Venous thromboembolism prevention with low molecular weight heparin may reduce hemorrhagic transformation in acute ischemic stroke.

BACKGROUND: Subcutaneous heparin at a prophylactic dose (SHPD) is a rather common treatment in ischemic stroke, but whether it confers an increased risk of hemorrhagic transformation of cerebral infarct (HT) and whether its reduction or discontinuation favors HT regression are presently poorly understood. METHODS: Two samples of ischemic stroke patients with a cerebral lesion diameter ≥ 3 cm on brain CT scan, admitted over 7 years to our stroke unit, were retrospectively examined: (1) patients treated or not treated with SHPD (enoxaparin 4000 U/day), with subsequent assessment of possible HT appearance (N = 267, mean age 75.9 ± 12.8 years) and (2) patients treated with SHPD, with HT and subsequent reduction/discontinuation or maintenance of the initial dose, and subsequent assessment of HT evolution (N = 116, mean age 75.7 ± 11.1 years). HT severity was quantified according to the ECASS study (HT score). RESULTS: In the first sample, after adjustment for age, sex, stroke severity, cerebral lesion diameter, and other possible confounders, SHPD was inversely associated with HT appearance (hazard ratio 0.62, 95% CI 0.39-0.98, P = 0.04). In the second sample, after adjustment for age, sex, stroke severity, cerebral lesion diameter, and initial HT severity, SHPD reduction/discontinuation had an inverse effect on both HT score improvement (odds ratio 0.42, 95% CI 0.18-0.99, P = 0.049) and HT improvement according to neuroradiological reports (odds ratio 0.34, 95% CI 0.14-0.82, P = 0.015). CONCLUSIONS: This retrospective study suggests that SHPD may play a protective role in HT appearance and evolution, which requires verification by a randomized clinical trial.

Management of cardiopulmonary bypass in patients with ischemic and hemorrhagic strokes in surgery for active infective endocarditis.

Stroke and intracranial hemorrhage (ICH) are serious complications that are difficult to manage during surgery for active infectious endocarditis (AIE). Relevant society guidelines still recommend delaying the cardiac surgery for AIE with ICH for 4 weeks. Some early studies indicated that the mortality rate decreases when cardiac surgery for ICH is delayed. In contrast, some reported that surgical intervention should not be delayed if an early operation is demanded, even in patients with ICH. The current literature on early vs. late surgery for infectious endocarditis (IE) with ICH is conflicting. Changing the cardiopulmonary bypass (CPB) strategy might be necessary to improve the surgical outcomes of IE with ICH. Some studies reported that cardiac surgery using nafamostat mesylate (NM) as an alternative anticoagulant during CPB was performed successfully. The combination of NM and low-dose heparin was beneficial for early surgery in patients with AIE complicated by cerebral infarction and ICH, without worsening cerebral lesions. In this report, we review and discuss the management of CPB in patients with ischemic and hemorrhagic stroke during surgery for AIE.

Anticoagulant therapies for the prevention of intravascular catheters malfunction in patients undergoing haemodialysis: systematic review and meta-analysis of randomized, controlled trials.

BACKGROUND: Catheter malfunction (CM), including thrombosis, is associated with reduced dialysis adequacy, as well as an increased risk of catheter-related bacteraemia (CRB) and mortality. The role of alternative anticoagulant regimens for CM prevention remains uncertain. METHODS: A systematic review and meta-analysis were performed examining all randomized controlled trials (RCTs) assessing interventions acting via an anticoagulant mechanism compared with conventional care for the prevention of CM in adult patients receiving haemodialysis for end-stage kidney disease. Medline, EMBASE and the Cochrane Register were searched to November 2012. The primary outcome was CM. Secondary outcomes were CRB, all-cause mortality and bleeding events (all bleeding events reported or as defined by authors). Relative risks with 95% confidence intervals (CIs) for individual trials were pooled using random effects models for treatment classes. RESULTS: The search yielded 28 trials including 3081 patients. Therapies assessed were alternative anticoagulant locking solutions (ALSs), systemic warfarin and low/no dose heparin locking solutions (normal saline locks). No significant effect on CM (18 trials, 1579 participants) was observed for alternative ALSs (9 trials, 887 participants, RR 0.85, 95% CI 0.68-1.07), or low/no dose heparin (4 trials, 231 participants, RR 0.99, CI 0.60-1.62), compared with heparin locking solutions (5000 units). Similarly, no significant effect was observed for warfarin (5 trials, 479 participants, RR 0.59, 95% CI 0.28-1.22) compared with placebo. No significant effect on CRB was observed (15 trials, 2367 participants) for alternative ALSs (11 trials, 2010 participants, RR 0.57, 95% CI 0.30-1.10), warfarin (1 trial, 174 participants, RR 2.40, 95% CI 0.88-6.52) or low/no dose heparin (3 trials, 183 participants, RR 0.76, 95% CI 0.35-1.64). All-cause mortality was not affected by alternative ALSs (9 trials, 1719 participants, RR 0.83, 95% CI 0.56-1.24) or warfarin (3 trials, 403 participants, RR 0.78, 95% CI 0.37-1.65). Bleeding events were only reported in seven trials, including only two trials of warfarin, with no clear effect demonstrated. Within the alternative ALSs group, the only agent with a reduction in CM was recombinant tissue plasminogen activator (rt-PA)-locking solution (RR 0.52, 95% CI 0.32-0.86) based on the results of a single trial. Trials were mainly of high risk of bias. CONCLUSIONS: There is uncertainty on the benefits and harms of anticoagulant therapies over conventional care for prevention of CM. Further high-quality randomized trials, including safety outcomes, are needed.

Aggressive early surgical strategy in patients with intracranial hemorrhage: a new cardiopulmonary bypass option.

OBJECTIVE: We present a novel strategy in cardiac surgery with a cardiopulmonary bypass with low-dose heparin and Nafamostat mesylate as an anticoagulant (NM-CPB), which reduces postoperative neurological complications. METHOD AND RESULTS: 19 patients with a mean age of 63.6 ± 20.2 years (range 24-91) and an indication of early cardiac surgery with intracranial complication (ICC) underwent surgery with NM-CPB. The preoperative diagnoses included seven cases of infective endocarditis and six of left atrial appendage thrombosis. ICC were noticed in seven cases with hemorrhages (hemorrhagic infarction: n = 4, subarachnoid hemorrhage: n = 3) and 12 without hemorrhage (large infarction: n = 10, small-multiple infarction at the risk for hemorrhagic transformation: n = 2). The mean interval between a diagnosis and cardiac surgery was 1.1 ± 1.5 days in the ICH cases and 1.4 ± 1.4 days otherwise. In-hospital mortality was 5.3%. The mean CPB time was 146.7 ± 66.03 min, the mean dose of NM, heparin were 2.23 ± 1.59 mg/kg/hr and 56.8 ± 20.3 IU/kg, respectively. The mean activated clotting time (ACT) was 426.8 ± 112.4 s. No further intracranial bleeding and no new hemorrhages were observed after surgery. CONCLUSIONS: In early cardiac surgery with ICC, especially with hemorrhage, NM-CPB reduced postoperative neurological complications. We plan to use NM-CPB to expand the indications and to establish an early aggressive treatment.

Inactive large cerebral hemorrhage is not exacerbated by the adjustment of anticoagulation post open-heart surgery.

Optimal timing of open-heart surgery for the treatment of patients with cerebral hemorrhage remains controversial because systemic heparinization may lead to catastrophic bleeding. Several recent reports have shown that patients who undergo open-heart surgery .within a few weeks of cerebral hemorrhage have a much lower risk of exacerbated bleeding than previously considered. Herein, we report a case of left atrial myxoma and large hemorrhagic embolic stroke, which was successfully operated on with no exacerbation of cerebral hemorrhage. Careful assessment of time-course changes in cerebral hemorrhage by neurological imaging and adjustment of anticoagulation can help prevent the exacerbation of postoperative cerebral hemorrhage and neurological deterioration. .

Low-dose heparin as treatment for early disseminated intravascular coagulation during sepsis: A prospective clinical study.

The present study aimed to investigate whether low-dose heparin improves the condition of patients suffering from early disseminated intravascular coagulation (pre-DIC) during sepsis. In total, 37 patients were randomly divided into low-dose heparin intervention and control groups. The heparin group received a low-dose of heparin for 5-7 days, while the other group received only saline. The two groups were treated for sepsis. Blood samples were collected at various times and acute physiology and chronic health evaluation (APACHE)-II scores were recorded at day 1 and 7. In addition, the number of days applying mechanical ventilation and in the intensive care unit (ICU) were recorded, as well as the 28-day mortality rate. APACHE-II scores in the two groups decreased following treatment, however, scores in the heparin group decreased more significantly. Prothrombin fragment and thrombin-antithrombin complex levels in the heparin group were significantly decreased. In addition, the number of days applying a ventilator was fewer and the total stay in ICU was significantly shorter compared with the control group. Significantly fewer complications were observed in the heparin group, however, there was no significant difference in the 28-day mortality rate. In conclusion, low-dose heparin improves the hypercoagulable state of sepsis, which subsequently reduces the incidence of DIC or multiple organ dysfunction syndrome, decreasing the number of days of mechanical ventilation and hospitalization.

Low-dose heparin micro-pump continuous regular infusion in the treatment of primary nephrotic syndrome / 中国小儿急救医学

Objective To explore the efficacy and safety of low-dose heparin in the treament of children with primary nephrotic syndrome (PNS). Methods It was an open and comparative trial. Eightyeight children with PNS in the hypercoagulable state,on the basis of administrating with glucocorticosteroid,were administrated with low-dose heparin that infused by micro pump oriented to time ( group A). Eighty patients only treated with glucocorticosteroid were chosen as control (group B). Results Serum-albumin and activated partial thromboplastin time (APTT) increased,but fibrinogen (Fib) decreased after therapy in the group A,and they all showed significant differences (P ＜ 0. 01 ). Serum-albumin increased after therapy in the group B and there was significant difference (P＜0. 01 ). However,APTT and Fib in the group B showed no significant difference( P ＞ 0. 05 ) between post-treatment and pretherapy. Post-treatment serum-albumin and APTT in the group A were significantly higher than those in group B, and Fib was significantly lower than that in group B ( P ＜ 0. 01 ). The rate of urine protein remission in group A (82/88) was significantly higher than that in group B (63/80). Urine protein remission time and edema disappearance time were significantly shorter in group A than group B ( P ＜ 0. 01 ). APTT of group A at the peak concentration of heparin after therapy was significantly higher than that of pretherapy ( P ＜ 0. 01 ), and the ratio was 2. 38. However, there was no significant difference in APTT at the valley concentration of heparin between post-treatment and pretherapy ( P ＞ 0.05 ). Conclusion Low dose-heparin infused by micro pump oriented to time in the treatment of children with PNS has an obvious anticoagulative effect. It can improve the rate of urine protein remission and shorten edema disappearance time. Meanwhile it is safety ,requires no laboratory monitor and has few drug side effects,thus it deserves further clinical application.