Genotypic variation and covariation in wheat seedling seminal root architecture and grain yield under field conditions.

KEY MESSAGE: Greater embryo size in a large and carefully phenotyped mapping population was genetically associated with a greater number of longer seminal roots to increase grain yield in droughted field environments. Breeding modification of root architecture is challenging in field environments owing to genetic and phenotypic complexity, and poor repeatability with root sampling. Seeds from a large mapping population varying in embryo size were harvested from a common glasshouse and standardised to a common size before assessing in rolled germination paper at 12 and 20 °C for seedling growth. Differences in genotype means were large and heritabilities high (h2 = 0.55-0.93) indicating strong and repeatable genotypic differences for most root traits. Seminal roots 1 to 3 were produced on all seedlings, whereas growth of seminal roots 4, 5 and 6 was associated with differences in embryo size. Increases in seminal root number from 4 to 6 per plant were strongly, genetically correlated with increases in total seminal length (rg = 0.84, < 0.01). Multivariate analysis confirmed initiation and growth of seminal roots 1, 2 and 3, and of roots 4, 5 and 6 behaved as genetically independent (rPg = 0.15 ns) cohorts. Tails representing extremes in seedling root length and number were associated with significant differences in grain yield of up to 35% in droughted field environments but were not different in irrigated environments. Increases in grain yield were linked to greater lengths of seminal roots 4, 5 and 6 and were largely independent of plant height or development. This is the first report on the genetic relationship of seedling root architecture and embryo size, and potential in selection of seminal root size for accessing deep-soil moisture in droughted environments.

D-dimer levels and risk of recurrence following provoked venous thromboembolism: findings from the RIETE registry.

BACKGROUND: Patients with venous thromboembolism (VTE) secondary to transient risk factors may develop VTE recurrences after discontinuing anticoagulation. Identifying at-risk patients could help to guide the duration of therapy. METHODS: We used the RIETE database to assess the prognostic value of d-dimer testing after discontinuing anticoagulation to identify patients at increased risk for recurrences. Transient risk factors were classified as major (postoperative) or minor (pregnancy, oestrogen use, immobilization or recent travel). RESULTS: In December 2018, 1655 VTE patients with transient risk factors (major 460, minor 1195) underwent d-dimer measurements after discontinuing anticoagulation. Amongst patients with major risk factors, the recurrence rate was 5.74 (95% CI: 3.19-9.57) events per 100 patient-years in those with raised d-dimer levels and 2.68 (95% CI: 1.45-4.56) in those with normal levels. Amongst patients with minor risk factors, the rates were 7.79 (95% CI: 5.71-10.4) and 3.34 (95% CI: 2.39-4.53), respectively. Patients with major risk factors and raised d-dimer levels (n = 171) had a nonsignificantly higher rate of recurrences (hazard ratio [HR]: 2.14; 95% CI: 0.96-4.79) than those with normal levels. Patients with minor risk factors and raised d-dimer levels (n = 382) had a higher rate of recurrences (HR: 2.34; 95% CI: 1.51-3.63) than those with normal levels. On multivariate analysis, raised d-dimers (HR: 1.74; 95% CI: 1.09-2.77) were associated with an increased risk for recurrences in patients with minor risk factors, not in those with major risk factors. CONCLUSIONS: Patients with raised d-dimer levels after discontinuing anticoagulant therapy for VTE provoked by a minor transient risk factor were at an increased risk for recurrences.

Splanchnic vein thrombosis in myeloproliferative neoplasms: risk factors for recurrences in a cohort of 181 patients.

We retrospectively studied 181 patients with polycythaemia vera (n=67), essential thrombocythaemia (n=67) or primary myelofibrosis (n=47), who presented a first episode of splanchnic vein thrombosis (SVT). Budd-Chiari syndrome (BCS) and portal vein thrombosis were diagnosed in 31 (17.1%) and 109 (60.3%) patients, respectively; isolated thrombosis of the mesenteric or splenic veins was detected in 18 and 23 cases, respectively. After this index event, the patients were followed for 735 patient years (pt-years) and experienced 31 recurrences corresponding to an incidence rate of 4.2 per 100 pt-years. Factors associated with a significantly higher risk of recurrence were BCS (hazard ratio (HR): 3.03), history of previous thrombosis (HR: 3.62), splenomegaly (HR: 2.66) and leukocytosis (HR: 2.8). Vitamin K-antagonists (VKA) were prescribed in 85% of patients and the recurrence rate was 3.9 per 100 pt-years, whereas in the small fraction (15%) not receiving VKA more recurrences (7.2 per 100 pt-years) were reported. Intracranial and extracranial major bleeding was recorded mainly in patients on VKA and the corresponding rate was 2.0 per 100 pt-years. In conclusion, despite anticoagulation treatment, the recurrence rate after SVT in myeloproliferative neoplasms is high and suggests the exploration of new avenues of secondary prophylaxis with new antithrombotic drugs and JAK-2 inhibitors.

High rate of recurrent venous thromboembolism in patients with myeloproliferative neoplasms and effect of prophylaxis with vitamin K antagonists.

The optimal duration of treatment with vitamin K antagonists (VKA) after venous thromboembolism (VTE) in patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) is uncertain. To tackle this issue, we retrospectively studied 206 patients with MPN-related VTE (deep venous thrombosis of the legs and/or pulmonary embolism). After this index event, we recorded over 695 pt-years 45 recurrences, venous in 36 cases, with an incidence rate (IR) of 6.5 per 100 pt-years (95% confidence interval (CI): 4.9-8.6). One hundred fifty-five patients received VKA; the IR of recurrent thrombosis per 100 pt-years was 4.7 (95% CI: 2.8-7.3) on VKA and 8.9 (95% CI: 5.7-13.2) off VKA (P=0.03). In patients receiving VKA, the IR of recurrent thrombosis per 100 pt-years was 5.3 (95% CI: 3.2-8.4) among 108 patients on long-term VKA and 12.8 (95% CI: 7.3-20.7) after discontinuation among the 47 who ceased treatment (P=0.008), with a doubled risk of recurrence after stopping VKA (hazard ratio: 2.21, 95% CI: 1.19-5.30). The IR of major bleeding per 100 pt-years was 2.4 (95%: CI: 1.1-4.5) on VKA and 0.7 (95% CI: 0.08-2.5) off VKA (P=0.08). In conclusion, in MPN patients with VTE recurrent thrombosis is significantly reduced by VKA and caution should be adopted in discontinuation; however, the incidence of recurrence on treatment remains high, calling for clinical trials aimed to improve prophylaxis in this setting.

Management of immune thrombocytopenic purpura in pregnancy.

Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by a low platelet count and mucocutaneous bleeding. Pregnancy does not increase the incidence of ITP nor does it exacerbate a preexisting disease. Although pregnant women with ITP may experience several maternal and fetal complications, in most cases even with a very low platelet count, there is neither maternal nor fetal morbidity or mortality. Corticosteroids are the first line of therapy in pregnant women; intravenous immune globulin is commonly used in steroid resistant patients. Other treatments such as intravenously administered anti-D (Rhogam) and splenectomy during pregnancy have been reported. Antiplatelet IgG antibodies can cross the placenta and can induce fetal thrombocytopenia. In most women there is no indication to assess fetal platelet counts during the pregnancy. The mode of delivery is determined by obstetrical considerations.

Molecular mapping of genes for Coleoptile growth in bread wheat (Triticum aestivum L.).

Successful plant establishment is critical to the development of high-yielding crops. Short coleoptiles can reduce seedling emergence particularly when seed is sown deep as occurs when moisture necessary for germination is deep in the subsoil. Detailed molecular maps for a range of wheat doubled-haploid populations (Cranbrook/Halberd, Sunco/Tasman, CD87/Katepwa and Kukri/Janz) were used to identify genomic regions affecting coleoptile characteristics length, cross-sectional area and degree of spiralling across contrasting soil temperatures. Genotypic variation was large and distributions of genotype means were approximately normal with evidence for transgressive segregation. Narrow-sense heritabilities were high for coleoptile length and cross-sectional area indicating a strong genetic basis for differences among progeny. In contrast, heritabilities for coleoptile spiralling were small. Molecular marker analyses identified a number of significant quantitative trait loci (QTL) for coleoptile growth. Many of the coleoptile growth QTL mapped directly to the Rht-B1 or Rht-D1 dwarfing gene loci conferring reduced cell size through insensitivity to endogenous gibberellins. Other QTL for coleoptile growth were identified throughout the genome. Epistatic interactions were small or non-existent, and there was little evidence for any QTL x temperature interaction. Gene effects at significant QTL were approximately one-half to one-quarter the size of effects at the Rht-B1 and Rht-D1 regions. However, selection at these QTL could together alter coleoptile length by up to 50 mm. In addition to Rht-B1b and Rht-D1b, genomic regions on chromosomes 2B, 2D, 4A, 5D and 6B were repeatable across two or more populations suggesting their potential value for use in breeding and marker-aided selection for greater coleoptile length and improved establishment.

Retrospective analysis of the use of inferior vena cava filters in routine hospital practice.

INTRODUCTION: Characteristics and outcomes of patients undergoing inferior vena cava (IVC) filter insertion are not well reported. Particularly, the role of long term anticoagulation in these patients is unclear. AIMS: (1) To describe in a cohort of patients undergoing IVC filter insertion, underlying diseases, indications for filter insertion, complications, and survival. (2) To determine the effect of long term anticoagulant treatment on thromboembolism and patient survival. STUDY DESIGN: A retrospective analysis of 109 consecutive patients undergoing IVC filter insertion in two university hospitals. RESULTS: Average age was 67.4 years. Median duration of follow up was two years. Indications for IVC filter insertion were: contraindication to anticoagulation (n = 61, 56%), prophylactic insertion (n = 29, 27%), thromboembolism while receiving adequate anticoagulation (n = 17, 15%), and non-compliance with anticoagulation (n = 2, 2%). Insertion related complications were groin haematoma in four patients (3.5%) and localised infection at the puncture site in one patient (0.9%). Fifty six patients (51.4%) died during the study period. Of these, 22 received long term anticoagulants and 34 did not. Overall and thrombosis free survival was greater in the anticoagulant treated group (median survival not reached) than in the untreated group (median survival = 12 months). Patients not receiving long term anticoagulation after IVC filter insertion were nearly 2.5-fold more likely to die or experience venous thromboembolism. CONCLUSION: IVC filter insertion was a safe procedure and was performed for appropriate indications in the patients studied. In patients surviving for longer than 30 days, prolonged administration of oral anticoagulants was associated with improved survival with no significant increase in haemorrhagic complications.

Molecular mapping of gibberellin-responsive dwarfing genes in bread wheat.

Opportunities exist for replacing reduced height (Rht) genes Rht-B1b and Rht-D1b with alternative dwarfing genes for bread wheat improvement. In this study, the chromosomal locations of several height-reducing genes were determined by screening populations of recombinant inbred lines or doubled haploid lines varying for plant height with microsatellite markers. Linked markers were found for Rht5 (on chromosome 3BS), Rht12 (5AL) and Rht13 (7BS), which accounted for most of the phenotypic variance in height in the respective populations. Large height differences between genotypes (up to 43 cm) indicated linkage to major height-reducing genes. Rht4 was associated with molecular markers on chromosome 2BL, accounting for up to 30% of the variance in height. Confirming previous studies, Rht8 was linked to markers on chromosome 2DS, whereas a population varying for Rht9 revealed a region with a small but significant height effect on chromosome 5AL. The height-reducing effect of these dwarfing genes was repeatable across a range of environments. The molecular markers developed in this study will be useful for marker-assisted selection of alternative height-reducing genes, and to better understand the effects of different Rht genes on wheat growth and agronomic performance.

Preventing venous thromboembolism in acute medical patients.

BACKGROUND: While extensive data support the clinical benefit and cost-effectiveness of routine thromboprophylaxis in surgical patients, the use of this approach in medical patients has been controversial. However, recent data, mainly from the MEDENOX trial, support routine thromboprophylaxis in acutely ill medical patients. AIM: To determine attitudes towards VTE prevention in such patients, in departments of internal medicine in Israel. DESIGN: Questionnaire-based survey. METHODS: A questionnaire regarding aspects of VTE prophylaxis was mailed to all heads of internal medicine departments in Israel (n = 90). The questionnaire also included data concerning VTE prevention measures in specific acute medical illnesses, based on the MEDENOX study population. RESULTS: Fifty-eight (64%) departments returned the questionnaire. Forty-seven (81%) of them considered VTE a clinical problem in their departments, but only 37 (63%) had a routine VTE prevention policy. The most frequently used modality for VTE prophylaxis was low-molecular-weight heparin. There was little agreement concerning the exact indications or risk factors in which VTE prophylaxis measures should be used, except the combination of acute medical disabling illness and previous VTE. DISCUSSION: The results emphasize the need for detailed guidelines and risk assessment models for VTE prevention treatments in acutely ill medical patients, as well as better education for physicians.

The sensitivity, specificity, and clinical relevance of gel versus tube DATs in the clinical immunology laboratory.

The DAT is a test used to demonstrate in vivo antibody and/or complement coating of RBCs. Typically, the DAT is performed in test tubes; however, recently a number of commercially available tests using gel-filled microtubes have become available. Few data comparing the sensitivity of these test media are available. To compare the rate of detection of a positive DAT performed in test tubes versus in gel-filled microtubes and to assess the clinical significance of the results in patients undergoing evaluation of anemia, we tested 310 consecutive EDTA-anticoagulated blood samples from adult patients. The samples were analyzed using both the conventional tube technique and a gel-based assay (DiaMed; Cressier sur Morat, Switzerland). Test results were expressed as either positive or negative. When a positive result by either technique was encountered, the treating physician was interviewed to determine whether the result warranted further patient investigation or treatment. In 268 out of 310 cases the DAT was negative by both methods. Of the 42 patients with a positive DAT, the test was positive by both methods in 18 patients. In the remaining 24 cases the DAT was positive by the gel test only. In all cases positive by both techniques the test result affected patient management. Of the 24 cases that were positive only by gel test, 3 were judged to be clinically significant. In this study, the gel test was more sensitive than the tube technique for performance of the DAT. However, the clinical significance of a DAT positive only by a gel test is doubtful. We believe that use of the gel-based DAT should be more extensively evaluated before it is adopted as a standard technique in general clinical laboratory practice.

Increased level of hemoglobin 1 enhances survival of hypoxic stress and promotes early growth in Arabidopsis thaliana.

Overexpression of a class 1 Hb (GLB1) protects Arabidopsis thaliana plants from the effects of severe hypoxia. Overexpression of the bifunctional symbiotic Hb (GLB1S) from Parasponia andersonii in A. thaliana also increases survival after hypoxia. Plants overexpressing the Hb 1 protein, mutated to have a low oxygen affinity, are as susceptible to hypoxia as WT plants, suggesting that the protection against hypoxia depends on the ability of the Hb to bind ligands, such as oxygen, with high affinity. A mild hypoxia pretreatment (5%) induces the Hb gene and increases the survival of plants after severe hypoxic treatment (0.1%). These results with Hb 1 show that plant Hbs have a role other than in nitrogen-fixing root nodules. Plants overexpressing the GLB1 protein show early vigorous growth in nonhypoxic conditions and are 50% larger in weight than the controls at 14 days. The constitutive expression of GLB1 also resulted in a reduced number of root hairs and increased number of laterals in the root system.

The effect of tourniquet application, tranexamic acid, and desmopressin on the procoagulant and fibrinolytic systems during total knee replacement.

STUDY OBJECTIVE: To assess the influence of tourniquet inflation-deflation as well as desmopressin and tranexamic acid (TA) administration on prothrombin fragment 1.2, fibrinogen, plasmin antiplasmin complex, and D-dimer concentrations during total knee replacement. DESIGN: Randomized, placebo-controlled study. SETTING: Large referral hospital. PATIENTS: 30 ASA physical status I, II, and III patients undergoing total knee replacement. INTERVENTIONS: Patients were randomized to one of three treatment groups. Patients received either tranexamic acid, desmopressin, or an equal volume of saline, intravenously. MEASUREMENTS AND MAIN RESULTS: Cubital blood was drawn immediately before induction of anesthesia, 1 hour after tourniquet application, and 2 and 15 minutes after tourniquet deflation. Fibrinogen and D-dimer levels were measured using the Clauss Method and latex agglutination, respectively. Plasmin antiplasmin complex and prothrombin fragment 1.2 levels were measured by enzyme-linked immunosorbent assay (ELISA). All assays were performed in duplicate, and intra-assay variability was documented. No statistically significant difference in fibrinogen, D-dimer, plasmin antiplasmin complex, or prothrombin fragment 1.2 levels was demonstrated among the groups. Similarly, within each group there were no statistically significant differences in the variables studied. However, despite the lack of statistical significance, when compared with their levels during tourniquet application, an increase in D-dimer and plasmin antiplasmin complex levels was observed in all three groups at 2 and 15 minutes after tourniquet release. In contrast, no increase in prothrombin fragment 1.2 generation was noted. Significantly more allogeneic blood was transfused in the Control and Desmopressin Groups when compared with the tranexamic acid group (p< 0.02). CONCLUSIONS: No evidence of tourniquet-induced fibrinolysis or thrombin generation was demonstrated in the systemic circulation. Desmopressin and tranexamic acid had no significant effect on the variables measured.

A comparative study of the postoperative allogeneic blood-sparing effects of tranexamic acid and of desmopressin after total knee replacement.

BACKGROUND: Tissue hypoxia and reperfusion induce abnormal hemostatic function. Therefore, bleeding after total knee replacement (TKR) may be a result of a tourniquet-induced imbalance of the procoagulant and fibrinolytic systems. Because laboratory confirmation of tourniquet-induced abnormal hemostasis is difficult to obtain, indirect evidence must be sought. STUDY DESIGN AND METHODS: A prospective, single-blind study of 40 patients undergoing TKR was performed. In the tranexamic acid (TA) group, in the 30 minutes before the limb tourniquet was deflated, an IV bolus dose of TA (15 mg/kg) was administered. Thereafter, a constant IV infusion of 10 mg per kg per hour was administered until 12 hours after tourniquet deflation. In the desmopressin group, desmopressin (0.3 mg/kg) and saline were administered by a similar protocol. No blood was administered intraoperatively. A postoperative Hct <27 percent constituted the postoperative transfusion trigger. Patients were examined daily for signs of lower-limb deep vein thrombosis, and they underwent lower-limb Doppler ultrasound on postoperative Day 5. Three months after surgery, the incidence of delayed thromboembolic events was assessed. RESULTS: During the first 12 postoperative hours, blood accumulation in the surgical drain was significantly (p<0.05) lower in the TA group (162 mL +/- 129) than in the desmopressin group (342 mL +/- 169). From the sixth postoperative hour until 3 days postoperatively, Hct levels were significantly lower in the desmopressin group than in the TA group. Significantly more allogeneic blood was transfused in the desmopressin group (11 patients received 16 units) than in the TA group (3 patients each received 1 unit) (p<0.02). There were no clinical signs of deep vein thrombosis or abnormal Doppler ultrasound studies. Three months postoperatively, there were no thromboembolic events among the 37 patients interviewed. CONCLUSION: TA induces better blood sparing than desmopressin. Therefore, a tourniquet-induced increase in fibrinolysis is the likely cause of delayed bleeding after TKR surgery. However, before routine administration, the effect of TA on the incidence of thromboembolic events requires further investigation.

The effect of external pressure, catheter gauge, and storage time on hemolysis in RBC transfusion.

BACKGROUND: RBC transfusions are often administered using externally applied pneumatic pressure. The effect of this practice on RBC hemolysis was studied during simulated transfusion performed in the laboratory. MATERIALS AND METHODS: RBC transfusions were performed sequentially via 16-, 18-, 20-, and 22-gauge cannulas with the application of a pneumatic pressure device at pressures of 150 and 300 mm Hg. Hb concentration, Hct, RBC count, free Hb, potassium, and LDH concentrations were measured in 5 mL of transfusate. RESULTS: Forty-seven RBC units, 20 fresh units (mean age, 10.8 days) and 27 old units (mean age, 28.9 days) were studied under all conditions. Multiple regression analysis revealed that the age of the unit and the external pressure applied were significant determinants of the degree of hemolysis. CONCLUSIONS: The application of an external pressure device results in minimal destruction of transfused RBCs, even under the most stringent conditions examined. Thus, external pressure application to expedite an RBC transfusion is likely to be a safe procedure for the majority of patients. Unusual clinical situations, such as massive transfusion in pediatric patients, should be specifically examined to confirm the safety of this procedure.

Once-daily budesonide inhalation suspension in infants and children < 4 and > or = 4 years of age with persistent asthma.

BACKGROUND: Budesonide inhalation suspension (Pulmicort Respules; AstraZeneca LP, Wilmington, DE), a nebulized corticosteroid, was developed for use in infants and young children with persistent asthma. OBJECTIVE: To compare the efficacy and safety of once-daily budesonide inhalation suspension in children < 4 years of age and in those > or = 4 years of age with persistent asthma. METHODS: A retrospective analysis stratified by age group was performed on data from two randomized, double-blind, placebo-controlled, parallel-group studies that evaluated the efficacy and safety of budesonide inhalation suspension 0.25 mg, 0.5 mg, or 1.0 mg once daily for 12 weeks in children 6 months to 8 years of age with persistent asthma. Clinical assessments included nighttime and daytime asthma symptoms, breakthrough medication use, adverse events, and hypothalamic-pituitary-adrenal-axis function. RESULTS: In both randomized studies, budesonide inhalation suspension demonstrated statistically significant improvement in nighttime and daytime asthma symptom scores compared with placebo. In the retrospective analysis of pooled data from these studies, the efficacy of budesonide was maintained when children were stratified by age group. Clinical improvements from baseline in nighttime and daytime asthma symptom scores were observed in both age groups at all budesonide inhalation suspension dose levels. No significant differences were observed between age groups in breakthrough medication use in any of the treatment groups. No differences were observed in the incidence of adverse events between the two age groups, and significant (P < 0.01) effect on hypothalamic-pituitary-adrenal-axis function was apparent only in children < 4 years of age at the 0.25-mg dose level. CONCLUSIONS: Once-daily budesonide inhalation suspension is effective in the treatment of persistent asthma in children aged < 4 and > or = 4 years of age.

The effect of storage on the expression of platelet membrane phosphatidylserine and the subsequent impacton the coagulant function of stored platelets.

BACKGROUND: Platelet concentrates (PCs) derived from whole blood and stored under standard blood bank conditions undergo changes that are referred to as the platelet storage lesion. This study assesses the effect of PC preparation and storage on the distribution of phosphatidylserine (PS) in the platelet membrane and the effect that this distribution may have on the thrombogenic potential of stored PCs. STUDY DESIGN AND METHODS: Fresh platelets and PCs donated by healthy donors were obtained. PCs derived from platelet-rich plasma were studied on Day 1, Day 3, and Day 6 of storage under blood bank conditions. RESULTS: Platelet aggregation after exposure to the platelet agonists ADP and epinephrine singly declined progressively, but, when ADP and epinephrine in combination and collagen and thrombin in combination were used as agonists, the decline in platelet aggregation was less marked. PS expression as measured by Annexin V binding (mean and SD) was 2.02 +/- 0.93 percent in fresh platelet samples and increased to 5.39 +/- 4.2 percent on Day 1, 22. 1 +/- 7.1 percent on Day 3, and 39.5 +/- 12.1 percent on Day 6. Platelet prothrombinase activity (mean +/- SD) as measured by thrombin generation increased from 1.49 +/- 0.7 micro per mL in fresh platelet samples to 3.68 +/- 1.1 micro per mL in Day 1 platelets (p<0.001), 5.15 +/- 2.5 micro per mL in Day 3 platelets (p<0.001), and 4.65 +/- 2.48 micro per mL in Day 6 platelets (p<0. 001). CONCLUSION: These results show that PS expression increases after preparation of PCs from platelet-rich plasma and rises progressively during platelet storage under blood bank conditions. Furthermore, the greater PS expression is associated with increased platelet- dependent thrombin-generating capacity.

Neurological complications of essential thrombocytosis (ET).

OBJECTIVE: To evaluate the prevalence of neurological abnormalities in patients with ET and attempt to identify risk factors for neurological complications. METHOD: Ninety-five patient charts were reviewed from January 1983-July 1999. Seventy patients fulfilled the Polycythemia Vera Study Group criteria for diagnosing ET. RESULTS: Eighteen patients (25.7%) had episodes of neurological impairment, 52 (74.3%) had none. Neurological features-- occlusive cerebrovascular event-9; chronic headache-3 and dizziness-3, mononeuritis multiplex, sinus vein thrombosis and epilepsy-1 each. The interval between diagnosis of ET and occurrence of neurological events ranged from time of presentation (10 patients) to 13 years (1 patient) with a high predominance of females, 88.8% and 55%, respectively. CONCLUSIONS: Neurological complications occurred at presentation or during follow-up in approximately 25% of patients with ET. Our observation suggests that further investigation focusing on the possible mechanisms for neurological deficits in females with ET should be considered.

Staphylococcus aureus bacteremia as a cause of early relapse of thrombotic thrombocytopenic purpura.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a multisystem disease characterized by the sudden onset of hemolytic anemia, thrombocytopenia, fever, renal failure, and neurologic dysfunction, occurring in various combinations. The most effective treatment of TTP is plasma exchange and the administration of corticosteroids, which reduces mortality from the 90 percent seen in untreated patients to 10 percent. CASE REPORTS: Two patients responded favorably to plasma exchange and corticosteroid therapy, but their TTP relapsed during treatment. In both cases, the early relapse of TTP was associated with Staphylococcus aureus bacteremia secondary to central line infection. Treatment of the infection and intensification of the plasma exchange regimen resulted in a sustained remission. CONCLUSION: Infection should be actively sought and treated in TTP patients who are refractory to treatment or in whom an exacerbation of the disease occurs while they are undergoing plasma exchange.

Value of prothrombin fragment 1.2 (F 1.2) in the diagnosis of stroke in young patients with antiphospholipid antibodies.

The presence in the serum of antiphospholipid antibodies (aPL) is associated with venous and arterial thrombosis. This observation has led to the search for these antibodies in young patients with ischemic neurologic syndromes. However, 1% to 5% of healthy people may be found to have circulating aPL without necessarily being at increased risk of thromboembolism. Thus, the finding of APLA in a patient with cerebral ischemia does not necessarily provide an explanation for the etiology of the clinical syndrome. The aim of this study was to determine whether the presence of aPL in young patients with stroke or transient ischemic attacks represents a possible cause of hypercoagulability as defined by ongoing thrombin formation with resultant elevation of prothrombin fragment 1.2 (F1.2) levels. This was a retrospective, case-control study involving 57 subjects. Twenty-seven patients had a recent cerebrovascular ischemic event--either TIA or a stroke. Fifteen were positive for aPL, and 12 were aPL-negative. Thirty subjects, matched for age and sex with no history of cerebrovascular disease, served as controls. Of this group, 20 were aPL-positive and 10 were aPL-negative. Causes of hypercoagulability other than aPL were excluded by laboratory testing. A positive test for aPL was repeated after a 6-week interval and two positive tests were required for a patient to be regarded as being aPL-positive. Levels of F1.2 were measured by an ELISA technique. There was a significant difference (p < 0.05) in the mean F1.2 levels between the aPL-positive group with a history of cerebrovascular disease (mean F1.2 = 2.3733) and each of the other study groups. There was no statistically significant difference between any of the other study groups. Our findings suggest that F1.2 levels are elevated in young patients with cerebrovascular syndromes who have aPL and in whom other causes of hypercoagulability and atherosclerotic vascular disease are absent. Elevated F1.2 in these patients may be a potential marker of the hypercoagulable state associated with aPL.