OBJECTIVE: To review current status of clinical application and research progress of different anticoagulants in perioperative period of free flap transplantation. METHODS: A comprehensive review of recent relevant literature was conducted, focusing on clinical research concerning the application of anticoagulants in the perioperative period of free flap transplantation. The administration route, timing, dosage selection, effectiveness, and safety of commonly used and novel anticoagulants were summarized. RESULTS: At present, the anticoagulants mainly used in the perioperative period of free flap transplantation include drugs for venous thrombosis prophylaxis, drugs for arterial thrombosis prophylaxis, and physical/colloidal anticoagulants, etc. The administration strategies can be classified into two major categories: single-agent anticoagulation and combined anticoagulation. Single-agent anticoagulation mainly includes unfractionated heparin, low-molecular-weight heparin, aspirin, and novel anticoagulants. Combined anticoagulation is commonly a synergistic anticoagulation regimen dominated by heparin drugs, combined with aspirin, different antiplatelet drugs, and expansion agents. Studies indicate that perioperative anticoagulant administration can effectively reduce the risk of thrombosis in free flaps and improve the overall flap survival rate. However, significant differences exist in the impact of drug types, administration routes, initiation timing, and dosage intensity on efficacy and bleeding risk. A unified, standardized application protocol has not yet been established. In addition, there has been a growing number of studies on novel anticoagulant drugs. However, their superiority and optimal application strategies in the field of free flap transplantation still necessitate more high-quality evidence. CONCLUSION Perioperative anticoagulation therapy represents one of the key strategies for improving the survival rate of free flaps. However, there is still a lack of high-level evidence to establish a standard protocol. Future research should focus on the optimization of individualized anticoagulation strategies, the validation of the effectiveness of new anticoagulants, and the exploration of the advantages of different anticoagulation strategies. At the same time, attention should be paid to balancing anticoagulation and bleeding risks to promote the standardization of clinical practice and the improvement of treatment safety.
Humans ; Anticoagulants/therapeutic use* ; Free Tissue Flaps/blood supply* ; Thrombosis/prevention & control* ; Perioperative Care/methods* ; Heparin/therapeutic use* ; Heparin, Low-Molecular-Weight/administration & dosage* ; Perioperative Period ; Aspirin/therapeutic use*

OBJECTIVE: To investigate the efficacy and safety of intravesical instillation of heparin/alkalized lidocaine (lidocaine mixed with sodium bicarbonate) combined with hydrodistension and transurethral fulguration in the treatment of female interstitial cystitis (IC). METHODS: Female patients who attended the Department of Urology at the First Hospital of China Medical University between January 2012 and December 2020 and met the diagnostic criteria proposed in the guidelines of the American Urological Association with a new diagnosis of IC were selected for retrospective analysis. Cystoscopy and biopsy of suspicious lesions were performed at the time of diagnosis. All the patients were treated with an intravesical instillation regimen of 2% lidocaine 10 mL + 5% sodium bicarbonate 5 mL + heparin 25 000 IU for a continuous period of 12 months, with or without water dilatation and transurethral electrocautery according to the patient's preference, categorized as hydrodistension and transurethral fulguration (HD/TF) group and non-HD/TF group. The patients were evaluated before and 1, 6, and 12 months after treatment for O'Leary-Sant interstitial cystitis patient symptom index scores (ICSI), interstitial cystitis patient problem index scores (ICPI), visual analog scale (VAS) of suprapubic pain, and functional bladder capacity (FBC) changes. RESULTS: A total of 79 patients were collected in this study. Four (5.1%) of these patients underwent cystectomy due to pathological diagnosis of cancer or treatment failure. The remaining patients were followed up 1, 6 and 12 months after treatment. Repeated-measures ANOVA showed a significant decrease in ICPI, ICSI and VAS and an increase in FBC after treatment compared with before treatment (P < 0.05). FBC continued to decrease during the 1, 6 and 12 months' post-treatment follow-ups, with statistically significant differences; ICSI continued to decrease during the 1 and 6 months post-treatment follow-ups, with statistically significant differences, while the difference between ICSI at 6 months post-treatment and at 12 months' post-treatment was not statistically significant. In the HD/TF group, ICPI continued to decrease in the follow-up from 1 and 6 months after treatment, and the difference was statistically significant, while the difference between ICPI 6 months after treatment and 12 months after treatment was not statistically significant. There was no statistically significant difference between the remaining indicators 1, 6 and 12 months after treatment. ICPI, ICSI, VAS and FBC improved earlier and the changes in VAS and FBC were more significant in the HD/TF group compared with the non-HD/TF group (P < 0.05). CONCLUSION Heparin/alkalized lidocaine combination of intravesical instillation with hydrodistension and transurethral fulguration for IC is an effective treatment option. Heparin/alkalized lidocaine combination of intravesical instillation may be the first choice of treatment, which can significantly reduce the economic burden of patients and medical insurance system. If patients can accept it, transurethral fulguration with hydrodistension may be considered.
Humans ; Female ; Cystitis, Interstitial/drug therapy* ; Administration, Intravesical ; Retrospective Studies ; Sodium Bicarbonate/therapeutic use* ; Treatment Outcome ; Lidocaine/therapeutic use* ; Heparin/therapeutic use* ; Electrocoagulation

Heparin-induced thrombocytopenia (HIT) is a relatively infrequent complication of heparin administration. HIT can cause devastating thrombosis, making it one of the most serious adverse drug reactions encountered in clinical practice. We successfully treated a case of severe HIT presenting with thrombosis and life-threatening bleeding complications with intravenous immunoglobulin (IVIG), platelet transfusion and oral anticoagulant Rivaroxaban. In this case, we considered that IVIG played the most important role by preventing further thrombosis, increasing the platelet count, and ensuring the efficacy of Rivaroxaban. We therefore suggest that IVIG might be the optimal treatment for patients with this urgent condition.
Aged, 80 and over ; Female ; Heparin ; administration & dosage ; adverse effects ; Humans ; Immunoglobulins, Intravenous ; administration & dosage ; Platelet Transfusion ; Rivaroxaban ; administration & dosage ; Thrombocytopenia ; chemically induced ; therapy

PURPOSE: To investigate the incidence of venous thromboembolism (VTE) after total knee arthroplasty (TKA) with chemoprophylaxis using acetylsalicylic acid (AA) or rivaroxaban in Korean patients. MATERIALS AND METHODS: Between May 2011 and November 2013, 268 TKA patients (330 cases) were randomly allocated to 3 groups (group A: subcutaneous injection of 5,000 IU low-molecular-weight heparin for 2 days followed by oral administration of 100 mg AA for 5 days; group X7: oral administration of 10mg rivaroxaban for 7 days; and group X10: oral administration of 10 mg rivaroxaban for 10 days). Multidetector-row computed tomography (MDCT) was performed at 10 days and 3 months postoperatively to evaluate VTE changes. RESULTS: The VTE incidence was 38.2%, 20.0%, and 10.0% in groups A, X7, and X10, respectively (p < 0.001). Pulmonary embolism (PE) was identified in 19.1%, 10.0%, and 2.7% in groups A, X7, and X10, respectively (p < 0.001). Proximal or symptomatic deep vein thrombosis (DVT) occurred primarily in group A, but the incidence was not significantly different among groups. On follow-up MDCT, PE was resolved completely with treatment in 29/30 (96.7%), and so was asymptomatic distal DVT in 24/27 (88.8%) without treatment. CONCLUSIONS: Rivaroxaban had a lower incidence of overall VTE than AA, but no difference was observed in symptomatic VTE. The 10-day course of rivaroxaban had a lower incidence of overall VTE than the 7-day course.
Administration, Oral ; Arthroplasty ; Arthroplasty, Replacement, Knee ; Aspirin ; Chemoprevention ; Follow-Up Studies ; Heparin, Low-Molecular-Weight ; Humans ; Incidence ; Injections, Subcutaneous ; Knee ; Multidetector Computed Tomography ; Pulmonary Embolism ; Rivaroxaban ; Venous Thromboembolism ; Venous Thrombosis

Acute cytomegalovirus (CMV) infection occurs commonly in immunocompromised and immunocompetent patients, but is usually asymptomatic in the latter. Vascular events associated with acute CMV infection have been described, but are rare. Hence, such events are rarely reported in the literature. We report a case of pulmonary embolism secondary to acute CMV colitis in an immunocompetent 78-year-old man. The patient presented with fever and diarrhea. Colonic ulcers were diagnosed based on colonoscopy findings, and CMV was the proven etiology on pathological examination. The patient subsequently experienced acute respiratory failure. Pulmonary embolism was diagnosed based on the chest radiography and computed tomography findings. A diagnosis of acute CMV colitis complicated by pulmonary embolism was made. The patient was successfully treated with intravenous administration of unfractionated heparin and intravenous ganciclovir.
Administration, Intravenous ; Aged ; Colitis* ; Colon ; Colonoscopy ; Cytomegalovirus* ; Diagnosis ; Diarrhea ; Fever ; Ganciclovir ; Heparin ; Humans ; Pulmonary Embolism* ; Radiography ; Respiratory Insufficiency ; Thorax ; Ulcer

Objective This study was designed to evaluate the efficacy and safety of aspirin-heparin treatment for un-explained recurrent spontaneous abortion (URSA). Methods Literatures reporting the studies on the aspirin-heparin treatment of un-explained recurrent miscarriage with randomized controlled trials (RCTs) were collected from the major publication databases. The live birth rate was used as primary indicator, preterm delivery, preeclampsia, intrauterine growth restriction, and adverse reactions (thrombocytopenia ) were used as the secondary indicators. The quality of the included studies was evaluated using RCT bias risk assessment tool in the Cochrane Handbook (v5.1.0). Meta-analysis was conducted using RevMan (v5.3) software. Subgroup analyses were conducted with an appropriately combined model according to the type of the treatments if heterogeneity among the selected studies was detected. Results Six publications of RCTs were included in this study. There were a total of 907 pregnant women with diagnosis of URSA, 367 of them were pooled in the study group with aspirin-heparin therapy and 540 women in the control group with placebo, aspirin or progesterone therapy. Meta-analysis showed that the live birth rate in the study group was significantly different from that in the control group [RR = 1.18, 95% CI (1.00-1.39), P=0.04]. Considering the clinical heterogeneity among the six studies, subgroup analysis were performed. Live birth rates in the aspirin-heparin treated groups and placebo groups were compared and no significant difference was found. There were no significant differences found between the two groups in the incidence of preterm delivery [RR=1.22, 95% CI (0.54-2.76), P=0.64], preeclampsia [RR=0.52, 95% CI (0.25-1.07), P=0.08], intrauterine growth restriction [RR=1.19, 95% CI (0.56-2.52), P=0.45] and thrombocytopenia [RR=1.17, 95% CI (0.09-14.42), P=0.90]. Conclusion This meta-analysis did not provide evidence that aspirin-heparin therapy had beneficial effect on un-explained recurrent miscarriage in terms of live birth rate, but it was relatively safe for it did not increase incidence of adverse pregnancy and adverse events. More well-designed and stratified double-blind RCT, individual-based meta-analysis regarding aspirin-heparin therapy are needed in future.
Abortion, Habitual ; drug therapy ; Aspirin ; administration & dosage ; adverse effects ; Female ; Heparin ; administration & dosage ; adverse effects ; Humans ; Pregnancy ; Publication Bias

PURPOSE: Compared with warfarin, novel oral anticoagulants (NOACs) are convenient to use, although they require a blanking period immediately before radiofrequency catheter ablation for atrial fibrillation (AF). We compared NOACs and uninterrupted warfarin in the peri-procedural period of AF ablation. MATERIALS AND METHODS: We compared 141 patients treated with peri-procedural NOACs (72% men; 58+/-11 years old; 71% with paroxysmal AF) and 281 age-, sex-, AF type-, and history of stroke-matched patients treated with uninterrupted warfarin. NOACs were stopped 24 hours before the procedure and restarted on the same procedure day after hemostasis was achieved. RESULTS: We found no difference in the CHA2DS2-VASc (p=0.376) and HAS-BLED scores (p=0.175) between the groups. The preprocedural anticoagulation duration was significantly shorter in the NOAC group (76.3+/-110.7 days) than in the warfarin group (274.7+/-582.7 days, p<0.001). The intra-procedural total heparin requirement was higher (p<0.001), although mean activated clotting time was shorter (350.0+/-25.0 s vs. 367.4+/-42.9 s, p<0.001), in the NOAC group than in the warfarin group. There was no significant difference in thromboembolic events (1.4% vs. 0%, p=0.111) or major bleeding (1.4% vs. 3.9%, p=0.235) between the NOAC and warfarin groups. Minor stroke occurred in two cases within 10 hours of the procedure (underlying CHA2DS2-VASc scores 0 and 1) in the NOAC group. CONCLUSION: Pre-procedural anticoagulation duration was shorter and intra-procedural heparin requirement was higher with NOAC than with uninterrupted warfarin during AF ablation. Although the peri-procedural thromboembolism and bleeding incidences did not differ, minor stroke occurred in two cases in the NOAC group.
Aged ; Anticoagulants/*therapeutic use ; Atrial Fibrillation/complications/*drug therapy/*surgery ; Catheter Ablation/*methods ; Female ; Follow-Up Studies ; Hemorrhage/epidemiology ; Heparin ; Humans ; Incidence ; Male ; Middle Aged ; Postoperative Complications/epidemiology ; Stroke/epidemiology ; Thromboembolism/epidemiology ; Treatment Outcome ; Warfarin/administration & dosage/*therapeutic use

We conducted this study to investigate the synergistic effect of human urine-derived stem cells (USCs) and surface modified composite scaffold for bladder reconstruction in a rat model. The composite scaffold (Polycaprolactone/Pluronic F127/3 wt% bladder submucosa matrix) was fabricated using an immersion precipitation method, and heparin was immobilized on the surface via covalent conjugation. Basic fibroblast growth factor (bFGF) was loaded onto the heparin-immobilized scaffold by a simple dipping method. In maximal bladder capacity and compliance analysis at 8 weeks post operation, the USCs-scaffold(heparin-bFGF) group showed significant functional improvement (2.34 ± 0.25 mL and 55.09 ± 11.81 microL/cm H2O) compared to the other groups (2.60 ± 0.23 mL and 56.14 ± 9.00 microL/cm H2O for the control group, 1.46 ± 0.18 mL and 34.27 ± 4.42 microL/cm H2O for the partial cystectomy group, 1.76 ± 0.22 mL and 35.62 ± 6.69 microL/cm H2O for the scaffold group, and 1.92 ± 0.29 mL and 40.74 ± 7.88 microL/cm H2O for the scaffold(heparin-bFGF) group, respectively). In histological and immunohistochemical analysis, the USC-scaffold(heparin-bFGF) group showed pronounced, well-differentiated, and organized smooth muscle bundle formation, a multi-layered and pan-cytokeratin-positive urothelium, and high condensation of submucosal area. The USCs seeded scaffold(heparin-bFGF) exhibits significantly increased bladder capacity, compliance, regeneration of smooth muscle tissue, multi-layered urothelium, and condensed submucosa layers at the in vivo study.
Adult Stem Cells/cytology/metabolism/*transplantation ; Animals ; Biocompatible Materials/chemistry ; Cell Differentiation ; Fibroblast Growth Factor 2/administration & dosage ; Heparin/administration & dosage ; Humans ; Materials Testing ; Models, Animal ; Poloxamer ; Polyesters ; Rats ; Reconstructive Surgical Procedures ; Regeneration ; Tissue Engineering/*methods ; Tissue Scaffolds/chemistry ; Urinary Bladder/anatomy & histology/physiology/*surgery ; Urine/*cytology

OBJECTIVETo observe the effects of low molecular weight heparin (LMWH) on the inflammatory response and vascular injury in rat after electric burn.

METHODSA homemade regulator and transformer apparatus was used to reproduce the model of electric burn (0.5 cm×0.5 cm in size) with depth from full-thickness to full-thickness skin plus muscle and bone on the middle of the inside of right hind limb in 60 Wistar rats. The open wounds were covered with 20 g/L sulfadiazine silver paste immediately after injury. The wound condition was observed every day. The injured rats were divided into group LMWH and control group (C) according to the random number table, with 30 rats in each group. Rats in group LMWH were given subcutaneous injection of LMWH (1 U/g) in abdominal wall, 2 times a day. No other treatment was given in rats in group C. On post burn day (PBD) 3, 5, and 10, 10 rats respectively of two groups were sacrificed. The damaged tissue of wound and that around the wound (1.0 cm×0.5 cm in size) were excised, and heart blood was obtained. The pathological changes and thrombosis in damaged tissue were observed with HE, Masson, and aldehyde fuchsin staining, and the thrombosis rate was calculated. Serum contents of TNF-α and endothelin-1 were determined with ELISA. The mRNA expression of TNF-α in damaged tissue was detected with RT-PCR. Data were processed with Levene homogeneity test, analysis of variance of factorial design, LSD- t test, SNK- q test, and Friedman M nonparametric test.

RESULTS(1) The injured limb of rats was obviously swollen after electric burn, which reached deeply to the muscle and bone. Compared with those of group C, the swelling of rats subsided slightly faster and the inflammatory response was lighter in group LMWH at each time point. (2) The necrosis of damaged tissue and profuse infiltration of inflammatory cells were observed. Dilatation of blood vessels, congestion and thrombosis, and swelling, necrosis, and desquamation of vascular endothelial cells were observed in the damaged tissue. Damaged blood vessel wall, ruptured elastic fiber, loss of internal elastic membrane, and other pathological changes were observed in the damaged tissue of rats in the two groups. Above lesions were improved gradually along with the passage of time, and the improvement was more obvious in rats of group LMWH compared with that of group C on PBD 5 and 10. (3) The thrombosis rates of rats in group LMWH were obviously lower than those of rats in group C (F = 4.921, P < 0.05). The thrombosis rates of rats in group LMWH on PBD 3 and 10 were respectively (0.07 ± 0.11)% and (0.03 ± 0.05)%, which were significantly lower than those of rats in group C [(0.16 ± 0.15)% and (0.13 ± 0.18)%, with t values respectively 2.17 and 2.07, P values below 0.05]. In group LMWH, the thrombosis rate of rats on PBD 10 was obviously lower than that on PBD 3 (t = 3.61, P < 0.05). (4) The serum contents of TNF-α and endothelin-1 of rats in group LMWH were significantly lower than those of rats in group C (F = 47.161, χ(2) = 81.46, P values below 0.01). In group LMWH, TNF-α contents were respectively (71 ± 24), (74 ± 14), (72 ± 20) pg/mL, and endothelin-1 contents were respectively (20.9 ± 3.2), (19.8 ± 5.2), (18.6 ± 1.1) ng/mL on PBD 3, 5, and 10, and they were significantly lower than those of rats in group C [(195 ± 148), (96 ± 20), (159 ± 46) pg/mL and (38.8 ± 15.4), (27.9 ± 3.6), (25.6 ± 7.6) ng/mL, with t values from 3.81 to 8.05, q values from 4.41 to 7.85, P < 0.05 or P < 0.01]. (5) The mRNA expression levels of TNF-α in damaged tissue of rats in group LMWH were significantly lower than those of rats in group C (F = 199.113, P < 0.01). The mRNA expression levels of TNF-α of rats in group LMWH were respectively 0.93 ± 0.10, 1.15 ± 0.12, 1.21 ± 0.11 on PBD 3, 5, and 10, and they were significantly lower than those of group C (1.68 ± 0.15, 1.43 ± 0.12, 1.50 ± 0.13, with t values from 3.75 to 6.12, P < 0.05 or P < 0.01). In group LMWH, the mRNA expression level of TNF-α of rats on PBD 10 was obviously higher than that on PBD 3 (t = 3.61, P < 0.05).

CONCLUSIONSLMWH intervention can ameliorate vascular injury and inflammatory response of electrically burned wounds in rats, and it decreases thrombosis rate in the vessels of injured limb.

Animals ; Anticoagulants ; administration & dosage ; Burns, Electric ; blood ; complications ; therapy ; Endothelin-1 ; Heparin, Low-Molecular-Weight ; administration & dosage ; Male ; Rats ; Rats, Wistar ; Serum ; metabolism ; Treatment Outcome ; Tumor Necrosis Factor-alpha ; blood ; Vascular System Injuries ; therapy

OBJECTIVETo learn application status of continuous blood purification (CBP) in pediatric intensive care unit (PICU), to provide reference to promote the development of CBP technology.

METHODThe survey of CBP application was conducted using questionnaire in 40 hospitals providing intensive care, which included children's hospitals and the pediatric sections of general hospitals from 28 provinces/municipalities/autonomous regions in China during March to July of 2012.

RESULTTotally 38 hospital replied, 25 hospitals carried out CBP technology, first carried out in 1997, the median year was 2008, 21 hospitals' PICU could independently carry out CBP device, 18 hospitals had the nurses who could professionally operate, routinely maintain the device. Continuous veno-venous hemodiafiltration was the largest implementation mode of CBP, accounting for 51.9%. Twenty-three hospitals used ordinary heparin, and 2 hospitals used low molecular weight heparin; 21 hospitals chose activated partial thromboplastin time as the coagulation testing, due to lack of equipment, only four hospitals chose activated clotting time as coagulation testing. Only 3 hospitals could apply before and after dilution joint technology. Kidney failure is still the disease accounting for the highest proportion of diseases requiring CBP application, accounting for 38.1%, followed by sepsis, 19.1%, drug poisoning 16.7%.

CONCLUSIONCBP started 10 years ago, and got attention and promotion nearly five years ago in China, but the associated personnel, equipment were inadequate, anticoagulation, before and after dilution and other technical applications were not complete enough, high volume hemofiltration mode was seldom used.

Anticoagulants ; administration & dosage ; Child ; China ; epidemiology ; Hemofiltration ; methods ; statistics & numerical data ; Heparin ; administration & dosage ; Hospitals, Pediatric ; Humans ; Infant ; Intensive Care Units, Pediatric ; Partial Thromboplastin Time ; Renal Dialysis ; methods ; Renal Insufficiency ; therapy ; Sepsis ; therapy ; Surveys and Questionnaires