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SummaryHaemorrhage, including intracranial bleeding, is a common, potentially lethal complication of warfarin therapy and rapid and complete reversal of anticoagulation may be life-saving. Fresh frozen plasma (FFP) and vitamin K are most frequently administered. Because of the variable content of vitamin K-dependent clotting factors in FFP, and the effects of dilution, the efficacy of this approach is open to doubt. We have therefore compared the effects of FFP and clotting factor concentrates on the INRs and clotting factor levels of orally anticoagulated subjects requiring rapid correction of their haemostatic defect. In many, the pre-treatment INR was considered to be dangerously above the target therapeutic range. In the 12 patients given FFP, the INR did not completely correct (range 1.6-3.8, mean 2.3) indicating an ongoing anticoagulated state in all. In contrast, the INR in 29 subjects given clotting factor concentrates was completely corrected in 28 (range 0.9-3.8, mean 1.3). Following treatment, marked differences were observed in clotting factor IX levels between the two groups. The median factor IX level was 19 u/dl (range 10-63) following FFP infusion and 68.5 u/dl (range 31-111) following concentrate. In FFP treated patients, poorer responses were also observed for each of the other vitamin K-depen- dent clotting factors but these were less marked than for factor IX, which was present in low concentrations in some batches of FFP. Thus, haemostatically effective levels of factor IX cannot be achieved, in most instances, by the conventional use of FFP in patients requiring reversal of their anticoagulant therapy. Clotting factor concentrates are the only effective option where complete and immediate correction of the coagulation defect is indicated in orally anticoagulated patients with life or limb-threatening haemorrhage.

SummaryUnselected coagulation testing is widely practiced in the process of assessing bleeding risk prior to surgery. This may delay surgery inappropriately and cause unnecessary concern in patients who are found to have 'abnormal' tests. In addition it is associated with a significant cost. This systematic review was performed to determine whether patient bleeding history and unselected coagulation testing predict abnormal perioperative bleeding. A literature search of Medline between 1966 and 2005 was performed to identify appropriate studies. Studies that contained enough data to allow the calculation of the predictive value and likelihood ratios of tests for perioperative bleeding were included. Nine observational studies (three prospective) were identified. The positive predictive value (0AE03-0AE22) and likelihood ratio (0AE94-5AE1) for coagulation tests indicate that they are poor predictors of bleeding. Patients undergoing surgery should have a bleeding history taken. This should include detail of previous surgery and trauma, a family history, and detail of anti-thrombotic medication. Patients with a negative bleeding history do not require routine coagulation screening prior to surgery.Keywords: surgery, coagulation screen, bleeding, clinical history. ObjectiveThe aim of this guideline is to provide a rational approach to the use of bleeding history and coagulation tests prior to surgery or invasive procedures to predict bleeding risk. The aim is to evaluate the use of indiscriminate testing. Appropriate testing of patients with relevant clinical features on history or examination is not the topic of this guideline. The target population includes clinicians responsible for assessment of patients prior to surgery and other invasive procedures. MethodsThe writing group was made up of UK haematologists with a special interest in bleeding disorders and an anaesthetist. First, the commonly employed coagulation screening tests were identified and their general and specific limitations considered. Second, Medline was systematically searched for English language publications from 1966 to September 2005. Relevant references generated from initial papers and published guidelines/reviews were also examined. Meeting abstracts were not included. Key terms: routine, screening, preoperative, surgery, coagulation testing, APTT, PT, bleeding, invasive procedures. Inclusion criteria: studies had to contain enough data to enable the calculation of (i) the predictive value (PV) and likelihood ratio (LR) of the coagulation test for postoperative bleeding and/or (ii) the PV and LR of the bleeding history for postoperative bleeding. The rationale and methods for the calculations are described in Appendix 1. Nine observational case series with usable data (Table I) and one systematic review were identified (Table II).Data elements extracted from these articles were study type, surgical setting, number and age of patients and coagulation tests performed. Outcome data extracted included abnormal tests, positive bleeding history,...

To assess whether treatment with enoxaparin and low-dose aspirin, along with intensive pregnancy surveillance, reduces rate of pregnancy loss compared with intensive pregnancy surveillance alone in women with history of 2 or more consecutive previous pregnancy losses, a parallel group, multicenter, randomized controlled trial was performed in the United Kingdom and New Zealand. Participants (n ‫؍‬ 294) presenting for initial antenatal care at fewer than 7 weeks' gestation with history of 2 or more consecutive previous pregnancy losses at 24 or fewer weeks' gestation and no evidence of anatomic, endocrine, chromosomal, or immunologic abnormality were randomly assigned to receive either enoxaparin 40 mg subcutaneously and 75 mg of aspirin orally once daily along with intense pregnancy surveillance or intense pregnancy surveillance alone from random assignment until 36 weeks' gestation. The primary outcome measure was pregnancy loss rate. Of the 147 participants receiving pharmacologic intervention, 32 (22%) pregnancy losses occurred, compared with 29 losses (20%) in the 147 subjects receiving intensive surveillance alone, giving an odds ratio of 0.91 (95% confidence interval, 0.52-1.59) of having a successful pregnancy with pharmacologic intervention. Thus, we observed no reduction in pregnancy loss rate with antithrombotic intervention in pregnant women with 2 or more consecutive previous pregnancy losses. Continuing Medical Education onlineThis activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of Medscape, LLC and the American Society of Hematology. Medscape, LLC is accredited by the ACCME to provide continuing medical education for physicians. Medscape, LLC designates this educational activity for a maximum of 0.5 AMA PRA Category 1 credits™. Physicians should only claim credit commensurate with the extent of their participation in the activity. All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test and/or complete the evaluation at http://cme.medscape.com/journal/blood; and (4) view/print certificate. For CME questions, see page 4319. Disclosures Andrew Thomson has received honoraria from Sanofi Aventis and Leo for lectures. Ian A. Greer has received honoraria from Sanofi Aventis and Leo for lectures and advisory boards. The remaining authors; Associate Editor David P. Lillicrap; and CME questions author Charles P. Vega, University of California, Irvine, CA, declare no competing financial interests. Learning objectivesUpon completion of this activity, participants will be able to:1. Describe hematologic factors associated with recurrent pregnancy loss and potential treatment to prevent pregnancy loss 2. Identify the efficacy of enoxaparin plus aspirin in improving rates of ...

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We have investigated the effects of purified IgG fractions from plasma containing the lupus anticoagulant (LAC) and/or IgG anticardiolipin antibody (ACA) on the degradation of factor Va by an activated protein C-protein S complex. Plasma samples from 10 patients were studied. LAC was detected by a Russell's Viper venom technique. ACA was determined by ELISA. IgG fractions were obtained from each plasma sample by protein A-Sepharose fractionation. This fraction was shown to exhibit ACA/LAC activity. Using purified activated protein C (APC), protein S and phosphatidylserine/phosphatidylcholine, factor Va degradation was assessed in the presence and absence of IgG fractions from LAC/ACA containing plasmas. After 2 min incubation the mean factor Va degradation by APC and protein S in the presence of IgG LAC/ACA fractions was 14% compared with 52% with normal IgG. A similar effect was seen when phospholipid was substituted by washed freeze-thawed platelets. Experiments employing varying concentrations of protein S and phospholipid revealed marked differences in respect of the inhibitory specificity of the different antiphospholipid antibodies. These results indicate that antiphospholipid antibodies have an inhibitory effect on the activated protein C/protein S complex and provide some explanation for a relationship between antiphospholipid antibodies and thrombosis.

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SummaryCombinedoral contraceptives,oral hormonereplacementtherapya nd thrombophiliasa re recognised riskf actors forv enous thromboembolism in women.Theobjectiveofthis study was to assess theriskofthromboembolismamongwomenwith thrombophilia who aret akingo ral contraceptives or hormoner eplacement therapy,conducting as ystematic reviewa nd metaanalysis. Of 201s tudiesi dentified,onlyn ine met the inclusion criteria. Sevenstudiesincluded pre-menopausal womenonoral contraceptives and twos tudiesi ncluded peri-menopausal womenonhormone replacement therapy.For oral contraceptiveu se,significant associations of the risko fv enous thromboembolismw eref oundi nw omenw ith factorV Leiden (OR 15.62; 95%CI 8.66 (OR 13.16; 95%CI 4.28 to 40.47).Although limited by the small number of studies, thefindingsofthis study supportthe presence of interaction between thrombophilia and venous thromboembolism among woment akingo ral contraceptives.H owever,f urther studies arerequired to establish with greaterconfidencethe associations of these,a nd other, thrombophilias with venous thromboembolismamonghormone users.