High-dose Low Molecular Weight Heparin Research Articles

Defibrotide improved the outcome of monocrotaline induced rat hepatic sinusoidal obstruction syndrome

Background and aimPyrrolizidine alkaloids (PA) induced hepatic sinusoidal obstruction syndrome (HSOS) occurred worldwide and the mortality rate remained high because there were no specific therapies. Defibrotide was effective for HSOS following hematopoietic stem cell transplantation. But the pathogenesis of the two types of HSOS were not equivalent. The purpose of this study was to see if defibrotide was also effective in PA induced rat HSOS.MethodsFirst we improved rat HSOS model by using higher dose (230 mg/kg) of monocrotaline (a kind of PA) as the dose of median lethal dose. So drug effectiveness could be assessed by survival time. Next, male SD rats were divided into 5 groups. They were control group, model group, low dose low molecular weight heparin (LMWH) treatment group, high dose LMWH treatment group and defibrotide treatment group. Rats’ survival time, liver function, white blood cell count and cytokines were compared among the groups. The DeLeve score was used to assess the severity of liver pathology.ResultsThe model group exhibited typical liver pathology of HSOS, such as hepatic sinus dilation, congestion, endothelial injury of central lobular vein, coagulative necrosis of hepatocytes and fibrin deposition in the subendothelial. The pathologic characteristics indicated that the model was built up successfully. The survival rate was significantly higher in defibrotide group (81.8%) than model group (43.7%), while the survival rates were similar in the two LMWH groups (62.5% and 75%) and model group. The survival time only be prolonged by defibrotide (P=0.028) but not LMWH (P>0.05). DeLeve score was improved most in the defibrotide group than the two LMWH groups (both P<0.01). Changes in DeLeve score, liver function, plasma level of tumor necrosis factor α and plasminogen activator inhibitor-1 exhibited the same trends.ConclusionDefibrotide could improve the outcome of monocrotaline-induced rat HSOS indicating that defibrotide might be a better choice than LMWH in clinical practice.

Standard Dose Prophylaxis Application and Venous Thromboembolism Findings in Patients Who Had Bariatric Surgery

Aim: Venous thromboembolism (VTE) events covering deep vein thrombosis (DVT) and pulmonary embolism (PE) constitute the most important morbidity-mortality cause in obesity surgery. The objective of this study was to assessment of thromboembolism results in patients who underwent bariatric surgery with standard dose prophylaxis. Patients and Methods: The patients who were operated for morbid obesity in our clinic between 2015 and 2019 were retrospectively examined. Cases that had laparoscopic sleeve gastrectomy and were applied standard dose Enoxaparin prophylaxis were included in the study. Demographic data, preoperative preparation and postoperative antiembolic treatment conditions of the patients were registered. Results: Eighty-seven patients who had laparoscopic sleeve gastrectomy were included in the study. 66 (%75,8) of the patients were female and 21 (%24,1) were male. The mean age was 38.7 (18-55). Mean hospitalization duration was 6.6 (3-69) days. Four patients (% 4,5) had postoperative complication. PE developed in two patients while leak-related mediastinitis and incisional hernia (%1,1) developed in one case each. Conclusion: Despite available prophylaxis methods, VTE constitutes an important morbidity and mortality cause in patients who had bariatric surgery. While high-dose low-molecular weight heparin (LMWH) use may cause bleeding, the possibility of VTE increases with using low-dose LMWH. This situation appears as a limitation of LMWHs. New studies are needed for increased dose at early period and standard dose application after discharge.

Enoxaparin-induced atraumatic acute compartment syndrome of the thigh: a case report

In this case, we present a case of atraumatic lateral compartment syndrome of the thigh in a patient undergoing anticoagulant treatment. The patient received high-dose low molecular weight heparin (LMWH) treatment due to the diagnosis of an ischemic cerebrovascular event and developed lateral compartment syndrome of the thigh after the LMWH injection into the thigh; therefore, an emergency fasciotomy was performed. After negative-pressure dressing and monitoring, the wound was closed on the sixth day and the patient was discharged. No complication occurred during the one-month follow-up. Compartment syndrome of the thigh is a rare, but potentially devastating. The purpose of the current report was to highlight this rare, but serious, complication of a routine treatment procedure.

Effect of low or high doses of low‐molecular‐weight heparin on thrombin generation and other haemostasis parameters in critically ill patients with COVID‐19

The clinical picture of the coronavirus 2 (SARS-CoV-2)/COVID-19-related acute respiratory syndrome is often associated with a coagulopathy. An elevated D-dimer has been linked with an unfavorable prognosis in COVID-19 patients.

COVID‐19 in lung transplant recipients: A case series from Milan, Italy

Limited data are currently available regarding the course of COVID-19 in lung and solid organ transplant recipients. We hereby present four cases of SARS-CoV-2 pneumonia in lung transplant recipients from our center, set in Milan, Italy. We reduced immunosuppressive regimen in all these patients, typically holding the antiproliferative agent and augmenting steroids; everybody received hydroxychloroquine, initial empiric antibiotic treatment with piperacillin/tazobactam, and high-dose low molecular weight heparin. Clinical course seemed favorable in three of our patients, but one of them deteriorated after 10days of hospitalization, probably due to an acute form of graft dysfunction triggered both by COVID-19 and a nosocomial bacterial infection, and eventually died. Although short-term prognosis could be considered benign in the majority of our patients, we should carefully monitor these individuals in order to detect early sign of clinical deterioration and graft dysfunction in the next few months.

Antiplatelet and anticoagulant agents for primary prevention of thrombosis in individuals with antiphospholipid antibodies.

Antiplatelet and anticoagulant agents for primary prevention of thrombosis in individuals with antiphospholipid antibodies.

A double centre retrospective study into rates of postpartum haemorrhage in women on low molecular weight heparin

A double centre retrospective study into rates of postpartum haemorrhage in women on low molecular weight heparin

Low molecular weight heparin (LMWH) improves peritoneal function and inhibits peritoneal fibrosis possibly through suppression of HIF-1α, VEGF and TGF-β1.

BackgroundPeritoneal fibrosis is the major cause of ultrafiltration failure, and intraperitoneal administration of Low Molecular Weight Heparin (LMWH) was reported to protect peritoneal function. But the exact mechanism of its influence on peritoneal structure and function is still unknown.MethodsA fibrosis model of rat was established by intraperitoneal (IP) administration of PD fluid and Erythromycin Lactobionate. Fifty-two rats were randomly divided into 6 groups: (1) normal control group (CON, n = 6); (2) normal saline group (NS, n = 10); (3) high-glucose group (GLU, n = 10); (4) heparin group (HEP, n = 6); (5) low dose LMWH group (LLMWH, n = 10); (6) high dose LMWH group (HLMWH, n = 10). Two hour peritoneal equilibration test was performed after 28 days of intervention. The peritoneum, mesentery and omentum were harvested, and evaluated by Hematoxylin-Eosin and Masson Trichrome staining. The expressions of HIF-1α, VEGF and TGF-β1 in parietal peritoneum were detected by IHC and RT-PCR (Reverse Transcriptase Polymerase Chain Reaction).ResultsCompared with group CON and NS, ultrafiltration volume and D2/D0 glucose in group GLU decreased significantly, D/Purea (Dialysate-Plasma ratio of urea), D/Palb (Dialysate-Plasma ratio of albumin), peritoneal thickness, neoangiogenesis and inflammatory reaction increased significantly (all P<0.05). Administration of heparin and LMWH markedly alleviated these above pathological changes. The protein and mRNA levels of HIF-1α, VEGF and TGF-β1 increased significantly in group GLU, and decreased significantly after administration of LMWH in a dose-dependent manner.ConclusionsLMWH ameliorates peritoneal function and inhibits peritoneal fibrosis, possibly through suppression of HIF-1α, VEGF and TGF-β1.

Management of venous thrombosis in fibular free osseomusculocutaneous flaps used for mandibular reconstruction: clinical techniques and treatment considerations

BackgroundMandibular reconstruction by means of fibula transplants is the standard therapy for severe bone loss after subtotal mandibulectomy. Venous failure still represents the most common complication in free flap surgery. We present the injection of heparine into the arterial pedicle as modification of the revising both anastomoses in these cases and illustrate the application with a clinical case example.MethodsMethods consist of immediate revision surgery with clot removal, heparin perfusion by direct injection in the arterial vessel of the pedicle, subsequent high dose low-molecular weight heparin therapy, and leeches. After 6 hours postoperatively, images of early flap recovery show first sings of recovery by fading livid skin color.ResultsThe application of this technique in a patient with venous thrombosis resulted in the complete recovery of the flap 60 hours postoperatively. Other cases achieved similar success without additional lysis Therapy or revision of the arterial anastomosis.ConclusionRescue of fibular flaps is possible even in patients with massive thrombosis if surgical revision is done quickly.

Appropriate dosage of unfraction heparin and low molecular weight heparin in hemodialysis patients

To investigate the appropriate dose of unfraction heparin and low molecular weight heparin (LMWH) in hemodialysis patients. Thirty-eight hemodialysis patients were enrolled and randomly allocated into four groups.The initial bolus dose for the Low-dose (LH, n = 10) and high-dose heparin (HH, n = 10) groups were 35 U/kg and 55 U/kg, respectively.The repeated maintenance dose for both groups were 10 U/kg.h and 16 U/kg.h, respectively. Fragmin were administered as single bolus (60 U/kg or 80 U/kg) at 30 minutes before hemodialysis in Low-dose LMWH(LLMWH, n = 10) and High-dose LMWH (HLMW, n = 8) group, respectively. Furthermore, the dialysis circuits in LUFH and LLMWUFH groups were primed with with 4 mg/dl heparinized saline before hemodialysis. Glass bead active clotting time (gbACT), clot rate (CR) and platelet function (PF) were examined using Sonoclot analysator at 0 h, 2 h and the end of hemodialysis at the arterial circuit and 2 h at the venous circuit. (1) LH and LUFH: the increase of gbACT and decrease of CR at the arterial circuit and the venous circuit at 2 h of hemodialysis were significant compared with baseline. While they recovered at the end of hemodialysis. No difference between the two groups at different time points was found, either. (2) LLMWH: No change were found in gbACT during hemodialysis. CR at the arterial circuit and the venous circuit were significantly decreased at 2 h and recovered at the end of hemodialysis. (3) LLMWUFH: gbACT at the arterial circuit was significantly increased only at 2 h of hemodialysis. CR at the arterial circuit and the venous circuit at 2 h of hemodialysis were significantly decreased and recovered when hemodialysis finished. (4) HH and HLMWH: gbACT were significantly increased and CR were rapidly decreased at both the arterial circuit and venous circuit at 2 h of hemodialysis. Low-dose heparin was effective and safe as anticoagulant in hemodialysis. Low-dose low-molecular-weight heparin was efficient in anticoagulation to some extent. However, High-dose low-molecular-weight heparin, high-dose heparin and flushing with heparinized saline may increase the risk of hemorrhage.

66 Anticoagulant treatment in a hypercoagulable woman with mechanical prosthetic mitral valve – failure of high-dose low molecular weight heparin (LMWH) treatment

66 Anticoagulant treatment in a hypercoagulable woman with mechanical prosthetic mitral valve – failure of high-dose low molecular weight heparin (LMWH) treatment

Lumbar epidural hematoma following lumbar puncture: the role of high dose LMWH and late surgery. A case report

Spinal epidural hematoma (SEH) is a known complication of spinal surgery, but the incidence of post-surgical SEHs that result in neurologic deficits is extremely rare (0.1%). Patients that require multilevel lumbar procedures and/or have a preoperative coagulopathy are at a significantly higher risk of developing an epidural hematoma. The introduction of higher dose of low molecular weight heparin (LMWH) twice daily 30 mg regimen) increased the reported incidence of neuroaxial hematomas. Surgery performed within 8 hours makes good or partial recovery of neurologic function. Our patient was also started on higher dose of LMWH and developed neurological deficits due to a SEH following lumbar puncture. She underwent operation after six days and she had a mild recovery following the operation. Current administration of high doses of LMWH can cause SEH even after a lumbar puncture, which was performed without multiple attempts. Although surgery performed within 8 hours makes good or partial recovery of neurologic function, laminectomy and epidural hematoma evacuation performed after three days can also have successful results.

A Systematic Review of Deep Venous Thrombosis Prophylaxis in Cancer Patients: Implications for Improving Quality

Deep venous thrombosis (DVT) prophylaxis is particularly important for surgical oncologists given the high rate of DVT in patients with malignancy. Additionally, DVT prophylaxis may soon be implemented by some payers as a "pay for performance" quality measure. This is a systematic review of randomized controlled trial (RCT) evidence for DVT prophylaxis in cancer patients undergoing surgery. We examine overall rates of DVT, the efficacy of high versus low-dose heparin prophylaxis, and the rate of bleeding complications. The Medline database was searched for English language RCTs using key words DVT, venous thromboembolism, prophylaxis, and general surgery. Inclusion criteria were RCTs evaluating surgical oncology patients. Fifty-five RCTs studied DVT prophylaxis in surgery (nonorthopedic) patients. Twenty-six RCTs evaluated 7,639 cancer patients. The overall DVT rate was 12.7% for pharmacologic prophylaxis and 35.2% for controls. High-dose low-molecular weight heparin (LMWH) was more effective than low dose, lowering the DVT rate from 14.5% to 7.9% (P < 0.01). Heparin decreased the rate of proximal DVTs. Bleeding complications requiring discontinuation of prophylaxis occurred in 3% of the patients. There was no difference between LMWH and unfractionated heparin in efficacy, DVT location, or bleeding complications. Using RCT data, this study demonstrates a greatly reduced DVT rate with pharmacologic prophylaxis in cancer patients, and higher doses appear more effective. Complication rates are low and should not prevent the use of prophylaxis in most patients. Finally, we found no difference between LMWH and unfractionated heparin in these RCTs. These results highlight the importance of routine pharmacologic prophylaxis in surgical patients with malignancy.

Perinatal Outcome of Pregnant Women Receiving High Dose Low-Molecular Weight Heparin

Perinatal Outcome of Pregnant Women Receiving High Dose Low-Molecular Weight Heparin

Low-dose low–molecular-weight heparin is anti-inflammatory during venous thrombosis

Purpose: Venous thrombosis results in a vein wall inflammatory response initiated by thrombus. Although anticoagulation with standard heparin (SH) and low–molecular-weight heparin (LMWH) is known to limit further thrombosis, their anti-inflammatory properties are poorly defined. The anti-inflammatory properties of these heparins were studied. Methods: Sprague-Dawley rats were divided into groups and underwent inferior vena caval (IVC) ligation just below the renal level producing IVC thrombosis. One hour before ligation, animals received subcutaneous SH or LMWH at either high or low dose; normal saline (NS) was used as control. Six hours after ligation, animals were killed, and the IVCs were analyzed for clot presence, vein wall morphometrics, and vein wall permeability (VP) to define injury. Results:Animals in both low-dose groups had no measurable anticoagulation, whereas those in both high-dose groups were adequately anticoagulated. There were statistically less IVC neutrophils for all groups compared with the control group, with low-dose LMWH showing the least cells (low-dose LMWH, 16 ± 3; high-dose LMWH, 37 ± 10; low-dose SH, 37 ± 6; high-dose SH, 32 ± 9; NS control, 63 ± 2). Similar results were noted for total inflammatory cells. The lowest VP was noted for low-dose LMWH. Conclusion: Although both SH and LMWH inhibited vein wall neutrophils and total inflammatory cells, low-dose LMWH was most effective limiting neutrophil extravasation and was the only intervention to decrease VP below control levels. This occurred without preventing thrombus formation or causing a state of anticoagulation. Low-dose LMWH possesses anti-inflammatory properties distinct from its anticoagulant properties. (J Vasc Surg 1998;28:848-54.)

Inhibition of fibro-intimal hyperplasia in a polytetrafluoroethylene vascular graft with standard heparin and low molecular weight heparin.

Fibro-intimal hyperplasia is a significant cause of late prosthetic vascular graft failure. The influence of standard unfractionated sodium heparin (SH) and low molecular weight heparin (LMWH) on intimal hyperplasia was studied in a sheep polytetrafluoroethylene (PTFE) end-to-side carotid artery vascular graft model. Sodium heparin was administered subcutaneously in a dose of 7250 units twice daily (n = 6). Enoxaparin, an LMWH, was administered subcutaneously in two different dose regimens of 2 mg/kg (n = 6) and 5 mg/kg (n = 6) daily. At 1 month the animals were killed and the grafts sectioned. An intima to media ratio was obtained under light microscopy, using an eyepiece graticule, from measurements taken from the floor of the native artery. Results were analysed with a rank-sum correlation test. Control sheep had a median ratio of 0.104, an SH level of 0.021, a low-dose LMWH level of 0.035 and a high-dose LMWH level of 0.017. There was a significant difference between control and SH (P < 0.001), control and high-dose LMWH (P < 0.05), and SH and low-dose LMWH (P < 0.05), but there were no differences between SH and high-dose LMWH or between the two LMWH groups. Both LMWH groups recorded high anti-Xa levels but only slight prolongation of thrombin time. Low molecular weight heparin has a similar effect to SH on the inhibition of fibro-intimal hyperplasia in this animal model but is safer, with less bleeding potential, and is more convenient to administer as a once-daily dose.

The influence of low molecular weight heparin on neointimal proliferation in cultured human saphenous vein

To investigate the effect of low molecular weight heparin (LMWH) on neointimal proliferation in cultured human saphenous vein, a model of human vein graft intimal hyperplasia. Dose ranging LMWH concentration study. Culture Laboratory, Department of Surgery. Fifteen segments of human long saphenous vein were incubated at 37 degrees C for 14 days in culture medium with 30% foetal calf serum. LMWH was added to one of the paired segments at 1, 10 and 100 micrograms/ml (five veins each dose). 5-bromo-2-deoxyuridine (Brd-U) was used to label proliferating cells. Neointimal thickness (micron and proliferation index (% labelled neointimal cells). Neointimal thickness and proliferation index were both significantly reduced by LMWH at 100 micrograms/ml [control vs. LMWH, reduction in thickness 21 microns vs. 7 microns (median difference 12 microns, 95% conf. int. 6-18), reduction in proliferation index 33% to 6% (median difference 19%, 95% C.I. 4-32)]. High dose LMWH reduces neointimal proliferation in cultured human saphenous vein. The practical clinical application of these results may require the use of non anticoagulant heparin-like molecules and/or local drug delivery systems.