Farjah H. AlGahtani

Sickle cell disease subphenotypes in patients from Southwestern Province of Saudi Arabia.

Sickle cell disease (SCD) is common in the Eastern and Southwestern (SW) Provinces of Saudi Arabia. We studied 159 patients with SCD to better characterize its phenotype in the SW Province, where patients usually have a HBB haplotype of African origin. All cases had history and examination, chart review, and laboratory testing. Blood tests were obtained during steady state and included: complete blood count, reticulocytes, hemoglobin electrophoresis, lactate dehydrogenase, and G6PD level. HBB haplotype and presence of &agr;-thalassemia were also determined. Frequency of various SCD complications was as follows: painful episodes of variable severity occurred in majority of patients (98%), osteonecrosis (14%), acute chest syndrome (22%), splenic sequestration (23%), gallstones (34%), stroke (7.5%), priapism (2.6%), serious infections (11.5%), and persistent splenomegaly (11%) beyond 5 years of age. No patient had leg ulcer. History of asthma and high steady state white blood cells count were associated with increased risk of acute chest syndrome. Coinheritance of &agr;-thalassemia was associated with a lower frequency of gallstones. Higher fetal hemoglobin level was associated with persistent splenomegaly but not with other complications. Splenic sequestration was more common among males and was associated with lower steady state hemoglobin. SCD phenotype in the SW Province is variable and comparable with African Americans except for the rarity of priapism and the absence of leg ulcers. Fetal hemoglobin level was not associated with SCD vaso-occlusive complications. New genetic modifiers and environmental factors might modulate the phenotype of SCD in Saudi Arabia.

Fetal hemoglobin in sickle cell anemia: Saudi patients from the Southwestern province have similar HBB haplotypes but higher HbF levels than African Americans†

Patients with sickle cell disease (SCD) from the Southwestern (SW) Province of Saudi Arabia have variable fetal hemoglobin (HbF) levels and have HBB gene cluster haplotypes of African origin. We studied 77 patients, aged 17.7 ±10 (range 4-46) years (69% HbS homozygotes and 31% HbS-β 0 thalassemia), to determine the associations of known HbF quantitative trait loci (QTL) with HbF concentration. HBB gene cluster haplotypes were 74% Benin, 22% Bantu, and 4% others. Genotyping Single nucleotide polymorphism (SNPs) in BCL11A, HBS1L-MYB, and OR51B5/6 showed that BCL11A was the sole QTL associated with HbF level. We compared these findings with two studies of African American with SCD. After adjusting for the BCL11A genotype, Saudi cases from the SW Province had HbF levels almost twice that of African Americans (P < 0.0001). When we examined the genetic population structure of the African Americans and Saudi patients using genome-wide data, we found that African Americans were similar to Yoruban, Mandenka, and Bantu Africans while Saudi patients resembled Arab populations. The commonality of HBB haplotypes coupled with the genetic distance between these populations suggests that genetic modifiers remote from the HBB cluster or unknown environmental influences are likely to account for the higher HbF in these Saudi patients.

Spectral detection of sickle cell anemia and thalassemia.

Sickle cell disease (SCD) and thalassemia (Thal) are the most common inherited, autosomal, recessive blood disorders which lead to complications such as vasoocclusion and splenomegaly. Patients who suffer from these diseases have poor quality of life and shorter life span. The most common techniques for detection of these diseases are complete blood cell count, followed by electrophoresis and high performance liquid chromatography. In this connection, the results of this paper indicate the potential of a new technique, based on spectral analysis of blood plasma and cellular components, to detect SCD and Thal with accuracy of 90% and above. To the best of our knowledge this would be the first report on spectral pathology of hemoglobinopathy.

Frequency, Clinical Pattern and Outcome of Thrombosis in Cancer Patients in Saudi Arabia

OBJECTIVES Thrombotic risk is increased in patients with cancer and there are important implications for those who suffer a venous thromboembolism (VTE). We undertook this study to determine the frequency, clinical patterns, and outcome of VTE in Saudi patients with cancer. METHODS Cancer (solid tumors and lymphoma) patients who developed VTE from January 2004 to January 2009 were studied retrospectively. Demographics and clinical characteristics related to thrombosis and cancer were evaluated. RESULTS A total of 701 patients with cancer were seen during the study period. VTE was diagnosed in 47 (6.7%) patients (median age 52, range 18-80 years). Lower limb DVT was the most common type, seen in 47% patients, followed by PE in 19%, and 19% patients had both DVT and PE. Thrombosis was symptomatic in 72% patients while it was an incidental finding on routine workup in 28% . Cancer and VTE were diagnosed at the same time in 38% of patients, and 47% patients developed VTE during the course of disease after the cancer diagnosis. The majority of VTE post cancer diagnoses occurred during the first year (median 4 months, range 1-14). Additional risk factors for VTE were present in 22 (47%) patients and 14 (30%) of these patients were receiving chemotherapy at the time of thrombosis. Only 5 (10.6%) patients were receiving thrombo-prophylaxis at the time of VTE diagnosis. Most common types of tumors associated with thrombosis were breast cancer, non-Hodgkins lymphoma and lung cancer. The majority of the affected patients (79%) had advanced stage of cancer. After a median follow-up of 13 (range 0.5-60) months, 38 (81%) patients had died. There was no difference in the mortality of patients with symptomatic or asymptomatic thrombosis (82% vs 78.6%). CONCLUSIONS Thrombotic complications can develop in a significant number of patients with cancer, and almost half of the patients have additional risk factors for VTE. Thrombosis is usually associated with advanced disease and can be asymptomatic in more than a quarter of cases. Thromboprophylaxis in cancer patients is under-utilized. Community based studies are needed to accurately define the extent of this problem and to develop effective prophylactic strategies.

Thromboprophylaxis and mortality among patients who developed venous thromboembolism in seven major hospitals in Saudi Arabia

Introduction: Venous thromboembolism (VTE) during hospitalization is a serious and potentially fatal condition. Despite its effectiveness, evidence-based thromboprophylaxis is still underutilized in many countries including Saudi Arabia. Objective of the Study: Our objectives were to determine how often hospital-acquired VTE patients received appropriate thromboprophylaxis, VTE-associated mortality, and the percentage of patients given anticoagulant therapy and adherence to it after discharged. Methods: This study was conducted in seven major hospitals in Saudi Arabia. From July 1, 2009, till June 30, 2010, all recorded deep vein thrombosis (DVT) and pulmonary embolism (PE) cases were noted. Only patients with confirmed VTE diagnosis were included in the analysis. Results: A total of 1241 confirmed VTE cases occurred during the 12-month period. Most (58.3%) of them were DVT only, 21.7% were PE, and 20% were both DVT and PE. 21.4% and 78.6% of confirmed VTE occurred in surgical and medical patients, respectively. Only 40.9% of VTE cases received appropriate prophylaxis (63.2% for surgical patients and 34.8% for medical patients; P < 0.001). The mortality rate was 14.3% which represented 1.6% of total hospital deaths. Mortality was 13.5% for surgical patients and 14.5% for medical patients (P > 0.05). Appropriate thromboprophylaxis was associated with 4.11% absolute risk reduction in mortality (95% confidence interval: 0.24%–7.97%). Most (89.4%) of the survived patients received anticoagulation therapy at discharge and 71.7% of them were adherent to it on follow-up. Conclusion: Thromboprophylaxis was underutilized in major Saudi hospitals denoting a gap between guideline and practice. This gap was more marked in medical than surgical patients. Hospital-acquired VTE was associated with significant mortality. Efforts to improve thromboprophylaxis utilization are warranted.

The Saudi Clinical Practice Guideline for the treatment of venous thromboembolism: Outpatient versus inpatient management

Venous thromboembolism (VTE) including deep vein thrombosis (DVT) and pulmonary embolism (PE) is commonly encountered in daily clinical practice. After diagnosis, its management frequently carries significant challenges to the clinical practitioner. Treatment of VTE with the inappropriate modality and/or in the inappropriate setting may lead to serious complications and have life-threatening consequences. As a result of an initiative of the Ministry of Health of the Kingdom of Saudi Arabia, an expert panel led by the Saudi Association for Venous Thrombo-Embolism (a subsidiary of the Saudi Thoracic Society) and the Saudi Scientific Hematology Society with the methodological support of the McMaster University Guideline working group, this clinical practice guideline was produced to assist health care providers in VTE management. Two questions were identified and were related to the inpatient versus outpatient treatment of acute DVT, and the early versus standard discharge from hospital for patients with acute PE. The corresponding recommendations were made following the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach.

Prophylaxis and treatment of venous thromboembolism in patients with cancer: the Saudi clinical practice guideline.

BACKGROUND AND OBJECTIVES Venous thromboembolism (VTE) is commonly encountered in the daily clinical practice. Cancer is an important VTE risk factor. Proper thromboprophylaxis is key to prevent VTE in patients with cancer, and proper treatment is essential to reduce VTE complications and adverse events associated with the therapy. DESIGN AND SETTINGS As a result of an initiative of the Ministry of Health of Saudi Arabia, an expert panel led by the Saudi Association for Venous Thrombo-Embolism (a subsidiary of the Saudi Thoracic Society) and the Saudi Scientific Hematology Society with the methodological support of the McMaster University working group produced this clinical practice guideline to assist health care providers in evidence-based clinical decision-making for VTE prophylaxis and treatment in patients with cancer. METHODS Six questions related to thromboprophylaxis and antithrombotic therapy were identified and the corresponding recommendations were made following the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. RESULTS Question 1 Should heparin versus no heparin be used in outpatients with cancer who have no other therapeutic or prophylactic indication for anticoagulation? Recommendation For outpatients with cancer, the Saudi Expert Panel suggests against routine thromboprophylaxis with heparin (weak recommendation; moderate quality evidence). Question 2 Should oral anticoagulation versus no oral anticoagulation be used in outpatients with cancer who have no other therapeutic or prophylactic indication for anticoagulation? Recommendation For outpatients with cancer, the Saudi Expert Panel recommends against thromboprophylaxis with oral anticoagulation (strong recommendation; moderate quality evidence). Question 3 Should parenteral anticoagulation versus no anticoagulation be used in patients with cancer and central venous catheters? Recommendation For outpatients with cancer and central venous catheters, the Saudi Expert Panel suggests thromboprophylaxis with parenteral anticoagulation (weak recommendation; moderate quality evidence). Question 4 Should oral anticoagulation versus no anticoagulation be used in patients with cancer and central venous catheters? Recommendation For outpatients with cancer and central venous catheters, the Saudi Expert Panel suggests against thromboprophylaxis with oral anticoagulation (weak recommendation; low quality evidence). Question 5 Should low-molecular-weight heparin versus unfractionated heparin be used in patients with cancer being initiated on treatment for venous thromboembolism? Recommendation In patients with cancer being initiated on treatment for venous thromboembolism, the Saudi Expert Panel suggests low-molecular-weight heparin over intravenous unfractionated heparin (weak; very low quality evidence). Question 6 Should heparin versus oral anticoagulation be used in patients with cancer requiring long-term treatment of VTE? Recommendation In patients with metastatic cancer requiring long-term treatment of VTE, the Saudi Expert Panel recommends low-molecular-weight heparin (LMWH) over vitamin K antagonists (VKAs) (strong recommendation; moderate quality evidence). In patients with non-metastatic cancer requiring long-term treatment of venous thromboembolism, the Saudi Expert Panel suggests LMWH over VKA (weak recommendation; moderate quality evidence).

Spectral detection of thalassemia: a preliminary study

BackgroundThalassemias (Thal) are forms of inherited autosomal recessive blood disorders arising out of mutations in the chromosomes 11 or 16. These disorders lead to poor oxygen delivery to blood vessels and consequent splenomegaly, bone deformities, and shorter life spans. The most common detection methods for Thal are complete blood count (CBC) followed by electrophoresis and molecular diagnosis methods, such as high-performance liquid chromatography (HPLC) and polymerase chain reaction (PCR) genotyping. These methods involve sophisticated instrumentations and are cumbersome and expensive.ResultsIn this study an innovative spectral detection method, based on the fluorescence spectra of a set of biomolecules (tyrosine, tryptophan, nicotinamide adenine dinucleotide, and flavin adenine dinucleotide and porphyrins) found in blood components is presented. An algorithm based on the spectral features of such biomolecules of blood components of 20 Thal patients (10 female and 10 male) and 18 age adjusted normal controls (4 female and 14 male) demonstrate reasonable level of classification with sensitivity and specificity values exceeding 90%.ConclusionThis new technique could be of significant value for Thal detection, diagnosis, and subsequent genetic counselling and could be adapted for use in small primary health centres.

Thromboembolic events in patients with inflammatory bowel disease.

Background/Aims: Inflammatory bowel disease (ulcerative colitis and Crohns disease) is characterized by a chronic inflammatory condition, and is accompanied by abnormalities in coagulation and a hyper-coagulable state. This study was conducted to examine the risk factors for developing Thromboembolic Events in Inflammatory Bowel Disease (IBD) in a population with prevalent consanguinity. Patients and Methods: Patients with a definitive diagnosis of IBD who were seen in the gastroenterology clinic of King Khalid University Hospital (Riyadh, Saudi Arabia) from 2010- to 2012, were asked to participate in this prospective cohort study, and were followed for one 1 year. Data was collected using specifically designed case report forms (CRF) by trained research personnel. Results: A total of 100 Saudi patients with IBD were studied. There were 51 (51%) women and the mean ± standard deviation (SD) age of the group was 31.24 ± 10.78 years. Those with Crohns disease constituted 72% of the patients, and 28% had ulcerative colitis. Eight patients (8%) had at least one Thrombotic Event ([six deep venous thrombosis (DVT), and two pulmonary embolism (PE)]. Family history of deep venous thrombosis was present in 5%, and family history of pulmonary embolism (PE) in 4% of the patients. After adjusting for age and gender, a family history of Thrombotic event was identified as to be the only statistically significant predictor of thrombosis in IBD patients (RR = 9.22, 95% CI: 2.10--40.43). Conclusion: In a population with high consanguinity, Thromboembolic events (DVT and PE) had a prevalence of 8% among IBD patients, positive family history of pulmonary embolism was a predictor of thrombosis. Further studies are needed to explore the role of genetic factors in this population.

Antibodies against human platelet alloantigens and human leucocyte antigen class 1 in Saudi Arabian multiparous women and multi-transfused patients

Objectives: To determine the frequency of alloimmunization against human platelet antigens (HPAs) and human leucocyte antigen class 1 (HLA1) in multiparous women and multi-transfused patients. Methods: This prospective study was conducted between January and August 2013, on 50 multiparous women with no history of previous blood transfusion recruited from the Obstetrics and Gynecology Clinic, and 50 patients, who received multiple platelet transfusions, recruited from the Hematology/Oncology Ward, King Khalid University Hospital, Riyadh, Saudi Arabia. Results: The frequency of alloimmunization among multiparous pregnant women was 76%, as follows: 16% against HLA1 only, 8% against HPAs only, 52% against both HPAs and HLA1 antigens. In multi-transfused patients, the rate of alloimmunization was 42% as follows: 2% against HLA1 only, 22% against HPAs only, 18% against both HPAs and HLA1 antigens. The frequency of alloimmunization increases with the number of pregnancies, but not with the number of platelet transfusions. Conclusion: Alloimmunization against HPAs and HLA1 is very common among Saudi multiparous women and multi-transfused patients, which encourages the search for the extent of the possible complications in the fetus and newborn and in multitransfused patients and how to prevent their occurrence.