Prevalence and Risk Factors for Diabetic Peripheral Neuropathy Among Saudi Hospitalized Diabetic Patients: A Nested Case-Control Study.

OBJECTIVE: To determine the prevalence and the risk factors of diabetic peripheral neuropathy (DPN) in hospitalized adult Saudi diabetics. METHODS: This is a retrospective, nested case-control study conducted at King Abdulaziz Medical City (KAMC) in Riyadh, Saudi Arabia. All diabetic patients admitted to the hospital between the January 1, and December 31, 2018 were considered for inclusion in the study. Patients with DPN were identified and three controls per case were randomly selected from the remaining diabetic patients without peripheral neuropathy (PN). RESULTS: A total of 2,096 adult diabetic patients were identified during the study period. Of these, 73 patients (3.5%) were confirmed to be suffering from DPN and 219 were included as controls. When comparing diabetic with the control cases, DPN cases were significantly older (p=0.002), had a significantly higher proportion of type 2 diabetes (p=0.023), chronic kidney disease (p<0.0001), cerebral vascular stroke (p=0.027), hypertension (p=0.005), dyslipidemia (p=0.002), peripheral vascular disease (p<0.0001), osteoarthritis (p=0.034), diabetic ketoacidosis (p=0.003), foot ulcers (p=0.006), gangrene (p=0.001), lower limb ischemia (p=0.001), increased duration with diabetic disease (p=0.031), increased BMI (p=0.003), higher serum creatinine (p<0.001) and lower serum albumin levels (p=0.035). In the multivariate logistic regression, only older age {odds ratio (OR) 1.02, 95% CI 1.01-1.04, p=0.031}, chronic kidney disease (OR 2.39, 95% CI 1.23-4.64, p=0.010) and peripheral vascular disease (OR 3.14, 95% CI 1.39-7.13, p=0.006) were independently associated with DPN. CONCLUSION: This study identified several risk factors that contributed to the development of DPN in Saudis. These must be considered in strategies and campaigns aimed at risk reduction of cardiovascular and chronic diseases, and consequently progression of DPN.

Comparison of the hypoglycemic and antithrombotic (anticoagulant) actions of whole bovine and camel milk in streptozotocin-induced diabetes mellitus in rats.

People with diabetes are at higher risk of fatal thromboembolic accidents in the cerebral and coronary circulations, especially stroke and ischemic heart disease. We have previously described the hypoglycemic, hypolipidemic, and anticoagulant activity of orally administered camel milk in streptozotocin-induced diabetic rats. In the present study in the same animal model, we extended these observations by comparing camel milk and the more available and widely consumed bovine milk with respect to their antidiabetic and antithrombotic actions. Rats were rendered diabetic by intraperitoneal streptozotocin (65 mg/kg), and then camel milk or bovine milk was administered orally for 8 wk. We evaluated the changes in body weight, fasting blood glucose, glucose tolerance, blood coagulation profile, and platelet function. Diabetic rats developed weight loss, hyperglycemia, glucose intolerance, inhibition of platelet aggregation responses to arachidonic acid and adenosine diphosphate, a marked decrease (>50%) in plasma fibrinogen levels, and short activated partial thromboplastin time. Treatment with camel milk or bovine milk reversed these abnormalities, resulting in weight gain, decreased blood glucose levels, and improved glucose tolerance. Despite the more remarkable antidiabetic action of camel milk, treatment with bovine milk was more effective in correcting plasma fibrinogen levels and restoring inhibited platelet aggregation responses. Long-term administration of camel milk or bovine milk counteracted streptozotocin-induced metabolic manifestations in rats, maintained platelet function, and abolished coagulopathy-associated fibrinogen consumption. Notably, the antidiabetic effect of camel milk was more pronounced than that of bovine milk, but bovine milk exhibited more potent anticoagulant activity than camel milk. These findings should encourage further clinical trials to assess the efficiency of camel milk and bovine milk or their derived peptides as food supplements or potential nonpharmacological therapies for dysglycemia and the vascular complications of diabetes mellitus.

Hepatitis C virus genotypes in Saudi Arabia: a future prediction and laboratory profile.

BACKGROUND: Hepatitis C virus (HCV) genotypes and subtypes are considered an important tool for epidemiological and clinical studies and valuable markers for disease progression and response to antiviral therapy. The aim of this study was to identify the prevalence of HCV genotypes and their relation to socio-demographic factors particularly age and sex, various biochemical profiles and viral load. METHODS: The records (630) of Saudi patients positive for HCV (2007-2011) reported in the system of the Molecular Pathology Laboratory at a tertiary reference hospital in Riyadh, Saudi Arabia were analyzed. Socio-demographic characteristics, liver biochemical profile, viral load and co-infection with HBV and HIV were retrieved from the hospital database. The associations of continuous and categorical variables with genotypes were analyzed. RESULT: The overall mean age of the surveyed patients was 59 years ±0.5 years (21% were <50 years (p = 0.02). The rate of infection is lower in males than in females (47.6% vs. 52.4%). HCV genotype 4 was the most prevalent (60.7%), followed by genotype 1 (24.8%). However, genotype 1 and 3 were found more in males (29.7% vs. 20.3% and 6% vs. 2.1%, respectively, p = 0.001), while genotype 2 and 4 were more among females (4.8% vs. 2% and 68.5% vs. 52.3%, respectively). In addition, genotype 1 was found dominant in younger males (33.8%). Biochemical parameters across gender showed significant variation in particular for the ALT (p = 0.007). The mean viral load was significantly higher in genotype 1 than genotype 4 (4,757,532 vs. 1,435,012, p = <001). There is a very low overall percentage of co-infection of HBV or HIV in this study (around 2% for each). CONCLUSION: Although HCV genotype 4 shows an overall high prevalence in this study, a clear decline in the rate of this genotype was also demonstrated in particular among the younger age group who displayed increasing trends toward the global trend of genotype 1, rather than genotype 4. This finding would be of clinical interest in relation to future planning of the therapy for HCV infected patient.

Long-term audit of the use of fresh frozen plasma in a university hospital.

OBJECTIVES: There is universal concern about the inappropriate use of fresh frozen plasma (FFP). This study aimed to determine the extent of the inappropriate use of FFP at a university hospital in KSA. METHODS: Medical records on the annual use of FFP were analysed from 1986 to 2007. Then, the results of the coagulation screening tests were extracted from the medical records of 531 consecutive patients in various departments of the hospital. RESULTS: As many as 68,480 FFP units were used during the 22 year study period. Consumption increased and then plateaued in 1995, but dropped dramatically by 30.9% and reached its lowest level in 2000. There was also a concomitant and overlapping drop in both FFP usage and the hospital mortality rate per patient admission. One-thousand-six-hundred-twenty FFP units were issued for 531 patients. Coagulation testing, before and after infusion, was adopted in almost all patients in the Department of Obstetrics and Gynaecology, in 90% of patients in the Department of Surgery and in approximately 70% of patients in other departments. CONCLUSIONS: Significant inappropriate use of FFP at our institute has been made evident by examining the remarkable drop in use following the universal "HIV scare" of the early 1990s. The resulting drop in the hospital mortality rate, accompanying the simultaneous drop in FFP use, reflects the benefits of resorting to the use of less blood therapy. Coagulation testing was used to a satisfactory extent. Transfusion audits and educational programs could result a better use of FFP.

The Levels of Tissue Factor Pathway Inhibitor in Sepsis Patients Receiving Prophylactic Enoxaparin.

OBJECTIVE: Sepsis syndrome is usually accompanied by activation of blood coagulation mechanisms. Earlier studies found deficiencies of the 3 main natural anticoagulants, antithrombin, protein C, and protein S. However, none of these inhibitors block tissue factor, the prime trigger of coagulation during sepsis that is controlled specifically by the tissue factor pathway inhibitor (TFPI). The aim of this study was to characterize the fluctuations in the levels of natural anticoagulants, particularly TFPI, in the course of sepsis and to find out their association with the anticoagulant action of the low-molecular-weight heparin enoxaparin. MATERIALS AND METHODS: We studied 51 consecutive patients with sepsis. Blood samples were collected from patients at baseline (0 h) and at 4, 12, and 24 h after enoxaparin administration. The following assays were undertaken using commercial kits: activated partial thromboplastin time, prothrombin time, thrombin time, total and free TFPI, protein C and protein S, antithrombin, fibrinogen, and anti-factor Xa. RESULTS: Before enoxaparin administration, there was significant prolongation of the prothrombin time and activated partial thromboplastin time, and this remained the case in the 3 subsequent samples. There was marked reduction in the levels of antithrombin, protein C, and total and free protein S to below control values throughout the study. In contrast, plasma levels of both total and free TFPI were markedly elevated and increased after enoxaparin therapy. Anti-factor Xa levels were within the therapeutic range throughout. There was no difference in TFPI levels between those patients who died and those who survived. CONCLUSION: Sepsis triggered marked release of TFPI from endothelial cells. This persisted and was increased further following the administration of enoxaparin. In contrast, there was marked consumption of the natural coagulation inhibitors antithrombin, protein C, and protein S. These results go some way towards explaining why the therapeutic use of recombinant TFPI fails to correct sepsis-associated coagulopathy.

A 23 years audit of packed red blood cell consumption in a university hospital in a developing country.

BACKGROUND: There is paucity of information on the blood transfusion practice in developing countries. The current audit aims to find out the long term trend in the consumption of packed red blood cells (PRBCs) in a large Saudi teaching hospital in Riyadh MATERIALS AND METHODS: We analyzed the annual consumption of PRBCs from 1985 to 2007 in seven major hospital divisions (Medicine, General Surgery, Pediatrics, Obstetrics and Gynecology, Cardiac Surgery, Accident and Emergency and Renal Dialysis Unit) at the 850-bed King Khalid University Hospital (KKUH), Riyadh. RESULTS: Grand total consumption of PRBCs was 345,642 units. The consumption increased gradually and peaked in the year 1994, dropped to 30.4% 6 years later and then increased gradually thereafter, due to the expansion in the number of patients cared for in the Departments of Medicine, Cardiac Surgery and Accident and Emergency, while in the Department of Pediatrics the drop in consumption continued unabated. In the Renal Dialysis Unit consumption was minimal with the use of erythropoietin therapy. The crossmatch:transfusion ratio uncovered gross over-ordering of PRBCs and wastage of blood bank resources in most hospital divisions most notably in the Department of Obstetrics and Gynecology. CONCLUSION: The results obtained indicate clearly that there has been overuse of blood products that dropped markedly in years coinciding with the worldwide apprehension about the safety of transfusion therapy particularly HIV transmission. This factor in addition to the current implementation of strict guidelines is gradually improving transfusion practices in our institute.

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.

Camel milk attenuates the biochemical and morphological features of diabetic nephropathy: inhibition of Smad1 and collagen type IV synthesis.

Diabetic nephropathy (DN) is a common microvascular complication of diabetes mellitus (DM) that worsens its morbidity and mortality. There is evidence that camel milk (CM) improves the glycemic control in DM but its effect on the renal complications especially the DN remains unclear. Thus the current study aimed to characterize the effects of CM treatment on streptozotocin (STZ)-induced DN. Using STZ-induced diabetes, we investigated the effect of CM treatment on kidney function, proteinuria, renal Smad1, collagen type IV (Col4), blood glucose, insulin resistance (IR), lipid peroxidation, the antioxidant superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH). In addition renal morphology was also examined. The current results showed that rats with untreated diabetes exhibited marked hyperglycemia, IR, high serum urea and creatinine levels, excessive proteinuria, increased renal Smad1 and Col4, glomerular expansion, and extracellular matrix deposition. There was also increased lipid peroxidation products, decreased antioxidant enzyme activity and GSH levels. Camel milk treatment decreased blood glucose, IR, and lipid peroxidation. Superoxide dismutase and CAT expression, CAT activity, and GSH levels were increased. The renoprotective effects of CM were demonstrated by the decreased serum urea and creatinine, proteinuria, Smad1, Col4, and preserved normal tubulo-glomerular morphology. In conclusion, beside its hypoglycemic action, CM attenuates the early changes of DN, decreased renal Smad1 and Col4. This could be attributed to a primary action on the glomerular mesangial cells, or secondarily to the hypoglycemic and antioxidant effects of CM. The protective effects of CM against DN support its use as an adjuvant anti-diabetes therapy.

Camel milk inhibits inflammatory angiogenesis via downregulation of proangiogenic and proinflammatory cytokines in mice.

Camel milk has traditionally been used to treat cancer, but this practice awaits scientific scrutiny, in particular its role in tumor angiogenesis, the key step involved in tumor growth and metastasis. We aimed to investigate the effects of camel milk on key components of inflammatory angiogenesis in sponge implant angiogenesis model. Polyester-polyurethane sponges, used as a framework for fibrovascular tissue growth, were implanted in Swiss albino mice and camel milk (25, 50 and 100 mg/kg/day) was administered for 14 days through installed cannula. The implants collected at day 14 post-implantation were processed for the assessment of hemoglobin (Hb), myeloperoxidase (MPO), N-acetylglucosaminidase (NAG), and collagen, which were used as indices for angiogenesis, neutrophil, and macrophage accumulation and extracellular matrix deposition, respectively. Relevant inflammatory, angiogenic, and fibrogenic cytokines were also determined. Camel milk treatment attenuated the main components of the fibrovascular tissue, wet weight, vascularization (Hb content), macrophage recruitment (NAG activity), collagen deposition and the levels of vascular endothelial growth factor (VEGF), interleukin (IL)-1ß, IL-6, IL-17, tumor necrosis factor-α, and transforming growth factor-ß. A regulatory function of camel milk on multiple parameters of the main components of inflammatory angiogenesis has been revealed, giving insight into the potential therapeutic benefit underlying the anti-cancer actions of camel milk.

Clotting factor VIII (FVIII) and thrombin generation in camel plasma: A comparative study with humans.

The objective of this study was to characterize the highly elevated levels of clotting factor VIII (FVIII) in camel plasma. Whole blood was collected from healthy camels and factor VIII clotting activity (FVIII:C) assays were conducted using both the clotting and the chromogenic techniques. The anticoagulant citrate phosphate dextrose adenine (CPDA) produced the highest harvest of FVIII:C, the level of plasma factor VIII, compared to heparin:saline and heparin:CPDA anticoagulants. Camel FVIII can be concentrated 2 to 3 times in cryoprecipitate. There was a significant loss of camel FVIII when comparing levels of FVIII in camel plasma after 1 h of incubation at 37°C (533%), 40°C (364%), and 50°C (223%). Thrombin generation of camel plasma is comparable to that of human plasma. It was concluded that camel plasma contains very elevated levels of FVIII:C, approaching 8 times the levels in human plasma, and that these elevated levels could not be attributed to excessive thrombin generation. Unlike human FVIII:C, camel FVIII:C is remarkably heat stable. Taken together, these unique features of camel FVIII could be part of the physiological adaptation of hemostasis of the Arabian camel in order to survive in the hot desert environment.

L'objectif de la présente étude était de caractériser les niveaux très élevés du facteur de coagulation VIII (FVIII) dans le plasma de chameau. Du sang entier a été prélevé de chameaux en santé et des épreuves d'activité de coagulation du facteur VIII (FVIII:C) ont été effectuées en utilisant des techniques chromogéniques et de coagulation. L'anticoagulant citrate phosphate dextrose adénine (CPDA) a permis la récolte la plus élevée de FVIII:C, le niveau plasmatique de facteur VIII, comparativement aux anticoagulants héparine:saline et héparine CPDA. Le FVIII de chameau peut être concentré 2 à 3 fois dans des cryoprécipités. Il y avait une perte significative de FVIII de chameau lorsque l'on comparait les niveaux de FVIII dans le plasma de chameau après 1 h d'incubation à 37 °C (533 %), 40 °C (364 %), et 50 °C (223 %). La génération de thrombine dans le plasma de chameau est comparable à celle dans le plasma humain. Il a été conclu que le plasma de chameau contient des niveaux très élevés de FVIII:C, atteignant près de 8 fois le niveau dans le plasma humain, et que ces niveaux élevés ne pouvaient pas être attribué à une génération excessive de thrombine. Comparativement au FVIII:C humain, le FVIII:C de chameau est très stable à la chaleur. Prises dans leur ensemble, ces caractéristiques uniques du FVIII de chameau pourraient faire partie de l'adaptation physiologique de l'hémostase du chameau arabe afin de lui permettre de survivre dans l'environnement chaud du désert.(Traduit par Docteur Serge Messier).

Tissue plasminogen activator and plasminogen activator inhibitor-1 levels in patients with acute myocardial infarction and unstable angina.

OBJECTIVE: To compare levels of tissue plasminogen activator and plasminogen activator inhibitor-1 levels in patients with acute myocardial infarction and unstable angina in order to understand the use of high sensitivity C-reactive protein (hsCRP), coagulation and fibrinolysis markers for cardiovascular risk assessment. METHODS: The cross-sectional case-control study compared circulating concentrations of high sensitivity C reactive protein (hsCRP), fibrinogen, tissue-type plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) between patients of acute myocardial infarction (AMI) (n = 67), Unstable Angina Pectoris (UA) (n = 35) and healthy control subjects (n = 39) at the King Khalid University Hospital, Riyadh, Saudi Arabia, from June 2006 to August 2007. RESULTS: The patients had significantly higher hsCRP (1.06 +/- 0.11 vs 0.52 +/- 0.14, p < 0.01), fibrinogen (426.21 +/- 24.09 vs 329.32 +/- 13.93, p < 0.05), PAL-1 (44.02 +/- 6.05 vs 19.35 +/- 3.94, p < 0.01) and tPA (12.31 +/- 1.16 vs 9.49 +/- 0.86, p < 0.05) compared to the controls. Fibrinogen (329.32 +/- 13.93) and PAL-1 (19.35 +/- 3.94) were higher in both angina and infarction groups compared to the healthy subjects (p < 0.01). Between the two categories of patients the difference between Fibrinogen (449.60 +/- 52.98 vs 419.46 +/- 23.42) and PAL-1 (52.00 +/- 17.34 vs 43.19 +/- 6.10) levels were non-significant. Also, the difference in tPA levels between the controls and angina patients was nonsignificant (9.49 +/- 0.86 vs 9.91 +/- 1.24 p > 0.05). It was higher in infarction patients (14.79 +/- 3.14) compared to angina patients and the controls, (p < 0.05). Compared to the controls, hsCRP levels were significantly higher in both the patient groups (0.52 +/- 0.14, 1.05 +/- 0.28, 1.40 +/- 0.20, p < 0.01). Moreover, they were significantly higher in infarction patients than those suffering from angina (p < 0.05). CONCLUSIONS: CAD patients had a procoagulant state and presented with higher levels of hsCRP compared to the healthy individuals. Moreover, there were significant differences in coagulation markers and hsCRP between angina and infarction patients.

Attitude to blood donation in Saudi Arabia.

BACKGROUND AND OBJECTIVES: The blood donor system in the Kingdom of Saudi Arabia depends on a combination of voluntary and involuntary donors. The aim of this study is to explore the attitudes, beliefs and motivations of Saudis toward blood donation. MATERIALS AND METHODS: The study was conducted at the Donor Centers at King Khalid University Hospital (KKUH) Blood Bank and King Saud University Students Health Center, Riyadh. A self-administered questionnaire was distributed to donors (n = 517) and nondonors (n = 316), between February and June 2008. All were males. RESULTS: Ninety-nine percent of the respondents showed positive attitude toward blood donations and its importance for patients care, and object the importation of blood from abroad. Blood donors: Ninety-one percent agree that that blood donation is a religious obligation, 91% think no compensation should be given, 63% will accept a token gift, 34% do not object to donating six times/year and 67% did not mind coming themselves to the donor center to give blood. Nondonors: Forty-six percent were not asked to give blood and those who were asked mentioned fear (5%) and lack of time (16%) as their main deterrents. Reasons for rejection as donors include underweight and age (71%) and health reasons (19%). Seventy-five percent objected to money compensation but 69% will accept token gifts and 92% will donate if a relative/friend needs blood. CONCLUSION: These results reflect an encouraging strong positive attitude toward blood donation. Further future planning with emphasis on educational/publicity programs and careful organization of donor recruitment campaigns could see the dream of total voluntary nonremunerated blood donations should not take long to be true.

The antiplatelet activity of camel urine.

BACKGROUND: For centuries, camel urine has been used for medicinal purposes and anecdotally proclaimed as a cure for a wide range of diseases. However, the apparent therapeutic actions of camel urine have yet to be subjected to rigorous scientific scrutiny. Recent preliminary studies from the authors' laboratory have indicated that camel urine possesses potent antiplatelet activity, not found in human or bovine urines, suggesting a possible role for camel urine in inhibiting platelet function. The goal of the current study was to characterize the antiplatelet activity of camel urine against normal human platelets based on agonist-induced aggregation and platelet function analyzer (PFA-100) closure time. MATERIALS AND METHODS: Urine was collected from healthy virgin, pregnant, and lactating camels aged 2-10 years. Platelet-rich plasma (PRP) was prepared from blood collected from healthy individuals' blood into citrated anticoagulant. Agonist-induced aggregometry using donor PRP and PFA-100 closure times in whole blood were carried out in the presence and absence of added camel urine. The responses of platelets to multiple doses of camel urine were also assessed. The experimental procedure was repeated in human and bovine urines. RESULTS: Camel urine completely inhibited arachidonic acid (AA) and adnosine diphosphate (ADP)-induced aggregation of human platelets in a dose-dependent manner. PFA-100 closure time using human whole blood was prolonged following the addition of camel urine in a dose-dependent manner. Virgin camel urine was less effective in inhibiting ADP-induced aggregation as compared to urine from lactating and pregnant camels; however, all three showed comparable inhibitory activity. Neither human nor bovine urine exhibited antiplatelet activity. CONCLUSIONS: Camel urine has potent antiplatelet activity against ADP-induced (clopidogrel-like) and AA-induced (aspirin-like) platelet aggregation; neither human nor bovine urine exhibited such properties. These novel results provide the first scientific evidence of the mechanism of the presumed therapeutic properties of camel urine.

Haemostatic and cytokine changes in gestational diabetes mellitus.

BACKGROUND: Limited data indicate the existence of a hypercoagulable state and the possible involvement of pro-inflammatory cytokines in the pathogenesis of gestational diabetes mellitus (GDM). AIM: To characterise the coagulation inhibitor and cytokine profiles in women with GDM. METHODS: Two groups of women in the third trimester of pregnancy were studied: GDM (n = 150) and controls: women with normal pregnancy (n = 100); GDM in their first post-delivery day (n = 52). LABORATORY ASSAYS: Plasma fibrinogen, antithrombin (AT), protein C, total and free protein S, interleukins-2, 6 and 8 (IL-2, 6, 8). RESULTS: During pregnancy, the only significant alterations noted were higher levels of body mass index, fibrinogen and total protein S in women with GDM when compared to normal pregnancy. In the post-delivery group, there was further elevation in the levels of plasma fibrinogen and significant drop in the level of total protein S, protein C and AT. Significant elevation of IL-2 and IL-6 levels was recorded only in post-delivery group. CONCLUSION: In GDM, the only indicator of a tendency towards hypercoagulability is the higher fibrinogen levels as compared to normal pregnancy. This feature along with the higher body mass index and presumed associated insulin resistance suggests that GDM may be a mild form of the metabolic syndrome. The lack of significant change in the levels of pro-inflammatory cytokines do not support the existence of an inflammatory state in GDM.

Natural anticoagulants and fibrinolytic activity following interferon therapy in chronic viral hepatitis.

Chronic liver disease is accompanied by derangement of hepatocyte function including the synthesis of haemostastic factors. It is, however, not known whether the improvement in liver functions as a result of interferon (IFN)-alpha therapy would be reflected in the plasma levels of these factors. To evaluate the effect of IFN-alpha therapy on the plasma levels of natural anticoagulants and on the fibrinolytic parameters, in patients with chronic viral hepatitis. Twenty one patients with chronic viral hepatitis (B and C) were treated with IFN-alpha, and were studied before commencement of therapy (first sample) 3 (second sample) and 6 months (third sample) later. The coagulation screening tests: activated partial thromboplastin time, prothrombin time, thrombin time, reptilase time and plasma fibrinogen and the natural anticoagulants: antithrombin, Protein C and free and total protein S as well as fibrinolytic parameters (tissue type plasminogen activator, plasminogen activator inhibitor type-1 and plasminogen) were measured. An increase in the levels of total protein S at 3 and 6 months after the commencement of IFN therapy was noted but the increase was statistically significant in the latter period. Reptilase time was prolonged in the first (pretreatment) and in the second samples and then began to decrease in the third sample but remained higher than the pretreatment level. Fibrinogen level increased in the second and third samples. No remarkable changes were noted in other haemostatic parameters. Total protein S level is a good marker of response to IFN therapy. IFN therapy does not affect other natural anticoagulants or fibrinolytic parameters. More detailed studies need to be done to confirm these findings.

Effects of heat on camel platelet structure and function-a comparative study with humans.

Camels and many other desert animals are uniquely adapted to conserve water and other fluids in order to survive intense heat for long periods. Earlier studies have suggested that human platelets may be the trigger for the coagulopathy involved in heat prostration and stroke. The present study has compared the resistance of camel and human platelets to heat in order to see if they might help to protect camels from the effects of high body temperature for prolonged periods. The findings demonstrate that camel platelets are significantly less sensitive to heat than human platelets. Temperatures (43 degrees C-45 degrees C) that cause human cells to undergo marked structural alterations and lose their ability to spread and aggregate have no effect on camel platelets. Even higher temperatures (50 degrees C) that destroy human platelets have minor effects on camel cells and do not seriously compromise their function. Temperatures of 55 degrees C do destroy camel platelets and their functional capability. The resistance of camel platelets to heat may help protect camels from the effects of extreme body temperature and dehydration, which are everyday conditions in the desert.

Tissue factor pathway inhibitor in childhood nephrotic syndrome.

It is now recognised that the extrinsic tissue factor pathway is the main trigger to the coagulation system in vivo. Its main inhibitor, tissue factor pathway inhibitor (TFPI), has never been studied in childhood nephrotic syndrome. The aim of the study was to monitor the level of TFPI in childhood nephrotic syndrome. One hundred and thirty-nine nephrotic children were classified into the following groups: group 1 (n=25), in relapse and receiving no treatment; group 2 (n=37), in relapse but receiving steroid treatment; group 3 (n= 45), in early remission and on steroids; group 4 (n=24), in established remission and receiving no steroids; group 5 (n=8), steroid-resistant. The controls (n=84) were healthy and age-matched. There was significant elevation of total TFPI levels in groups 1 and 2 and 3; levels were comparable to those of the healthy controls in group 4. The highest levels of total TFPI were recorded in group 5. Like total TFPI, the levels of the free form of TFPI showed a statistically significant increase in groups 1, 2, 3 and 4, when compared with levels in healthy controls. The highest levels of free TFPI were recorded group 5. We concluded that the elevated levels of both the total and free TFPI in various phases of nephrotic syndrome add another natural anticoagulant mechanism, which will attenuate the hypercoagulability of childhood nephrotic syndrome.

Stroke in Saudi children. Epidemiology, clinical features and risk factors.

OBJECTIVES: To describe the epidemiology and clinical features of stroke in a prospective and retrospective cohort of Saudi children and ascertain the causes, pathogenesis, and risk factors. METHODS: The Retrospective Study Group (RSG) included children with stroke who were evaluated at the Division of Pediatric Neurology, or admitted to King Khalid University Hospital, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia during the period July 1992 to February 2001. The Prospective Study Group (PSG) included those seen between February 2001 and March 2003. RESULTS: During the combined study periods of 10 years and 7 months, 117 children (61 males and 56 females, aged one month-12 years) were evaluated; the majority (89%) of these were Saudis. The calculated annual hospital frequency rate of stroke was 27.1/100,000 of the pediatric (1 month-12 years) population. The mean age at onset of the initial stroke in the 104 Saudi children was 27.1 months (SD = 39.3 months) and median was 6 months. Ischemic strokes accounted for the majority of cases (76%). Large-vessel infarcts (LVI, 51.9%) were more common than small-vessel lacunar lesions (SVLL, 19.2%). Five patients (4.8%) had combined LVI and SVLL. Intracranial hemorrhage was less common (18.2%), whereas sinovenous thrombosis was diagnosed in 6 (5.8%) patients. A major risk factor was identified in 94 of 104 (89.4%) Saudi children. Significantly more hematologic disorders and coagulopathies were identified in the PSG compared to the RSG (p=0.001), reflecting a better yield following introduction of more comprehensive hematologic and coagulation laboratory tests during the prospective study period. Hematologic disorders were the most common risk factor (46.2%), presumed perinatal ischemic cerebral injury was a risk factor in 23 children (22.1%) and infectious and inflammatory disorders of the circulatory system in 18 (17.3%). Congenital and genetic cerebrovascular anomalies were the underlying cause in 7 patients (6.7%) and cardiac diseases in 6 (5.8%). Six patients (5.8%) had moyamoya syndrome, which was associated with another disease in all of them. Inherited metabolic disorders (3.8%) included 3 children with Leigh syndrome and a 29-month-old girl with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. Systemic vascular disease was a risk factor in 3 children (2.9%) including 2 who had hypernatremic dehydration; and post-traumatic arterial dissection was causative in 3 cases (2.9%). Several patients had multiple risk factors, whereas no risk factor could be identified in 11 (10.6%). CONCLUSION: Due to the high prevalence and importance of multiple risk factors, a comprehensive investigation, including hematologic, neuroimaging and metabolic studies should be considered in every child with stroke.

Hematologic risk factors for stroke in Saudi children.

OBJECTIVE: To explore the hematologic risk factors for stroke in a cohort of Saudi children. METHODS: We evaluated children at the Division of Pediatric Neurology at King Khalid University Hospital, College of Medicine, King Saud University, Riyadh, during the periods July 1992 to February 2001 (retrospective study) and February 2001 to March 2003 (prospective study). Investigations for suspected cases included neuroimaging, transcranial Doppler (TCD) for cases of sickle cell disease (SCD), and Duplex scan. Hemostatic assays included coagulation screening tests, tests of thrombin generation and fibrinolysis, coagulation inhibitors, and activated protein C resistance. RESULTS: During the study period, 104 Saudi children (aged one month to 12 years) with stroke were seen. The mean age of the cohort was 27.1 months (SD = 39.3 months) and median was 6 months. Ischemic strokes accounted for the majority of cases (76%). A major risk factor was identified in 93 of 104 cases of stroke (89.4%). Hematologic disorders were the most common (46.2%), followed by prothrombic disorders (31.7%); microcytic hypochromic anemia (26%); sickle cell disease (SCD), or SCbeta(0)-thalassemia, (11.5%), and factor IX deficiency (2.9%). Raised anticardiolipin antibodies (13/49, 26.5%) was the most frequent abnormality. Deficiencies of the natural anticoagulants (protein S, protein C and antithrombin III) were as follows: protein S (15/70, 21.4%); protein C (15/70, 21.4%) and combined deficiency of 2 or more inhibitors (9/70, 12.9%). Activated protein C resistance has not been detected. Contrary to the findings of previous studies from Saudi Arabia, SCD is a common risk factor and is severe, as it resulted in multiple strokes. Moyamoya syndrome was diagnosed in 2 patients with SCD, one of whom had revascularization surgery (encephaloduroarteriosynangiosis). Assessment of children with SCD at risk of stroke was helped by the introduction of TCD followed by neuroimaging, using MRI and magnetic resonance angiography. CONCLUSIONS: The study strongly highlights the importance of prothrombotic disorders and the severe phenotype of SCD as risk factors for stroke in Saudi children.