Use Of Other Anticoagulants Research Articles

Exploring Pleiotropic Effects of Lipid Modifiers and Targets on Measures of the Coagulation System with Genetics.

Statins have long been suspected to have pleiotropic effects via thrombotic factors. Randomized controlled trials are too limited to be definitive. We examined the associations of genetically mimicking effects of statins, PCSK9 inhibitors, and alternative lipid targets (in genes LDLR, APOC3, and LPL) on key indicators of coagulation system function, i.e., prothrombin time (PT) and activated partial thromboplastin time (aPTT). We assessed the effect of established genetic mimics of effects of lipid modifiers and alternative lipid treatment targets on PT (n = 58,110) and aPTT (n = 37,767), all transformed to z-scores, using Mendelian randomization taking advantage of Biobank Japan. Ischemic heart disease (IHD) was a control outcome. Genetically mimicked effects of statins increased PT by 0.31 standard deviation (SD) per SD increase in low-density lipoprotein (95% confidence interval [CI]: 0.10-0.51) based on rs12916 but did not affect aPTT. Genetically mimicking effects of targeting LDLR increased PT based on rs688 (0.33 SD per SD increase in triglyceride, 95% CI: 0.03-0.63) but did not affect aPTT. Genetically mimicking effects of PCSK9 inhibitors or targeting APOC3 or LPL had no effect on PT or aPTT. Genetically mimicking effects of statins, PCSK9 inhibitors, and alternative lipid targets reduced risk of IHD in Biobank Japan. Statins, and possibly targeting LDLR, may also act via a coagulation cascade factor, likely specific to the extrinsic or common pathway. Further elucidation of the mechanistic pathway may facilitate development of new interventions and inform use of statins particularly in relation to use of other anticoagulants.

Cardiac transplantation after heparin-induced thrombocytopenia: A systematic review.

Heparin-induced thrombocytopenia (HIT) presents a unique challenge in patients requiring orthotopic heart transplantation (OHT). We sought to pool the existing evidence in a systematic review. Electronic search was performed to identify all relevant studies on OHT in patients with HIT. Patient-level data for 33 patients from 21 studies were extracted for statistical analysis. Median patient age was 51 [IQR 41, 55] years, with 75.8% (25/33) males. All patients had a clinical diagnosis of HIT, and anti-PF4/Heparin antibodies were positive in 87.9% (29/33). Median lowest reported platelet count was 46 × 109 /L [27.2, 73.5]. Intraoperatively, 61% (20/33) of patients were given unfractionated heparin (UFH), while 39% (13/33) were given alternative anticoagulants. The alternative agent subgroup required more antifibrinolytics [54% (7/13) vs 10% (2/20), P=.02] and clotting factors [69.2% (9/13) vs 15.0% (3/20), P<.01]. Perioperative thrombosis occurred more [53.8% (7/13) vs 0% (0/20, P<.01) in alternate agent subgroup. More patients in the alternate agent subgroup required post-operative transfusions [54% (7/13) vs 0% (0/20), P<.01]. Thirty-day mortality of 15.2% (5/33) was comparable between the subgroups. Heparin use during OHT may be associated with less adverse effects compared to use of other anticoagulants with no difference in 30-day mortality.

Antithrombin supplementation and risk of bleeding in patients with sepsis-associated disseminated intravascular coagulation

IntroductionAlthough antithrombin is commonly used for the treatment of sepsis-associated disseminated intravascular coagulation (DIC) in Japan, the factors influencing the incidence of bleeding complications have not been sufficiently studied. The purpose of this survey was to identify the factors that predict clinically relevant bleeding in patients receiving antithrombin for DIC. MethodsWe analyzed data from 1026 sepsis-associated DIC patients with a baseline antithrombin activity ≤70% who underwent antithrombin supplementation at two dosages (1500IU/day or 3000IU/day) for three consecutive days. The patients' demographic characteristics, parameters before and after the treatment, and co-administered anticoagulants were analyzed in relation to the bleeding events. ResultsOverall, 55 patients (5.36%) experienced bleeding events (major bleeding: 1.75%). Logistic regression analysis revealed that sustained DIC>7days was significantly associated with bleeding (odds ratio: 2.761, P=0.001). In contrast, the higher dose of antithrombin or the co-administration of recombinant thrombomodulin or heparins were not associated with bleeding events. ConclusionA higher dose of antithrombin or the concomitant use of other anticoagulants were not associated with bleeding events. On the other hand, sustained DIC lasting more than one week was associated with an increased risk of bleeding in patients with sepsis-associated DIC.

Current Practice Patterns and Patient Persistence on Anticoagulant Treatments for Cancer-Associated Thrombosis

▪Introduction: Therapeutic options for the management of venous thromboembolism (VTE) in patients with cancer remain limited. Guidelines recommend anticoagulation with low molecular weight heparin (LMWH) monotherapy for ≥3-6 months, and possibly indefinitely, for patients with active cancer. However, drug cost and patient preference issues may lead to non-compliance with these recommendations. The objective of this study is to describe current treatment patterns and to evaluate patient persistence on various anticoagulants.Methods: Medical and pharmacy claims from the Humana Database were analyzed. To reflect recent treatment patterns, the study population was restricted to patients who had their first VTE between 1/1/2013 and 12/31/2014. Newly diagnosed cancer patients with a first VTE diagnosis (deep vein thrombosis [DVT] or pulmonary embolism [PE]) occurring after their first cancer diagnosis (a 30-day window before the cancer diagnosis was allowed), and with ≥1 dispensing of an anticoagulant agent within 30 days after their VTE diagnosis, were selected. Based on the first anticoagulant agent received, patients were classified into one of the following cohorts: LMWH, LMWH/warfarin, warfarin and rivaroxaban. Use of other anticoagulants including fondaparinux, heparin, apixaban, or dabigatran was low and could not be analyzed due to small sample size. The observation period spanned from the date of the first anticoagulant dispensing to the end of insurance eligibility or the end of data availability, whichever occurred earlier. Discontinuation of the index therapy was defined by a time gap without refill of the index anticoagulant for more than 60 days after the presumed exhaustion of the last known dispensing. For patients in the LMWH/warfarin group, the 2 medications were filled simultaneously as an index therapy, with the expectation that the patients were bridged to warfarin; therefore, their persistence was evaluated based on warfarin therapy. Persistence on therapy was assessed for 12 months using Kaplan-Meier rates, and unadjusted Cox proportional hazards models were used to compare the time to discontinuation between cohorts.Results: A total of 2,941 newly diagnosed patients with cancer who developed VTE and received anticoagulation in outpatient settings were identified. Of these, 97% received anticoagulation with either LMWH (n=735; 25%), LMWH/warfarin (n=550; 18.7%), warfarin (n=853; 29%), rivaroxaban (n=709; 24.1%). Mean age and gender were similar across treatment cohorts. Approximately 90% of the patients had diagnoses of solid tumors. Diagnoses for DVT, PE, and DVT/PE were 55%, 27%, and 18%, respectively, and were similar across cohorts. Treatments for cancers associated with very high VTE risk (stomach, pancreas, and brain) ranged from 15% in LMWH to 6% in rivaroxaban cohorts, while high VTE risk (lung, lymphoma, gynecologic, bladder, testicular, and renal) ranged from 39% in LMWH to 30% in warfarin and LMWH/warfarin cohorts. Around 75% (warfarin) to 58% (rivaroxaban) of the VTE cases were diagnosed in inpatient settings.The median treatment durations for LMWH, LMWH/warfarin, warfarin, and rivaroxaban users were 3.29, 7.76, 8.12, and 7.92 months, respectively. Kaplan-Meier rates of persistence to the initial therapy were 37%, 60%, 62%, and 61% at 6 months, and 21%, 37%, 34%, and 36% and at 12 months for the LMWH, LMWH/warfarin, warfarin and rivaroxaban cohorts, respectively (Figure 1). LMWH/warfarin, warfarin, and rivaroxaban users were significantly more likely to remain on their initial therapy compared to LMWH, with hazard ratios (HRs; 95% CI) of 0.38 (0.32-0.45), 0.40 (0.34-0.46), and 0.42 (0.36-0.50), respectively (all p-values <0.0001). The proportion of patients that switched from their initial treatment to another anticoagulation treatment was 22.9%, 8.9%, 7.3% and 4.7% in the LMWH, LMWH/warfarin, warfarin, and rivaroxaban cohorts, respectively.Conclusion: This real-world analysis showed that despite guidelines recommendations, warfarin and rivaroxaban are nearly equally utilized as LMWH for the treatment of cancer-associated thrombosis. LMWH was associated with significantly lower persistence and shorter duration of treatment than warfarin and rivaroxaban. More patients switched from LMWH to other anticoagulants compared to patients starting on warfarin or rivaroxaban treatments. [Display omitted] DisclosuresKhorana:sanofi: Consultancy, Honoraria; Leo Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria; Boehringer-Ingelheim: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Honoraria. McCrae:Janssen Scientific Affairs: Membership on an entity's Board of Directors or advisory committees. Milentijevic:Janssen Scientific Affairs: Employment, Equity Ownership. Fortier:Janssen Scientific Affairs: Research Funding. Nelson:Johnson & Johnson: Equity Ownership; Janssen Scientific Affairs: Employment. Laliberté:Janssen Scientific Affairs: Research Funding. Crivera:Janssen Scientific Affairs, LLC: Employment, Equity Ownership. Lefebvre:Janssen Scientific Affairs: Research Funding. Yannicelli:Janssen Scientific Affairs: Employment, Equity Ownership. Schein:Janssen Scientific Affairs, LLC: Employment.

Vitamin K antagonists and cognitive impairment: results from a cross-sectional pilot study among geriatric patients.

Vitamin K is involved in brain physiology, suggesting that its deficiency induces cognitive decline. Our objective was to determine whether using vitamin K antagonists (VKAs) was associated with cognitive impairment among geriatric patients. Two hundred sixty-seven older patients (mean, 83.4 ± 8.1 years; 56.9% female) were categorized according to cognitive impairment (ie, Mini-Mental State Examination ≤ 25). The regular use of VKAs was sought by questioning the patients, relatives, and family physicians. Age, gender, body mass index, comorbidity burden, mood and executive functioning, history of atrial fibrillation, ischemic stroke, intracranial hemorrhage and transient ischemic attack, use of other anticoagulants and antiplatelet medications, and severe renal failure were used as potential confounders. Compared with participants without cognitive impairment (n = 70), those with Mini-Mental State Examination ≤ 25 used more frequently VKAs (p = .038). The risk of cognitive impairment was 15% higher with VKAs, specifically with fluindione. Using VKAs was independently associated with cognitive impairment (fully adjusted odds ratio = 17.4 [95% CI: 1.4-224.2], p = .028). We found more frequent cognitive impairment associated with the use of VKAs, specifically fluindione, among geriatric patients.

Postmarketing Surveillance of Recombinant Human Soluble Thrombomodulin (Thrombomodulin α) in Pediatric Patients With Disseminated Intravascular Coagulation

Recombinant human soluble thrombomodulin (thrombomodulin α [TM-α]) has been marketed as a novel anticoagulant for disseminated intravascular coagulation (DIC) in Japan since 2008. Postmarketing surveillance (PMS) has been conducted since its approval. As effectiveness and safety were not previously determined in pediatric patients, this study evaluated PMS data and examined the usefulness of TM-α in treating pediatric DIC. After excluding newborn infants, data for 210 pediatric patients were analyzed and compared to 3786 adult patients. The day after the last TM-α administration, DIC had resolved in 58.5% of the patients. At 28 days after the last TM-α administration, the survival rate was 71.6%. Nineteen episodes of adverse drug reactions were observed in 11 patients but no significant differences were noted for effectiveness and safety. Although this study was limited by its retrospective design, including selection biases and no limitation on concomitant use of other anticoagulants, TM-α appears to be useful for the treatment of DIC in both pediatric and adult patients.

The platelet count in EDTA‐anticoagulated blood from patients with thrombocytopenia may be underestimated when measured in routine laboratories

Spuriously low platelet counts (PCs) can be observed in normal blood samples anticoagulated with ethylenediamine tetra-acetic acid (EDTA)and, much less frequently, with citrate-tris-pyridossalphosphate (CPT),due to time-dependent in vitro platelet agglutination. Accuracy in PC determination is essential as PC is one of the parameters that usually guides treatment for thrombocytopenic patients. PCs of 93 thrombocy to penic patients were measured in EDTA- or CPT-anticoagulated blood samples immediately after sampling (t0) and 90 min (t90) after storage at room temperature. The presence of platelet agglutinates in blood samples was determined by examining blood smears using optical microscopy.PCs decreased at t90 with both anticoagulants. Platelet agglutinates were present at t90 in 27% of EDTA-samples vs. 2% of CPT-samples with decreased PCs (P < 0.001). Based on PCs in EDTA-samples, 15 patients (16%) shifted from a lower bleeding risk at t0 to a higher bleeding risk category at t90 (P 5 0.019), compared to 5 (5%) patients, based on PCs in CPT-samples. Therefore, time-dependent in vitro platelet agglutination in EDTA-blood samples may cause underestimation of PCs in thrombocytopenic patients, possibly leading to improper management.

Omega-3 and Fish Oil Supplements Do Not Cause Increased Bleeding During Spinal Decompression Surgery

Retrospective case-control study. The purpose of this study was to assess whether preoperative use of fish oil supplements increases intraoperative blood loss and postoperative bleeding complications during lumbar decompression surgery. Omega-3 fatty acids (n-3FA) are widely used as over-the-counter supplements because of well-established cardioprotective and antiplatelet effects. Concern over bleeding associated with changes in platelet function have led to prohibiting these supplements before surgery although there are no clinical data available in the spinal surgery literature to guide such recommendations. Ninety-five consecutive patients who underwent posterior-only lumbar decompression by a single surgeon were included. Patients who had taken n-3FA within 14 days of surgery were compared with a control group with respect to demographics, preoperative use of other anticoagulants, surgical time, estimated intraoperative blood loss, and postoperative complications including reoperation for epidural hematoma and wound infection. Power analysis suggested 11 patients taking n-3FA were necessary to reach statistical significance based on pilot data. Sixteen patients took n-3FA supplements, stopping an average of 2.3 days before surgery. These were no significant between-group differences in demographic parameters, use of other anticoagulants, and surgical time. Estimated blood loss was higher in the control group but the difference was not significant (154 vs. 138 mL, P=0.53). There were 2 complications related to bleeding in the control group and none in the n-3FA group. We found no increase in intraoperative blood loss or postoperative bleeding complications associated with preoperative use of n-3FA supplements up to an average of 2.3 days before surgery. Although further studies are necessary before this finding can be generalized to other types of spinal surgery, our study corroborates findings from investigations in other surgical specialties that suggest preoperative n-3FA is not associated with increased risk of intraoperative and postoperative bleeding.

EDTA-dependent lymphoagglutination in persistent polyclonal B-cell lymphocytosis

A 38-year-old female smoker was referred for assessment of a persistent polyclonal B-cell lymphocytosis (PPBL). She complained of profound asthenia and arthralgia. There was no palpable enlargement of lymph nodes, liver or spleen. Laboratory investigations showed moderate isolated lymphocytosis (4AE9 · 10/l) with 3% binucleated cells, increased polyclonal immunoglobulin (Ig) M (8AE2 g/l), HLA-DR7 phenotype and the presence of an abnormal karyotype: 47,XY,+i(3)(q10)[4]/46,XY[29]. Peripheral blood immunophenotyping demonstrated a polyclonal increase in the B-cell pool with IgM, IgD, CD19, CD20, CD21, CD22, CD24, CD27, CD40, CD79b and FMC7 positivity and CD5, CD10, CD23, CD25, CD30, CD34, CD38, CD43, CD54, CD122, CD138 and CD154 negativity, in keeping with a memory B-cell origin. In addition, clumps of lymphocytes including binucleated cells were observed under the microscope (left), but were absent when a specimen was taken into citrate (right), suggesting an artifactual EDTA-dependent lymphoagglutination. PPBL occurs mainly in middle-aged female smokers, presenting with a moderate chronic lymphocytosis with atypical binucleated lymphocytes comprising 1–10% of the lymphocytes and increased polyclonal serum IgM. The B cells are polyclonal with kappa and lambda light-chain expression and no clonal rearrangement of the immunoglobulin heavy chain genes. The cytogenetic profile includes an additional isochromosome for the long arm of chromosome 3, genetic instability and premature chromosome condensation. About 3% of patients develop lymphoma. Lymphoagglutination is a rare EDTA-dependent phenomenon; the use of other anticoagulants (citrate or heparin) avoids this artefact in nearly all cases. It occurs most often in B-cell lymphoproliferative disorders, particularly marginal zone lymphoma. The occurrence in PPBL may be attributed to the likely origin of these cells from the splenic marginal zone.

Ulceration and antihypertensive use are risk factors for infection after skin lesion excision

A prospective audit was performed of wound complications of skin lesion excision in a private practice setting. For 924 consecutive skin lesion excisions performed by a single surgeon, information was collected on tumour size and site, closure method and on risk factors of age, known diabetes, use of steroids, antihypertensives or anticoagulants and ulceration of the lesion. Patients were given written instructions to wet the wound in the shower after one or two days. A wound 'infection' event was recorded if the wound appeared inflamed or if the patient had been treated with antibiotics by any practitioner. Wound bleeding was recorded if the patient returned or attended elsewhere for management of bleeding. Sixty-seven wounds (7.25%) met the broad definition of 'infection' and 18 (1.9%) wounds suffered bleeding. Ulceration (odds ratio (OR) 3.15, P= 0.008) and use of antihypertensives (OR 2.5, P= 0.006) were independent risk factors for infection along with site and closure method. The patients who did not wet their wounds post-operatively were also at an increased risk of infection (OR 2.1, P= 0.018). Aspirin caused a slight, non-statistically significant increase in bleeding rate, and warfarin caused a larger, but still not statistically significant, increase in bleeding. Use of other anticoagulants caused a significant increase in bleeding (OR 10.9, P= 0.006). Ulceration of the skin lesion and use of antihypertensives are significant risk factors for wound infection. Wetting surgical wounds with clean tap water does not increase, and may even reduce, wound infection rate.

Prévention de la maladie thromboembolique en orthopédie et traumatologie

Orthopaedic and trauma surgery are classified according 3 groups of venous thromboembolic risk. Elective total hip replacement (THR) or total knee replacement (TKR), hip fracture surgery or trauma patients are at high risk. Isolated lower extremity injury with fracture is at moderate risk whereas this risk is low without fracture as well as with knee arthroscopy. In THR and TKR, low molecular weight heparin (LMWH), fondaparinux or melagatran–ximelagatran are strongly recommended. The routine use of other anticoagulants, in particular vitamin K antagonist are not recommended. In patients at high risk of venous thromboembolism as for example trauma patients, optimal use of intermittent pneumatic compression is an alternative option in case of contra-indication to anticoagulant prophylaxis. Graduated compression stockings enhance the efficacy of pharmacological methods. In schedule surgery, initiation of prophylaxis with LMWH may be started postoperatively. To reduce the haemorrhagic risk of anticoagulants, timing of first postoperative dose is essential and is proper to each drug. Duration of prophylaxis depends on the surgical and the individual patients' risk. Extended prophylaxis in THR for up to 42 days with LMWH and up to 35 days with fondaparinux in hip fracture surgery is recommended. However extended prophylaxis after 14 days in TKR has not demonstrated a higher efficacy and should only be considered for patients with additional risk factors. In patients with isolated lower extremity injury or undergoing knee arthroscopy, LMWH should not be routinely used according to a low or a moderate risk and/or the duration of prophylaxis required. But LMWH has to be considered for patients with additional risk factors. Prophylaxis in other orthopedic procedures has not been assessed and will be extrapolated from the above recommendations.

Safety of the use of IIb/IIIa receptor blockers with or without the use of other anticoagulants.

Safety of the use of IIb/IIIa receptor blockers with or without the use of other anticoagulants.

Recent advances in the management of unstable angina and non-Q-wave myocardial infarction

Recent advances in the management of unstable angina and non-Q-wave myocardial infarction

The Effect of Dicumarol, Diphacinone and Pivalyl Upon Blood Prothrombin Time of Chicks

INCREASED prothrombin time due to feeding dicumarol has been observed with the chick (Quick and Stefanini, 1948; Harms and Tarver, 1957) and laying hens (Waldroup and Harms, 1962; Day et al., 1964). The action of dicumarol in the inhibition of the blood clotting process is lessened by the presence of vitamin K in the diet according to Quick and Stefanini (1948). Although sulfaquinoxaline is used to induce hypoprothrombinemia in chick assays of vitamin K compounds (Perdue and Frost, 1961; Griminger and Daves, 1959), the use of other anticoagulants may prove of value in studies on vitamin K activity or the mechanism of blood clotting as related to the occurrence of blood spots in eggs.The experiments reported herein were designed to evaluate the effects of three anticoagulants on the prothrombin time of chicks. EXPERIMENTALFour experiments were conducted using broiler strain chicks obtained from a commercial hatchery. All chicks were …