Long-term neuropsychological sequelae, emotional wellbeing and quality of life in patients with acquired thrombotic thrombocytopenic purpura.

Neurological symptoms related to microthrombosis are the hallmark of acute manifestations of acquired thrombotic thrombocytopenic purpura (TTP). Despite the achievement of hematological remission, patients may report persisting neurological impairment that affects their quality of life. To assess the long-term neuropsychological consequences of acute TTP, we recruited 35 acquired TTP patients (77% females, median age at onset 41 years, interquartile range: 35-48) regularly followed at our out-patient clinic of thrombotic microangiopathies in Milan (Italy) from December 2015 to October 2016. Patients underwent a psychological evaluation of memory and attentional functions, emotional wellbeing and health-related quality of life at least three months after their last acute TTP event (median 36 months, interquartile range: 17-54). During the psychological consultation, 17 patients (49%) referred persisting subjective neurological impairment in the frame of a remission phase, with at least one symptom as disorientation, loss of concentration, dizziness, lack of balance, headache and diplopia. Neuropsychological assessment revealed lower scores than the Italian general population pertaining to direct, indirect and deferred memory. A higher degree of impairment of memory domains was found in patients with neurological involvement at the time of presentation of the first acute TTP episode. Anxiety and depression were detected in seven (20%) and 15 (43%) patients, respectively. Health-related quality of life was lower than the Italian general population, with mental domains more impacted than physical domains (mean difference 58.43, 95% confidence interval: 71.49-45.37). Our study demonstrates compromised memory and attention functions, persisting anxiety/depression symptoms and a generally reduced quality of life in patients recovering from acute acquired TTP. New clinical strategies should be considered to improve these symptoms.

Evaluation of the Utility of von Willebrand Factor Propeptide in the Differential Diagnosis of von Willebrand Disease and Acquired von Willebrand Syndrome.

An increased von Willebrand factor propeptide (VWFpp) to VWF antigen (VWF:Ag) ratio (VWFpp/VWF:Ag) indicates an enhanced clearance of VWF. This finding has been described in von Willebrand disease (VWD) and in acquired von Willebrand syndrome (AVWS). A distinction between these two diseases, one congenital and the other acquired, is primarily based on family and personal history of bleeding. However, if this information is scanty, the diagnosis might be challenging due to the lack of an effective diagnostic biomarker. In this cross-sectional study, we assessed the ability of VWFpp/VWF:Ag for the differential diagnosis between VWD and AVWS. VWFpp/VWF:Ag was measured in a group of 153 patients (125 with VWD and 28 with AVWS). Most patients with AVWS and VWD showed an increased VWFpp/VWF:Ag, although to variable degrees. A marked increase of VWFpp/VWF:Ag was mainly associated with the diagnosis of AVWS and VWD type 1 Vicenza. A receiver operating characteristic curve was used to identify the optimal cutoff of VWFpp/VWF:Ag for discrimination of patients with a modestly increased (most VWD cases) versus those with a markedly increased clearance (AVWS and VWD type 1 Vicenza), and this cutoff was identified at the value of 3.9 (sensitivity: 0.70, specificity: 0.97). The ROC curve sorting from a logistic model containing VWFpp/VWF:Ag, age, and sex had an area under the curve (AUC) of 0.88 (95% confidence interval: 0.80-0.95). A subsequent molecular evaluation discriminated VWD type 1 Vicenza from AVWS. In conclusion, VWFpp/VWF:Ag appears helpful to discriminate patients with a markedly increase VWF clearance (AVWS or VWD type 1 Vicenza) from those with a modestly increased clearance (most VWD patients).

Hypercoagulability and the risk of recurrence in young women with myocardial infarction or ischaemic stroke: a cohort study.

BACKGROUND: We aimed to investigate the role of hypercoagulability on the risk of lifetime cardiovascular recurrences after myocardial infarction or ischaemic stroke. METHODS: Young women (< 50 years) with either myocardial infarction (n = 197) or ischaemic stroke (n = 107) were followed between 1995 and 2012 in the RATIO follow-up study. To determine whether hypercoagulability affects the risk or recurrence, a coagulation score based on acquired and inherited markers was compiled and used in a quartile analysis. Hazard ratios (HRs) obtained from Cox proportional models and adjusted for several cardiovascular risk factors were used to compare quartiles of the coagulation score for the risk of recurrence. RESULTS: During a median follow-up of 19 years, 59 cardiovascular recurrences occurred. In patients with myocardial infarction no association was found between a high prothrombotic score and recurrences (highest quartile vs lowest quartile HR 0.7, 95% CI, 0.3-1.8). Conversely, ischaemic stroke patients with a high prothrombotic score showed a doubling in risk of long-term cardiovascular recurrences (HR 1.9, 95% CI 0.6-6.3) compared with ischaemic stroke patients and low levels of the score, with a dose response relationship. CONCLUSIONS: An increased coagulation tendency might be associated with long-term cardiovascular risk in women with ischaemic stroke, but not in women with myocardial infarction.

Pregnancy loss and risk of ischaemic stroke and myocardial infarction.

We investigated whether pregnancy loss increases the risk of arterial thrombosis in young women. Women (age 18-50 years) with ischaemic stroke (IS) or myocardial infarction (MI) and at least one pregnancy were compared for pregnancy loss in a control group. Odds ratios (OR) with 95% confidence intervals (CI), adjusted for matching variables, cardiovascular risk factors, cardiovascular family history and the presence of antiphospholipid antibodies, were calculated for the number of pregnancy losses as well as the type of unsuccessful pregnancy (early miscarriage, late miscarriage and stillbirth). 165 IS cases, 218 MI cases and 743 controls were included. Women with multiple (≥3) pregnancy loss had a doubled risk of arterial thrombosis (OR 2·37, 95%CI 0·99-5·70) compared with women without pregnancy loss, similarly to women who experienced stillbirth (OR 1·68, 95%CI 0·79-3·55). Both relative risks were higher for IS (OR 3·51, 95%CI 1·08-11·35 and 2·06, 95%CI 0·81-5·23, respectively) than for MI (OR 2·04, 95%CI 0·71-5·86 and 1·04, 95%CI 0·39-2·79). Adjustment for antiphospholipid antibodies did not affect the estimates. Multiple pregnancy loss and stillbirth increases the risk of IS and, to a lesser extent, of MI, even when other cardiovascular risk factors and antiphospholipid antibodies are accounted for.

Concomitant headache influences long-term prognosis after acute cerebral ischemia of noncardioembolic origin.

BACKGROUND AND PURPOSE: Acute cerebral ischemia is frequently associated with headache. It is unknown whether concomitant headache reflects a partly different pathogenesis, and thus, may influence long-term prognosis after stroke. Here, we compared the long-term risk of recurrent vascular events in patients in whom a transient ischemic attack or minor ischemic stroke of noncardioembolic origin was associated with headache with those without headache. METHODS: We used data from the Life Long After Cerebral ischemia (LiLAC) cohort. Participants were grouped on the basis of presence or absence of headache at presentation. We calculated the hazard ratios (HRs) and corresponding 95% confidence intervals (CI) for any first vascular event (primary outcome) or any cardiac or cerebral event (secondary outcomes). Adjustments were made for baseline clinical characteristics. RESULTS: Of 2473 participants, 420 (17%) experienced headache during the acute event. Median follow-up was 14.1 years. For the primary outcome, the crude HR of headache versus no headache was 0.75 (95% CI, 0.66-0.89) and the adjusted HR 0.83 (95% CI, 0.71-0.97). For cardiac events the adjusted HR was 0.88 (95% CI, 0.67-1.14) and for cerebral events, 0.97 (95% CI, 0.76-1.24). The ratio of cardiac versus cerebral events, however, did not differ between the 2 groups. Participants with headache were at lower risk of vascular death (adjusted HR, 0.73; 95% CI, 0.61-0.87). CONCLUSIONS: Patients who experienced headache in association with a transient ischemic attack or minor ischemic stroke have a better vascular prognosis than those without concomitant headache. This may, at least partly, reflect a different pathogenesis.

Factor V Leiden but not the factor II 20210G>A mutation is a risk factor for premature coronary artery disease: a case-control study in Iran.

Background: Factor V Leiden (FVL) and factor II c.∗97G>A (rs1799963) are genetic risk factors for venous thromboembolism. Their contribution to coronary artery disease (CAD) is less clear. Objectives: This study aimed to investigate the association between FVL, rs1799963, and premature CAD in Iranians. Methods: We performed a genetic case-control study of 944 cases and 1081 controls from the premature CAD Milano-Iran study, including patients aged 18-55 (female) and 18-45 years (male) who underwent coronary angiography at the Tehran Heart Centre (Iran) in 2004-2011. Cases had luminal stenosis ≥50% in at least 1 main coronary artery or branch. Controls were age- and sex-matched with no CAD history. FVL and rs1799963 were genotyped using TaqMan SNP genotyping assays. Association was tested by logistic regression adjusted for matching factors and ethnicity. Effect modification by sex and cardiovascular risk factors (metabolic [obesity, hypertension, hyperlipidemia, and diabetes], and smoking) was assessed. Results: The risk of premature CAD was increased by 50% in FVL carriers (adjusted odds ratio [adjOR] 1.54 [95% CI, 0.95-2.48]) and slightly reduced in rs1799963 carriers (adjOR 0.71 [95% CI, 0.40-1.27]). These effects were more pronounced in women than men (FVL, adjOR 1.66 vs 1.25; rs1799963, adjOR 0.60 vs 1.07). The risk of premature CAD was substantially increased in carriers of FVL with at least 1 metabolic risk factor compared with noncarriers without metabolic risk factors (adjOR 25.14 [95% CI, 12.51-50.52]). Conclusion: FVL but not FII rs1799963 was associated with an increased risk of CAD in young Iranians. This risk increased considerably when combined with metabolic cardiovascular risk factors.

Opium as a risk factor for early-onset coronary artery disease: Results from the Milano-Iran (MIran) study.

The spreading of opium use poses new health related concerns. In some areas of Asia its use is believed to protect from cardiovascular disorders, such as coronary artery disease (CAD). However, whether opium use has an association with CAD is unclear. We aimed to investigate the association between non-medical opium use and CAD. We set up a case-control analysis, i.e., the Milano-Iran (MIran) study by enrolling consecutive young patients who underwent a coronary angiography at the Tehran Heart Center, between 2004 and 2011. Incident cases with CAD were contrasted with controls for opium use. Relative risks were calculated in terms of odds ratios (ORs) by logistic regression models adjusted for age, sex, cigarette smoking, body mass index, hypertension, hyperlipidaemia, and diabetes. Interaction analyses were performed between opium and major cardiovascular risk factors. 1011 patients with CAD (mean age 43.6 years) and 2002 controls (mean age 54.3 years) were included in the study. Habitual opium users had a 3.8-fold increased risk of CAD (95%CI 2.4-6.2) compared with non-users. The association was strongest for men, with a fully adjusted OR of 5.5 (95%CI 3.0-9.9). No interaction was observed for the combination of opium addiction and hypertension, or diabetes, but an excess in risk was found in opium users with hyperlipidaemia (OR 16.8, 95%CI 8.9-31.7, expected OR 12.2), suggesting supra-additive interaction. In conclusion, despite common beliefs, we showed that non-medical opium use is associated with an increased risk of CAD, even when other cardiovascular risk factors are taken into account.

Renin-angiotensin system modulation and outcomes in patients hospitalized for interstitial SARS-CoV2 pneumonia: a cohort study.

AIM: The role of cardiovascular (CV) pharmacotherapies in patients with severe COVID-19 pneumonia remains controversial. This study aims to assess the impact of renin-angiotensin system modulation (RASi) (either angiotensin-converting enzymes (ACEIs) or angiotensin-receptor blockers (ARBs)) on COVID-19 outcome. METHODS: We performed a cohort study on consecutive patients admitted for COVID-19 pneumonia at the Internal Medicine Unit of Sant'Orsola-Malpighi Hospital in Bologna, Italy. Patients with a possible alternative cause of respiratory failure other than COVID-19 were excluded. Clinical, pharmacological and laboratory data at admission and during the hospitalization were collected. Patients were treated with intravenous dexamethasone, low molecular weight heparin and nasal flow or Venturi mask oxygen. Subjects were followed until discharge, Intensive Care Unit (ICU) admission or death. Severe cases were defined by acute respiratory distress syndrome (arterial oxygen partial pressure and the fraction of inhaled oxygen ratio (P/F) ≤ 100 mmHg/%, or P/F ≤ 150 mmHg/% and respiratory rate ≥ 26/min). Patients with chronic use of RAS modulation were compared with those without for the composite outcome of in-hospital mortality or ICU admission. Hazard ratios (HR) were obtained by Cox regression, adjusted for several clinical factors. RESULTS: Of the 268 patients enrolled in the study, 93 (35%, mean age 68 ± 13 years, 67% males) were treated with RASi (58% ACEIs and 42% ARBs). There were no meaningful differences between the RASI and no RASI group regarding clinical and laboratory parameters at admission. As expected, patients in the RASi group had a higher prevalence of hypertension, diabetes mellitus, atrial fibrillation, and ischemic heart disease. One hundred eight patients (40%) were admitted to ICU during hospitalization due to severe respiratory failure, and 24 (9%) died. The risk of in-hospital death or ICU admission was lower in the RASI group than in the non-RASI group (age and sex-adjusted HR 0.57, 95% CI 0.37-0.8), even after adjustment for several comorbidities (fully adjusted HR 0.44, 95% CI 0.26-0.74). Seven (7.5%) patients died in the RASi group vs 17 (9.7%) in the non-RASi group, leading to a non-statistically significant mortality risk reduction (fully adjusted HR 0.69, 95% CI 0.18-1.90). The lower risk in the RASi group was primarily related to ARBs use compared to ACEIs (HR 0.5, 95% CI 0.28-0.92 and HR 0.82, 95% CI 0.51-1.32, respectively). CONCLUSIONS: Our study showed an inverse association between the chronic use of RASi and COVID-19 pneumonia severity (either ICU admissions or in-hospital death), even when significant comorbidities are considered.

Different clinical severity of first episodes and recurrences of thrombotic thrombocytopenic purpura.

The clinical course of thrombotic thrombocytopenic purpura (TTP) is characterized by recurrent disease episodes in up to 50% of cases. The clinical presentation and severity of different TTP episodes have not been systematically compared. Laboratory and clinical information from 51 patients with recurrent disease, derived from 136 patients with TTP included in the Milan TTP registry (URL: http://www.ttpdatabase.org), were used to compare mortality, symptoms and disease-related laboratory measurements in different disease episodes. The prevalence of severe neurological symptoms (coma, seizures, and focal neurological defects) was significantly lower in recurrences than in the first episode. Platelet counts and haemoglobin levels at presentation were higher in recurrences than in the first disease episode, and lactate dehydrogenase levels were lower. Also, mortality tended to be lower in the second and third disease episodes than in the first. Recurrences of TTP are generally milder than first episodes. These differences in severity should be taken into account in clinical research on TTP and in patient management.

Urinary balantidiasis: diagnosis at a glance by urine sediment examination.

A 56-year-old Caucasian man with non-Hodgkin's lymphoma, who had previously been treated with prolonged intensive chemotherapy, was hospitalized for an acute and reversible kidney injury of multifactorial origin. The urinary sediment examination, performed daily, demonstrated the presence of renal tubular cells and renal tubular cell casts. Surprisingly, it also showed the presence of trophozoites of the protozoan Balantidium coli, which were identified on the basis of its characteristic morphology and rapid movements across the slide, and transient leukocyturia. The patient was asymptomatic, his medical history was negative for gastrointestinal disease, and no Balantidium coli was found in the feces. In spite of this, due to the previous chemotherapy, the patient was treated with oral metrodinazole. Only one other case with Balantidium coli in the urine sediment has been described so far and this paper stresses the importance of the examination of the urinary sediment.

Red cell distribution width and the risk of cerebral vein thrombosis: A case-control study.

BACKGROUND: Red cell distribution width (RDW) is a marker of cardiovascular diseases and venous thromboembolism, but its role in cerebral vein thrombosis (CVT) is unknown. AIMS: To investigate whether high values of RDW are associated with an increased risk of CVT. METHODS: A case-control study of CVT patients (≥18years-old) referred to our center contrasted with healthy individuals. Odds ratios (ORs) were calculated for RDW values >90th percentile by multivariable logistic regression and adjusted for demographic characteristics, hemorheological parameters, renal function, fibrinogen and CRP. Quartiles based on the distribution of RDW values were used in an additional model to assess a dose-response relationship. The risk of CVT associated with the combined presence of high RDW and either thrombophilia abnormalities or oral contraceptive use was also estimated. RESULTS: 143 cases (median age 36years, 18-79) and 352 controls (42years, 18-80) were investigated. RDW values >90th percentile (>14.6%) were associated with an increased risk of CVT (OR 2.44, 95% CI 1.39-4.28). The association remained after further adjustment for hemorheological parameters (OR 3.73, 95% CI 1.72-8.09), inflammatory markers (OR 3.77, 95% CI 1.72-8.25) and renal function (OR 3.62, 95% CI 1.53-8.55). The risk appeared restricted to these extreme levels (>14.6%), as there was no graded association between values of RDW and CVT risk over quartiles. There was a synergistic effect on the risk of CVT for the combination of high RDW and thrombophilia abnormalities (OR 33.20, 95% CI 6.95-158.55) or oral contraceptive use (OR 37.99, 95% CI 8.78-164.45). CONCLUSIONS: Values of RDW >90th percentile are associated with CVT.

Thrombosis after liver transplantation for hepatocellular carcinoma.

The influence of thrombosis on the prognosis of patients with hepatocellular carcinoma (HCC) after liver transplantation (LT) and the role of the commonest inherited thrombophilia abnormalities factor V Leiden and prothrombin G20210A in the development of thrombosis are unknown. We investigated a cohort of patients who underwent LT for HCC with the aim to estimate the incidence rate (IR) of thrombosis, its influence on mortality and re-transplantation rates and, in the frame of a nested case-control study, the role of thrombophilia in donors and recipients for the development of thrombosis. Four-hundred and thirty patients underwent LT and were followed for a median of 7.2 years. Twenty-six recipients (6%) developed thrombosis (IR 1.06 [95%CI: 0.71-1.53] per 100 pts-yr). Mortality rate after LT was 3.95 (95%CI: 3.22-4.79) per 100 pts-yr and was not influenced by thrombosis. Re-transplantation was planned for 33 patients and was more common in patients with thrombosis than in those without (HR 2.50 [95%CI: 0.87-7.17]). The risk of thrombosis was 4 times higher in recipients with thrombophilia than in those without (OR 4.23 [95%CI: 0.99-18.04]) and 6 times higher when the analysis was restricted to venous thrombosis (OR 6.26 [95%CI: 1.19-32.85]). The presence of inherited thrombophilia in the donors did not increase the risk of thrombosis of the recipient. In conclusion, thrombosis is a complication of 6% of patients transplanted for HCC and increases the risk of re-transplantation but not of mortality. The risk of thrombosis, particularly venous, is increased in the presence of thrombophilia abnormalities in the recipients.

European Stroke Organization guideline for the diagnosis and treatment of cerebral venous thrombosis - Endorsed by the European Academy of Neurology.

The current proposal for cerebral venous thrombosis guideline followed the Grading of Recommendations, Assessment, Development, and Evaluation system, formulating relevant diagnostic and treatment questions, performing systematic reviews of all available evidence and writing recommendations and deciding on their strength on an explicit and transparent manner, based on the quality of available scientific evidence. The guideline addresses both diagnostic and therapeutic topics. We suggest using magnetic resonance or computed tomography angiography for confirming the diagnosis of cerebral venous thrombosis and not screening patients with cerebral venous thrombosis routinely for thrombophilia or cancer. We recommend parenteral anticoagulation in acute cerebral venous thrombosis and decompressive surgery to prevent death due to brain herniation. We suggest to use preferentially low-molecular weight heparin in the acute phase and not using direct oral anticoagulants. We suggest not using steroids and acetazolamide to reduce death or dependency. We suggest using antiepileptics in patients with an early seizure and supratentorial lesions to prevent further early seizures. We could not make recommendations due to very poor quality of evidence concerning duration of anticoagulation after the acute phase, thrombolysis and/or thrombectomy, therapeutic lumbar puncture, and prevention of remote seizures with antiepileptic drugs. We suggest that in women who suffered a previous cerebral venous thrombosis, contraceptives containing oestrogens should be avoided. We suggest that subsequent pregnancies are safe, but use of prophylactic low-molecular weight heparin should be considered throughout pregnancy and puerperium. Multicentre observational and experimental studies are needed to increase the level of evidence supporting recommendations on the diagnosis and management of cerebral venous thrombosis.

Duration of oral contraceptive use and the risk of venous thromboembolism. A case-control study.

INTRODUCTION: Oral contraceptive (OC) use increases the risk of venous thromboembolism (VTE), but the effect of duration of use remains to be elucidated. PATIENTS AND METHODS: This case-control study was aimed to investigate the duration of OC use on the risk of VTE according to women age, periods of use, prevalence of other risk factors and the role of thrombophilia abnormalities. Seven-hundred patients and 209 controls who used OC were stratified into short users (≤1year), long users (1 to 5years), and very long users (>5years). RESULTS AND CONCLUSIONS: Compared to non-users, the odds ratio (OR) for VTE was 9.0 (95% CI 6.9-12.2) in short, 6.5 (95% CI 4.8-83.7) in long and 5.9 (95% CI 4.4-8.1) in very long users. The risk of VTE in short users was highest in women ≤30years and in the first year of use (OR 13.1, 95% CI 7.7-22.4) and decreased afterward (OR 7.7, 95% CI 5.0-11.9). This trend was not observed in women >30years. Compared to non-carriers and non-users, a joint effect of thrombophilia abnormalities and OC use on VTE risk was observed particularly in short users (OR 62.2, 95% CI 29.8-129.6), but also afterward (OR 25.4, 95% CI 16.5-39.2). Other transient risk factors for VTE were present in 25% of very long and 16% of short users. In conclusion, the risk of VTE in OC users decreases over time only before 30years and in first users. Thrombophilia abnormalities strongly interact with the duration of OC use in determining VTE.

Hemostasis changes during veno-venous extracorporeal membrane oxygenation for respiratory support in adults.

BACKGROUND: We investigated the coagulation system in patients during extracorporeal membrane oxygenation (ECMO) initiated for respiratory failure and the influence of the ECMO circuit on coagulation tests; we compared different coagulation tests for monitoring unfractionated heparin (UH) therapy; we investigated whether or not coagulation parameters were predictive of bleeding during ECMO. METHODS: Pilot study on twelve consecutive adult patients admitted at our general ICU for acute respiratory failure and placed on ECMO from November 2011 to October 2012. Coagulation tests were performed before ECMO start and daily, including day of circuit change and day of circuit removal. UH was monitored with activated partial thromboplastin time (APTT) ratio, at a therapeutic range of 1.5-2.0. RESULTS: We observed no effect of ECMO circuit on coagulation parameters measured pre- and postlung, but platelet count decreased significantly over time (-82x10(3)/mmc, 95%CI 40-123). APTT showed a correlation with antifactor Xa activity, whereas other global coagulation tests such as activated clotting time, thromboelastography and endogenous thrombin potential did not. Major bleeding occurred in three patients but no difference in any coagulation parameter was observed between them and those who did not bleed. CONCLUSIONS: This pilot study shows that ECMO initiated for respiratory support in adults does not change coagulation parameters. Over time a statistically significant reduction of platelet count was observed, possibly due to consumption within the circuit, consumption microangiopathy or the underlying patients' diseases. Although APTT was appropriate to monitor UH, major bleedings occurred and a lower therapeutic range may be advisable.

Hypercoagulability Is a Stronger Risk Factor for Ischaemic Stroke than for Myocardial Infarction: A Systematic Review.

BACKGROUND AND PURPOSE: Hypercoagulability increases the risk of arterial thrombosis; however, this effect may differ between various manifestations of arterial disease. METHODS: In this study, we compared the effect of coagulation factors as measures of hypercoagulability on the risk of ischaemic stroke (IS) and myocardial infarction (MI) by performing a systematic review of the literature. The effect of a risk factor on IS (relative risk for IS, RRIS) was compared with the effect on MI (RRMI) by calculating their ratio (RRR = RRIS/RRMI). A relevant differential effect was considered when RRR was >1+ its own standard error (SE) or <1-SE. RESULTS: We identified 70 publications, describing results from 31 study populations, accounting for 351 markers of hypercoagulability. The majority (203/351, 58%) had an RRR greater than 1. A larger effect on IS risk than MI risk (RRE>1+1SE) was found in 49/343 (14%) markers. Of these, 18/49 (37%) had an RRR greater than 1+2SE. On the opposite side, a larger effect on MI risk (RRR<1-1SE) was found in only 17/343 (5%) markers. CONCLUSIONS: These results suggest that hypercoagulability has a more pronounced effect on the risk of IS than that of MI.

Association between red cell distribution width and risk of venous thromboembolism.

BACKGROUND: An association between high red cell distribution width (RDW) and venous thromboembolism (VTE) has been observed. However, it is not known whether this association differs within various manifestations of VTE, nor if there is an interaction between RDW and thrombophilia abnormalities on the risk of VTE. AIMS: To investigate whether RDW is a marker of the risk of VTE; to identify subgroups of patients in which the association between RDW and VTE is stronger; to investigate a possible interaction between RDW and thrombophilia abnormalities. METHODS: Case-control study on 730 patients with a first objectively-confirmed VTE episode (300 unprovoked and 430 provoked) consecutively referred to our Center between 2007 and 2013, and 352 healthy controls. Blood was taken for a thrombophilia work-up and a complete blood count, including RDW, at least three months after VTE. RESULTS: Individuals with RDW above the 90(th) percentile (>14.6%) had a 2.5-fold increased risk of VTE compared to those with RDW ≤90(th) percentile, independently of age, sex, body mass index, other hematological variables and renal function (adjusted odds ratio: 2.52 [95%CI:1.42-4.47]). The risk was similar for unprovoked and provoked VTE, and slightly higher in patients with pulmonary embolism (adjusted odds ratio 3.19 [95%CI:1.68-6.09]) than in those with deep vein thrombosis alone (2.29 [95%CI:1.22-4.30]). No interaction between high RDW and thrombophilia abnormalities on the risk of VTE was observed. CONCLUSION: Our findings confirm RDW as an independent and easily available marker for stratification of the risk of VTE.

A bioclinical pattern for the early diagnosis of cardioembolic stroke.

Background and Scope. Early etiologic diagnosis of ischemic stroke subtype guides acute management and treatment. We aim to evaluate if plasma biomarkers can predict stroke subtypes in the early phase from stroke onset. Methods. Plasma N-terminal prohormone of brain natriuretic peptide (NT-proBNP), D-dimer, C-reactive protein, serum albumin, and globulin levels have been investigated in 114 consecutive patients presenting at the emergency room within 6 hours of the ischemic stroke onset. Plasma levels of biomarkers have been correlated with stroke aetiology (based on TOAST criteria) by multivariable logistic regression analysis, adjusted for several covariates. Results. Of the 114 patients, 34 (30%) had cardioembolic stroke, 27 (23%) atherothrombotic stroke, 19 (17%) lacunar stroke, and 34 (30%) stroke of undetermined origin. Patients with cardioembolic stroke had significantly higher levels of NT-proBNP and lower globulin/albumin (G/A) ratio compared with the other subgroups. At multiple logistic regression NT-proBNP > 200 pg/mL, G/A ratio > 0.70, and NIHSS score were independent predictors of cardioembolic stroke with high accuracy of the model, either including (AUC, 0.91) or excluding (AUC, 0.84) atrial fibrillation. Conclusions. A prediction model that includes NT-proBNP, G/A ratio, and NIHSS score can be useful for the early etiologic diagnosis of ischemic stroke.

Pregnancy complications in acquired thrombotic thrombocytopenic purpura: a case-control study.

BACKGROUND: Pregnant women with a history of acquired thrombotic thrombocytopenic purpura (TTP) are considered at risk for disease recurrence and might be at risk for miscarriage, similar to other autoimmune disorders. However, the exact entity of these risks and their causes are unknown. The aim of this study was to evaluate risk factors associated with adverse pregnancy outcome, in terms of both gravidic TTP and miscarriage, in women affected by previous acquired TTP. METHODS: We conducted a nested case-control study in women with a history of acquired TTP enrolled in the Milan TTP registry from 1994 to October 2012, with strict inclusion criteria to reduce referral and selection bias. RESULTS: Fifteen out of 254 women with acquired TTP were included, namely four cases with gravidic TTP, five with miscarriage, and six controls with uncomplicated pregnancy. In the cases, ADAMTS13 activity levels in the first trimester were moderately-to-severely reduced (median levels <3% in gravidic TTP and median levels 20% [range 14-40%] in the women with miscarriage) and anti-ADAMTS13 antibodies were invariably present, while in the control group ADAMTS13 activity levels were normal (median 90%, range 40-129%), with absence of detectable anti-ADAMTS13 antibodies. Reduced levels of ADAMTS13 activity (<25%) in the first trimester were associated with an over 2.9-fold increased risk for gravidic TTP and with an over 1.2-fold increased risk for miscarriage (lower boundary of the confidence interval of the odds ratio). In addition, the presence of anti-ADAMTS13 antibodies during pregnancy was associated with an over 6.6-fold increased risk for gravidic TTP and with an over 4.1-fold increased risk for miscarriage. CONCLUSIONS: ADAMTS13 activity evaluation and detection of anti-ADAMTS13 antibody could help to predict the risk of complications in pregnant women with a history of acquired TTP.

Prevalence of disease and relationships between laboratory phenotype and bleeding severity in platelet primary secretion defects.

BACKGROUND: The prevalence of platelet primary secretion defects (PSD) among patients with bleeding diathesis is unknown. Moreover, there is paucity of data on the determinants of bleeding severity in PSD patients. OBJECTIVE: To determine the prevalence of PSD in patients with clinical bleeding and to study the relationships between the type of platelet defect and bleeding severity. METHODS: Data on patients referred for bleeding to the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan (Italy) in the years between 2008 and 2012 were retrieved to study the prevalence of PSD. Demographic, clinical and laboratory information on 32 patients with a diagnosis of PSD was used to compare patients with or without associated medical conditions and to investigate whether or not the type and extension of platelet defects were associated with the bleeding severity score (crude and age-normalized) or with the age at first bleeding requiring medical attention. RESULTS: The estimated prevalence of PSD among 207 patients with bleeding diathesis and bleeding severity score above 4 was 18.8% (95% confidence interval [CI]: 14.1-24.7%). Patients without associated medical conditions had earlier age of first bleeding (18 vs 45 years; difference: -27 years; 95% CI: -46 to -9 years) and different platelet functional defect patterns (Fisher's exact test of the distribution of patterns, P = 0.007) than patients with accompanying medical conditions. The type and extension of platelet defect was not associated with the severity of bleeding. CONCLUSIONS: PSD is found in approximately one fifth of patients with clinical bleeding. In patients with PSD, the type and extension of laboratory defect was not associated with bleeding severity.