A low molecular weight heparin in hemodialysis

Summary The purpose of our study was to check whether the dosage recommended for the low molecular weight heparin tested here, i.e., 50% of the corresponding unfractionated heparin dose, is adequate to prevent clot formation in the extracorporeal system. Sixteen dialysis treatments of 4–5 h were given to each of six chronic dialysis patients. In dialyses 1, 2, 15 and 16 unfractionated heparin (initial dose 35 IU/kg, continuous dose 20 IU/kg/h) was given, and in dialyses 3–14 low molecular weight heparin (initial dose 17.5 anti-Xa U/kg, continuous dose 10 anti-X U/kg/h). At these dose levels of low molecular weight heparin, clot formation occurred in the extracorporeal system in five of the six patients, despite the fact that the plasma anti-Xa level of 0.5 U/ml recommended by the manufacturer had been attained. For this reason the continuous dose of low molecular weight heparin had to be raised to approx. 80% of the corresponding continuous dose of unfractionated heparin. A plasma anti-Xa level of 0.7 U/ml is necessary to prevent extracorporeal clot formation.Abbreviations anti-Xa U Anti-factor Xa unit - aPTT Activated partial thromboplastin time - AT III Antithrombin III - IU International unit - LMWH Low molecular weight heparin - UFH Unfractionated heparin     

Perioperative prophylaxis with a low molecular weight heparin reduces late PAI-1 levels after gynaecological surgery

Plasminogen activator inhibitor (PAI-1) antigen and fibrin/ogen degradation products (FbDP, FgDP) were measured before and 8 days after gynaecological surgery in 50 patients randomly submitted to prophylaxis with low molecular weight heparin (Alfa LMW1-OP 2123, Alfa Wassermann, Bologna, Italy; LMWH group) or standard calcium heparin (CH group). All patients were screened for deep venous thrombosis by the ¹²⁵I Fibrinogen uptake test. In the CH group, but not in LMWH group, postoperative PAI-1 levels were significantly higher (p<0.01) than at baseline. The percent variation of PAI-1 between pre- and postoperative values was significantly higher in the CH than in LMWH group (p<0.01). Postoperative FbDP values were significantly increased in both groups (p<0.01) but FgDP only in LMWH group (p<0.01). No significant differences in pre- and postoperative PAI-1 values were found between patients with positive or negative ¹²⁵I Fibrinogen uptake test.In conclusion, the patients treated with the low molecular weight heparin had lower PAI-1 and higher FgDP levels at the eighth day after gynaecological surgery compared with patients receiving traditional heparin. These results seem to indicate a greater profibrinolytic effect of the low molecular weight heparin in comparison with standard heparin.     

Plasma lipolytic activity and substrate oxidation after intravenous administration of heparin and a low molecular weight heparin fragment

This study examines the effects of heparin and a low molecular weight heparin (LMWH) fragment on plasma lipolytic activity and substrate oxidation. Indirect calorimetry was performed continuously in healthy male subjects receiving a constant infusion of fat emulsion (0.2 g min-1) and glucose (0.8 g min-1) during a period of 4 h. After 2 h an infusion of heparin (n = 6) or LMWH (n = 6) (100 antifactor Xa units kg-1) or saline (n = 6) was given over 1 h. Plasma concentration of the fat emulsion decreased by 76 +/- 5% with heparin and by 12 +/- 7% with LMWH (P less than 0.01). In the case of LMWH the initial fall was followed by a consistent rise in fat emulsion concentration for the entire remaining study period. Compared to the control experiments, plasma FFA increased five times with heparin and three times with LMWH (P less than 0.05). The average respiratory quotient (RQ) and energy expenditure (EE) increased constantly during the study period and did not differ significantly between the groups. In all groups the average increase in glucose oxidation was 40-50%, while fat oxidation decreased to a comparable extent. Infusions of heparin and LMWH had no effect on RQ or EE. A microcalorimetric study on isolated rat adipocytes in buffer solutions containing glucose, fat emulsion, heparin or LMWH was also made. The heat output from the adipocytes was not influenced by the presence of heparin or LMWH. In conclusion, infusion of heparin resulted in a pronounced increase in FFA availability, whereas LMWH exerted a less marked lipolytic effect. However, the heparin-induced elevations in plasma FFA were not accompanied by measurable rises in lipid oxidation rate.     

Clinical efficacy of low molecular weight heparin in postoperative thrombosis prophylaxis

Summary In a randomized controlled clinical trial, the efficacy and safety of two low molecular weight heparin (LMWH) fractions in the prophylaxis of deep vein thrombosis (DVT) were assessed. One hundred twenty-six patients undergoing major abdominal surgery received alternatively 2,500 APTT units b.i.d. of two LMWH fractions or 5,000 APTT units b.i.d. of an unfractionated sodium mucosal heparin (UFH). LMWH 2 differed from LMWH 1 by presenting a lower mean molecular weight and a higher anti-Xa/APTT ratio in vitro. Patients were randomly allocated to the three groups, and the development of DVT was studied with the¹²⁵I-fibrinogen uptake test (RFUT).The study was interrupted and the code broken prematurely because of otherwise unexplainable bleeding events.While no thrombosis and no severe bleeding were detected in the UFH group, three (7%) RFUT-positive DVT and two (5%) hemorrhagic complications occurred in the LMWH 1 group. No thrombosis and nine (22%) cases of severe bleeding were observed in the LMWH 2 group. Thus, the latter group differed significantly from the control group with regard to subjective and objective criteria for postoperative bleeding.Although these results do not allow general conclusions as to the value of LMWH fractions in the prevention of DVT, they indicate that these preparations just as ordinary heparin have a limited therapeutic range.Supported by a grant (Schm 345/4-2) from the Deutsche Forschungsgemeinschaft     

Subcutaneous low molecular weight heparin administration promotes wound healing in rats.

The influence of subcutaneous low molecular weight heparin (LMWH) compared with physiologic saline on the healing of abdominal wounds with and without prolene mesh was studied in rats. The collagen concentration was determined in the wound tissue and in prolene mesh 14, 21, 28 and 42 days after the skin incision in controls and in two groups of rats treated either with LMWH for 7 (I group) or 14 (II group) days after skin incision and prolene insertion. LMWH administration resulted in a significant increase of collagen content both in wound and in prolene mesh in total dose-dependent manner.     

In vivo treatment of rats with unfractionated heparin (UFH) or low molecular weight heparin (LMWH) does not affect experimentally induced colon carcinoma metastasis

Recent randomized trials have suggested that treatment with low molecular weight heparin (LMWH) improves survival of cancer patients with venous thromboembolism, as compared to treatment with unfractionated heparin (UFH). Experimental studies have shown that UFH has activities besides its anticoagulant function which may affect progression of malignancy, including stimulation of new blood vessel formation. In contrast, LMWH has been suggested to inhibit angiogenesis. In the present study, we compared quantitatively the effects of treatment with UFH, LMWH or placebo on the development of experimentally induced colon carcinoma metastases in rat liver and on tumor-associated angiogenesis. It is shown that UFH and LMWH in therapeutic dosages neither affect development of metastases nor tumor blood vessel formation in this animal model. These results indicate that heparins do not affect colon cancer metastasis in liver. Further studies in other animal models are required to establish the mechanisms by which heparins potentially affect cancer.     

Clinical benefit of low molecular weight heparin for ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with glycoprotein IIb/IIIa inhibitor

The efficacy of low molecular weight heparin (LMWH) with low dose unfractionated heparin (UFH) during percutaneous coronary intervention (PCI) with or without glycoprotein (Gp) IIb/IIIa inhibitor compared to UFH with or without Gp IIb/IIIa inhibitor has not been elucidated. Between October 2005 and July 2007, 2,535 patients with ST elevation acute myocardial infarction (STEMI) undergoing PCI in the Korean Acute Myocardial Infarction Registry (KAMIR) were assigned to either of two groups: a group with Gp IIb/IIIa inhibitor (n=476) or a group without Gp IIb/IIIa inhibitor (n=2,059). These groups were further subdivided according to the use of LMWH with low dose UFH (n=219) or UFH alone (n=257). The primary end points were cardiac death or myocardial infarction during the 30 days after the registration. The primary end point occurred in 4.1% (9/219) of patients managed with LMWH during PCI and Gp IIb/IIIa inhibitor and 10.8% (28/257) of patients managed with UFH and Gp IIb/IIIa inhibitor (odds ratio [OR], 0.290; 95% confidence interval [CI], 0.132-0.634; P=0.006). Thrombolysis In Myocardial Infarction (TIMI) with major bleeding was observed in LMHW and UFH with Gp IIb/IIIa inhibitor (1/219 [0.5%] vs 1/257 [0.4%], P=1.00). For patients with STEMI managed with a primary PCI and Gp IIb/IIIa inhibitor, LMWH is more beneficial than UFH.     

Effect of unfractionated heparin and a low molecular weight heparin fragment on the DNA synthesis of human thymocytes

The effect of unfractionated heparin and a low molecular weight heparin fragment was tested on the DNA synthesis of human thymocytes cultured for 5 and 48 h. At 5 h, in the absence of serum, there was a stimulation with the highest concentration of unfractionated heparin, 11.1 mg/ml. At 48 h, there was an inhibition with the highest concentration of both the unfractionated heparin and the heparin fragment. In the presence of serum unfractionated heparin in the highest concentration gave an inhibitory effect at 48 h. With 0.01-1.0 mg/ml of unfractionated heparin, a stimulating effect was obtained instead.     

Pathogenicity of human anti-platelet factor 4 (PF4)/heparin in vivo: generation of mouse anti-PF4/heparin and induction of thrombocytopenia by heparin

Heparin-induced thrombocytopenia/thrombosis (HIT) is a severe thrombotic disorder that occurs in ≈1% of patients treated with heparin. Affected patients commonly develop antibodies that recognize PF4/heparin complexes that may form on the surface of activated platelets and on the endothelium. However, it has not been established that anti-PF4/heparin antibodies are responsible for the clinical manifestations of HIT. To address this issue, we employed a recently developed model of active immunity to study the effect of IgG anti-PF4/heparin antibody in vivo. In previous studies we have shown that it is possible to induce autoimmune diseases such as systemic lupus erythematosus (SLE), anti-phospholipid syndrome (APS) or vasculitis in naive mice by active immunization with anti-DNA, anti-cardiolipin and anti-neutrophil cytoplasmic antibodies, respectively. Immunized animals develop anti-idiotypic antibodies (Ab₂) and, after 2–4 months, anti-anti-idiotypic antibodies (Ab₃). Ab₃s generated in this manner often simulate the binding activity of Ab₁ and their expression correlates with the development of specific clinical manifestations typical of the respective human disease. Based on this experience, naive BALB/c mice were immunized with IgG anti-PF4/heparin antibodies isolated from two patients with HIT. The actively immunized mice developed mouse anti-PF4/heparin antibody (Ab₃). Administration of unfractionated heparin, but not low molecular weight heparin (LMWH), to the actively immunized animals induced thrombocytopenia by day 4 of drug exposure. There was no evidence of thrombosis. The results of this study support the importance of anti-PF4/heparin antibodies in the pathogenesis of HIT. Further, this model may help to elucidate the factors responsible for thrombosis as well as providing means to assess new treatment options for patients with this disorder.     

低分子肝素治疗重度子痫前期患者外周血vWF、AT的变化

目的探讨低分子肝素能否改变重度子痫前期患者血浆中vWF含量,AT的活性水平,为低分子肝素用于重度子痫前期的治疗提供新的理论基础。方法选择2010年3月1日～2010年11月30日在天津医科大学宝坻临床学院、天津医科大学总医院分娩的重度子痫前期病人39例为研究组。根据入院顺序随机分成2组,传统治疗组20人,给予传统常规的治疗。低分子肝素治疗组19人,在传统常规治疗的基础上给予低分子肝素钙0.4m1,每天一次,皮下注射,两组分别于入院时及治疗3～5天后抽取孕妇静脉血,检测血浆vWF：Ag和AT：A及常规凝血试验。结果两组重度子痫前期患者治疗前血浆中vWF：Ag与同期对照组比较明显升高,而AT：A与同期对照组比较明显减少,低分子肝素治疗后血浆中vWF：Ag与治疗前比较明显降低,而AT：A与治疗前比较明显增高,传统方法治疗后血浆vWF：Ag和AT：A与治疗前比较差异无统计学意义。结论低分子肝素结合传统疗法治疗重度子痫前期患者,可改变患者血浆中vWF含量,AT的活性水平。     

A nonelutable low-molecular weight heparin stent coating for improved thromboresistance

Low-molecular weight heparin (LMWH) has been widely used as a systemic anticoagulant during percutaneous coronary intervention. In this study, LMWH was covalently immobilized to the surface of a cobalt chromium reservoir-based sirolimus-eluting stent to create a nonelutable nanoscale coating for enhanced thromboresistance. Toludine-blue stained stents revealed uniform heparin coverage on all surfaces of the stent. Scanning electron microscopy of stent strut cross-sections showed identical coating thickness on all sides; while the thickness was determined to be 320 nm by a focus-ion beam system. Secondary ion mass spectrometry showed constant concentrations of O, N, and S atoms throughout the depth of the surface, confirming the uniformity of the heparin coating. The nonelutable nature of the coating was confirmed in a modified Factor Xa inhibition assay which showed the stent had an equivalent of 3-5 heparin units/cm(2), while no elutable heparin was detected in wash solutions. The antithrombin binding capacity of the immobilized heparin was determined to be 60-80 pmol/cm(2) in an antithrombin uptake assay. The enhanced thromboresistance of the heparin coating was demonstrated in an in-vitro bovine blood flow loop which showed minimal visual thrombus accumulation and 95% reduction in platelet deposition compared to uncoated control stents. Drug-eluting stents with such nonelutable LMWH coating would represent a significant advance in the treatment of patients with complex lesions who are at increased risk of developing stent thrombosis.     

Stimulating effect of unfractionated heparin and a low molecular weight heparin fragment on the DNA synthesis response of human thymocytes to mercuric chloride

The effect of unfractionated heparin and a low molecular weight heparin fragment was tested on the DNA synthesis response of human thymocytes to mercuric chloride. In a concentration of 0.01-0.11 mg/ml, unfractionated heparin somewhat stimulated this response, while the heparin fragment at 11.1 mg/ml gave an evident stimulation of the response and a lower stimulation degree at 1.1 mg/ml.     

The role of heparin self-association in the gelation of heparin-functionalized polymers

The extensive use of the glycosaminoglycan (GAG) heparin in the design of emerging biomaterials has made the physical characterization of this heterogeneous biomacromolecule increasingly important. In this work, heparin solutions are characterized via dynamic light scattering to investigate heparin's self-association, since this behavior was recently hypothesized to play a role in the gelation of heparin-functionalized polymer hydrogels. Samples of either low molecular weight heparin or high molecular weight heparin were filtered using membranes with 100, 220, or 450 nm average pore sizes. The 100 and 220 nm filters produce a single population of monomers with a diameter range of 3-10nm in the intensity-weighted size distribution. However, the 450 nm filters reveal a second population of associated heparin. Increasing the solution concentration of high molecular weight heparin (HMWH) from 2.5 to 10 wt% causes the magnitude of the smaller population to decrease, while the diameter of the larger associated species approximately doubles. HMWH from different manufacturers displays varying degrees of association. Therefore, weaker associating HMWH can potentially be identified to control heparin self-interactions. Finally, fractionated, N-deacetylated low molecular weight heparin (LMWH) is compared to unmodified LMWH. The chemically modified heparin exhibits a heightened degree of association, suggesting an enhanced self-interaction. The increased negative charge of LMWH in the fractionated sample likely enhances polyelectrolyte interactions proposed to drive the association of these similarly charged polysaccharides. A more detailed understanding of heparin-heparin interactions will assist in the design of new scaffold materials with controlled release profiles, in the clinical use of heparin as an anticoagulant, and in investigations of interactions of other like-charged biomacromolecules.     

Low molecular weight heparin in the treatment of puromycin-induced nephrosis

Heparin may have a beneficial effect in proteinuric renal diseases, where negative charges of the glomerular capillary membrane are compromised. We evaluated the role of low molecular weight heparin (LMWH - 3000 Da) in puromycin aminonucleoside (PAN)-induced focal and segmental glomerulosclerosis in male Wistar rats: Controls (C) n=7, LMWH-treated group, n=9, subcutaneously (SC), 6 mg/kg every day. The PAN group (n=7) received 7 doses on weeks 0, 1, 2, 4, 6, 8, 10 (SC - 2mg/100g), and a group PAN+LMWH (n=6). After 12 weeks, cholesterol and triglycerides were higher in nephrotic groups, as well as proteinuria and urinary IgG. Kidney weight, glomerular volume, and glomerular sclerosis index were higher in the PAN-treated groups. Glomerular capillary length density (L(Vcap)) and glomerular capillary surface density (S(Vcap)) were lower in the PAN group, and mesangial fractional volume was higher. Fibronectin immunostaining was more intense in the PAN group, and collagens I and III were absent in the studied glomeruli. Thus, LMWH prevented mesangial expansion and capillaries changes, showing antiproliferative properties, despite worsening glomerular permeability changes in the PAN model. In conclusion, LMWH interferes in the complications of PAN model, but not through inhibition of the proteinuria.     

Influence of heparin and various glycosaminoglycans on activation of single chain urokinase-type plasminogen activator (scu-PA) by plasmin

Increase in the rate of activation of single chain urokinase-type plasminogen activator (scu-PA) to two chain urokinase (tcu-PA) by plasmin caused by heparin was observed to be molecular mass dependent. A heparin fraction of 30 kDa increased the catalytic efficiency of activation by 3.7-fold as opposed to 1.4-fold by heparin of average molecular weight. All of a range of glycosaminoglycans tested were observed to cause some increase in the rate of activation through chondroitin sulphate K (Glc UA-3-SO₄- Gal-NAc-4-SO₄) was twice as potent as unfractionated heparin. Increase in rate was due to variation in kcat and Km. This effect was concentration-dependent such that Km was decreased at low heparin concentration, but at high concentration of heparin increased to beyond that in its absence. A progressive increase in kcat was observed with heparin concentration. Heparin also caused increase in catalytic efficiency of K5 plasmin suggesting that the observed effects may be due to interaction with scu-PA rather than plasmin. Heparin had no influence on kallikrein activation of scu-PA. The influence of glycosaminoglycans upon this reaction may be of importance in controlling the physiological function of scu-PA.     

Effect of low molecular weight heparin on bone metabolism and hyperlipidemia in patients on maintenance hemodialysis

The effect of low molecular weight heparin (LMWH) on serum lipid profile in hemodialysis remains controversial and its effect on bone metabolism has not been studied. A crossover study was conducted in 40 patients on stable hemodialysis using unfractionated heparin (UFH) for more than 24 months. These patients were then treated with a LMWH (nadroparin-Ca) for 8 months during hemodialysis and subsequently switched back to UFH for 12 months. Serum lipid profile, biochemical markers for bone metabolism, and bone densitometry (BMD) were monitored at four-month intervals while all medications remained unchanged. Cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), lipoprotein(a) (Lp(a)), apolipoprotein B (Apo B) were raised in 35%, 29%, 12%, 24% and 24% of patients respectively. High-density lipoprotein-cholesterol (HDL-C) and apolipoprotein A1 (Apo A-1) were reduced in 47% and 9% of patients. Bone-specific alkaline phosphatase (BALP) and intact osteocalcin (OSC), both reflecting osteoblastic activity, were raised in 65% and 94% of patients. Tartrate-resistant acid phosphatase (TRACP) reflecting osteoclastic activity and parathyroid hormone (PTH) were elevated in 35% and 88% of patients. Following LMWH treatment, TC, Tg, Lp(a) and Apo B were reduced by 7%, 30%, 21% and 10% respectively (p<0.05 or <0.01) while Apo A-1 were raised by 7% (p<0.01). Simultaneously, TRACP was reduced by 13% (p<0.05). These biochemical changes were detected soon after 4 months of LMWH administration. Although BMD values in our patients were lower than those of age-matched normal subjects, significant changes were not observed with LMWH treatment. After switching back to UFH for hemodialysis, these biochemical indices reverted to previous values during UFH treatment with a significant higher level in TC and Apo B while serum Apo A-1 remained elevated. Our study suggests LMWH may partially alleviate hyperlipidemia and, perhaps, osteoporosis associated with UFH administration in patients on maintenance hemodialysis.     

Investigation of the effects of heparin and low molecular weight heparin on E-cadherin and laminin expression in rat pregnancy by immunohistochemistry

BACKGROUND: Heparin and low molecular weight heparin (LMWH) are used widely to improve the pregnancy outcome in women with thrombophilia, miscarriage, recurrent miscarriage and fetal death. This study was designed to investigate the effects of heparin and LMWHs, enoxaparin and tinzaparin, on E-cadherin and laminin expression in placental and decidual tissues in rat pregnancy. METHODS: Wistar albino female rats (n = 48) were randomly assigned to four study groups (normal saline, heparin, enoxaparin and tinzaparin) in the preconceptional period. Tissue sections of placenta and decidua were immunohistochemically examined for the expression of E-cadherin and laminin. RESULTS: E-cadherin placental staining score of heparin group was significantly lower and E-cadherin decidual staining score of heparin and enoxaparin groups were significantly lower than control group. There were no significant differences in placental and decidual laminin staining scores among the study groups. CONCLUSIONS: Heparin and enoxaparin can reduce E-cadherin expression but not laminin expression in rat pregnancy. They might modulate trophoblast invasion. We suggest that this is the possible underlying mechanism involving in improvement of trophoblast invasion by the use of heparin and LMWH in patients with the history of miscarriage.     

Dalteparin, a low-molecular-weight heparin, promotes angiogenesis mediated by heparin-binding VEGF-A in vivo

Norrby K, Nordenhem A. Dalteparin, a low‐molecular‐weight heparin, promotes angiogenesis mediated by heparin‐binding VEGF‐A in vivo. APMIS 2010; 118: 949–57. Tumors are angiogenesis dependent and vascular endothelial growth factor‐A (VEGF‐A), a heparin‐binding protein, is a key angiogenic factor. As chemotherapy and co‐treatment with anticoagulant low‐molecular‐weight heparin (LMWH) are common in cancer patients, we investigated whether angiogenesis in vivo mediated by VEGF‐A is modulated by metronomic‐type treatment with: (i) the LMWH dalteparin; (ii) low‐dosage cytostatic epirubicin; or (iii) a combination of these two drugs. Using the quantitative rat mesentery angiogenesis assay, in which angiogenesis was induced by intraperitoneal injection of very low doses of VEGF, dalteparin sodium (Fragmin^®) and epirubicin (Farmorubicin^®) were administered separately or in combination by continuous subcutaneous infusion at a constant rate for 14 consecutive days. Dalteparin was administered at 27, 80, or 240 IU/kg/day, i.e., doses that reflect the clinical usage of this drug, while epirubicin was given at the well‐tolerated dosage of 0.4 mg/kg/day. While dalteparin significantly stimulated angiogenesis in an inversely dose‐dependent manner, epirubicin did not significantly affect angiogenesis. However, concurrent treatment with dalteparin and epirubicin significantly inhibited angiogenesis. The effect of dalteparin is the first demonstration of a proangiogenic effect of any LMWH in vivo. The fact that co‐treatment with dalteparin and epirubicin significantly inhibited angiogenesis suggests a complex drug effect.     

Inhibitory effect of non-anticoagulant heparin (S-NACH) on pancreatic cancer cell adhesion and metastasis in human umbilical cord vessel segment and in mouse model

Metastasis is the most devastating aspect of cancer and it is the main cause of morbidity and mortality in cancer patients. Tumor cell adhesion to the vascular endothelial cell lining is an important step in metastatic progression and is prompted by platelets. Mucin 1 is over-expressed and aberrantly glycosylated in more than 60% of pancreatic ductal adeno-carcinomas, which mediate adhesion of pancreatic cancer cells to platelets via P-selectin. The anticoagulant low molecular weight heparins (LMWHs), which are commonly used in venous Thromboprophylaxis and treatment, appear to have an effect on cancer survival. The aim of this study is to investigate the effect of platelets on human pancreatic cancer MPanc96 cell adhesion to the endothelial cell vessel wall, and to examine the effect of heparin derivatives on MPanc96 adhesion using a novel, in vitro model of human umbilical cord vein. The modified heparin S-NACH (sulfated non-anticoagulant heparin), which is devoid of antithrombin (AT) binding and devoid of inhibition of systemic AT-dependent coagulation factors such as factor Xa and IIa, and the LMWH tinzaparin both potently reduced adhesion and invasion of fluorescence-labeled MPanc96 cancer cells to the endothelial layer of umbilical cord vein in a dose-dependent manner. S-NACH effectively inhibited P-selectin mediated MPanc96 cell adhesion, and inhibited cell adhesion and invasion similar to tinzaparin, indicating that systemic anticoagulation is not a necessary component for heparin attenuation of cancer cell adhesion, invasion, and metastasis. Also, S-NACH and tinzaparin versus unfractionated heparin, heparin derivatives enoxaparin, deltaparin, fraxiparin, and fondaparinux were evaluated for their effect on platelet-cancer cell adhesion. An in vivo anti-metastatic S-NACH-treated nude mouse model of MPanc96 pancreatic cancer cell metastasis demonstrated potent anti-metastasis efficacy as evidenced by IVIS imaging and histological staining.     

A comparison of the sensitivity of APTT reagents to the effects of enoxaparin, a low-molecular weight heparin

Low-molecular weight heparin (LMWH) is the product of enzymatic or chemical degradation of unfractionated heparin (UFH). It has been found to have better bio-availibility, more predictable dose response and can be used as an alternative to UFH for prophylaxis and treatment of thrombotic disorders. It is claimed that no laboratory monitoring is necessary for LMWH therapy; however, for the aged, renal impaired, obese or grossly underweight, monitoring of dose effect with anti-Xa assay is recommended. The activated partial thromboplastin time (APTT), which is the test of choice for UFH monitoring, is believed to be insensitive to the effect of LMWH. The sensitivity of the APTT to heparin lies in the APTT reagent used. In this study, eight different APTT reagents were used to compare the APTT with anti-Xa activity in ex vivo plasma from patients who were on enoxaparin (LMWH, Clexane) therapy. It was found that, as with UFH, APTT reagents show variable sensitivity to LMWH. The APTTs from all eight reagents were found to have a linear relationship to anti-Xa activity. The APTT results using three of the reagents gave an indication of the use of LMWH therapy. It was also found that patients who were lupus anticoagulant (LA)-positive had much more prolonged APTTs when on LMWH therapy; however, a linear correlation between APTT and anti-Xa was not present in these patients.