The thrombotic risk in Cushing's syndrome-questions, answers, and the algorithm to consider in its assessment: part I-thrombotic risk not related to surgery.

Introduction: Recently, it has been reported that there is a great diversity in strategies used for thromboprophylaxis in patients with Cushing's syndrome (CS). An aim of this review was to discuss these practices in light of the existing data on the thrombotic risk in patients with CS and guidelines for medically ill patients. Methods: The four relevant topics and questions on thrombotic risk in CS were identified. The current guidelines on prevention and diagnosis of venous thromboembolism (VTE) were reviewed for the answers. An algorithm to consider in the assessment of the thrombotic risk in patients with CS was proposed. Results: To address both generic and CS-specific risk factors for VTE, the algorithm includes the stepwise approach consisting of Padua Score, urine free cortisol, and CS-VTE score, with no indication for routine thrombophilia testing in the prediction of an index VTE episode. Having confirmed VTE, selected patients require thrombophilia testing to aid the duration of anticoagulant treatment. The separate part of the algorithm is devoted to patients with ectopic adrenocorticotropic hormone syndrome in whom exclusion of VTE precedes introducing routine thromboprophylaxis to prevent VTE. The cancer-related VTE also prompts thromboprophylaxis, with the possible vessel invasion. The algorithm presents a unifactorial and multifactorial approach to exclude high-bleeding risks and safely introduce thromboprophylaxis with low-molecular-weight heparin. Summary: Our article is the first to present an algorithm to consider in the thrombotic risk assessment among patients with Cushing's syndrome as a starting point for a broader discussion in the environment. A plethora of factors affect the VTE risk in patients with CS, but no studies have conclusively evaluated the best thromboprophylaxis strategy so far. Future studies are needed to set standards of care.

Assessment-based management of placenta-mediated pregnancy complications: Pragmatism until a precision medicine approach evolves.

The management of pregnant women with thrombophilia and a history of gestational vascular complications remains debatable. Treatment of the latter is often based on clinical outcome rather than disease mechanism. While the use of venous thromboembolism prophylaxis in pregnancy is recommended for those at increased risk, the ability of anticoagulant and/or antiplatelet agents to lower the risk of placenta-mediated complications in this clinical setting remains controversial. The available guidelines are inconsistent in some situations, which reflects the limited evidence base. This review critically discusses risk assessment models (RAMs) and management strategies of women with thrombophilia and pregnancy complications, using clinical vignettes. RAMs, taking into account obstetric and thrombotic history as well as thrombophilia status, could drive a precision medicine approach, based on disease mechanism, and guide individual therapeutic interventions in high-risk clinical settings.

A Retrospective Assessment of Thrombophilia in Pregnant Women with First and Second Trimester Pregnancy Loss.

Recurrent Pregnancy Loss (RPL) affects between 1% to 5% of women of reproductive age. It is widely believed that RPL is a complex disorder that is influenced by chromosomal abnormalities, genetic mutations, uterine anatomic deformity, endocrine dysfunction, immunologic factors, infections, and the environment. Thrombotic disorders are a frequent cause of RPL, accounting for almost half of all cases; however, in the rest of the cases, the cause of RPL remains unclear. Therefore, in this study, it was planned to determine the genetic mutations involved in RPL during the first and second trimester of pregnancy. An observational retrospective cohort study was conducted in 2021, collecting data from 157 first trimester miscarriages and 54 s trimester pregnancies. All patients with a panel of laboratory and genetic analysis for thrombophilia were included for data analysis. It was observed that four factors were significantly more prevalent in one of the groups. Factor V Leiden (FVL) homozygosity and antiphospholipid syndrome (APS) antibodies were statistically significantly more common in pregnant women who suffered first trimester pregnancy losses. On the other hand, Protein C deficiency and Glycoprotein Ia polymorphism were statistically significantly more frequent in the second trimester group. The strongest independent risk factors for first trimester pregnancy loss were FVL and prothrombin (PT) compound mutations (OR = 3.11), followed by FVL homozygous mutation (OR = 3.66), and APS antibodies (OR = 4.47). Regarding second trimester pregnancy loss risk factors, the strongest were FVL and PT compound (OR = 3.24), followed by Glycoprotein Ia polymorphism (OR = 3.61), and respectively, APS antibodies (OR = 3.85). Numerous thrombophilic risk factors for early and late pregnancy loss have been found, including several mutations that seem to occur more often either during the first or the second trimester. Even though we are aware of risk-free and efficient diagnostics for thrombophilia abnormalities, no intervention has been proved to be clearly successful after the detection of these variables.

Thrombosis risk assessment in patients with congenital thrombophilia during COVID - 19 infection.

BACKGROUND: Coagulation dysfunction represents a serious complication in patients during the COVID-19 infection, while fulminant thrombotic complications emerge as critical issues in individuals with severe COVID-19. In addition to a severe clinical presentation, comorbidities and age significantly contribute to the development of thrombotic complications in this disease. However, there is very little data on association of congenital thrombophilia and thrombotic events in the setting of COVID-19. Our study aimed to evaluate the risk of COVID-19 associated thrombosis in patients with congenital thrombophilia. METHODS: This prospective, case-control study included patients with confirmed COVID-19 infection, followed 6 months post-confirmation. The final outcome was a symptomatic thrombotic event. In total, 90 COVID-19 patients, 30 with known congenital thrombophilia and 60 patients without thrombophilia within the period July 2020-November 2021, were included in the study. Evaluation of hemostatic parameters including FVIII activity and D-dimer was performed for all patients at 1 month, 3 months and 6 months post-COVID-19 diagnosis. RESULTS: Symptomatic thrombotic events were observed in 7 out of 30 (23 %) COVID-19 patients with thrombophilia, and 12 out of 60 (20 %) without thrombophilia, P = 0.715. In addition, the two patient groups had comparable localization of thrombotic events, time to thrombotic event, effect of antithrombotic treatment and changes in FVIII activity, while D-dimer level were significantly increased in patients without thrombophilia. CONCLUSION: Our findings suggest that patients with congenital thrombophilia, irrespective of their age, a mild clinical picture and absence of comorbidities, should receive anticoagulant prophylaxis, adjusted based on the specific genetic defect.

Assessment of Coagulation Profiles by Rotational Thromboelastometry in COVID 19 Patients.

BACKGROUND: According to recent studies, thrombotic complications frequently occur in Coronavirus Disease-19 (COVID-19) and are associated with increasing disease severity and poor prognosis. However, conventional coagulation assays are unable to identify these patients' hypercoagulable states, raising questions about the appropriate assessment tool. We aimed to evaluate coagulation abnormalities in patients with different severity of CO-VID-19 using viscoelastic tests. METHODS: This was a single center retrospective observational study in a group of 50 adult patients with SARS-COV-2 infection and different severity of pneumonia (20 moderate, 30 severe). Coagulation status was evaluated using rotational thromboelastometry (ROTEM®) in conjunction with conventional coagulation assays (platelet count, PT, aPTT, fibrinogen, and D-dimer levels). RESULTS: Shorter than normal EXTEM CFT, higher than normal A10 and MCF in INTEM, EXTEM, and FIBTEM and higher than normal α-angle were classified as markers of hypercoagulable state. Forty-four (88%) patients had at least two hypercoagulable ROTEM parameters. Seven patients developed thromboembolic complications. All were classified as having severe COVID-19 pneumonia. With increment increases in disease severity, we observed an increase in the number of patients with hypercoagulable parameters and higher INTEM, EXTEM, and FIBTEM MCF but without being statistically significant. On the other hand, we noted a significant decrement of PT (p = 0.039), higher fibrinogen (p = 0.001), higher D dimer (p < 0.001), and shorter CT EXTEM (p < 0.001). CONCLUSIONS: Our findings support the presence of a hypercoagulable state in COVID-19 patients, especially in the severe forms. It also highlights the role of viscoelastic tests in assessing COVID-19 coagulopathy and, therefore, their potential use in thrombophrophylactic management.

Thrombophilia Testing After Ischemic Stroke: Why, When, and What?

Thrombophilia testing is frequently performed after an ischemic stroke, particularly when cryptogenic. However, there is minimal evidence supporting a significant association between most conditions assessed through thrombophilia testing and ischemic stroke, and the rationale for thrombophilia testing in many clinical situations remains uncertain. In this topical review, we review and contextualize the existing data on the risks, predictors, and outcomes of thrombophilic conditions in patients with ischemic stroke. We report that inherited thrombophilias have an uncertain relationship with ischemic stroke. Conversely, antiphospholipid syndrome, an acquired immune-mediated thrombophilia, seems to be a strong risk factor for arterial thromboembolic events, including ischemic stroke, and especially among young patients. Our findings suggest that certain circumstances may warrant targeted thrombophilia testing, such as stroke in the young, cryptogenic stroke, and high estrogen states. Future prospective studies should investigate the utility and cost effectiveness of thrombophilia testing in various stroke settings, including among patients with patent foramen ovale; as well as the optimal secondary stroke prevention regimen in patients with confirmed thrombophilia, particularly if no other potential stroke mechanism is identified.

The Utility of the Markers of Coagulation and Hemostatic Activation Profile in the Management of Embolic Strokes of Undetermined Source.

BACKGROUND: Potential causes of embolic stroke of undetermined source (ESUS) include occult malignancy, venous thrombosis (VTE) with paradoxical embolism, and hypercoagulable disorders. Given the association of markers of coagulation and hemostatic activation (MOCHA) with these causes, the objective of this study was to validate the utility of the MOCHA profile in identifying the underlying cause of stroke. METHODS: We prospectively identified ESUS patients from January 1, 2017 to December 1, 2019 who underwent MOCHA profile (plasma d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, fibrin monomer) testing. Abnormal MOCHA profile was defined as ≥ 2 abnormal markers. New diagnoses of malignancy, VTE, hypercoagulable disorders and recurrent stroke were identified during routine clinical follow-up. RESULTS: Of 236 ESUS patients, 104 (44%) patients had an abnormal MOCHA profile. In multivariable analyses the number of MOCHA abnormalities was significantly associated with malignancy, VTE, and hypercoagulable disorders (OR 2.59, CI 95% 1.78-3.76, p<0.001). Sensitivity, specificity, positive predictive value, and negative predictive value of an abnormal MOCHA profile for the combined outcome of malignancy, VTE, and hypercoagulability was 96%, 62%, 23%, and 99% respectively. DISCUSSION: The MOCHA profile was able to identify ESUS patients more likely to have malignancy, VTE, and hypercoagulable disorders during follow-up. Our results show that a normal MOCHA profile in ESUS patients can effectively rule out these potential causes of ESUS.

Current diagnosis-related group-based bundling for upper-extremity arthroplasty: a case of insufficient risk adjustment and misaligned incentives.

BACKGROUND: The current Centers for Medicare & Medicaid Services diagnosis-related group (DRG) bundled-payment model for upper-extremity arthroplasty does not differentiate between the type of arthroplasty (anatomic total shoulder arthroplasty [ATSA] vs. reverse total shoulder arthroplasty vs. total elbow arthroplasty [TEA] vs. total wrist arthroplasty) or the diagnosis and indication for surgery (fracture vs. degenerative osteoarthritis vs. inflammatory arthritis). METHODS: The 2011-2014 Medicare 5% Standard Analytical Files (SAF5) database was queried to identify patients undergoing upper-extremity arthroplasty under DRG-483 and -484. Multivariate linear regression modeling was used to assess the marginal cost impact of patient-, procedure-, diagnosis-, and state-level factors on 90-day reimbursements. RESULTS: Of 6101 patients undergoing upper-extremity arthroplasty, 3851 (63.1%) fell under DRG-484 and 2250 (36.9%) were classified under DRG-483. The 90-day risk-adjusted cost of an ATSA for degenerative osteoarthritis was $14,704 ± $655. Patient-level factors associated with higher 90-day reimbursements were male sex (+$777), age 75-79 years (+$740), age 80-84 years (+$1140), and age 85 years or older (+$984). Undergoing a TEA (+$2175) was associated with higher reimbursements, whereas undergoing a shoulder hemiarthroplasty (-$1000) was associated with lower reimbursements. Surgery for a fracture (+$2354) had higher 90-day reimbursements. Malnutrition (+$10,673), alcohol use or dependence (+$6273), Parkinson disease (+$4892), cerebrovascular accident or stroke (+$4637), and hyper-coagulopathy (+$4463) had the highest reimbursements. In general, states in the South and Midwest had lower 90-day reimbursements associated with upper-extremity arthroplasty. CONCLUSIONS: Under the DRG-based model piloted by the Centers for Medicare & Medicaid Services, providers and hospitals would be reimbursed the same amount regardless of the type of surgery (ATSA vs. hemiarthroplasty vs. TEA), patient comorbidity burden, and diagnosis and indication for surgery (fracture vs. degenerative pathology), despite each of these factors having different resource utilization and associated reimbursements. Lack of risk adjustment for fracture indications leads to strong financial disincentives within this model.

Lymphocytic thrombophilic arteritis and cutaneous polyarteritis nodosa: Clinicopathologic comparison with blinded histologic assessment.

BACKGROUND: Lymphocytic thrombophilic arteritis (LTA), or macular lymphocytic arteritis, is defined by a primary lymphocytic vasculitis. However, the nosology of LTA has been controversial, with speculation that it may represent an indolent non-nodule-forming variant of cutaneous polyarteritis nodosa (cPAN). OBJECTIVE: This study compares the clinicopathologic features of patients with LTA or cPAN to assess if these conditions should be considered distinct entities. METHODS: This is a cross-sectional study of all LTA and cPAN cases at a single tertiary center using prospectively collected clinical data and blinded histologic assessment. RESULTS: The study included 17 patients with LTA and 13 patients with cPAN. Clinically, cases of LTA were distinguished by a more widespread pattern of livedo racemosa, which was noninfiltrated and asymptomatic. In contrast, cPAN was associated with localized starburst livedo, purpura, and episodic features including nodules, pain, and large inflammatory ulcers. When patients were separated according to the presence (>5%) or paucity (≤5%) of neutrophils on blinded histology review, they had distinct clinical features and differences in disease course. LIMITATIONS: This was a single-center study. CONCLUSION: Our data support the classification of LTA and cPAN as separate entities rather than a spectrum of the same disorder and highlight the importance of clinicopathologic correlation in distinguishing these conditions.

Thromboelastometry as a Comprehensive Assessment of Hypercoagulation After Aneurysmal Subarachnoid Hemorrhage: A Case Report and Literature Review.

Subarachnoid hemorrhage after cerebral aneurysm rupture (aSAH) leads to delayed cerebral ischemia (DCI) in 25-35% of surviving patients. It is believed that DCI has a multifactorial etiology, including vasospasm. Furthermore, aSAH is associated with the development of hypercoagulation and microthrombosis; thus, its pharmacological correction may help to prevent DCI. We encountered a case where hypercoagulation was detected using rotational thromboelastometry (ROTEM), although the standard coagulation test results were within the normal ranges. Based on reviews of viscoelastic tests in cases of aSAH, ROTEM could be more sensitive to hypercoagulation after aSAH, compared to standard coagulation testing.

Genetic risk assessment of thrombophilia in patients with adverse obstetric outcomes.

OBJECTIVES: To investigate the incidence of inherited thrombophilias in patients with adverse obstetric outcomes and to compare detection rates of thrombophilias between standard blood tests and a novel genetic test. METHODS: This is a case-control prospective study performed in Hospital Sant Joan de Déu in Barcelona, Spain. Cases had a history of intrauterine growth restriction requiring delivery before 34 weeks gestation, placental abruption before 34 weeks gestation, or severe preeclampsia. Controls had at least two normal, spontaneously conceived pregnancies at term, without complications or no underlying medical disease. At least 3 months after delivery, all case and control women underwent blood collection for standard blood tests for thrombophilias and saliva collection for the genetic test, which enables the diagnosis of 12 hereditary thrombophilias by analyzing genetic variants affecting different points of the blood coagulation cascade. RESULTS: The study included 33 cases and 41 controls. There were no statistically significant differences between cases and controls in the standard blood tests for thrombophilias in plasma or the TiC test for genetic variables. One clinical-genetic model was generated using variables with the lowest P values: ABO, body mass index, C_rs5985, C_rs6025, and protein S. This model exhibited good prediction capacity, with an area under the curve of almost 0.7 (P <0.05), sensitivity of almost 67%, and specificity of 70%. CONCLUSION: Although some association may exist between hypercoagulability and pregnancy outcomes, no significant direct correlation was observed between adverse obstetric outcomes and inherited thrombophilias when analyzed using either standard blood tests or the genetic test. Future studies with a larger sample size are required to create a clinical-genetic model that better discriminates women with a history of adverse pregnancy outcomes and an increased risk of poor outcomes in subsequent pregnancies.

Calciphylaxis: A Disease of Pannicular Thrombosis.

OBJECTIVE: To identify coagulation risk factors in patients with calciphylaxis and the relationship between anticoagulation use and overall survival. PATIENTS AND METHODS: Study subjects were 101 patients with calciphylaxis seen at Mayo Clinic from 1999 to September 2014. Data including thrombophilia profiles were extracted from the medical records of each patient. Survival status was determined using patient registration data and the Social Security Death Index. Survival was estimated using the Kaplan-Meier method, and associations were evaluated using Cox proportional hazards models. RESULTS: Sixty-four of the 101 patients underwent thrombophilia testing. Of these, a complete test panel was performed in 55 and a partial panel in 9. Severe thrombophilias observed in 60% (33 of 55) of the patients included antiphospholipid antibody syndrome protein C, protein S, or antithrombin deficiencies or combined thrombophilias. Of the 55 patients, severe thrombophilia (85%, 23 of 27) was noted in patients who were not on warfarin at the time of testing (27). Nonsevere thrombophilias included heterozygous factor V Leiden (n=2) and plasminogen deficiency (n=1). For the comparison of survival, patients were divided into 3 treatment categories: Warfarin (n=63), other anticoagulants (n=20), and no anticoagulants (n=18). There was no statistically significant survival difference between treatment groups. CONCLUSION: Laboratory testing reveals a strikingly high prevalence of severe thrombophilias in patients with calciphylaxis, underscoring the importance of congenital and acquired thrombotic propensity potentially contributing to the pathogenesis of this disease. These findings may have therapeutic implications; however, to date, survival differences did not vary by therapeutic choice.

Prenatal Screening for Thrombophilias: Indications and Controversies, an Update.

Pregnancy is associated with increased clotting potential and decreased fibrinolysis. Women with thrombophilias have an increased risk of venous thromboembolism during pregnancy. At least 50% of cases of venous thromboembolism in pregnant women are associated with an inherited or acquired thrombophilia. Acquired thrombophilias have also been linked with adverse pregnancy outcomes such as recurrent pregnancy loss, intrauterine fetal demise, early onset severe preeclampsia, placental abruption, and fetal growth restriction. This article addresses indications for thrombophilia testing, the appropriate laboratory tests, and timing of testing to ensure reliability of results.

When children become adults and adults become most hypercoagulable after trauma: An assessment of admission hypercoagulability by rapid thrombelastography and venous thromboembolic risk.

BACKGROUND: Thrombelastography (TEG) maximal amplitude (mA) has also been shown to reflect hypercoagulability and increased venous thromboembolism (VTE) risk in adult trauma patients. Based on these previous works, we sought to identify when children become adults with respect to TEG mA values and whether this correlated with VTE risk. METHODS: We evaluated all trauma patients admitted from January 2010 to December 2013 who were highest-level activations. Age was evaluated as a continuous variable, followed by a categorical evaluation. TEG mA values were evaluated as continuous and dichotomous (hypercoagulable, mA ≥ 65 mm). Logistic regression was then constructed controlling for age categories, sex, and injury severity to assess the association with TEG mA values and VTE risk. RESULTS: A total of 7,194 Level 1 trauma patients were admitted during this time frame (819 were <18 years of age). The likelihood of mA equal to or greater than 65 mm remained at 35% to 37% through age 30 years with significant increases observed at ages 31 years to 35 years (45%) and 46 years to 50 years (49%), both p < 0.01. When controlling for injury severity, race, and sex, logistic regression demonstrated that every 5-year increase in age (after age 30 years) was associated with a 16% increased likelihood of hypercoagulability at admission. Beginning with age 1 year, VTE risk remained at 1.5% or less until age 13 years where it increased to 2.3%, increasing again at age 15 years to 5.1%. Two additional significant increases were identified between ages 31 years and 35 years (5.5%) as well as 46 years and 50 years (7.6%), both p < 0.001. Logistic regression demonstrated a 3.4-fold increased risk for VTE among those aged 31 years to 50 years compared with those who are younger than 30 years. The same model noted a 2.3-fold increased risk compared with those who are older than 50 years. CONCLUSION: Beginning at age 13 years, children transition toward adult hypercoagulability, as evidenced by elevated TEG mA values and VTE risk. However, the greatest VTE risk (and highest likelihood of hypercoagulable mA) is among those adults 31 years to 50 years of age. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level III.

Inflammation and Thrombophilia in Pregnancy Complications: Implications for Risk Assessment and Clinical Management.

In Italy, each year 500,000 couples refer to specialized centers due to reproductive problems. Among them, recurrent pregnancy loss (RPL) represents a problem of great importance, given that it affects up to 5% of women of childbearing age. Infertility, on the other hand, is a condition that currently covers 10-20% of couples of reproductive age, being idiopathic in 20% of cases. Accumulating evidence support the concept that changes of blood coagulation, generically defined as the presence of a thrombophilic state (congenital or acquired), are the basis of 40-70% of cases of multiple abortions or infertility. Several evidences support the hypothesis that endothelial dysfunction, a hallmark of a condition of low-grade inflammation, is one of the earliest manifestations of thrombotic phenomena. To date, it's believed that, while the antiinflammatory Th2 cytokines (i.e. interleukin-10) can exert a protective role in pregnancy, the pro-inflammatory Th1 ones (i.e. interferon-γ, tumor necrosis factor-α,) have deleterious effects on pregnancy outcome, including fertilization and implantation failure. Moreover, development of many pregnancy complications, first and foremost venous thromboembolism (VTE), recognizes similar mechanism(s). As VTE is the main preventable cause of mortality during pregnancy, thromboprophylaxis is mandatory according to individual VTE risk, influenced by the presence of thrombophilic conditions. In this review, we will analyze the relationship between thrombophilia and pregnancy complications, with particular focus on the role of inflammation. Subsequently, we will consider some issues related to the thromboembolic risk in pregnancy. Finally, the role of thromboprophylaxis in pregnancy will be discussed.

Risk assessment of venous thrombosis in families with known hereditary thrombophilia: the MARseilles-NImes prediction model.

BACKGROUND: Although predicting the risk of venous thrombosis (VT) in an individual from a family with inherited thrombophilia is of major importance, it is often not feasible. OBJECTIVES: To develop a simple risk assessment model that improves prediction of the risk of VT for individuals of families with inherited thrombophilia. PATIENTS/METHODS: 1201 relatives from 430 families with inherited thrombophilia (deficiencies of antithrombin, protein C or protein S, and the factor V Leiden and F2 20210A mutations) were recruited at the referral center for thrombophilia in Marseilles, France, from 1986 to 2008. One hundred and twenty-two individuals had a personal history of VT. Sixteen preselected clinical and laboratory variables were used to derive the VT risk score. RESULTS: The scores based on the 16 variables and on the five most strongly associated variables performed similarly (areas under receiver operating characteristic curves of 0.85 and 0.83, respectively). For the five-variable score, named the MARNI score, derived from family history score of VT, von Willebrand factor antigen levels, age, severity of thrombophilia, and FGG rs2066865, the risk of VT ranged from 0.2% for individuals with a score of 0 (n = 186) to > 70% for individuals with a score of ≥ 7 (n = 27). The model was validated with an internal bootstrap method. CONCLUSIONS: With the use of a simple scoring system, assessment of the risk of VT in subjects from families with inherited thrombophilia can be greatly improved. External validation is now needed to replicate these findings.

Hyperimmune globulins and same-day thrombotic adverse events as recorded in a large healthcare database during 2008-2011.

Thrombotic events (TEs) are rare serious complications following administration of hyperimmune globulin (HIG) products. Our retrospective claims-based study assessed occurrence of same-day TEs following administration of HIGs during 2008-2011 and examined potential risk factors using HealthCore's Integrated Research Database (HIRD(SM) ) and laboratory testing of products' procoagulant Factor XIa activity by U.S. Food and Drug Administration. Multivariable regression was used to estimate same-day TE risk for different products. Of 101,956 individuals exposed to 23 different HIG product groups, 86 (0.84 per 1,000 persons) had a TE diagnosis code (DC) recorded on the same day as HIG administration. Unadjusted same-day TE DC rates (per 1,000 persons) ranged from 0.4 to 148.9 for different products. GamaSTAN S/D IG >10 cc had statistically significantly higher same-day TE DC risk compared to Tetanus IG (OR = 57.57; 95% CI = 19.72-168.10). Increased TE risk was also observed with older age (≥45 years), prior thrombotic events, and hypercoagulable state(s). Laboratory investigation identified elevated Factor XIa activity for GamaSTAN S/D, HepaGam B, HyperHep B S/D, WinRho SDF, HyperRHO S/D full dose, and HyperTET S/D. Our study, for the first time, identified increase in the same-day TE DC risk with GamaSTAN S/D IG >10 cc and suggests potentially elevated TE risk with other HIGs.

Assessment of genetic risk factors for thromboembolic complications in adults with idiopathic nephrotic syndrome.

AIMS: Nephrotic syndrome (NS) may occur with acquired hypercoagulability, however, the fact that it is accompanied by an underlying hereditary thrombophilia, especially combined hereditary thrombophilia would lead to thrombotic events. In this study, we aimed to evaluate the contribution of genetic thrombophilia to development of thrombotic events in adult patients with NS. MATERIAL AND METHODS: Factor V Leiden (FVL), prothrombin, and methylenetetrahydrofolate reductase (MTHFR) gene mutation were studied in 51 newly diagnosed idiopathic NS patients and age- and gender-matched 20 healthy control subjects included in the study. Renal vein Doppler ultrasound was conducted in order to investigate the prevalence of subclinical renal vein thrombosis. RESULTS: Of 51 patients, 6 (11.8%) were established to have thromboembolic (TE) complications at the time of diagnosis (4 symptomatic, 2 subclinical), and no recurring thrombotic episode was observed. Genetic mutation was established in all patients that were found to have TE complications. Acquired hypercoagulability factors were similar in patients without and with TE complication. CONCLUSIONS: The coexistence of inherited thrombophilia in NS may facilitate thromboembolic complications. If the cause of thrombosis cannot be explained by the usual factors attributed to the occurrence of thrombosis in NS, screening for the other factors, such as FVL, MTHFR, and prothrombin gene mutation, may be beneficial.

A longitudinal analysis of risk factors associated with central retinal vein occlusion.

PURPOSE: To identify risk factors associated with central retinal vein occlusion (CRVO) among a diverse group of patients throughout the United States. DESIGN: Longitudinal cohort study. PARTICIPANTS: All beneficiaries aged ≥ 55 years who were continuously enrolled in a managed care network for at least 2 years and who had ≥ 2 visits to an eye care provider from 2001 to 2009. METHODS: Insurance billing codes were used to identify individuals with a newly diagnosed CRVO. Multivariable Cox regression was performed to determine the factors associated with CRVO development. MAIN OUTCOME MEASURES: Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of being diagnosed with CRVO. RESULTS: Of the 494 165 enrollees who met the study inclusion criteria, 1302 (0.26%) were diagnosed with CRVO over 5.4 (± 1.8) years. After adjustment for known confounders, blacks had a 58% increased risk of CRVO compared with whites (HR, 1.58; 95% CI, 1.25-1.99), and women had a 25% decreased risk of CRVO compared with men (HR, 0.75; 95% CI, 0.66-0.85). A diagnosis of stroke increased the hazard of CRVO by 44% (HR, 1.44; 95% CI, 1.23-1.68), and hypercoagulable state was associated with a 145% increased CRVO risk (HR, 2.45; 95% CI, 1.40-4.28). Individuals with end-organ damage from hypertension (HTN) or diabetes mellitus (DM) had a 92% (HR, 1.92; 95% CI, 1.52-2.42) and 53% (HR, 1.53; 95% CI, 1.28-1.84) increased risk of CRVO, respectively, relative to those without these conditions. CONCLUSIONS: This study confirms that HTN and vascular diseases are important risk factors for CRVO. We also identify black race as being associated with CRVO, which was not well appreciated previously. Furthermore, we show that compared with patients without DM, individuals with end-organ damage from DM have a heightened risk of CRVO, whereas those with uncomplicated DM are not at increased risk of CRVO. This finding may provide a potential explanation for the conflicting reports in the literature on the association between CRVO and DM. Information from analyses such as this can be used to create a risk calculator to identify possible individuals at greatest risk for CRVO.