Determination of vWF, ADAMTS-13 and Thrombospondin-1 in Venous Thromboembolism and Relating Them to the Presence of Factor V Leiden Mutation.

Thrombophilia in venous thromboembolism (VTE) is multifactorial. Von Willebrand factor (vWF) plays a major role in primary hemostasis. While elevated vWF levels are well documented in VTE, findings related to its cleaving protease (ADAMTS-13) are contradicting. The aim of this study was to determine vWF, ADAMTS-13, and the multifactorial Thrombospondin-1 (TSP-1) protein levels in patients after 3-6 months following an unprovoked VTE episode. We also explored a possible association with factor V Leiden (FVL) mutation. vWF, ADAMTS-13 and TSP-1 were analyzed using ELISA kits in 60 VTE patients and 60 controls. Patients had higher levels of vWF antigen (P = .021), vWF collagen-binding activity (P = .008), and TSP-1 protein (P < .001) compared to controls. ADAMTS-13 antigen was lower in patients (P = .046) compared to controls but ADAMTS-13 activity was comparable between the two groups (P = .172). TSP-1 showed positive correlation with vWF antigen (rho = 0.303, P = .021) and negative correlation with ADAMTS-13 activity (rho = -0.244, P = .033) and ADAMTS-13 activity/vWF antigen ratio (rho = -0.348, P = .007). A significant association was found between the presence of FVL mutation and VTE (odds ratio (OR): 9.672 (95% confidence interval (CI) 2.074-45.091- P = .004), but no association was found between the mutation and the studied proteins (P > .05). There appears to be an imbalance between vWF and ADAMTS-13 in VTE patients even after 3-6 months following the onset of VTE. We report that the odds of developing VTE in carriers of FVL mutation are 9.672 times those without the mutation, but the presence of this mutation is not associated with the studied proteins.

Neutrophil gelatinase-associated lipocalin as a biomarker of nephropathy in sickle cell disease.

Sickle cell nephropathy (SCN) develops via altered hemodynamics and acute kidney injury, but conventional screening tests remain normal until advanced stages. Early diagnostic biomarkers are needed so that preventive measures can be taken. This study evaluates the role of neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker of SCN in steady state and vaso-occlusive crisis (VOC). In this case-control study, 74 sickle cell disease (SCD) patients (37 in steady state and 37 in VOC) and 53 control subjects had hematological and biochemical measurements including plasma and urine NGAL. Univariate and logistic regression analyses were used to find the associations between variables. The receiver operating characteristic (ROC) curve was used to determine the diagnostic performance characteristics of plasma and urine NGAL for detection of VOC. Plasma and urine NGAL, urine microalbumin:creatinine ratio, and urine protein:creatinine ratio were significantly higher in VOC. Microalbuminuria was present in 17.1% steady state and 32.0% VOC patients. Microalbuminuria showed significant correlations with age, plasma NGAL, WBC, and hemolytic parameters. Area under the ROC curve for plasma NGAL was 0.69 (95%CI = 0.567-0.813; p = 0.006) and 0.86 (95%CI = 0.756-0.954; p < 0.001) for urine NGAL. Urine NGAL cut-off value of 12.0 ng/mL had 95% sensitivity and 65% specificity. These results confirm the presence of nephropathy during VOC and suggest that plasma and urine NGAL would be useful in the identification of SCN. Urine NGAL should be used as the screening biomarker, and patients with VOC and urine NGAL > 12.0 ng/mL should be selected for aggressive management to prevent progression of renal damage.

Relationship of Thrombospondin 1 to von Willebrand Factor and ADAMTS-13 in Sickle Cell Disease Patients of Arab Ethnicity.

BACKGROUND: Thrombospondin 1 (TSP-1) is a multifunctional glycoprotein secreted by platelets. In sickle cell disease (SCD), TSP-1 promotes red cell adhesion to the endothelium by binding to von Willebrand factor (vWF) and inhibiting its degradation by the protease ADAMTS-13. We investigated a possible correlation between TSP-1, vWF and ADAMTS-13 in adult and pediatric SCD patients. METHODS: Using commercially available ELISA kits, TSP-1, vWF and ADAMTS-13 levels were measured in 59 SCD patients (20 children and 39 adults) and compared with 59 age- and sex-matched controls. Associations between TSP-1 and parameters of interest were analyzed using Pearson's correlation coefficient. RESULTS: Although TSP-1 levels were higher in adult and pediatric SCD patients than in controls, the increase was not statistically significant (p > 0.05). We found a significant positive correlation between TSP-1 and platelet count in both adult (r = 0.402, p = 0.01) and pediatric (r = 0.589, p = 0.01) patients, which is expected due to increased platelet activation in SCD. There was a positive correlation between TSP-1 and vWF in normal adults (r = 0.305, p = 0.049) and children (r = 0.633, p = 0.005) but not in patients (p > 0.05). A significant negative correlation between TSP-1 and ADAMTS-13 activity (r = -0.41, p = 0.01) was found in adult patients. Also, a significant negative correlation between TSP-1 and ADAMTS-13/vWF antigen ratio in both normal controls (r = -0.595, p = 0.009) and patients (r = -0.493, p = 0.032) is reported for the pediatric group. CONCLUSIONS: Our findings confirm the inhibitory effects of TSP-1 on ADAMTS-13 activity in adult SCD patients. The negative correlation reported between TSP-1 and ADAMTS-13/vWF antigen ratio in pediatric subjects suggests a possible protective mechanism in younger individuals, although this is not related to the presence of SCD. This work emphasizes the impact of age on interpreting results related to the regulation of vWF expression and interaction with TSP-1 and ADAMTS-13 in SCD.

The Sub-Phenotypes of Sickle Cell Disease in Kuwait.

Kuwaiti patients with sickle cell disease generally have a mild phenotype, but exhibit considerable heterogeneity, in spite of high Hb F levels. We have carried out a cross-sectional study of patients with sickle cell disease in the five major hospitals in Kuwait. Details of their hemoglobin (Hb) genotypes, clinical presentations and complications are presented. The study was over a span of 3 years and involved 396 patients, made up of 351 (88.6%) Kuwaitis and 45 (11.4%) expatriates. They were aged <1 to 73 years. Hb SS (ßS/ßS) was the most common (in 246 patients, i.e. 62.1%) followed by Hb S (HBB: c.20A>T)-ß-thalassemia (Hb S-ß-thal) in 138 (34.8%) and 11 (2.8%) Hb S/Hb D-Punjab (HBB: c.364G>C). Hb F ranged from 1.0 to 55.0%, with a mean of 21.2 ± 9.8%. The most common presentation was vaso-occlusive crises (VOCs), with 230 (54.8%) having had at least one prior to the study with 54 (13.2%) and 74 (18.9%) having between 2-3 and >3 VOCs, respectively. Hydroxyurea (HU) was prescribed to 157 (39.6%) patients. The most common complication was gallstones in 131 (33.1%), followed by acute splenic sequestration in 26.8% and avascular necrosis of the femoral head in 21.2% patients, respectively. Stroke, priapism and leg ulcers were rare. Gallstones, splenic sequestration and osteonecrosis were significantly more common in patients aged >16 years. Patients with Hb S-ß-thal were similar to those with Hb SS in their clinical profiles. The phenotypic expression of sickle cell disease in Kuwaitis is unique in many respects. The role(s) of Hb F and other genetic modifiers require further elucidation.

Evaluation of von Willebrand factor and ADAMTS-13 antigen and activity levels in sickle cell disease patients in Kuwait.

Sickle cell disease (SCD) is a severe form of hemolytic anemia characterized by chronic hemolysis and is associated with increased thrombotic risk. Elevated von Willebrand factor (vWF) levels in SCD have been attributed to increased secretion and impaired processing by its cleaving protease ADAMTS-13. In this study we measured vWF and ADAMTS-13 antigen and activity levels in our SCD patients. Hematological and biochemical parameters for 59 SCD patients (20 children and 39 adults) were analyzed and compared to 59 age- and sex-matched controls. Commercially available ELISA kits were used to measure vWF and ADAMTS-13 antigen and activity levels in patients and controls. Patients had significantly higher levels of vWF (p < 0.006) and ADAMTS-13 activity (p < 0.006) compared to controls. When patients were analyzed according to age and genotype, adult patients (23 SS and 16 Sß0thal) maintained higher vWF antigen levels (p < 0.001), but with reduced ADAMTS-13 activity to vWF:Ag ratio (p < 0.003) compared to controls. Pediatric patients (8 SS and 12 Sß0thal) had comparable vWF antigen levels to controls (p > 0.05), but had higher levels of ADAMTS-13 activity (p < 0.011) and ADAMTS-13 activity to vWF:Ag ratio (p < 0.038). Age is an important factor to consider when vWF and ADAMTS-13 proteins are analyzed among our patients. Increased vWF in adult patients may be attributed to increased production and resistance of vWF to proteolysis rather than ADAMTS-13 deficiency. This outcome was not seen in pediatric patients as higher ADAMTS-13 activity maintained vWF antigen at comparable levels to normal controls.

Clinical and Molecular Characteristics of Non-Transfusion-Dependent Thalassemia in Kuwait.

Although not regularly transfused, patients with non-transfusion-dependent thalassemia (NTDT) are prone to iron overload and its complications. Their molecular, phenotypical and laboratory characteristics vary in different populations and there is a need to document local prevailing patterns. We have reviewed the records of our patients with NTDT in Kuwait and documented their clinical and molecular characteristics in addition to iron status [serum ferritin and liver magnetic resonance imaging (MRI) T2*], management and complications. There were 41 patients, made up of 20 with ß-thalassemia intermedia (ß-TI), 18 with Hb H (ß4) disease and three with Hb E (HBB: c.79G > A)-ß-thalassemia (Hb E-ß-thal); their ages ranged from 3 to 36 years (mean 12.5 ± 7.7). While 18 (43.9%) had been transfused at least once, only three (7.3%) had been transfused on multiple occasions. Three patients had serum ferritin >500 ng/mL; while four of 38 had mild or moderate liver iron overload. Seven (35.0%) of the ß-TI patients were managed with hydroxyurea (HU) with good response. Other complications included five patients with gallstones and one each of hypothyroidism and moyamoya. The most common mutations among the ß-TI patients were IVS-II-1 (G > A) and IVS-I-6 (T > C), while among the Hb H patients, the Saudi α2-globin gene polyadenylation (polyA) (AATAAA > AATAAG) mutation was responsible for all cases either as homozygotes (61.1%) or compound heterozygotes with the α-thal-2 (-α(3.7)) allele (33.3%). Although the pattern of NTDT in Kuwaiti patients is generally mild, there is a need to follow them to adulthood as the complications are cumulative and more prevalent in this group.

Circulating cell-free DNA in sickle cell disease: is it a potentially useful biomarker?

CONTEXT: Vascular occlusion in sickle cell disease causes increased levels of plasma cell-free DNA as a result of cell death and tissue damage. OBJECTIVES: This study investigates plasma cell-free DNA concentrations in sickle cell disease patients, and aims at exploring the significance of plasma cell-free DNA as a potential biomarker in predicting its complications. DESIGN: Plasma cell-free DNA levels were measured using real-time quantitative polymerase chain reaction to quantitatively measure ß-globin gene in blood samples from 57 sickle cell disease patients with acute vaso-occlusive crisis, 42 patients in steady state, 16 individuals with sickle cell trait, and 40 healthy controls. RESULTS: Plasma cell-free DNA level was significantly elevated in samples from patients with acute vaso-occlusive crisis when compared with those in steady state (P = .002), and was significantly higher both in crisis and in steady state when compared with individuals with sickle cell trait and healthy controls (P < .001). There was no difference in cell-free DNA levels between individuals with sickle cell trait and healthy controls. There was no association between plasma cell-free DNA levels and various clinical complications of sickle cell disease and comorbidity. CONCLUSIONS: Plasma cell-free DNA, as quantified by polymerase chain reaction amplification of the ß-globin and human telomerase reverse transcriptase genes, is increased in sickle cell disease patients in vaso-occlusive crisis and in steady state compared with individuals with sickle cell trait and healthy controls, and may be used as a tool to diagnose and monitor the sickle cell crisis and differentiate post-packed red cell transfusion sickle cell disease patients from individuals with sickle cell trait.

Transthoracic echocardiography and 6-minute walk test in Kuwaiti sickle cell disease patients.

OBJECTIVE: The aim of this study was to investigate cardiac abnormalities in Kuwaiti sickle cell disease (SCD) patients using markers such as tricuspid regurgitant jet velocity (TRJV), pulmonary artery systolic pressure (PASP), and the 6-minute walk (6MW) test and correlate these findings with clinical, hematological, and biochemical parameters. MATERIALS AND METHODS: Seventy-three patients with SCD and 70 matched controls were studied. The cardiac status was investigated using transthoracic echocardiography in 57 patients; the 6MW test was carried out in patients and controls. Complete blood counts and hemolytic parameters were assessed. RESULTS: Reticulocytes, bilirubin, and lactate dehydrogenase were significantly higher (p < 0.0001) in patients, while hemoglobin (Hb) and haptoglobin were lower (p < 0.0001) than in controls. The mean fetal Hb among patients was 15.85 ± 8.7%. Of the 57 patients, 14 (24.5%) and 15 (26%) had mild tricuspid and mitral regurgitation, respectively. The mean ejection fraction, TRJV, and PASP were 63.9 ± 6.3%, 1.7 ± 0.5 m/s, and 23.0 ± 7.3 mm Hg, respectively. Three (5.2%) patients had mildly raised TRJV (2.6-2.97 m/s, normal range <2.5 m/s) while 8 (14%) had high PASP (mean 35.3 ± 5.1 mm Hg, normal range <30 mm Hg). Hb, hematocrit, and reticulocytes were different (p = 0.010, p = 0.006, and p = 0.011, respectively) between patients with normal and high PASP. All 3 patients who had a high TRJV had a high PASP, and 2 of these patients died during follow-up. The systolic and diastolic blood pressure, oxygen saturation before and after the 6MW test, and distance walked were lower (p = 0.006, p = 0.000, p = 0.002, p = 0.000, and p = 0.000, respectively) in patients compared to controls. CONCLUSION: Raised PASP was common in Kuwaiti SCD patients while raised TRJV was not.

Therapeutic effect of low-molecular weight heparin and incidence of lower limb deep venous thrombosis and pulmonary embolism after laparoscopic bariatric surgery.

BACKGROUND: The aim of our study was to determine the therapeutic effect of low-molecular weight heparin after laparoscopic Roux-en-Y gastric bypass. METHODS: We prospectively analyzed data of 39 patients who underwent Roux-en-Y gastric bypass from 1093 consecutive patients who underwent bariatric procedures from May 1999 to May 2012. All patients were given 40 mg enoxaparin subcutaneously once daily preoperatively and continued for 5 days. RESULTS: There were 31 females. Mean age was 32.48 years and mean body mass index was 44.59 kg/m. Only 46.1% of patients reached the defined therapeutic dose on the second day and 41% on the fifth day. One fatal pulmonary embolism was recorded (1/1093, 0.09%) in the entire series. CONCLUSIONS: Anti-Xa surveillance did not correlate strongly with outcome. Further studies are required for proper dose adjustments of low-molecular weight heparin in these obese patients and whether anti-Xa monitoring should be continued.

Blood transfusion in sickle cell disease.

Sickle cell anemia is an inherited disease that causes chronic hemolytic anemia. Its pathognomonic signs and symptoms are caused by hemoglobin (Hb) S, which results from a single nucleotide substitution in the ß-globin gene that places the amino acid valine with glutamic acid at codon 6 of the ß-globin chain. Hb S is an insoluble Hb that crystalizes at low oxygen tension and other precipitating conditions leading to rigidity of red cells and clumping in small blood vessels. Patients with sickle cell disease have a variable Hb level that may range from 7.0 to 11.0 g/dL in their steady state condition. The most common cause of hospital presentation is due to acute painful crisis that results from vaso-occlusion by sickled cells. These episodes are treated with hydration and analgesia and do not require blood transfusion. Blood transfusion should be aimed to increase tissue delivery of oxygen. Hb S is known to be a low affinity Hb and so delivers oxygen at a lower partial pressure of oxygen compared to Hb A. Even with adequate pre transfusion testing and precautions, blood transfusion is never totally safe and short or long term complications may occur. Blood transfusion in patients with sickle cell disease has only limited indications such as acute hemolytic, aplastic or sequestration crises. Chronic transfusion protocols are implemented in cases of strokes or high cerebral blood flow ultrasonic studies as a prophylactic measure. Exchange blood transfusion is used in some complications of the disease such as acute chest syndrome (ACS), priapism or peri operatively. Once it is decided to transfuse blood, the transfused blood should be Hb S negative, Rh and Kell antigen matched.

Genotypic and phenotypic differences between nodal and extranodal diffuse large B-Cell lymphomas.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of diseases that have diverse clinical, pathological, and biological features. Here, it is shown that primary nodal and extranodal DLBCLs differ genomically and phenotypically. Using conventional comparative genomic hybridization (CGH), the authors assessed the chromosomal aberrations in 18 nodal, 13 extranodal, and 5 mixed DLBCLs. The results demonstrate significantly distinct chromosomal aberrations exemplified by gains of chromosomal arms 1p, 7p, 12q24.21-12q24.31, and 22q and chromosome X and loss of chromosome 4, 6q, and 18q22.3-23 in extranodal compared with nodal DLBCLs. Nodal DLBCLs showed an increased tendency for 18q amplification and BCL2 protein overexpression compared with extranodal and mixed tumors. Using a panel of five antibodies against GCET1, MUM1, CD10, BCL6, and FOXP1 proteins to subclassify DLBCLs according to the recent Choi algorithm, the authors showed that the genomic profiles observed between the nodal and extranodal DLBCLs were not due to the different proportions of GCB vs ABC in the two groups. Further delineation of these genomic differences was illuminated by the use of high-resolution 21K BAC array CGH performed on 12 independent new cases of extranodal DLBCL. The authors demonstrated for the first time a novel genome and proteome-based signatures that may differentiate the two lymphoma types.

Pattern of bone mineral density in sickle cell disease patients with the high-Hb F phenotype.

Low bone mineral density (BMD) is common in sickle cell disease (SCD) patients of all ages due to erythropoietic stress and consequent bone marrow hyperplasia. Kuwaiti SCD patients have a mild clinical phenotype because of their high Hb F level. There has been no previous documentation of BMD in this population of patients. SCD patients (n = 81) and controls (n = 67) were recruited from hematology clinics of Mubarak Hospital, Kuwait. BMD was measured using dual X-ray absorptiometry (Hologic) in the lumbar spine and the hip (left femoral neck). Among the 53 adult patients, the prevalence of low BMD was 67.4% in the spine and 33.3% in the hip while among controls, the figures were 23.1 and 11.3%, respectively. These differences are significant (p < 0.01). In SCD children, the figures were 17.9% (in the lumbar spine) and 3.6% (in the hip), while in controls the figures were 13.3 and 0%, respectively. The differences are not significant (p > 0.05). Patients with frequent vaso-occlusive crisis had significantly lower mean BMD, but those with MRI evidence of avascular necrosis of the femoral head were more likely to have normal or osteosclerotic BMD. Our study showed that osteopenia/osteoporosis is uncommon among Kuwaiti children with SCD but quite common in adults.

Hypercoagulable state and methylenetetrahydrofolate reductase (MTHFR) C677T mutation in patients with beta-thalassemia major in Kuwait.

INTRODUCTION: Patients with thalassemia major often present with a hypercoagulable state, the pathogenesis of which is still not understood. MATERIALS AND METHODS: This study evaluates the risk factors for hypercoagulability in 50 beta-thalassemia major patients and 50 healthy controls. Fasting total homocysteine, protein C (PC), protein S (PS), antithrombin (AT), activated protein C resistance (APCR) and lupus anticoagulant (LA) were assessed. MTHFR C677T mutation was determined. RESULTS: Significant reductions in PC, PS and AT were noted in patients. Only 4% of the patients had hyperhomocysteinemia. Thirty-two percent of the patients were heterozygous and 4% were homozygous for MTHFR C677T mutation. CONCLUSION: The natural coagulation inhibitors PC, PS and AT were significantly reduced in patients with beta-thalassemia major and were thus important risk factors for the hypercoagulable state, but hyperhomocysteinemia and MTHFR mutation do not seem to be significant risk factors for thromboembolic events.

Determinants and associations of homocysteine and prothrombotic risk factors in Kuwaiti patients with cerebrovascular accident.

OBJECTIVE: The objective of this study was to evaluate the determinants and associations of some prothrombotic risk factors in patients with cerebrovascular accidents (CVAs). SUBJECTS AND METHODS: In this case-control study, plasma total homocysteine (tHcy), lupus anticoagulant, protein C, protein S, activated protein C resistance (APC-R) and antithrombin were measured in 102 patients (60 males and 42 females) and 167 controls (87 males, 80 females). Serum vitamin B(12), folate, red cell folate, creatinine, lipid profile and glucose were also determined. Glomerular filtration rate (GFR) was calculated. RESULTS: 13 (22%) of the 60 male patients, and 16 (39%) of the 42 female patients had hyperhomocysteinemia. Median (interquartile range) tHcy was higher in male patients [11.22 micromol/l (9.60-15.40)] than female patients [10.05 micromol/l (8.72-17.54)]. On binary logistic regression analysis, the significant (p < 0.05) determinants of tHcy were urea, creatinine and GFR. Comparing patients with control subjects showed that tHcy, age, fasting glucose, urea, serum creatinine, white blood cell count, protein S, APC-R and factor VIII were significantly higher, while protein C, factor II, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were significantly lower in patients. Lupus anticoagulant was not associated with tHcy and not detected in patients and controls. Low concentrations of vitamins B(12) and folate were not associated with tHcy. Logistic regression analysis showed a significant association of tHcy with CVA (OR = 9.55; p = 0.047) in males in the presence of other traditional CVA risk factors but tHcy is not independently associated with CVA in females. CONCLUSION: Hyperhomocysteinemia is common in Kuwaiti patients with CVA and tHcy probably interacts with prothrombotic factors (protein C, APC-R and factor VIII) to increase CVA risk. The main determinants, age and GFR markers, should be kept in mind when determining the risk associated with tHcy.

Body iron stores in relation to the metabolic syndrome, glycemic control and complications in female patients with type 2 diabetes.

BACKGROUND AND AIM: Studies suggest that iron plays a significant role in the development of diabetes and its complications. This study evaluates the associations of iron metabolism parameters with the metabolic syndrome (MS), control and complications in female patients with type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: Ferritin, soluble Transferrin Receptor (sTfR), sTfR/Log ferritin ratio (sTfR-F index), iron, full blood count and high-sensitivity C-reactive protein (hs-CRP) were determined in 110 female patients with T2DM. Steady state beta cell function (%B), insulin sensitivity (%S) and insulin resistance were assessed with homeostasis model. Patients were divided into tertiles of ferritin and sTfR-F index and according to the presence or absence of the MS and diabetic complications. Patients within the lowest tertile of the sTfR-F index had significantly higher fasting insulin, percent B, low-density lipoprotein cholesterol and Apolipoprotein B than those in the highest tertile. Ferritin showed significant correlations with insulin, percent B and inverse correlations with adiponectin and percent S. The sTfR-F index was significantly correlated with insulin, percent B and lipid parameters. Correcting for hs-CRP abolished the correlations with ferritin but not the sTfR-F index. Higher indices of body iron were significantly associated with diabetes complications but no associations were found with MS, glucose or glycemic control. Multiple regression analysis with confounding variables showed ferritin and the sTfR-F index were not independently associated with diabetes complications. CONCLUSIONS: Association of ferritin with metabolic derangements and complications in diabetes is partly dependent on association with inflammation. Iron status, estimated with the sTfR-F index, is associated with metabolic derangements and complications but the associations are dependent on other risk factors. Prospective studies that use the sTfR-F index as a marker of iron status are required to confirm the role of iron in the etiopathogenesis of T2DM and its complications.

Regional cerebral blood flow in patients with sickle cell disease: study with single photon emission computed tomography.

OBJECTIVE: Neurological complications have been reported in patients with sickle-cell disease (SCD) using positron emission tomography (PET), magnetic resonance imaging (MRI), and computed tomography (CT), but not with single photon emission computed tomography (SPECT). The objective of this study was to investigate brain perfusion in the patients with SCD using SPECT after technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO), was administered and compare the findings with those of demography, physical examination, MRI and hematological profile. METHODS: The study involved 21 patients (12 males, 9 females, age at study 8-45 years) who were known to be having SCD for a duration of at least 5 years. The patients were not in acute crisis and had normal neurological assessments with no known history of stroke or transient ischemic episode or previous abnormal CT or MRI brain scan, and were right-handed. The brain SPECT was performed after intravenous injection of 740 MBq (20 mCi) 99mTc-HMPAO in adults or an appropriate dose in pediatric patients. The scans were visually interpreted by two nuclear medicine physicians and a decision was reached by consensus. An MRI done 3 months later was interpreted by a radiologist. The demographic data and hematological profile were obtained from the medical records of the patients. RESULTS: Of the 21 patients, 7 (age 11-22 years) had brain perfusion deficit mostly in the frontal lobe either alone or in combination with temporal and/or parietal lobe. The MRI was abnormal in 2 patients. The brain perfusion deficit was not associated with the demographic data of the patients or hematological profiles. CONCLUSIONS: The findings show that SPECT was useful in detecting brain perfusion deficit in SCD patients, and such an early detection may be clinically useful in the subsequent follow-up of such patients, since it is known that cerebral perfusion deficit can lead to silent infarct and/or overt stroke, and affect cognitive skills.

Plasma homocysteine and hematological factors in patients with venous thromboembolic diseases in Kuwait.

BACKGROUND: Venous thromboembolic disease (VTE) is a common cause of morbidity in Kuwait, but the risk factors have not been studied. Hyperhomocysteinemia has been suggested as one of the risk factors. We postulate that hyperhomocysteinemia acts synergistically with hematological variables to increase VTE risk. This study evaluates the roles of hyperhomocysteinemia and hematological variables in patients with VTE. METHODS: We measured fasting plasma total homocysteine (tHcy), activated protein C resistance, protein C (PC), protein S (PS) and antithrombin (AT) in 201 patients with VTE and 166 healthy controls. We also measured factor VIII, factor II, lupus anticoagulant, anticardiolipin, serum vitamin B12, folate, creatinine, lipid profile, glucose, full blood count and red cell folate. The glomerular filtration rate (GFR) was calculated from creatinine. RESULTS: When patients on warfarin were excluded, 13.1% of patients (18 out of 137) had a deficiency in PC, 16.8% (23 out of 137) had a deficiency in PS, and when patients on heparin were excluded, 8.3% of patients (14 out of 168) had low AT. Spearman's rank correlation analysis showed that tHcy had significant correlations with age, creatinine and PS, and significant inverse correlations with GFR, high-density lipoprotein cholesterol and serum folate. Partial correlation analysis after correcting for age and sex showed that tHcy retained a significant correlation with creatinine, GFR and serum folate. Binary logistic regression analyses of the determinants of hyperhomocysteinemia included age, creatinine, GFR and serum folate. Multivariate logistic regression analysis showed significant association of tHcy with VTE (OR = 5.6; p < 0.0001) in the presence of known risk factors for VTE. CONCLUSION: We conclude that elevated tHcy is a significant risk factor for the development of VTE, and therefore, it should be included in the workup for patients at risk of VTE, but the determinants of tHcy should be kept in mind.