Heparin Assays and Bleeding Complications in Treatment of Deep Venous Thrombosis with Particular Reference to Retroperitoneal Bleeding

1985 ◽  
Vol 53 (02) ◽  
pp. 278-281 ◽  
Author(s):  
H Asbjørn Holm ◽  
Ulrich Abildgaard ◽  
Sigmund Kalvenes

SummaryBleeding complications occurred in 30 (11%) out of 280 patients who received continuous heparin infusion for deep venous thrombosis (DVT). 22 (8%) had minor while 8 patients (3%) had major bleeding complications (1 intrathoracic [fatal], 2 gastrointestinal and 5 retroperitoneal). Heparin activity, in daily drawn blood samples, was determined by four assays (chromogenic substrate [CS] assay, activated partial thromboplastin time [APTT], thrombin time with citrated plasma [CiTT] and thrombin time with recalcified plasma [CaTT]). The differences in median heparin activity between patients with minor bleeding and patients with no bleeding did not reach significance for any of the tests. In patients with major bleeding, the differences were significant with the CS (p = .011) and the CaTT (p = .030) assays. Patients with retroperitoneal bleeding had significantly increased median activity judged by all four assays: CS (p = .002), CaTT (p = .003), APTT (p = .010), CiTT (p = .029). The difference was most pronounced after four days of heparin treatment, but there was a considerable overlap with patients without bleeding.

1993 ◽  
Vol 27 (12) ◽  
pp. 1429-1433 ◽  
Author(s):  
Robert J. Kandrotas ◽  
Peter Gal ◽  
Jean B. Douglas ◽  
James B. Groce

OBJECTIVE: To compare heparin dosage adjustment using only activated partial thromboplastin time (APTT) with a method using non-steady-state heparin concentrations (HCs) to rapidly achieve and maintain an APTT ratio greater than or equal to 1.5 times baseline throughout the first 24 hours of therapy. DESIGN: Randomized, blind, parallel comparison of an empiric dosing method based only on APTT with a dosing method based on the calculation of heparin clearance using non-steady-state HCs. SETTING: A private community teaching hospital. The patient, physician, nurses, and investigators were blinded to the dosing method. Only the clinical staff pharmacist, who received the consult and made all dosage adjustments, was not blinded. PATIENTS: All patients requiring heparin for the treatment of thromboembolic disease were evaluated for potential inclusion in the study. Patients were enrolled in the study if they had a clinical diagnosis of deep venous thrombosis confirmed by objective means such as venography or ultrasonography. Patients were excluded if they had active bleeding, platelet dysfunction, thrombocytopenia, severe hepatic disease (total bilirubin >25.7 μmol/L), renal disease, or evidence of stroke. Patients were also excluded if they were receiving heparin prior to enrollment. MAIN OUTCOME MEASURE: Maintenance of an APTT ratio greater than or equal to 1.5 times baseline throughout the first 24 hours of heparin therapy. RESULTS: Thirty-four patients were enrolled in the study; 17 in each group. The groups were not significantly different with regard to gender, age, baseline APTT, or mean loading dose (p>0.5). Mean initial infusion rates for the control and HC groups were 1042 ± 194 and 1071 ± 143 units/h, respectively (p>0.5). After the first rate adjustment at 4 hours, the difference achieved significance at 1032 ± 232 and 1367 ± 317 units/h for the control and HC groups, respectively (p<0.01). At 12 hours, 18.8 percent of the patients in the control group were subtherapeutic; by 24 hours, 33.3 percent were subtherapeutic. No patients became subtherapeutic in the HCs group during the first 24 hours. CONCLUSIONS: This study demonstrates that, in contrast to standard heparin dosing methods, the use of non-steady-state HCs allows patients with deep venous thrombosis to rapidly achieve and maintain therapeutic APTT ratios throughout the critical first 24 hours of therapy.


Author(s):  
H.A. Holm ◽  
U. Abildgaard ◽  
Chr. Bjerkelund

280 patients with phlebographically proven DVT have been treated with heparin infusion for 5 days followed by control phlebography. Daily blood samples were analyzed for heparin activity by 3 different assays (amidolytic assay, APTT, thrombin cl. time) to see if there exists a correlation between the clinical effects (on the local thrombotic process, on embolization, and on bleeding complications) and the results of laboratory tests.Four patients suffered from major bleedings, and one was fatal. Compared to mean results, heparin activity was clearly exessive in three of these patients, particularly with the amidolytic assay. About ten per cent of the patients had minor bleedings.A transient drop in the antithrombin concentration was observed in most patients, but sustained subnormal concentration (<70 %) was seen in ten patients. One patient developed thrombocytopenia and DIC. The influence of heparin dosage on heparin activity / concentration and on the thrombotic process will be evaluated.


Lupus ◽  
2018 ◽  
Vol 27 (10) ◽  
pp. 1679-1686 ◽  
Author(s):  
C M Yelnik ◽  
M Lambert ◽  
E Drumez ◽  
V Le Guern ◽  
J-L Bacri ◽  
...  

Purpose The purpose of this study was to evaluate the safety of antithrombotic treatments prescribed during pregnancy in patients with antiphospholipid syndrome (APS). Methods This international, multicenter study included two cohorts of patients: a retrospective French cohort and a prospective US cohort (PROMISSE study). Inclusion criteria were (1) APS (Sydney criteria), (2) live pregnancy at 12 weeks of gestation (WG) with (3) follow-up data until six weeks post-partum. According to APS standard of care, patients were treated with aspirin and/or low-molecular weight heparin (LMWH) at prophylactic (pure obstetric APS) or therapeutic doses (history of thrombosis). Major bleeding was defined as abnormal blood loss during the pregnancy and/or post-partum period requiring intervention for hemostasis or transfusion, or during the peripartum period greater than 500 mL and/or requiring surgery or transfusion. Other bleeding events were classified as minor. Results Two hundred and sixty-four pregnancies (87 prospectively collected) in 204 patients were included (46% with history of thrombosis, 23% with associated systemic lupus). During pregnancy, treatment included LMWH ( n = 253; 96%) or low-dose aspirin ( n = 223; 84%), and 215 (81%) patients received both therapies. The live birth rate was 89% and 82% in the retrospective and prospective cohorts, respectively. Adverse pregnancy outcomes occurred in 28% of the retrospective cohort and in 40% of the prospective cohort. No maternal death was observed in either cohort. A combined total of 45 hemorrhagic events (25%) occurred in the retrospective cohort, but major bleeding was reported in only six pregnancies (3%). Neither heparin nor aspirin alone nor combined therapy increased the risk of hemorrhage. We also did not observe an increased rate of bleeding in the case of a short interval between last LMWH (less than 24 hours) or aspirin (less than five days) doses and delivery. Only emergency Caesarean section was significantly associated with an increased risk of bleeding (odds ratio (OR) 5.03 (1.41–17.96); p=.016). In the prospective cohort, only one minor bleeding event was reported (vaginal bleeding). Conclusion Our findings support the safety of antithrombotic therapy with aspirin and/or LMWH during pregnancy in high-risk women with APS, and highlight the need for better treatments to improve pregnancy outcomes in APS. PROMISSE Study ClinicalTrials.gov identifier: NCT00198068.


1979 ◽  
Author(s):  
J.J.F. Belch ◽  
G.D.O. Lowe ◽  
J.G. Pollock ◽  
C.D. Forbes ◽  
C.R.M. Prentice

In a randomised double-blind controlled trial 24 patients undergoing elective aortic bifurcation graft surgery received subcutaneous calcium heparin (2, 500 u preoperatively then 5,000 u 12 hourly or 7 days) and 25 control patients received saline injections. All patients received the routine dose of intravenous sodium heparin intraoperatively. The trial was terminated because of excess bleeding complications in patients on subcutaneous heparin (8 vs. 1, p<0.05). Deep venous thrombosis was diagnosed by 125I-fibrinogen scanning in 8 control patients and 3 patients on heparin (p>0.05). In this group of patients the risk of bleeding due to subcutaneous heparin appeared to outweigh the benefit of thrombotic prophylaxis.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 708-708
Author(s):  
Manuel Monreal ◽  
José Nieto ◽  
Ana de Tuesta ◽  
Pablo Marchena ◽  
Gregorio Tiberio ◽  
...  

Abstract Introduction Patients who have experienced a recent major bleeding episode are usually excluded from clinical trials of venous thromboembolism (VTE) treatment. Therefore, recommendations based on evidence from clinical trials of VTE treatment may not be optimal for these patients. The Registro Informatizado de la Enfermedad TromboEmbólica (RIETE), initiated in March 2001, is a multicenter, observational registry gathering data on VTE treatment practices and clinical outcomes in patients with objectively confirmed, symptomatic, acute VTE. The aim of this analysis was to study outcomes in patients with VTE who had experienced major bleeding <30 days prior to VTE diagnosis. Methods Patients with objectively confirmed symptomatic acute VTE are consecutively enrolled into the RIETE registry. Patients are excluded if they are participating in a therapeutic clinical trial or not available for 3-months follow-up. Patient characteristics, details of antithrombotic therapy, and clinical outcomes at 3-months are recorded. Results Of 6361 patients enrolled up to January 2004, 170 (2.7%) had experienced recent major bleeding prior to VTE diagnosis: 69 (40.6%) gastrointestinal tract; 60 (35.3%) intracranial; 41 (24.1%) other. More patients with recent major bleeding had cancer compared with those without recent major bleeding (26.4% vs 20.4%, respectively; p=0.05). More patients who experienced recent major bleeding had undergone surgery <2 months prior to enrollment or had immobility ≥4 days. The incidences of recurrent PE and minor, major, and fatal bleeding complications were also higher in patients who had experienced recent major bleeding (table 1). Patients with recent major bleeding and cancer had an increased incidence of major bleeding compared to those without cancer (20.0% vs. 2.4%, respectively; OR 10.0; 95% CI 2.3–50.0; p<0.001); 11.0% of patients who had recent major bleeding prior to VTE diagnosis and cancer experienced fatal PE compared with none in patients who had recent major bleeding but without cancer (OR 4.1; 95% CI 4.98–17; p<0.05). Conclusion Patients with VTE and recent major bleeding prior to VTE diagnosis (2.7% of total enrolled patients) had poorer clinical outcomes, in terms of bleeding complications, fatal PE and overall mortality compared with those who had not experienced recent major bleeding. In patients who had recent major bleeding prior to VTE diagnosis, those with cancer had a poorer clinical outcome than those without cancer. Table 1. Clinical outcome of enrolled patients 3-month outcome Recent major bleeding No recent major bleeding OR (95% CI) p value n (%) n=170 n=6191 Fatal bleeding 7 (4.1) 41 (0.6) 6.4 (2.6-15) <0.001 Major bleeding 12 (7.1) 146 (2.3) 3.1 (1.6-5.9) 0.001 Minor bleeding 12 (7.1) 172 (2.8) 2.6 (1.4-5.0) <0.005 Fatal (initial) PE 1 (0.6) 14 (0.2) 2.6 (0.2-19) NS Fatal (recurrent) PE 4 (2.4) 33 (0.5) 4.5 (1.3-14) <0.05 Recurrent VTE 8 (4.7) 184 (2.9) 1.6 (0.7-3.4) NS Overall mortality 25 (15.0) 479 (7.7) 2.1 (1.3-3.2) <0.005


2017 ◽  
Vol 44 (04) ◽  
pp. 348-352 ◽  
Author(s):  
Reinhard Raggam ◽  
Franz Hafner ◽  
Alexander Avian ◽  
Gerald Hackl ◽  
Gerhard Cvirn ◽  
...  

AbstractThe aim of this study was prospective evaluation of the performance of the HAS-BLED score in predicting major bleeding complications in a real-world outpatient cohort, during long-term anticoagulation for venous thromboembolism (VTE), treated with a broad spectrum of anticoagulants. We analyzed 111 outpatients objectively diagnosed with VTE and treated long-term with various anticoagulants. Patients were grouped in three cohorts based on the anticoagulant regimen. Calculation of the HAS-BLED score and documentation of bleeding events were performed every 6 months for 1 year. Patients with a HAS-BLED score ≥ 3 had an increased risk for major bleeding events (odds ratio [OR]: 13.05, 95% confidence interval [CI]: 0.96–692.58, p = 0.028) and a trend to higher risk for minor bleeding events as well (OR: 2.25, 95% CI: 0.87–5.85, p = 0.091) when compared with patients with a HAS-BLED score < 3.This indicates that a HAS-BLED score ≥ 3 allows for identification of patients with VTE on long-term anticoagulation at an increased risk for major bleeding events, irrespective of the anticoagulant agent used.


1990 ◽  
Vol 64 (02) ◽  
pp. 222-226 ◽  
Author(s):  
M Pini ◽  
C Pattacini ◽  
R Quintavalla ◽  
T Poli ◽  
A Megha ◽  
...  

Summary271 patients with acute symptomatic deep venous thrombosis of lower limbs, confirmed by strain-gauge plethysmography and/ or venography, were randomly assigned to receive intermittent subcutaneous heparin calcium or heparin sodium by continuous intravenous infusion for 6–10 days. Heparin dosage was adjusted to maintain activated partial thromboplastin time values (Throm-bofax reagent) at 1.3–1.9 times the basal ones. Strain-gauge plethysmography was repeated at the end of heparin treatment, and evaluation of therapy was performed by comparing the indexes of venous hemodynamics and by assessing the incidence of pulmonary embolism and of bleeding complications.In the intravenous group, Maximal Venous Outflow (MVO) increased from 20.8 ± 12.8 to 28.4 ± 17.5 ml/min per 100 ml of tissue and Venous Capacitance (VC) from 1.39 ± 0.92 to 1.94 ± 1.0 ml/100 ml of tissue (mean ± SD). In the subcutaneous group, MVO increased from 21.0 ± 12.7 to 27.5 ± 18.1 and VC from 1.60 ± 0.86 to 2.06 ± 1.0. The median improvement of MVO and VC were 22% and 36% respectively in the IV group and 20% and 24% in the SC group. Clinical pulmonary embolism occurred in 2 patients in the intravenous group (1 fatal) and in 4 in the subcutaneous group (1 fatal). 9 major bleeding complications occurred in the intravenous group (1 fatal) and 5 in the subcutaneous group (1 fatal). The differences were not significant at the statistical analysis.The results suggest that subcutaneous intermittent heparin has a comparable efficacy to continuous intravenous heparin in the treatment of deep venous thrombosis.To the same conclusion points an overview of the seven randomized trials which compared these treatment modalities.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
F Picard ◽  
M Diefenbronn ◽  
D Laghlam ◽  
J F Llitjos ◽  
A Sokoloff ◽  
...  

Abstract Background Data is scarce on hemorrhagic and thrombotic complications in patients with ST-elevation myocardial infarction (STEMI) associated with out-of-hospital cardiac arrest (OHCA). Purpose We sought to evaluate the difference in the thrombotic-hemorrhagic balance in STEMI patients with or without associated cardiac arrest. Methods This is a monocentric, retrospective study conducted from January 2012 to December 2017. Over the study period, all consecutive patients who were treated for STEMI with our without OHCA were included. Baseline characteristics, treatments, haemorrhagic and thrombotic events were compared between STEMI patients associated or not with OHCA. Univariate and multivariate analysis were performed to identify predictors of 30-day mortality, occurrence of major bleeding, defined by BARC score ≥3 and early stent thrombosis. Results A total of 549 patients treated for STEMI and 146 patients for STEMI associated with OHCA were included. The incidence of stent thrombosis and major bleeding after coronary angioplasty in patients treated for STEMI was significantly higher when associated with OHCA (2.7% vs. 12.3%, p=0.04 and 3.3% vs. 19.2%, p<0.001, respectively). Independent predictors of major bleeding in OHCA patients were effective anticoagulation (HR=3.11, 95% CI [1.22–7.98], p=0.02) and the use of glycoprotein IIb/IIIa inhibitors (HR=4.16, 95% CI [1.61–10.79], p=0.003). Independent predictors of mortality in STEMI associated with OHCA were age (HR=1.05, 95% CI [1.02–1.09], p=0.004) and stent thrombosis (HR=5.62, 95% CI [1.61–19.65], p=0.007, with a protective effect of new anti-P2Y12 treatments (HR=0.20, 95% CI [0.08–0.46], p<0.001). Clinical outcomes at 30 days follow-up Conclusion Patients treated for STEMI associated with OHCA are at higher-risk of stent thrombosis and bleeding than those who did not experience cardiac arrest. The use of effective anticoagulation and glycoprotein IIb/IIIa inhibitors contributes to increase bleeding complications. In this subset of patients, prospective studies are needed to better evaluate thrombotic and haemorrhagic balance.


Vascular ◽  
2020 ◽  
pp. 170853812097114
Author(s):  
Mostafa El Mokadem ◽  
Ahmed Hassan ◽  
Abdulaziz Z Algaby

Objectives Low-molecular weight heparin (LMWH) has been approved for treatment of deep venous thrombosis and venous thromboembolism which are associated with cancer. The efficacy and safety of apixaban in management of acute deep venous thrombosis associated with active malignancy is still an unresolved issue. The aim of our study is to evaluate the efficacy and safety of apixaban in patients with acute deep venous thrombosis and active malignancy compared with weight adjusted subcutaneous LMWH. Methods Of 138 randomized patients, 100 patients with active malignancy presenting with acute deep venous thrombosis and still treated with chemotherapy were assigned to either oral apixaban therapy or subcutaneous low-molecular weight heparin (enoxaparin) through randomized clinical study in 1:1 ratio. All patients were followed up to six months. The primary end point was major bleeding, while secondary end points were recurrent deep venous thrombosis or venous thromboembolism, minor or non-fatal bleeding and mortality related to massive pulmonary embolism. Results Both groups were matched regarding their baseline demographic, clinical and laboratory characteristics. We had 84 patients with metastatic cancer (stage 4). The most prevalent type of malignancy was cancer colon (42% of cases). There was no significant difference between both groups regarding the incidence of primary and secondary end points. There were no reported mortality cases related to massive pulmonary embolism in both groups. Conclusion In this limited study, there was no difference in the major bleeding, recurrent deep venous thrombosis or minor bleeding in patients with active malignancy when treated with either apixaban or LMWH. Trial registration: ClinicalTrials.gov (NCT04462003). Registered 7 July 2020 – Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04462003


2012 ◽  
Vol 28 (6) ◽  
pp. 305-307 ◽  
Author(s):  
D Huber ◽  
J Huber ◽  
E De young

Objective: A pilot study to clarify the association between popliteal vein compression (PVC)and deep venous thrombosis (DVT). Method: It is assumed that PVC and the associated change in blood flow increases the likelihood of DVT. We have selected patients who were referred to a vascular laboratory for a DVT duplex and scanned for both DVT and PVC. Duplex criteria for the diagnosis of a DVT were lack of flow and inability to compress the vein. The study was performed over 12 weeks. Results: Of the 54 eligible patients, 16 had a DVT. Five of 18 patients with PVC had a distal DVT (27.7%), while five of 36 patients without PVC had distal DVT (16.7%). The difference was statistically significant (relative risk 2.9, P < 0.05). Conclusion: There appears to be an association between the presence of PVC and an increased likelihood of developing a DVT. If confirmed in larger studies, this will have strong implications for patient positioning in theatres, as there is a high incidence of PVC in supine anaesthetized patients.


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