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.

Gene frequency of human platelet alloantigens-1 to -6 and -15 in Saudi blood donors.

BACKGROUND: Human platelet antigens (HPAs) are involved in the pathogenesis of several clinical conditions, such as platelet transfusion purpura (PTP), refractoriness to platelet transfusion and neonatal alloimmune thrombocytopenia (NAITP). Typing of HPA (1-6 and 15) has not been carried on the Saudi population. This is the first study of all the seven HPA systems on Arabs. The aim of this prospective study was to determine the frequency of HPA (1-6 and 15) in Saudis. STUDY DESIGN AND METHODS: A total of 100 randomly selected Saudi blood donor samples were genotyped using the polymerase chain reaction with sequence-specific primers (PCR-SSP). RESULTS: The most common HPA genotypes among Saudis were HPA-1 a + b- (75%), HPA-2 a + b- (62%), HPA-3 a + b- (51·5%), HPA-4 a + b- (99%), HPA-5 a + b- (76·5%), HPA-6 a + b- (100%) and HPA-15 a + b + (50%). The prevalent allele among the HPA systems was (a), except in the HPA-15 system where the (b) allele was found in 52% of the subjects. Comparisons with other ethnic populations uncovered marked differences in the distribution of HPA alleles. CONCLUSION: Studying the prevalence of HPA antigens in Saudi population will help in the understanding of its role in platelet-related disorders. It will also enable the blood bank to establish an HPA-based donor registry that will be a valuable source of compatible platelet-therapeutic products to alloimmunised patients. This will also enhance the safety and efficacy of platelet transfusion. This data obtained will form an addition to the existing body of literature in transfusion research.

Plasma homocysteine levels in cardiovascular disease, malaria and protein-energy malnutrition in Sudan.

This study investigated the role of hyperhomocysteinaemia as a risk factor in Sudanese adults suffering from cardiovascular disease or malaria and children with protein-energy malnutrition. Mean total plasma homocysteine levels (micromol/L) were significantly higher in patients with coronary heart disease (17.64; SD 11.68) recurrent venous thrombosis (5.06; SD 10.55) and recurrent malaria (13.61; SD 4.82) than in healthy adult controls (7.85; SD 3.39). The mean homocysteine level was also significantly higher in children with protein-energy malnutrition (8.41; SD 1.61) than in healthy control children (5.72; SD 1.99).

Plasma homocysteine levels in cardiovascular disease, malaria and protein-energy malnutrition in Sudan

This study investigated the role of hyperhomocysteinaemia as a risk factor in Sudanese adults suffering from cardiovascular disease or malaria and children with protein-energy malnutrition. Mean total plasma homocysteine levels [micro mol/L] were significantly higher in patients with coronary heart disease [17.64; SD 11.68] recurrent venous thrombosis [5.06; SD 10.55] and recurrent malaria [13.61; SD 4.82] than in healthy adult controls [7.85; SD 3.39]. The mean homocysteine level was also significantly higher in children with protein-energy malnutrition [8.41; SD 1.61] than in healthy control children [5.72; SD 1.99]

Retinal periphlebitis resembling frosted branch angiitis with nonperfused central retinal vein occlusion.

PURPOSE: To report the unusual association between severe retinal periphlebitis resembling frosted branch angiitis and nonperfused central retinal vein occlusion (CRVO). METHODS: Observational case reports. RESULTS: Patient 1 was a 28-year-old man who presented with extensive sheathing involving all retinal veins in one eye followed by nonperfused CRVO. Twenty-seven months after initial presentation, he developed perfused CRVO in the other eye followed by periphlebitis that progressed into nonperfused CRVO. Patient 2 was a 47-year-old man who presented with unilateral severe retinal periphlebitis associated with nonperfused CRVO. Despite systemic administration of corticosteroid therapy, rubeosis iridis developed in both patients and neovascular glaucoma developed in Patient 1 despite full panretinal photocoagulation. Extensive systemic workup and coagulation studies were unremarkable except for the presence of antiphospholipid antibodies in both patients and elevated plasma homocysteine level in Patient 2. CONCLUSIONS: Severe retinal periphlebitis complicated by nonperfused CRVO is associated with poor visual outcome despite appropriate medical and surgical treatment.

The coagulopathy in acute head injury: comparison of cerebral versus peripheral measurements of haemostatic activation markers.

Brain injury is known to result in various degrees of disordered haemostasis. Moreover, the recently developed assays of molecular markers of haemostasis can give an accurate reflection of its activation in vivo. The aim of this study was to monitor the levels of prothrombin fraction 1 + 2 (F1 + 2), thrombin antithrombin complexes (TAT) and D-dimer on the admission of patients to the ICU and up to the fourth day postinjury. Seventeen patients with head injury (Glasgow Coma scale 12 or less) were studied at King Khalid University Hospital, Riyadh. Their ages ranged from 10 to 40 years (mean 26). Blood samples were collected from the internal jugular vein, peripheral vein and artery. The mean levels of TAT and F1 + 2 in the internal jugular vein was significantly higher than in both peripheral venous and arterial blood on admission and 24 h later. Thereafter, the levels in the three locations dropped significantly, but remained elevated above controls. D-dimer levels were very markedly elevated to a similar extent in the three locations throughout the study period. The prothrombin time was significantly prolonged in the three locations in the first two days. Plasma fibrinogen levels dropped very significantly in the jugular vein, and increased to above reference values later. Protein S and factor VII showed a significant drop in the first two days and increased to normal range thereafter. Outcome was evaluated using the Glasgow Outcome Scale at 6 months postinjury. Haemostatic measurements could not predict good outcome (12 patients) or bad outcome (four deaths). It was concluded that haemostatic activation is a transient, but common phenomenon after head injury and is more prominent in cerebrovascular than in peripheral blood. The number of patients studied is too small to allow reliable association to be drawn between haemostatic changes on admission and prediction of outcome.

Hyperhomocysteinemia and retinal vascular occlusive disease.

PURPOSE: Elevated plasma homocysteine is an independent risk factor for thrombosis and vascular disease. This prospective study compared plasma total homocysteine levels in patients with retinal vascular occlusive disease and in matched healthy controls. METHODS: We measured plasma total homocysteine in 56 consecutive patients with recently diagnosed retinal vascular occlusive disease: 36 had central retinal vein occlusion, 12 branch retinal vein occlusion, and 8 retinal artery occlusion, and compared them with 59 age- and sex-matched healthy controls. Homocysteine levels were determined by high-performance liquid chromatography with electrochemical detection. Hyperhomocysteinemia was defined as a plasma homocysteine level above the 95th percentile in the control group (13.6 micromol/L). RESULTS: Mean plasma total homocysteine levels were significantly higher in patients than controls (16.1 +/- 8.3 vs. 8.96 +/- 5.6 micromol/L p < 0.001). Mean homocysteine levels were significantly higher in the retinal vein occlusion and retinal artery occlusion groups than the control group (15.3 +/- 8.2 and 20.95 +/- 6.9 vs 8.96 +/- 5.6 micromol/L, p < 0.001). Estimates of the relative risk indicated that the risk of hyperhomocysteinemia was significantly higher in patients with retinal vascular occlusive disease than controls. Hyperhomocysteinemia was present in 37 (66.1%) of the 56 patients with retinal vascular occlusive disease but only 2 (3.4%) controls (odds ratio [OR] 47.5, 95% confidence interval [CI] 9.8-149.9). Hyperhomocysteinemia was present in 29 (60.4%) of the patients with retinal vein occlusion (OR 43.5, 95% CI 8.77-141.93) and in 6 (75%) patients with retinal artery occlusion (OR 85.5, 95% CI 7.49-1,173.1). CONCLUSIONS: High plasma homocysteine is a risk factor for retinal vascular occlusive disease so it may be useful to measure homocysteine in the management of these patients. A randomized, controlled trial is required to study the effect of lowering with homocysteine folic acid and other B vitamins on the risk of recurrent vascular occlusion in the same eye or its development in the fellow eye.

Anterior ischaemic optic neuropathy associated with central retinal vein occlusion.

PURPOSE: To report the unusual association between non-arteritic anterior ischaemic optic neuropathy (NAION) and non-ischaemic central retinal vein occlusion (CRVO) in two patients. METHODS: Case reports are presented. RESULTS: Non-ischaemic CRVO was manifested by dilated, tortuous retinal veins with flame-shape retinal haemorrhages. Fluorescein angiography showed prolonged arteriovenous transit time and normal retinal capillary perfusion without macular oedema. The presence of colour vision abnormalities, relative afferent pupillary defects, pale disc swelling and visual field deficits indicated that the visual loss was attributable entirely to NAION. Laboratory investigations disclosed impaired fibrinolytic function in case 1 and the presence of antiphospholipid antibodies in case 2. CONCLUSIONS: Compression of the central retinal vein by the swollen optic nerve could have predisposed to CRVO. The presence of thrombophilic abnormalities may have contributed to the concomitant occlusion of posterior ciliary arteries and central retinal vein. Ischaemic optic neuropathy needs to be considered in patients with CRVO when the visual acuity is not consistent with the retinal pathology.

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.

Fibrinolytic activity in retinal vein occlusion.

PURPOSE: Impaired fibrinolytic function is a common finding in patients with thrombotic disease. The present study was initiated to evaluate the fibrinolytic response to a venous occlusion test (VOT) in patients with retinal vein occlusion. METHODS: Euglobulin clot lysis time (ECLT), tissue plasminogen activator (t-PA) activity, and plasminogen activator inhibitor (PAI) activity were measured before and after VOT in a group of 26 consecutive patients presenting with retinal vein occlusion and in 15 healthy age- and sex-matched controls. RESULTS: Before VOT (baseline), a higher proportion of patients (54%) had an ECLT of more than 5 h compared with controls (6.7%) (p = 0.0027) indicating decreased overall fibrinolytic activity. Patients had non-significantly lower t-PA and higher PAI activities compared with controls. After VOT, a higher proportion of patients (34.6%) had an ECLT of more than 5 h compared with controls (6.7%) (p = 0.05). Patients had significantly lower t-PA activity (p = 0.0232) and significantly higher PAI activity (p = 0.0292). Subgroup analysis revealed that patients with an ECLT of more than 5 h had significantly higher levels of PAI activity at baseline (p = 0.0326) and after VOT (p = 0.0184) compared with patients with an ECLT of less than 5 h. However, t-PA activity was significantly higher (p = 0.0153) at baseline, and non-significantly higher after VOT in patients with an ECLT of more than 5 h when compared with patients with an ECLT of less than 5 h. CONCLUSIONS: These findings suggest that impaired fibrinolysis due to increased PAI activity may play a role in the pathogenesis of retinal vein occlusion.

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.

Normal levels of the natural anticoagulants (proteins C & S and antithrombin III) and the fibrinolytic factors (tPA and PAI) in Arab children.

The diagnosis of many hemostatic defects in infancy and childhood depends on the establishment of normal levels of various hemostatic factors. In this study, measurements of the natural anticoagulants (proteins C, S, and antithrombin III), as well as the fibrinolytic factors (tPA and PAI) were undertaken in healthy neonates (cord blood; n = 56), as well as in healthy children, up to 12 years of age (n = 103). The results were compared to normal adult values obtained from blood donors (n = 49). Neonatal values were found to be 50% of those obtained in adults and their mean concentrations were as follows: ATIII antigen = 48.4%, ATIII activity = 61.6%, protein C antigen = 47.7%, protein C activity = 57.2%, total protein S = 41.8% and tPA = 1.9 ng/mL. PAI level (25.7 ng/mL) was similar to adult values. In the first three years of life, almost all the hemostatic factors, other than PAI, gained adults levels. The diminished concentrations of the natural anticoagulants, in addition to the hypofibrinolysis in neonates, shifts the hemostatic balance towards fibrin formation and safeguards effective hemostasis. The values obtained in this study may serve as local reference values.

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.

A study of ambrein treatment for the evaluation of change in plasma biochemical parameters in rats.

Biochemical effects of acute and subacute treatments with ambrein were investigated in rats by measuring the total proteins, cholesterol, triglycerides, GOT, GPT and alkaline phosphatase in the blood plasma. Also, determinations of prothrombin time (PT), partial thrombin time (PTT), thrombin time (TT) and fibrinogen level were performed. Furthermore, changes in plasma electrolyte concentration were studied. Ambrein administered i.p. did not cause any toxic symptoms in the liver as revealed by the histology of the liver tissue both in acute and subacute treatments. Ambrein itself did not significantly affect the plasma protein, cholesterol, GOT and GPT profiles, but lowered alkaline phosphatase at high doses (50 and 250 mg/kg) after subacute treatment. Thus far, no specific pattern of action of ambrein in electrolyte control has been found. However, it increased PT, PTT and TT and decreased fibrinogen levels in both the acute and subacute studies, pointing towards its potential as an anticoagulant and antifibrinogenic agent.

The coagulopathy of heat stroke: alterations in coagulation and fibrinolysis in heat stroke patients during the pilgrimage (Haj) to Makkah.

Haemostatic measurements were undertaken in 132 patients diagnosed with heat stroke during the pilgrimage to Makkah, in two successive summers of 1989-90. The control group comprised 49 patients, all pilgrims, with a wide range of clinical conditions, but without hyperpyrexia or deranged haemostasis. Heat stroke patients showed (i) significant prolongation of the prothrombin (PT), activated partial thromboplastin (aPTT) and thrombin times (TT) but normal reptilase time (RT); (ii) significant reduction in plasma levels of antithrombin III (AT-III), factor V, proteins C and S, plasminogen activator inhibitor (PAI) and platelet count; (iii) increase in plasma factor VIII, tissue plasminogen activator (t-PA) and serum FDP; (iv) no significant changes in plasma fibrinogen, plasminogen, alpha 2-antiplasmin and factors VII and X. Heat stroke patients were then grouped into those with and those without bleeding symptoms. Bleeders showed greater prolongation of the PT, aPTT and TT and significant reductions in fibrinogen, AT-III, factors V, VIII and X, plasminogen, alpha 2-antiplasmin and platelet count. Logistic regression and discriminant analysis showed that AT-III was the parameter associated most with heat stroke and reliable enough to predict its occurrence, whether or not bleeding occurred. The results indicate that activation of the haemostatic mechanism, consumptive in nature, regularly accompanies heat stroke and highlights the physiological role of AT-III in checking this activation process.

Hemostatic variables in Arab diabetics.

Blood coagulation studies showed that patients with non-insulin-dependent diabetes mellitus (NIDDM) had significantly higher fibrinogen, FVIII:C, ristocetin co-factor, FV, FIX, lower ATIII, and PCV than those with insulin-dependent diabetes mellitus (IDDM). Diabetics with IDDM had a significantly higher ATIII, ristocetin co-factor, lower plasminogen and alpa-2-antiplasmin, and more enhanced platelet aggregation responses to ristocetin than age-matched controls. Patients with NIDDM as compared with controls, exhibited higher levels of fibrinogen, ristocetin co-factor, FVIII:C, FIX, and platelet count, but lower plasminogen, alpha-2-antiplasmin and PCV, reduced platelet aggragability to collage, ADP, and ristocetin. Diabetics with retinopathy and nephropathy had still higher levels of fibrinogen, FVIII:C, ATIII and ristocetin co-factor than those without complications. These results are in accord with many similar studies in Caucasians. It is concluded that the pattern of the changes in hemostatic variables noted in Saudi diabetic do not confirm the existence of racial and/or geographical variations in the hemostatic changes associated with diabetes mellitus.

IgA antiphospholipid and adrenal insufficiency: is there a link?

We present two females with antiphospholipid antibody (APA) syndrome who came with adrenal insufficiency (Addison's disease), recurrent abortions and extensive deep vein thrombosis (DVT). Both cases were positive for lupus anticoagulant (LA), global antiphospholipid test (APA), and IgG, IgA, IgM APA antibodies. Seventeen other cases with documented lupus anticoagulant and various clinical associations were tested for APA IgG, IgA, IgM. Only two were positive for IgA as well as IgG and IgM APA. Thirty volunteer blood donors (24 males and 6 females, aged 19-35 years) were taken as a control group. One person was moderately positive for LA and showed low positivity for IgG APA. These data suggest that the presence of IgA APA may signify a severe disease. Further studies are needed to confirm this observation.

The effect of fasting in Ramadan on hemostatic variables.

Hemostatic measurements were performed in 33 volunteers in the morning and afternoon in one day during the Muslim fasting month of Ramadan, and were then repeated on an ordinary nonfasting day. There were no significant diurnal fluctuations in plasmatic hemostatic parameters either in Ramadan or on a nonfasting day. There was no difference in the morning and afternoon platelet aggregation responses between Ramadan and the nonfasting period. However, aggregation responses to ADP (2 microM/L), adrenaline, collagen, and arachidonic acid were diminished during Ramadan as compared to the nonfasting day. It is concluded that the stress encountered during the Ramadan fast, as depicted in the platelet aggregation responses, is less than that encountered on an ordinary nonfasting day.