Long-term audit of platelet consumption in a university hospital.

OBJECTIVES: To determine the long-term trend in platelet consumption in a university hospital. MATERIALS AND METHODS: The annual consumption of platelets concentrate (PC) was analyzed over 23 years (1985-2007) in King Khalid University Hospital (KKUH), Riyadh, Saudi Arabia. RESULTS: The total 23 years consumption was 100,466 units of PC. Consumption went through 3 phases: the first, 1985-1994: the annual consumption increased from 1706 to 5912 which coincided with the increase in the number of patient admissions; the second, 1994-2003:featured a remarkable drop (48.9%) in annual consumption while patient admission remained stable. There was a concurrent decline in platelet consumption and all-cause mortality/patient. Third phase: 2003-2007, the consumption increased to reach 5642 units/year in 2007. The Department of Medicine consumed (52%), followed by Pediatrics (21%), and General Surgery (16%). CONCLUSION: This audit uncovered evidence of inappropriate platelet consumption that reached 48.9% in the period 1994 to 2003, which coincided with widely publicized HIV scare that dominated blood transfusion during that period. We also found evidence suggesting that reducing platelet transfusion could improve patient outcome.

Rituximab as a single agent in the management of adult patients with haemophilia A and inhibitors: marked reduction in inhibitor level and clinical improvement in bleeding but failure to eradicate the inhibitor.

Management of patients with severe haemophilia A who develop inhibitors is difficult and expensive. Standard treatment of this complication is immune tolerance induction (ITI) therapy, but is successful in only 60-80% of the patients. Failure of ITI results in a higher risk of morbidity and mortality. We used rituximab, an anti-CD20 antibody, in three patients with severe haemophilia A and inhibitors. Two patients with high-titre inhibitors had marked reduction in the inhibitor level; the third patient with low-titre inhibitor had a disappearance of the inhibitor. All patients improved clinically, with fewer bleeding episodes and a better quality of life. Inhibitor level increased with time in these patients, but the clinical benefit continued in two patients with high-titre inhibitors initially, after a follow-up of 48 and 22 months. One of the patients with concomitant human immunodeficiency virus (HIV) infection and a very low CD4 lymphocyte count developed severe truncal herpes zoster after the third weekly dose of rituximab. Caution is required in such patients, and we recommend avoiding rituximab use in HIV-infected patients with very low CD4 lymphocyte count. In conclusion, rituximab is useful in reducing the inhibitor level with clinical benefit in patients with severe haemophilia A and inhibitors, but it cannot eradicate the inhibitors for long periods with the currently used protocol of up to five doses.

Toxoplasmosis in a group of glucose-6-phosphate dehydrogenase deficient patients.

OBJECTIVE: This was a retrospective study that aimed at evaluating the relative risk of Toxoplasma infection in patients with glucose-6-phosphate dehydrogenase deficiency as compared to a control group with no glucose-6-phosphate dehydrogenase deficiency. METHODS: Ninety-one blood donor volunteers had serology testing from Toxoplasma gondii and were screened for glucose-6-phosphate dehydrogenase deficiency by a qualitative method using fluorescent spot test. They were all males and their ages ranged from 17 to 52 years. RESULTS: Fifty-three persons (58%) were glucose-6-phosphate dehydrogenase deficient and 38 (42%) were glucose-6-phosphate dehydrogenase normal. In the glucose-6-phosphate dehydrogenase deficient group, 31 (58.5%) had positive titers for Toxoplasma; while in the glucose-6-phosphate dehydrogenase normal group 9 persons (24%) had positive titers for Toxoplasma. The relative risk of infection was 2.5 times more in the glucose-6-phosphate dehydrogenase deficient group, a statistically significant difference with a p value of 0.002. CONCLUSION: Glucose-6-phosphate dehydrogenase deficiency seems to increase the risk for Toxoplasma infection by 2.5 fold probably due to decreased killing effect, of phagocytic cells.

Hypocalcemia due to hypoparathyroidism in beta-thalassemia major patients.

BACKGROUND: This is a retrospective analysis of case records of AA(2)-thalassemia major patients who developed hypoparathyroidism (HPT). The objective of this study was to assess the prevalence of hypocalcemia and hypoparathyroidism in AA(2)-thalassemia major patients being followed at King Khalid University Hospital (KKUH), Riyadh, Saudi Arabia. PATIENTS AND METHODS: Diagnosis was based on low serum calcium (S/Ca), high serum phosphate (Po4), normal serum magnesium and alkaline phosphatase, and low serum parathyroid hormone levels. Other parameters analyzed included age, sex, serum ferritin levels, age of onset of HPT, any symptoms of hypocalcemia, and presence of other complications in these patients. RESULTS: Out of 40 patients, eight (20%) were diagnosed to have HPT. The mean age at diagnosis was 13.6 years (range 11-16 years), mean serum calcium was 1.88 mmol/L (range 1.58-2.04), mean serum ferritin was 7490 AA(1/4)g/L (range 2000-23,064) and mean serum phosphate was 1.88 mmol/L (range 1.50-2.73). Serum parathyroid hormone (PTH) levels were low in most of the patients. Only two patients (25%) had mild symptoms of hypocalcemia. Growth retardation was present in all patients, while four patients had liver dysfunction, two had diabetes mellitus and two had cardiac dysfunction. CONCLUSION: HPT due to iron overload may develop in a significant number of thalassemia major patients, especially when chelation therapy is not optimal, therefore, all thalassemics should be carefully watched for this complication from early in their second decade.

Hypercoagulable states in patients with retinal venous occlusion.

BACKGROUND AND PURPOSE: The pathogenesis of thrombus formation in the retinal vein resulting in retinal vein occlusion is not well understood. This study was carried out to ascertain the role of hypercoagulable states in patients with retinal vein occlusion. METHODS: Fifty seven consecutive patients with acute retinal vein occlusion (mean age 48 +/- 11.5 years) were investigated for possible hypercoagulable states. Levels of antithrombin III (AT III), protein C (PC), Protein S (PS), factor XII, and fibrinogen as well as the presence of antiphospholipid antibodies (APAs) were investigated. The APAs and fibrinogen results obtained in these patients were compared to those of healthy controls. RESULTS: We detected APAs in 15 out of 57 patients compared to 3 out of 74 controls (p = 0.0002). Fibrinogen levels were significantly higher in patients compared with the controls (p < 0.001). Deficiencies in the naturally occurring anticoagulant proteins including AT III (4 out of 54 patients tested), PC (8 out of 42 patients tested), and PS (12 out of 56 patients tested) were detected. Seven patients out of 32 patients tested had reduced levels of factor XII. Subgroup analysis of the thrombophilic differences between patients who aged 45 years or less and older patients and patients with major trunk vein occlusion and patients with branch vein occlusion revealed no significant differences. CONCLUSION: Hypercoagulable states are common in patients with retinal vein occlusion and may contribute to the etiology of the disease.

Coagulopathy of childhood nephrotic syndrome--a reappraisal of the role of natural anticoagulants and fibrinolysis.

In an attempt to characterise further the coagulopathy of childhood nephrotic syndrome, this study concentrates on simultaneous measurements of the natural anticoagulants [antithrombin III (ATIII), proteins C and S] and the fibrinolytic factors, tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI). The study groups consisted of 41 children (ages ranging from 2 to 14 years; median 7.1) in the relapse of nephrosis and 48 children (ages ranging from 3 to 14 years; median 7.6) in remission. The results obtained were compared with normal values obtained in healthy age- and sex-matched controls (n = 103). During relapse, there was a marked increase in the plasma level of fibrinogen, protein C, and protein S and reduced plasma ATIII level; tPA level was similar to control but PAI level exhibited a significant reduction. During remission, the protein C level either remained elevated or increased further, but some decreased. Protein S and plasma ATIII level normalised. The fibrinolytic activator tPA dropped slightly but the PAI level remained significantly below control levels. We conclude that in the relapse of childhood nephrosis, despite the existence of a significant prothrombotic tendency as featured by hyperfibrinogenaemia and markedly reduced ATIII level, the simultaneous elevation of the natural anticoagulant, protein C level and enhanced fibrinolysis that persist until the remission phase, seem to be major preventive mechanisms guarding nephrotic children against thromboembolic phenomena.

Intravenous iron sucrose complex in the treatment of iron deficiency anemia during pregnancy.

OBJECTIVE: To evaluate the safety and efficacy of intravenous iron sucrose complex (ISC) as compared with oral ferrous sulfate in the treatment of iron deficiency anemia during pregnancy. STUDY DESIGN: prospective, open, controlled study in which pregnant women with iron deficiency anemia were sequentially selected from the antenatal clinic and assigned either to ISC (study group) or to ferrous sulfate (control group). METHODS: Each study patient was given the total calculated amount of ICS (Hb deficit (g/l) x body weight (kg) x 0.3) in divided doses (200 mg (elemental iron) in 100 ml normal saline intravenously over 1 h daily) followed by 10 mg/kg to replenish iron stores. Each patient of the control group was given ferrous sulfate 300 mg (60 mg elemental iron) orally three times a day. All patients were monitored for adverse effects, clinical and laboratory response. RESULTS: There were 52 patients and 59 controls. ISC group achieved a significantly higher Hb level (128.5 +/- 6.6 g/l vs. 111.4 +/- 12.4 g/l in the control group P < or = 0.001) in a shorter period (6.9 +/- 1.8 weeks vs. 14.9 +/- 3.1 weeks in the control group, P < or = 0.001). ISC complex group showed no major side effects while 4 (6%) of the control group could not tolerate ferrous sulfate, 18 (30%) complained of disturbing gastrointestinal symptoms and 18 (30%) had poor compliance. CONCLUSION: We conclude that ISC is safe and effective in the treatment of iron deficiency anemia during pregnancy.

Bilateral central retinal vein thrombosis in Behçet's disease.

Behçet's disease is a multisystem disorder affecting the skin, mucous membranes, eye, joints, central nervous system, and blood vessels. One of the known vascular complications of Behçet's disease is venous thrombosis or aneurysm formation. We report, herewith, a patient with Behçet's disease who developed radial artery aneurysm, deep venous thrombosis, and bilateral central retinal vein thrombosis. To our knowledge, this is the first report of bilateral central retinal vein thrombosis in association with Behçet's disease.

Hereditary bleeding disorders in Riyadh, Saudi Arabia.

The result of an eight-year retrospective analysis of patients with hereditary bleeding disorders (HBD) at King Khalid University Hospital, Riyadh, is presented. One hundred and sixty-eight patients referred for investigation for suspected bleeding disorders had bleeding symptoms which fulfilled the criteria for HBD and were categorized as follows: 1) coagulation factor deficiencies: 41 patients had hemophilia A, while 16 had hemophila B; two patients each had factors XI and XII deficiency; four patients each had factors V and VIII deficiency and one patient had factor VII deficiency. There were two patients with dysfibrinogenemias and one with afibrinogenemia. 2) Von Willerbrand's disease was the second most common cause of HBD-25 patients were encountered in 15 different families. 3) Qualitative platelet disorders consisted of Glanzmann's thrombasthenia, with 18 patients, Bernard-Soulier disease, with five patients, and other qualitative platelet disorders, with 33 patients. 4) In 14 patients who presented with a history of bleeding, the only abnormality noted was prolongation of the bleeding time and normal coagulation and platelet function, and no definitive diagnoses could be established. The distribution of hereditary bleeding disorders obtained in this study resembles what has already been established in Western countries, with the exception of an increase of platelet disorders, mostly due to the increased rate of consanguinity in the community.

Correlation of fundus lesions and hematologic findings in leukemic retinopathy.

This prospective study evaluated the relationship between the fundus findings in leukemic retinopathy and hematologic parameters. Seventy-four newly diagnosed consecutive patients with acute leukemia were included, 49 with acute myelocytic leukemia (AML), and 25 acute lymphocytic leukemia (ALL). Blood parameters were based on data obtained before starting any therapeutic modalities. Leukemic retinopathy was detected in 32 patients (43%). Patients with ALL and retinal hemorrhages had significantly lower hemoglobin and hematocrit levels than those without hemorrhages (p = 0.004 and 0.018 respectively). AML patients with white-centered hemorrhages had a significantly higher leukocyte count than those without (p = 0.0002). ALL patients with cotton-wool spots had significantly lower hemoglobin levels and hematocrit than patients without such lesions (p = 0.044 and 0.05 respectively). AML patients with cotton wool spots had significantly lower leukocyte and platelet counts than those without (p = 0.019 and 0.003 respectively). Our results suggest that anemia is related to the findings of retinal hemorrhage and cotton-wool spots in ALL patients, that high leukocyte count is associated with white centered hemorrhage in AML patients, and that thrombocytopenia is not associated with retinal hemorrhage in this group of patients.

Coagulation inhibitors and fibrinolytic parameters in patients on peritoneal dialysis and haemodialysis.

Coagulation inhibitors and fibrinolytic parameters were studied in twelve patients on continuous ambulatory peritoneal dialysis (CAPD) and ten patients on haemodialysis (HD). Patients on CAPD exhibited higher levels of ATIII and proteins C and S than those on HD. No significant differences were noted in tPA and PAI levels. Both groups of patients showed higher levels of tPA than controls. Besides, patients on HD had significantly lower levels of ATIII and protein C than controls. PAI levels in both patient groups were similar to those of the controls, but tPA levels were higher in patients than in controls. These results indicate that HD is associated with marked diminution in the circulating levels of coagulation inhibitors. This is in contrast to CAPD patients who showed elevated levels of these inhibitors, despite their significant loss in the dialysate. The finding of enhanced fibrinolysis in both patient groups may be a natural protective mechanism against the development of a thrombotic tendency.

Prothrombotic states associated with retinal venous occlusion in young adults.

BACKGROUND: The etiology of retinal venous occlusion in young patients is not well understood although thrombosis does occur histologically. A search for the risk factors that may lead to thrombosis is highly desirable may contribute to our understanding of the pathogenesis of this complication and may improve our therapeutic strategies. METHODS: We studied 17 patients with retinal venous occlusion. All patients were under 45 years of age (mean 37.8 +/- 7.1). Antiphospholipid antibodies (APAs) and certain hemostatic factors were determined. The results obtained in these patients were compared to those of normal controls. RESULTS: We found APAs in 8 out of 17 patients compared to 5 out of 60 controls (p = 0.0002). In patients with major trunk occlusion, there was a trend for the presence of APAs in those with poor visual acuity at presentation. Deficiencies of the coagulation inhibitor proteins C and S and antithrombin III activities were detected in 6 patients, and reduced levels of Factor XII were found in 4 patients. Levels of hematocrit, erythrocyte sedimentation rate. Fibrinogen, alpha 1-globulin, and alpha 2-globulin were significantly higher in patients compared to the controls (p = 0.019; 0.014; 0.0001; 0.011; 0.047), indicating increased blood viscosity in patients with retinal venous occlusion. CONCLUSION: Prothrombotic changes in the form of APAs and/or deficiencies of coagulation inhibitors and Factor XII may contribute to the etiology of retinal venous occlusion in young adults. Young patients with retinal venous occlusion should be evaluated for these prothrombotic states.

One-year experience of very low doses of subcutaneous erythropoietin in continuous ambulatory peritoneal dialysis and its effect on haemostasis.

Recombinant human erythropoietin (rHuEpo) is now well established in the management of the anaemia associated with chronic renal failure. The aim of this study was to assess the efficacy and safety of low doses of subcutaneous (s.c.) erythropoietin in continuous ambulatory peritoneal dialysis (CAPD) patients and particularly its effects on haemostasis. Seven CAPD patients were given s.c. erythropoietin for more than 1 year. Their mean age was 36.2 +/- 9.2 years and their mean pretreatment haemoglobin (Hb) was 7.05 +/- 0.53 g/dl. All patients were started on 20 U/kg, 3 times/week, to be doubled every 4 weeks if no response was obtained. Five patients had a good response and attained the target Hb of 10-12 g/dl and were maintained on low doses of rHuEpo (20 U/kg s.c., twice a week). A marked improvement in haemostatic function was noted when comparing the pre- with the post-treatment measurements. There was a significant reduction in the bleeding time, significant increases in fibrinogen and factor VIII clotting activity but not in von Willebrand factor antigen or ristocetin cofactor. There was also simultaneous enhancement of the platelet aggregation responses to adrenalin, collagen, arachidonic acid and ADP. In conclusion, long-term treatment with small doses of s.c. rHuEpo is safe, convenient and effective in correcting anaemia in patients on CAPD, rHuEpo caused significant improvement of bleeding time which can be explained partly through the correction of anaemia and in part by the improvement in haemostatic function.

Diminished vitamin B12 levels in patients with severe sickle cell disease.

OBJECTIVE: The aim of this study was to estimate the levels of vitamin B12 in patients with severe sickle cell disease compared to normal controls. Complete blood count, iron studies and vitamin B12 levels were obtained in 85 consecutive patients with severe sickle cell disease (56 males, 29 females, aged 14-49 years) and 100 healthy blood donors (67 males, 33 females, aged 17-60 years) as a normal control group. RESULTS: Thirty-seven of the 85 patients (43.5%) had serum vitamin B12 levels below normal values (mean 84.3 +/- 28.7, range 7-145 pmol L-1) without macrocytosis or hypersegmented neutrophils. The mean level of vitamin B12 in the remaining 48 patients (56.5%) was normal (mean 233.3 +/- 73.9, range 152-435 pmol L-1) which is below the mean of normal control levels (mean 327.7 +/- 168.7, range 178-897 pmol L-1). Patients with low B12 achieved a significant symptomatic improvement when treated with vitamin B12, 1 mg intramuscularly weekly for 12 weeks when compared with patients with normal B12 levels. CONCLUSION: We conclude that many patients with severe sickle cell disease may suffer from unrecognized vitamin B12 deficiency.

Systemic lupus erythematosus flare-up manifesting as a cilioretinal artery occlusion.

In this report we describe a patient with systemic lupus erythematosus who was clinically stable after treatment with the antimalarial drug chloroquine and pulse cyclophosphamide therapy. Three months after the discontinuation of chloroquine, the patient developed cilioretinal artery occlusion that was the only the manifestation of a clinical flare-up without evidence of clinical disease activity elsewhere. This case report confirms the clinical belief that the antimalarial agents can maintain the clinical quiescence of systemic lupus erythematosus and its discontinuation is associated with an increase in the risk of clinical flare-up.

Tuberculosis presenting as immune thrombocytopenic purpura.

Various haematological abnormalities commonly occur in active tuberculosis (TB). However, thrombocytopenia is rare and immune thrombocytopenic purpura (ITP) is mentioned only in few case reports. We found that of 846 cases with active TB, 9 (1%) presented with ITP as the only abnormality. Three out of these 9 cases had disseminated miliary TB, 3 an abdominal abscess or lymphadenitis, and 3 pulmonary TB; none had palpable splenomegaly. All patients had purpura and the platelet count varied between 4 and 21 x 10(9)/l, and the bone marrow showed increased megakaryocytes. All tuberculous patients showed initially a poor platelet count response to steroid therapy. The platelet count returned to normal 2-6 weeks after oral prednisone combined with antituberculous drugs.

Prognostic importance of retinopathy in acute leukemia.

This prospective study evaluates the relationship, between the fundus findings in leukemic retinopathy and the survival in patients with newly diagnosed acute leukemia. Fifty-four newly diagnosed consecutive patients with acute leukemia were included in this study. The patients were examined within few days of initial admission and diagnosis. Leukemic retinopathy was detected in 19 (35%) patients. The observation period ranged from 434 days to 1220 days (mean +/- SD 880 +/- 225) for those patients who survived. Despite similar chemotherapy compared to those without retinopathy (332.4 +/- 99.6 and 76 vs. 640.7 +/- 106 and 192 days respectively) although survival did not differ significantly (p = 0.073). Patients with cotton-wool spots had lower mean and median survival times than did those without such lesions (168.8 +/- 70.9 and 27 vs. 609.4 +/- 91.4 and 289 days respectively) and survival differed significantly (p = 0.04). The presence of cotton-wool spots and age > or = 40 years were the major adverse prognostic factors for survival in multivariate analysis. Cotton-wool spots had a more significant adverse prognostic effect than age > or = 40 years (hazard function coefficients: 1.0708 for cotton-wool spots vs 0.0355 for age > or = 40 years). The relative odds of dying among patients with cotton-wool spots were about 8 times higher than that for those without this feature, and about 7 times higher in patients aged > or = 40 years than that for patients aged < 20 years. Our findings suggest that the presence of leukemic retinopathy in general, and cotton-wool spots, in particular is a poor prognostic sign for survival in acute leukemia.

Platelet Aggregometry - Dose-related Responses to Arachidonic Acid in Childhood Nephrotic Syndrome.

A recent unexpected finding of inhibited platelet aggregation in response to a single (1.64 mmol/l) dose of arachidonic acid (AA), during the relapse of childhood nephrosis, prompted us to assess aggregation in response to multiple doses of AA: 1.64,0.82,0.41,0.20 mmol/l, in two groups of children, in the relapse (n = 34) or remission (n=41) phase of nephrotic syndrome. During relapse: the highest dose of AA (1.64 mmol/l) evoked reversible and inhibited aggregation in 91% of patients. However, at the lower doses there were enhanced responses as measured by both maximum aggregation (%) and slopes of the aggregation curves. In contrast, during remission, irreversible aggregation was obtained at the highest AA dose, while at the lowest two doses (0.41 and 0.20 mmol/l), no aggregation responses were obtained in 4 (9%) and 7 (17%) patients respectively; in those who responded there was a long lag phase. Healthy controls (n = 21) exhibited their highest responses to 1.64 and 0.82 mmol/l AA and at the lowest AA doses (0.41 and 0.20 mmol/l), a total absence of responses was noted in 40% and 71% of samples respectively. We conclude that during relapse platelet sensitivity, as shown by irreversible aggregation in response to multiple AA doses, shifts towards the lower doses, when compared with healthy controls; while during remission responses fall in-between the relapse and control groups, indicating the maintenance of platelet sensitivity during this phase of nephrosis.