One half of survivors remain disabled, and one seventh requires institutional care. Aspirin remains the cornerstone of primary and secondary stroke prevention; meanwhile, aspirin resistance is one of the possible causes of stroke recurrence. We aimed to evaluate the clinical and biochemical aspirin resistance in patients with recurrent ischemic stroke. PATIENTS AND METHODS We studied demographic characteristics, vascular risk factors, stroke subtypes, radiologic findings and biochemical aspirin resistance tests using both arachidonic acid (AA) and adenosine diphosphate (ADP)-induced light transmittance aggregometry (LTA) on admission and 24 h after observed aspirin ingestion. RESULTS Of the 82 patients with recurrent cerebral ischemia included in this study, 37 (45%) patients were poor compliant with aspirin. There were no statistically significant differences between the two groups regarding the demographic characteristics, stroke severity, laboratory tests, radiological findings or vascular risk factors. On admission, 19.6% and 4.8% of patients showed aspirin resistance, while 24 h after supervised 300 mg single aspirin dose ingestion, it was 9.8% and 2.4% using ADP and AA-induced LTA respectively. Of the eight aspirin resistant patients, two only showed resistance using both AA and ADP. Aspirin resistance was statistically significantly higher in the male gender, older age, hyperlipidemia, smokers and in all lacunar strokes using AA. CONCLUSION Biochemical aspirin resistance in ones series was rather rare (2.4%) and was more prevalent in patients with lacunar strokes. Clinical aspirin failure may often be contributed to poor compliance with aspirin intake.

The expression and concentration of CD40 ligand in normal pregnancy, preeclampsia, and hemolytic anemia, elevated liver enzymes and low platelet count (HELLP) syndrome.

Preeclampsia has been associated with increased platelet activation detected before disease onset. Inappropriate activation of platelets may be involved in pathogenesis in preeclampsia by promoting coagulation and thrombosis and also as a mediator of inflammation. The exaggerated platelet activation and inflammation leading to endothelial damage in preeclampsia can be explained by the CD40–CD40 ligand (CD40L) system. Expression of CD40L on platelets was determined by whole-blood flow cytometry, and serum levels of soluble CD40L (sCD40L) were measured by enzyme-linked immunosorbent assay in 11 women with mild preeclampsia, 11 women with severe preeclampsia, and six women with hemolytic anemia, elevated liver enzymes and low platelet count (HELLP) syndrome compared with 13 normotensive pregnant women as a control group. The platelet surface expression of CD40L was significantly higher in women with mild and severe preeclampsia and HELLP compared with normal pregnancy group (P = 0.001; P ⩽ 0.001; P = 0.003, respectively), with no significant difference being found between women with mild preeclampsia compared with HELLP and severe preeclampsia compared with HELLP (P = 0.2; P = 0.8, respectively). The serum concentration of sCD40L was significantly higher in women with mild and severe preeclampsia and HELLP compared with the normal pregnancy group (P = 0.001; P ⩽ 0.001; P = 0.022, respectively), with no significant difference being found between women with mild compared with severe preeclampsia or HELLP and severe preeclampsia compared with HELLP (P = 0.7; P = 0.6; P = 0.6, respectively). In conclusion, the higher expression and concentration of CD40L in women with preeclampsia and HELLP syndrome compared with normal pregnant women may indicate an exaggerated activation of platelets and endothelial cells in the disorder.