Pharmacomechanical catheter thrombolysis for pregnancy-related proximal deep venous thrombosis: prevention of post-thrombotic syndrome.

OBJECTIVE: The efficacy of pharmacomechanical catheter-directed thrombolysis (PCDT) in preventing post thrombotic syndrome (PTS) for pregnancy related deep vein thrombosis (DVT) is unknown. STUDY DESIGN: An observational cross section study of women with pregnancy related proximal (femoral/iliofemoral) DVT who underwent PCDT followed by anticoagulation (study group), and women who were treated with anticoagulation alone (control group). Women were evaluated for PTS using the Villalta scale (primary outcome) and VEINES-QOL/Sym questionnaires. RESULTS: Eleven women with iliofemoral DVT underwent PCDT, two during their first trimester and nine postpartum; 18 women were treated with anticoagulation only. There were no significant differences in age, number of previous pregnancies, and duration of anticoagulation or thrombophilia between the groups. The time between DVT diagnosis and study inclusion was longer in the study group [median 50.5 (range 16-120) months] compared to the control group [median 27 (range 11-64) months], p = .4. None of the women in the PCDT group developed PTS, compared to six (33.3%, p = .03) in the control group, four of whom developed severe PTS. One patient in each group developed recurrent DVT, and one patient in the study group developed a calf hematoma. A reduced frequency of lower extremity symptoms was observed in the PCDT group (VEINES-Sym questionnaire), but no differences in quality of life (VEINES-QOL questionnaire) were reported. CONCLUSION: This study suggests that PCDT may reduce the incidence of PTS in women with pregnancy related proximal DVT.Bullet pointsDVT involving the iliofemoral veins and development of post thrombotic syndrome is frequent among pregnant or postpartum womenStudies of pharmacomechanical catheter-directed thrombolysis (PCDT) for deep vein thrombosis did not include pregnant or postpartum womenIn our observational cross section study women who underwent PCDT (mainly in the postpartum period) had reduced frequency of post-thrombotic syndrome compared to women who received anticoagulation onlyLarger studies are required to confirm the use of PCDT for prevention of PTS in this population.

Risk factors associated with neonatal thrombocytopenia in pregnant women with immune thrombocytopenic purpura.

Objectives: To characterize the risk factors associated with neonatal thrombocytopenia among pregnant women with immune thrombocytopenic purpura (ITP).Methods: We reviewed the records of ITP patients who delivered during 2006-2016 at our medical center.Results: Of 253 pregnancies, median maternal age at diagnosis was 29 [25-33] years, 222 (87.7%) had previously-diagnosed ITP and 31 (12.3%) were diagnosed with new-onset ITP during pregnancy. Baseline characteristics were comparable between the groups except for a higher proportion of nulliparity among those with new-onset disease (p = .002). Maternal nadir platelet count was significantly lower among those with new-onset compared to previously diagnosed ITP (median 62 × 109/L versus 81 × 109/L, p = .005). Neonatal thrombocytopenia (<150 × 109/L) was encountered in 24 (9.5%) pregnancies and required treatment in 12 (50%) of them. Neonatal platelet count was directly correlated with maternal platelet count at delivery (r = 0.23, p = .01), with significantly lower maternal platelet count among those whose newborns experienced thrombocytopenia (p < .001). Neonatal thrombocytopenia followed a higher proportion of pregnancies of women with new-onset than previously diagnosed ITP (22.6 versus 7.7%, p = .02). In multivariate analysis, the presence of new-onset ITP (odds ratio [95% CI]: 4.88 (1.68, 14.16), p = .004) was the only independent predictor of the development of neonatal thrombocytopenia.Conclusion: Neonatal thrombocytopenia presented following almost one-tenth of pregnancies with ITP. New pregnancy-onset disease was the only prognostic marker for neonatal thrombocytopenia. This finding could contribute to risk stratification and individualized patient management.

Assessment of the procoagulant potential and associated risk factors in pregnant patients with inflammatory bowel diseases.

OBJECTIVE: Both inflammatory bowel diseases (IBDs) and pregnancy are established risk factors for thrombotic complications, thus IBD pregnant patients can be considered at even greater risk for thrombosis as compared to non IBD pregnant women. We aimed to evaluate the risk factors associated with this prothrombotic tendency among IBD women throughout gestation. METHODS: Women with IBD attending a multidisciplinary clinic for the preconception,antenatal and postnatal treatment were prospectively recruited during 2017-2018. Prothrombotic tendency was assessed by thrombin generation, a global marker of the activation of the coagulation system, expressed as the endogenous thrombin potential (ETP). RESULTS: Overall, 145 IBD women and 50 healthy control subjects were enrolled in this study. Body mass index (BMI) and gestational age were comparable between the groups. ETP level was significantly higher in women with IBD compared to control subjects in all time period (P < .0001). Among women with IBD, ETP level positively correlated with disease activity, as assessed by physician global assessment (P = .005), gestational age (P < .0001), extra-intestinal involvement (P = .04), C-reactive protein level (P < .0001), erythrocyte sedimentation rate (P < .0001), white blood cell count (P = .008), BMI (P = .02) and was inversely correlated with hemoglobin level (P < .0001). ETP level did not correlate with the occurrence of adverse pregnancy outcomes. In a multivariate analysis, active disease (ß = 0.20, P = .009), gestational age (ß = 0.45, P < .0001), extra-intestinal involvement (ß = 0.17, P = .02) and BMI (ß = 0.15, P = .05) retained independent predictors of high ETP levels. CONCLUSION: As determined by thrombin generation, the procoagulant potential among IBD pregnant patients was independently associated with disease activity, BMI and extra-intestinal disease involvement.

Antiphospholipid antibody profile-based outcome of purely vascular and purely obstetric antiphospholipid syndrome.

Antiphospholipid syndrome (APLS) is caused by antiphospholipid autoantibodies, and manifests with vascular and/or obstetric complications. The factors associated with initial disease presentation and course are unknown. We assessed the antibody profile associated with disease presentation and with the development of vascular and obstetric complications in women with initially vascular or initially obstetric APLS. A review of records of APLS women at childbearing age followed at one center during 2006-2015. Of 126 women, median age at diagnosis 29 [23-37] years, 62 were initially diagnosed with purely obstetric APLS and 64 with purely vascular APLS. Baseline characteristics and antibody profile did not differ according to the initial diagnosis. At a mean follow-up duration of 61 ± 23 months, 19 (30.6%) with initially obstetric disease, and 20 (31.3%) with initially vascular disease, developed vascular and obstetric complications, respectively (P = 1.0). Among those with triple positivity [lupus anticoagulant (LAC)+, anticardiolipin (ACL)+, anti beta2-glycoprotein I (AB2GPI)+], a higher proportion developed both obstetric and vascular complications, compared to those with single or double positivity (42.3 vs. 16.4%, P = 0.002). In multivariate analysis, the presence of LAC (P = 0.008), ACL IgG (P = 0.009) or AB2GPI IgG (P = 0.01) was the only independent predictor of the development of both obstetric and vascular complications. Almost one-third of women with initially vascular or initially obstetric APLS developed mixed disease. The antibody profile was the only prognostic marker for disease course. The association found between LAC, ACL IgG or AB2GPI IgG, and patient outcomes could contribute to risk stratification and individualized patient management.

Direct-acting oral anticoagulant drug level monitoring in clinical patient management.

The role of drug-level monitoring among patients using direct-acting oral anticoagulant (DOAC) is unclear. We aimed to investigate its 'real-life' utilization and effect on clinical management. A review of records of patients who underwent DOAC level testing during 2013-2017. Overall, 212 patients (median age 77 years) underwent 292 DOAC measurements [apixaban (n = 147), rivaroxaban (n = 102), dabigatran (n = 43)]. Monitoring volume increased by 460% during study period. DOAC level testing was performed during routine follow-up in 51 (17.5%) cases, whereas the remaining 241 (82.5%) measurements were performed due to selected clinical circumstances, most commonly: bleeding (n = 60), perioperative status (n = 45), breakthrough thrombosis (n = 37) and renal failure (n = 35). Drug levels were within the expected range in 210 (71.9%), above the expected range in 62 (21.2%) and lower than expected range in 20 (6.8%). In multivariate analysis, older age (P = 0.005), lower glomerular filtration rate (P = 0.001) and lower body mass index (P = 0.006) were associated with DOAC levels above the expected range. Clinical decisions were affected by DOAC monitoring following most (140/241, 58.1%) measurements for which we identified an indication for testing; yet only rarely when monitoring was performed during routine follow-up (7.8%, 4/51) (P < 0.0001). While no benefit of routine DOAC monitoring was observed, drug level measurement has an important role in the management of patients in selected circumstances. Age, body weight and creatinine clearance were found to be significant predictors of drug levels. Future studies are warranted to establish associations between drug levels and outcomes, and better delineate the role of DOAC monitoring.

Implementation of an institutional protocol to improve inferior vena cava utilization and outcomes.

To evaluate the impact of an institutional protocol on patterns of use and outcomes of inferior vena cava filters (IVCF). Following a multidisciplinary effort, an institutional protocol involving dedicated follow-up of patients receiving IVCF and a physician education program regarding IVCF utilization, was established. We prospectively collected data of patients who received IVCF during 2015-2016, following protocol implementation (POST group). For comparison, we reviewed records of patients who received IVCF during 2009-2014, before implementation of the institutional protocol (PRE group). In the PRE and POST groups, 76 and 38 IVCF per year were inserted respectively, with an overall decrease of 50%. IVCF were more likely to be placed for therapeutic rather than prophylactic indications in the POST compared to the PRE group (P = 0.003). Follow-up rates at our coagulation clinic were significantly higher in the POST than the PRE group (100 vs. 22.9%, P < 0.0001), as were rates of attempted retrieval: 60.5% (23/38) vs. 16.7% (76/455), P < 0.0001. Failed retrieval occurred at similar rates: 15.8% (12/76) vs. 18.2% (4/22), P = 0.75. There was a trend towards a lower thrombotic complication rate in the POST than the PRE group: 2.6 vs. 11.2%, P = 0.16. Implementation of an institutional protocol significantly decreased the use of IVCF and increased the retrieval rate. Such intervention could potentially lead to lower rates of IVCF-related complications in the future.

Patterns of use and outcome of inferior vena cava filters in a tertiary care setting.

BACKGROUND: Inferior vena cava (IVC) filter placement is increasing although the evidence to justify their use is limited. Many filters are left in place indefinitely, thereby exposing patients to long-term complications. OBJECTIVES: To review indications, complications, and follow-up data of patients undergoing IVC filter placement at our center. METHODS: A retrospective review of consecutive admitted patients who underwent IVC filter insertion in a large university hospital with a level I trauma center. Thrombosis specialists retrospectively assessed the appropriateness of indication for IVC filter placement as well as referral for retrieval. RESULTS: Overall, 405 filters were inserted between 2009 and 2013. All filters were retrievable. IVC filter was placed as a primary prevention in 42% of patients. Fifty-two patients (12.8%) experienced at least one filter-related complication. The most common complication was deep vein thrombosis occurring in 6.9% of cases. Almost a third of all complications occurred in filters originally placed for prophylactic indications. Only 13.6% of filters were successfully removed. Nevertheless, according to our reviewers, an attempt for filter retrieval should have been made in 57% of all cases and in 86% of trauma patients. A significantly higher retrieval rate was found in patients followed at our thrombosis clinic (P < 0.01). During follow-up, 95 patients (23.4%) died, most of them with active cancer. CONCLUSIONS: IVC filters are placed in many cases for prophylactic indications. Their low retrieval rates together with relatively high risk of long-term complications, questions their extensive utilization. Prospective trials addressing the safety and efficacy of IVC filters are still warranted.

Platelet adhesion defect in type I Gaucher Disease is associated with a risk of mucosal bleeding.

Patients with type I Gaucher Disease (GD) may have a clinically significant bleeding tendency that is disproportionate to their platelet count. We hypothesized that impaired platelet adhesion might contribute to bleeding tendency. Adult patients with type I GD with platelet counts ≥130×10(9) /l and haematocrit ≥30% (n=48), obligatory carriers (n=52), and healthy controls (n=19) were studied. Platelet adhesion, using the IMPACT-R (Cone and Plate(let) Analyser), and platelet aggregation were determined. Type I GD patients had significantly lower platelet adhesion [surface coverage %, median (interquartile range)] 4·6 (3·2-7·5), compared to controls, 8·7 (7·6-10·3), or carriers, 8·1 (6·5-9·4; P=0·001). Platelet adhesion was not affected by the use of disease-specific enzyme replacement therapy but was improved in patients after splenectomy, 7·2 (5·8-9·3). Mixing tests showed that the reduced adhesion was an intrinsic platelet defect. Mucosal bleeding was reported in 17 (35·4%) patients and was associated with abnormal adhesion [P=0·037, with an Odds Ratio (95% confidence interval) of 5·73 (1·1-29·6)]. Five patients (22%) had reduced platelet aggregation, all of whom had reduced platelet adhesion. Platelet aggregation defect was not associated with mucosal bleeding. In conclusion, platelet adhesion defect is a major thrombocytopathy in type I GD patients and can explain part of the increased tendency to bleeding.

Transient severe eosinophilia precipitating massive venous thrombosis in a patient with hereditary thrombophilia.

We describe a patient homozygous for both the prothrombin G20210A and methylenetetrahydrofolate reductase C667T mutations who was symptom-free for 40 years and developed near-catastrophic thrombotic complications following transient, severe eosinophilia. This course of events raises the possibility of an increased risk of thrombosis associated with transient eosinophilia in the presence of hereditary thrombophilia and supports the concept of multifactorial etiology of venous thrombosis. Our experience suggests that in patients with severe eosinophilia, evaluation for known causes of hereditary or acquired thrombophilia may be useful for identifying subjects at increased risk of thrombosis.