Journal articles: 'Subcutaneous heparin injection'

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Baer, CL, WM Bennett, DA Folwick, and RS Erickson. "Effectiveness of a jet injection system in administering morphine and heparin to healthy adults." American Journal of Critical Care 5, no. 1 (January 1, 1996): 42–48. http://dx.doi.org/10.4037/ajcc1996.5.1.42.

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BACKGROUND: Jet injection eliminates the risk of contaminated needlestick injuries when giving intramuscular or subcutaneous medications. Clinical efficacy of the Biojector System was equivalent to that of needle and syringe injection in unpublished trials with vaccines, but had not been studied using other drugs. OBJECTIVE: To compare the effectiveness of the Biojector with conventional needle and syringe injection in administering intramuscular morphine and subcutaneous heparin to healthy adults, as measured by plasma drug concentration. METHODS: Intramuscular injections of morphine 8 mg (5 mg if weight < or = 65 kg) were given 24 hours apart with the jet injector and with a needle and syringe to 30 subjects at the deltoid site and 10 subjects at the dorsogluteal site. Blood samples for plasma concentrations of free morphine were drawn at 15, 30, 45, 60, 120, and 240 minutes and were analyzed using radioimmunoassay. Abdominal subcutaneous injections of heparin 3500 U were given every 8 hours for 5 days with both injection methods to 29 subjects, with 48 hours between the two series. Daily blood samples for plasma heparin were analyzed by colorimetric assay for antifactor Xa activity. RESULTS: Mean free morphine concentration, peak value, and area under the curve did not differ significantly between the deltoid and dorsogluteal sites or between the jet injector and needle and syringe. Values of mean daily heparin concentrations and area under the curve were low and did not differ between the two injection methods. CONCLUSION: Plasma drug concentrations provided by the Biojector were equivalent to those provided by conventional needle and syringe when administering intramuscular morphine and low-dose subcutaneous heparin.

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Hadley, SA, M. Chang, and K. Rogers. "Effect of syringe size on bruising following subcutaneous heparin injection." American Journal of Critical Care 5, no. 4 (July 1, 1996): 271–76. http://dx.doi.org/10.4037/ajcc1996.5.4.271.

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BACKGROUND: Bruising and induration associated with subcutaneous heparin injection often result in sustained tenderness and severe ecchymosis at the injection site. Research-based practice guidelines for subcutaneous heparin administration are needed to reduce these adverse effects. OBJECTIVES: The purpose of this study was to investigate the effect of syringe size (1-mL vs 3-mL) on postinjection-site bruising and induration following the administration of subcutaneous heparin. METHODS: A convenience sample of 29 subjects receiving 5000 units of subcutaneous heparin at least twice a day was recruited from a large urban hospital. Subjects received their regularly scheduled subcutaneous heparin injections with a 3-mL or a 1-mL syringe in a randomized sequence using a standardized procedure. Injection sites were assessed for bruises and induration at 24, 48, and 72 hours after injection. RESULTS: The incidence of injection site bruising with 1- and 3-mL syringes was 79% and 69%, respectively. The use of a 3-mL vs 1-mL syringe resulted in significantly smaller bruises at 48 and 72 hours after injection. Induration at the injection site occurred in three patients. CONCLUSIONS: Findings suggest that 3-mL syringes are preferable to 1-mL syringes for heparin administration. The effect of other injection-related variables should be studied with the use of the 3-mL syringe, and tested on various populations.

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Morrison, F. S. "Site for subcutaneous heparin injection." Archives of Internal Medicine 152, no. 1 (January 1, 1992): 202a—202. http://dx.doi.org/10.1001/archinte.152.1.202a.

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Inwood, M. J. "Site for subcutaneous heparin injection." Archives of Internal Medicine 153, no. 2 (January 25, 1993): 263. http://dx.doi.org/10.1001/archinte.153.2.263.

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Morrison, Francis S. "Site for Subcutaneous Heparin Injection." Archives of Internal Medicine 152, no. 1 (January 1, 1992): 202. http://dx.doi.org/10.1001/archinte.1992.00400130192027.

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Inwood, Martin J. "Site for Subcutaneous Heparin Injection." Archives of Internal Medicine 153, no. 2 (January 25, 1993): 263. http://dx.doi.org/10.1001/archinte.1993.00410020105014.

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Mar, Adrian W.-Y., Barry Dixon, Kamal Ibrahim, and John D. Parkin. "Skin necrosis following subcutaneous heparin injection." Australasian Journal of Dermatology 36, no. 4 (November 1995): 201–3. http://dx.doi.org/10.1111/j.1440-0960.1995.tb00974.x.

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Tsapatsaris, Nicholas P. "Site for Subcutaneous Heparin Injection-Reply." Archives of Internal Medicine 152, no. 1 (January 1, 1992): 202. http://dx.doi.org/10.1001/archinte.1992.00400130192028.

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Tsapatsaris, Nicholas P. "Site for Subcutaneous Heparin Injection-Reply." Archives of Internal Medicine 153, no. 2 (January 25, 1993): 263. http://dx.doi.org/10.1001/archinte.1993.00410020105015.

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Tonn, Michael E., Robyn A. Schaiff, and Marin H. Kollef. "Enoxaparin-Associated Dermal Necrosis: A Consequence of Cross-Reactivity with Heparin-Mediated Antibodies." Annals of Pharmacotherapy 31, no. 3 (March 1997): 323–26. http://dx.doi.org/10.1177/106002809703100310.

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Objective To describe a patient with enoxaparin-induced dermal necrosis and to review previously reported cases of skin manifestations associated with low-molecular-weight heparins. Case Summary A 43-year-old white woman with adult respiratory distress syndrome developed localized dermal necrosis and thrombocytopenia secondary to subcutaneous administration of unfractionated heparin. Upper extremity thrombi that had developed after administration of subcutaneous heparin at an outside hospital were treated with subcutaneous enoxaparin. Although platelet counts remained stable during enoxaparin therapy, dermal necrosis developed at the injection site. Parenteral anticoagulant therapy was discontinued and the necrotic lesions secondary to enoxaparin resolved with minimal local care. Discussion Numerous cases of dermal necrosis secondary to heparin administration have been reported while this reaction secondary to enoxaparin use has been reported only briefly. It has been postulated that dermal necrosis secondary to heparin is associated with heparin-induced thrombocytopenia and is a result of heparin-mediated thrombosis in the microvasculature. Antibodies to heparin have cross-reactivity with enoxaparin; therefore, dermal necrosis secondary to enoxaparin may occur by a similar mechanism. Conclusions Although enoxaparin-associated dermal necrosis appears to be a rare occurrence, we advise against the use of enoxaparin or other low-molecular-weight heparins in patients with a previous history of heparin-associated thrombocytopenia or heparin-induced dermal necrosis.

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Anderson, David R., Jeffrey S. Ginsberg, Robert Burrows, and Pat Brill-Edwards. "Subcutaneous Heparin Therapy during Pregnancy: a Need for Concern at the Time of Delivery." Thrombosis and Haemostasis 65, no. 03 (1991): 248–50. http://dx.doi.org/10.1055/s-0038-1647659.

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SummarySubcutaneous heparin is the treatment of choice for women requiring anticoagulant therapy during pregnancy. However, heparin therapy presents a management problem at delivery because of its potential to cause a persistent anticoagulant effect and thus increase the risk of bleeding. In order to avoid therapeutic complications it has been our practice to have women eithei discontinue their heparin injections with the onset of labour or to terminate heparin injections 12 h prior to elective induction. To determine the safety of our anticoagulant protocol at delivery we reviewed consecutive patients treated with subcutaneous heparin therapy during pregnarcl, at our centre. Over a 23 month period we found that six of 11 women receiving subcutaneous heparin during pregnancy delivered while their aPTT was prolonged. In addition, three women received intravenous protamine sulphate prior to delivery and in one patient major bleeding occurred during an emergency cesarean section. Those women who had elevated aPTTs at the time of delivery all gave birth within 28 h of their last injection of heparin. In order to avoid a prolonged aPTT at delivery, we have now adopted a more conservative approach to the management of subcutaneous heparin use at term. Subcutaneous heparin is discontinued 24 h prior to commencing an elective induction of labour.

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Rohrich, Rod, Lee Thornton, and Edmund Billings. "Skin Necrosis Following Subcutaneous Injection of Heparin." Seminars in Plastic Surgery 9, no. 02 (1995): 83–87. http://dx.doi.org/10.1055/s-2008-1080306.

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O’Brien, J. R., M. D. Etherington, and Michelle A. Pashley. "The Heparin-Mobilisable Pool of Platelet Factor 4: A Comparison of Intravenous and Subcutaneous Heparin and Kabi Heparin Fragment 2165." Thrombosis and Haemostasis 54, no. 04 (1985): 735–38. http://dx.doi.org/10.1055/s-0038-1660121.

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SummarySome clinical advantages are claimed for low molecular weight heparin so the mobilisation of platelet factor 4 (PF 4) from the endothelial pool by the heparins may be relevant. Unfractionated (UF) heparin has been compared with Kabi heparin fragment 2165. A single intravenous (i. v.) injection of 60 iu/kg heparin was compared with 5000 anti-Xa units of Kabi-2165. Less PF 4 was mobilised by Kabi-2165 and some apparently remained in the pool and was released when the pool was subsequently challenged by giving i.v. heparin. Subcutaneous (s. c.) injections of 5000 iu heparin twice daily were compared with 5000 anti-Xa units of Kabi-2165 once daily, each given for a week. The plasma PF 4 was never raised yet when finally challenged with i.v. heparin the pool was “empty” or refractory after the s.c. heparin but some PF 4 remained after the s.c. Kabi-2165. The two glycosaminogly-cans (GAGs) had widely differing half-lives but the t/2 of the PF 4 mobilised by the two GAGs was similar even though the PF 4 is apparently bound to the GAG.

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Mangar, Amrita, Th Bhimo Singh, Th Sachin Deba Singh, B. Romita, Nungsangla Pongener, and Deepa Mala Subba. "Low Molecular Weight Heparin Induced Bullous Hemorrhagic Dermatosis." International Journal of Medical and Dental Sciences 5, no. 1 (January 17, 2016): 1067. http://dx.doi.org/10.19056/ijmdsjssmes/2016/v5i1/83577.

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Heparin-induced bullous hemorrhagic dermatosis is a rare, recently described side-effect of subcutaneous heparin injection. We present a case of a male patient with a bullous hemorrhagic eruption following the administration of subcutaneous LMWH. A diagnosis of Heparin-induced bullous hemorrhagic dermatosis was made by HPE (Histopathological examination) of tissue biopsy from the bullous lesion and the exclusion of other laboratory finding.

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Alfeky, Haz, Paul McArthur, and Yasser Helmy. "Salvaging Digital Replantation and Revascularisation: Efficiency of Heparin Solution Subcutaneous Injection." Surgery Research and Practice 2018 (November 21, 2018): 1–6. http://dx.doi.org/10.1155/2018/1601738.

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Background. Distal digital replantation and revascularisation remains one of the demanding microsurgical procedures due to the difficulty of vascular anastomosis. Venous congestion is the most commonly encountered problem after replantation due to the difficulty of venous anastomosis in traumatic injuries. Heparin, among other drugs, is commonly used to facilitate venous drainage and prevent thrombosis. However, systemic heparin can be contraindicated in some patients. The senior author has experience of subcutaneous heparin injection for venous congestion in thirteen patients. Methods. An amount of 1 ml of calcium heparin (25,000 U) was mixed in 2.4 ml of normal saline making a solution that has 1000 U per 0.1 ml. 1000 U (0.1 ml) of the solution was injected directly into the congested replanted digits. This was repeated twice daily until venous congestion improved. Results. All the congested replanted digits survived without systemic side effects. There were no local side effects of the treatment. The PT and APTT have shown slight increase but they remained within the normal range. Haemoglobin levels have dropped slightly but no patients were at any risk of developing anaemia or needed blood transfusion. Conclusions. Subcutaneous heparin injections can salvage the replanted digits when venous congestion is a warning flag for replantation failure. It is safe and very efficient in patients where systemic heparin cannot be administered. However, this article shows the results in only thirteen patients which is a small number to show the efficacy, safety, and side effects.

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Saivin, S., C. Caranobe, M. Petitou, J. C. Lormeau, G. Houin, and B. Boneu. "Pharmacodynamic Properties of Long Lasting Butyryl Heparin Derivatives in the Rabbit." Thrombosis and Haemostasis 67, no. 05 (1992): 550–55. http://dx.doi.org/10.1055/s-0038-1648492.

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SummaryThis paper reports on the pharmacodynamic properties of butyryl derivatives of unfractionated heparin (C4-UH) and of low molecular weight heparin (C4-CY 216) after bolus intravenous injection, constant infusion and subcutaneous administration to rabbits. The pharmacodynamic properties of the two butyryl derivatives were compared to those of the parent compounds, unfractionated heparin (UH) and low molecular weight heparin (CY 216). After bolus intravenous injection of increasing doses, the disposition of the butyryl derivatives were comparable to that of their parent compounds up to 3 mg kg-1. Over this dose, their clearances became 2 to 3 times lower. These long lasting properties were confirmed by constant intravenous infusion experiments. After subcutaneous administration, the bioavailability of C4-UH remained low (10%) at any dose while that of C4-CY 216 ranged from 42 to 120%. If these findings are confirmed in man, these new derivatives open the possibility of treating established deep vein thrombosis with only one daily injection of a butyryl derivative of low molecular weight heparin.

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Real, Esperanza, Enric Grau, Miguel Rubio, and Teresa Torrecilla. "Skin necrosis after subcutaneous low molecular weight heparin injection." American Journal of Hematology 49, no. 3 (July 1995): 253–54. http://dx.doi.org/10.1002/ajh.2830490316.

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Eriksson, E., I. M. Wollter, B. Christenson, L. Stigendal, and B. Risberg. "Heparin and Fibrinolysis - Comparison of Subcutaneous Administration of Unfractionated and Low Molecular Weight Heparin." Thrombosis and Haemostasis 59, no. 02 (1988): 284–88. http://dx.doi.org/10.1055/s-0038-1642772.

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SummaryThe effects on the fibrinolytic system after a single s.c. bolus injection (at 9 a.m.) of either 5000 IU conventional heparin or 5000 anti-Xa U of a fractionated low molecular weight heparin (Fragmin, KabiVitrum, Sweden) were investigated in 9 healthy volunteers. The effects were compared to those of an injection of normal saline in 6 volunteers. Samples for biochemical analyses were taken regularily during 6 hours after drug or placebo administration.In the coagulation system the following parameters were measured: Activated partial thromboplastin time (APTT), anti- Xa activity, thrombin time and fibrinogen. The fibrinolytic system was monitored by analysing: plasminogen, ɑ2-antiplasmin, fibrinogen) degradation products (FDP), euglobulin clot lysis time (ECLT), tissue plasminogen activator (t-PA) activity, t-PA antigen and plasminogen activator inhibitor (PAI) activity. Injection of the 2 drugs was followed by elevations in APTT and anti-Xa activity, and were more pronounced for Fragmin than heparin. The fibrinolytic system exhibited a diurnal variation with decreasing PAI activity and increasing t-PA activity during the day. Volunteers receiving normal saline (placebo) showed a similar pattern. The results were unrelated to heparin.It is concluded from this study that neither heparin nor Fragmin had any significant effect on the fibrinolytic parameters when measured after a single s.c. bolus injection since the observed variations were within the diurnal range.

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Schindewolf, Marc, Jochen Utikal, Edelgard Lindhoff-Last, Wolf-Henning Boehncke, and Ralf Ludwig. "Management of cutaneous type IV hypersensitivity reactions induced by heparin." Thrombosis and Haemostasis 96, no. 11 (2006): 611–17. http://dx.doi.org/10.1160/th06-04-0210.

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SummaryLocalized hypersensitivity reactions to subcutaneous heparin injections have been described since 1952. Yet, the incidence of these reactions, which are distinct from skin lesions associated with heparin-induced thrombocytopenia type II (HIT II), remains uncertain. However, in the last 10 years an increasing number of patients have been reported, leading to the assumption that cutaneous hypersensitivity reactions towards heparin are underreported. Clinically patients present with itching, sometimes infiltrated, and blistering erythemas at the injection sites of heparins. The diagnosis of cutaneous heparin allergy may, on the one hand, lead to delay of required medical or surgical treatment. On the other hand, delayed initiation of treatment may lead to a generalized eczematous reaction. Hence, from review of 223 cases of patients with cutaneous hypersensitivity reactions to heparin, we here summarize the clinical picture of cutaneous type IV allergic reactions, define risk factors on both the patient- and drug-side, and give an overview of principle therapeutic alternatives, as well as recommendations for treatment options for emergency and elective patients. As the proposed management of patients with cutaneous hypersensitivity reactions to heparin may have fatal consequences when applied in patients with HIT type II, diagnosis of skin lesions in heparin-treated patients needs to be precise.

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Schiele, F., A. Vuillemenot, Ph Kramarz, Y. Kieffer, J. Soria, C. Soria, A. Camez, M. C. Mirshahi, and J. P. Bassand. "A Pilot Study of Subcutaneous Recombinant Hirudin (HBW 023) in the Treatment of Deep Vein Thrombosis." Thrombosis and Haemostasis 71, no. 05 (1994): 558–62. http://dx.doi.org/10.1055/s-0038-1642482.

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SummaryBackground: Recombinant hirudin, a pure, specific antithrombin could be more effective than heparin in the treatment of deep vein thrombosis, but its short half-life requires constant intravenous infusion, whereas subcutaneous administration of recombinant hirudin can ensure stable and prolonged plasma levels. The aim of our study was to assess the pharmacokinetics, the results on the coagulation variables, and the safety of a recombinant hirudin (HBW 023) administered subcutaneously in patients suffering from deep vein thrombosis.Methods: Recombinant hirudin (HBW 023) was administered subcutaneously to 10 patients with recent deep vein thrombosis, at a dose of 0.75 mg/kg of body weight twice daily for 5 days, after which standard heparin and acenocoumarol were introduced. Bilateral lower limb venography, and pulmonary angiography, and/or ventilation-perfusion lung scan were carried out on day 1 prior to recombinant hirudin injection and repeated on day 5. aPTT and recombinant hirudin plasma levels were serially assessed after the 1st and the 10th injections. Prothrombin fragments 1 + 2, thrombin-antithrombin III complexes, fibrin degradation products were collected on days 1 and 5.Results: Clinical evolution was uneventful in all but one patient who had a probable recurrence of pulmonary embolism on day 4. No hemorrhagic complication, no untoward biological event was observed. On days 5, Mardcr score was unchanged or had decreased. Plasma levels of recombinant hirudin peaked in between 3 and 4 h following the injection. aPTT values paralleled, and were significantly correlated with plasma levels of recombinant hirudin on day 1 as well on day 5 (r = 0.903, r = 0.948 respectively). Fragment 1 + 2, and thrombin antithrombin complexes non-significantly decreased from day 1 to day 5.Conclusions: Subcutaneous administration of recombinant hirudin ensures prolonged stable plasma levels of recombinant hirudin which results in efficient anticoagulation. A dose-ranging study conducted with subcutaneous recombinant hirudin in comparison to conventional heparin therapy may answer the question as to efficacy.

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Trautmann, Axel, and Cornelia S. Seitz. "Heparin Allergy: Delayed-Type Non–IgE-Mediated Allergic Hypersensitivity to Subcutaneous Heparin Injection." Immunology and Allergy Clinics of North America 29, no. 3 (August 2009): 469–80. http://dx.doi.org/10.1016/j.iac.2009.04.006.

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Greinacher, Andreas. "Treatment of Heparin-Induced Thrombocytopenia." Thrombosis and Haemostasis 82, no. 08 (1999): 457–67. http://dx.doi.org/10.1055/s-0037-1615866.

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IntroductionUnfractionated heparin (UFH) and low molecular weight heparin (LMWH) are the most widely used anticoagulants when parenteral anticoagulation with a short half-life is required. Both can be administered subcutaneously and intravenously, and both have been shown to be effective in a variety of clinical settings.1 UFH has several limitations. One is its poor bioavailability after subcutaneous injection and the marked variability in its anticoagulant response in patients with an acute thromboembolic complication.2,3 Another major issue associated with UFH is the induction of heparin-induced thrombocytopenia (HIT). Both limitations are closely linked,4 as the underlying cause is the high density of negative charges on the heparin molecule and its molecular weight. Both are responsible for the binding of heparin to plasma proteins other than antithrombin (AT), such as platelet factor 4 (PF4) and to several cell types. This leads to heparin-platelet interaction, the formation of HIT antigen (i.e., PF4/heparin complexes), and inhibition of the anticoagulant effect of heparin (aPTT-nonresponder).

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Tibballs, J., and S. K. Sutherland. "The Efficacy of Heparin in the Treatment of Common Brown Snake (Pseudonaja textilis) Envenomation." Anaesthesia and Intensive Care 20, no. 1 (February 1992): 33–37. http://dx.doi.org/10.1177/0310057x9202000106.

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The efficacy of heparin therapy after subcutaneous injection of Common Brown Snake (Pseudonaja textilis) venom was studied in anaesthetised, mechanically ventilated dogs. Intravenous heparin (100 U/kg), administered fifteen minutes after envenomation, neither prevented nor hastened the recovery from cardiovascular depression and coagulopathy observed after venom administration. Heparin therapy is not recommended for the treatment of established human envenomation.

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Stevenson, Heather P., G. Pooler, R. Archbold, Paul Johnston, Ian S. Young, and Brian Sheridan. "Misleading serum free thyroxine results during low molecular weight heparin treatment." Clinical Chemistry 44, no. 5 (May 1, 1998): 1002–7. http://dx.doi.org/10.1093/clinchem/44.5.1002.

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Abstract Measured free thyroxine concentrations in serum increase markedly after intravenous heparin administration, but the effect of heparin administered subcutaneously has not been adequately documented. We found in vitro increases of up to 63% in measured FT4 after a single dose of subcutaneous heparin (enoxaparin, 2000 units) in nine healthy volunteers, and the magnitude of these increases was correlated with initial serum triglyceride concentrations (r = 0.93, P <0.005) and in vitro free fatty acid release (r = 0.88, P <0.005). In 10 cardiac inpatients receiving repeated doses of enoxaparin (2000 units twice daily), measured FT4 increased by up to 171% in specimens taken 2–6 h after injection. When specimens were obtained 10 h after injection, the effect appeared to be minimized, with in vitro increases of <40%, but such increases may still be sufficient to cause interpretative errors. If FT4 estimation is absolutely necessary in patients receiving enoxaparin, specimens should be taken ≥10 h postdose and analyzed within 24 h.

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Jueakaew, Sommapun, Rattana Piancharoensin, Natchayakorn Pinkesorn, Sarunya Thippayarom, and Nuttawut Sermsathanasawadi. "Novel subcutaneous low-molecular-weight heparin injection technique to reduce post-injection bruising." Phlebology: The Journal of Venous Disease 34, no. 6 (November 19, 2018): 399–405. http://dx.doi.org/10.1177/0268355518813512.

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Objective To investigate the efficacy of a novel low-molecular-weight heparin injection technique compared to the standard technique relative to bruising incidence, bruise size, and pain. Methods A randomized controlled trial was conducted in 44 patients with acute deep vein thrombosis. Patients who were randomized into the control group received a 10-s duration injection with immediate needle withdrawal, whereas study group patients received a 30-s duration injection with a 10-s pause before needle withdrawal. Two injection sites were assessed for pain and bruising between 48 and 60 h after injection. Results Bruises occurred in 50.0% and 18.2% of control and study group patients, respectively ( p = 0.03). Mean bruise size between 48 and 60 h after injection was 172.73 ± 372.60 mm2 and 28.18 ± 70.01 mm2 in the control group and study group, respectively ( p = 0.026). Pain scores were comparable between groups. Conclusion A 30-s duration injection with a 10-s pause before needle withdrawal resulted in significantly fewer and smaller bruises.

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Hadley, S. A., M. Chang, and K. Rogers. "Effect of syringe size on bruising following subcutaneous heparin injection." International Journal of Trauma Nursing 2, no. 4 (October 1996): 119–20. http://dx.doi.org/10.1016/s1075-4210(96)80077-0.

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Zeraatkari, Khadijeh, Mehri Karimi, Mohammad K. Shahrzad, and Tahereh Changiz. "Comparison of heparin subcutaneous injection in thigh, arm & abdomen." Canadian Journal of Anesthesia/Journal canadien d'anesthésie 52, S1 (June 2005): A109. http://dx.doi.org/10.1007/bf03023147.

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Bendetowicz, A. Vicky, Hu Kai, Richard Knebel, H. Caplain, H. Coenraad Hemker, Theo Lindhout, and Suzette Béguin. "The Effect of Subcutaneous Injection of Unfractionated and Low Molecular Weight Heparin on Thrombin Generation in Platelet Rich Plasma - A Study in Human Volunteers." Thrombosis and Haemostasis 72, no. 05 (1994): 705–12. http://dx.doi.org/10.1055/s-0038-1648946.

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SummaryWe administered a dose of unfractionated heparin (UFH) and two doses of a low molecular weight heparin (LMWH) to healthy volunteers by SC injection. The doses given were: a) UFH, 5000IU, which represents 8.7 mg of >5,400 MW active heparin (ACLM) and no <5,400 active heparin (BCLM), b) enoxaparin 40 mg (3.4 mg ACLM, 2.2 mg BCLM) and c) enoxaparin 1 mg/kg body weight (on the mean 75 mg, containing 6.4 mg ACLM and 4.1 mg BCLM). We determined the effect on thrombin generation in platelet rich plasma (PRP) between 1 and 8 h after injection. UFH administration caused only a 5-8% inhibition of the thrombin potential (i. e. the area under the thrombin generation curve). Significantly higher inhibition of the thrombin potential was seen after administration of both doses of enoxaparin. To wit 9-26% at the low dose and 29-46% at the high dose. UFH injection caused a prolongation of the lag-time before the thrombin burst. Only with the high dose of enoxaparin the lag-times were significantly more prolonged with enoxaparin than with UFH.Excess amounts of platelet factor 4 (PF4) were able to neutralize completely the anti-thrombin activity in normal plasma spiked with enoxaparin as well as in plasma samples obtained after SC enoxaparin injection. With a large excess of PF4 the anti-factor Xa activity could be inhibited to a maximum of 50%. This indicates that ACLM (above critical length material, MW >5400) is neutralized completely by PF4 whereas BCLM (below critical length material, MW <5400) is not. The anti-thrombin heparin-activity, hence the ACLM fraction of heparin, was shown to have disappeared from the serum of PRP samples. The BCLM fraction was found after coagulation of PRP in concentrations that were indistinguishable from those in the PPP.We conclude that in PRP the activity of the BCLM fraction of injected LMWH remains after platelet activation. The possible role of this activity in thrombin inhibition and in the antithrombotic action of low molecular weight heparins is discussed.

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Gray, Angel, Debra Hoppensteadt, Matthew Hejna, and Jawed Fareed. "Effect of heparin and its derivatives on the progression of tumor growth in mouse Lewis lung carcinoma model." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): e13115-e13115. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e13115.

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e13115 Background: Preclinical evidence suggests that heparins have an effect on tumor progression independent of their anticoagulant activity. Heparins have also been shown to exhibit interactions with growth factors and other cellular receptors. This study was designed to investigate whether heparin and its derivatives are able to inhibit tumor growth. Methods: Female C57BL/6 mice were obtained at 6-8 weeks of age and were implanted with 5X105 LN7 tumor cells by dorsal subcutaneous injection of in the upper back. When tumors were first palpable, after 7-10 days of growth, mice were treated with subcutaneous injections of heparin, a low molecular weight heparin (LMWH), namely enoxaparin, an ultra LMWH, semuloparin or saline, daily for two weeks in a dose range of 1.0 – 0.25 mg/kg. After the treatment period, animals were sacrificed and the spleens and tumors were removed and their weight, volume, spleen weight and size were measured. Results: At the 1.0 and 0.5 mg/kg dosages, both enoxaparin (p<0.01) and semuloparin (p<0.01) showed a decrease in tumor volume compared to the saline control animals. At the 1.0 mg/kg dosage, the mortality was high in the heparin group due to bleeding. At 0.5 mg/kg heparin was not different from the saline control. In addition, at a dosage of 0.25 mg/kg, only semuloparin showed a difference compared to the saline control (p<0.01). Similar results were observed for the tumor weight. There were no significant differences noted in spleen weight or spleen size among these agents. The mortality rates between the mice treated with enoxaparin and semuloparin were comparable. Conclusions: These studies suggest that heparin and its derivatives are capable of inhibiting tumor growth in a dose dependent manner. Enoxaparin and semuloparin are more effective at reducing tumor growth compared to heparin. Clinical studies have shown that semuloparin is safe and effective for the prevention of venous thromboembolism in cancer patients and compares favorably to enoxaparin in terms of antithrombotic effect and safety profile. Therefore, semuloparin may be a better alternate for the prevention of cancer associated thrombosis.

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Wang, Haifeng, Jingjing Guan, Xiaohan Zhang, Xinxin Wang, Tianliang Ji, Dandan Hou, Guiru Wang, and Jiao Sun. "Effect of Cold Application on Pain and Bruising in Patients With Subcutaneous Injection of Low-Molecular-Weight Heparin: A Meta-Analysis." Clinical and Applied Thrombosis/Hemostasis 26 (January 1, 2020): 107602962090534. http://dx.doi.org/10.1177/1076029620905349.

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To evaluate the effect of cold application on pain and bruising after the subcutaneous injection of low-molecular-weight heparin, 8 electronic databases were searched for randomized controlled trials and quasiexperimental studies from the inception of the databases to June 2019. Review Manager 5.3 software was used for the heterogeneity test and meta-analysis. A total of 8 studies including 694 participants were analyzed. The cold application group assessed with the Verbal Descriptor Scale pain assessment tool showed significant reductions in pain intensity immediately after injection. Compared to the control group, the cold application group showed a reduction in the occurrence of bruises at 12 hours, 24 hours, and 48 hours after injection. There was no significant difference in the area of bruising in the cold application group at 48 hours after injection, but the area of bruising at 72 hours after injection was significantly reduced. These results show that cold application can reduce the incidence of pain and bruising after subcutaneous injection of low-molecular-weight heparin and reduce the area of bruising 72 hours after injection. Additional studies with larger sample sizes are needed to confirm these findings.

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31

Dawes, J., C. V. Prowse, and D. S. Pepper. "Absorption of heparin, LMW heparin and SP54 after subcutaneous injection, assessed by competitive binding assay." Thrombosis Research 44, no. 5 (December 1986): 683–93. http://dx.doi.org/10.1016/0049-3848(86)90169-6.

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32

Mismetti, P., J. Reynaud, B. Tardy-Poncet, S. Laporte-Simitsidis, M. Scully, C. Goodwyn, P. Queneau, and H. Decousus. "Chrono-Pharmacological Study of Once Daily Curative Dose of a Low Molecular Weight Heparin (200IU antiXa/kg of Dalteparin) in Ten Healthy Volunteers." Thrombosis and Haemostasis 74, no. 02 (1995): 660–66. http://dx.doi.org/10.1055/s-0038-1649794.

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SummaryLow molecular weight heparin (LMWH) is currently prescribed for the treatment of deep vein thrombosis at the dose of 100 IU antiXa/kg twice daily or at a dose of 175 IU antiXa/kg once daily with a similar efficacy. We decided to study the chrono-pharmacology of curative dose of LMWH once daily administrated according to the one previously described with unfractionated heparin (UFH).Ten healthy volunteers participated in an open three-period crossover study according to three 24 h cycles, separated by a wash-out interval lasting 7 days: one control cycle without injection, two cycles with subcutaneous injection of 200 IU antiXa/kg of Dalteparin (Fragmin®) at 8 a.m. or at 8 p.m. Parameters of heparin activity were analysed as maximal values and area under the curve.Activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT) and tissue factor pathway inhibitor (TFPI) were higher after 8 p.m. injection than after 8 a.m. injection (p <0.05) while no chrono-pharmacological variation of anti factor Xa (AXa) activity was observed. Thus the biological anticoagulant effect of 200 IU antiXa/kg of Dalteparin seems to be higher after an evening injection than after a morning injection.A chrono-therapeutic approach with LMWH, as prescribed once daily, deserves further investigation since our results suggest that a preferential injection time may optimise the clinical efficacy of these LMWH.

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Briant, L., C. Caranobe, S. Saivin, P. Sié, B. Bayrou, G. Houin, and B. Boneu. "Unfractionated Heparin and CY 216: Pharmacokinetics and Bioavailabilities of the Antifactor Xa and IIa Effects after lntravenous and Subcutaneous Injection in the Rabbit." Thrombosis and Haemostasis 61, no. 03 (1989): 348–53. http://dx.doi.org/10.1055/s-0038-1646593.

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SummaryThis report compares the pharmacokinetics and the bioavailabilities of the antifactor Xa and of the antifactor II a activities generated by intravenous (IV) and subcutaneous (SC) injections of increasing doses of unfractionated heparin (UH) and of a low molecular weight heparin (CY 216). Rabbits were injected with 500, 1,000, 2,500 and 5,000 antifactor Xa u/kg of both heparins and their biological activities were followed at various time intervals. After IV injection the clearance of the antifactor Xa activities was independent of the dose and the clearance of UH was significantly higher than that of CY 216; after SC injection the bioavailability estimated from the antifactor Xa effect was consistently over 100% for CY 216 while that of UH increased from 27% at the lowest dose to 93% at the highest dose. The pharmacokinetic parameters estimated by the antifactor IIa activity of UH were superimposable to those calculated with the antifactor Xa activity. For CY 216 no direct comparison between the two activities was made since the dose injected expressed in antifactor IIa units was 3.4 times lower. UH and CY 216 were therefore injected intravenously to other animals at equivalent and increasing doses expressed in antifactor IIa units (50-5,000 u/kg). The pharmacokinetic parameters calculated from the curves of the antifactor IIa activities were basically identical except at the two lower doses (50 and 100 u/kg) for which UH was cleared faster than CY 216. These results indicate that the antifactor IIa activity generated by an injection of CY 216 disappears faster than the corresponding antifactor Xa activity and therefore that the antifactor Xa/antifactor IIa activity ratio of CY 216 progressively increases after SC or IV injection.

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34

Grimaudo, V., A. Omri, E. K. O. Kruithof, J. Hauert, and F. Bachmann. "Fibrinolytic and Anticoagulant Activity After a Single Subcutaneous Administration of a Low Dose of Heparin or a Low Molecular Weight Heparin-Dihydroergotamine Combination." Thrombosis and Haemostasis 59, no. 03 (1988): 388–91. http://dx.doi.org/10.1055/s-0038-1647501.

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SummaryThe anticoagulant and potential profibrinolytic effect of a combination of low molecular weight heparin with dihydroergotamine (LMWH-DHE) and of unfractionated heparin was studied in eight healthy volunteers. Each volunteer received a subcutaneous injection of either LMWH-DHE (1,500 U anti-Xa of LMWH + 0.5 mg DHE), unfractionated heparin (5,000 IU) or of placebo (saline) between 7 and 8 h in the morning on three different occasions. Anti-Xa activity, and fibrinolytic activity measured by the euglobulin clot lysis time (ECLT) and by the fibrin plate assay were determined before and at different times after administration of the three substances. Anti-Xa activity in plasma reached a maximum four hours after injection of both LMWH-DHE and unfractionated heparin. LMWH-DHE showed a better bioavailability when compared to unfractionated heparin; the anti-Xa activity peak was two and a half fold higher after LMWH-DHE despite injection of a three fold lower dose of anti-Xa units. The half-life of anti-Xa activity was approximately 4 hours for LMWH-DHE but only 90 min for unfractionated heparin. The fibrinolytic activity measured by ECLT as well as by fibrin plate assay, showed a significant increase during the day reaching a peak 8–12 h after injection regardless of the product administered (including the placebo). The profile of the diurnal fibrinolytic activity curve was identical for all three substances. The increase in fibrinolytic activity, observed after administration of LMWH-DHE or unfractionated heparin, was therefore not due to these drugs but reflected the circadian physiological fluctuation of fibrinolysis.

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Pourghaznein, Tayebe, Amir Vahedian Azimi, and Mohammad Asghari Jafarabadi. "The effect of injection duration and injection site on pain and bruising of subcutaneous injection of heparin." Journal of Clinical Nursing 23, no. 7-8 (July 12, 2013): 1105–13. http://dx.doi.org/10.1111/jocn.12291.

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Shin, Jae Ho, Yunsun Song, Jae Jon Sheen, Dongwhane Lee, Jaewoo Chung, Ga Young Lee, Hyunhee Jeong, et al. "Safety and Effectiveness of Percutaneous Low-Dose Thrombin Injection for Femoral Puncture Site Pseudoaneurysms in Neurointervention: Single-Center Experience." Neurointervention 15, no. 1 (March 31, 2020): 25–30. http://dx.doi.org/10.5469/neuroint.2019.00206.

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Purpose: We present ultrasound-guided percutaneous low-dose thrombin (200–250 IU) injection for the treatment of iatrogenic femoral pseudoaneurysms. Second, we compared patient and procedure factors between subcutaneous hematoma and pseudoaneurysm groups.Materials and Methods: From April 2012 to May 2018, 8425 patients underwent neurointervention. Among these patients, 18 had small subcutaneous hematomas and 6 had pseudoaneurysms. Pseudoaneurysms in the neck and entire sac were visualized, and low-dose thrombins were injected while visualizing a “whirlpool” hyperechoic core in the pseudoaneurysm sac. Subcutaneous hematomas were treated with simple compression. We compared the following parameters between the subcutaneous hematoma group and pseudoaneurysm group: sex, age, body mass index (BMI), type of procedure, heparin usage, sheath size, procedure time, and number of previous neurointervention procedures with the Mann-Whitney U test.Results: Most of the pseudoaneurysms were successfully occluded with 200 IU of thrombin (n=5). Only 1 pseudoaneurysm required a slightly higher thrombin concentration (250 IU, n=1). During the short-term follow-up, no residual sac was observed and no surgical repair was necessary. Pain in the groin region was alleviated. During the 1-month follow-up, no evidence of pseudoaneurysm recurrence nor subcutaneous hematoma was noted. Patient factors (sex, age, and BMI) and procedure factors (heparin usage, sheath size, procedure time, number of previous procedures) were not statistically different between the subcutaneous hematoma and pseudoaneurysm groups.Conclusion: Ultrasound-guided percutaneous low-dose thrombin injection (200–250 IU) is safe, effective, and less invasive for treating iatrogenic femoral pseudoaneurysm in neurointervention.

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Pérez, M., J. Sancho, C. Ferrer, O. García, and J. P. Barret. "Management of flap venous congestion: The role of heparin local subcutaneous injection." Journal of Plastic, Reconstructive & Aesthetic Surgery 67, no. 1 (January 2014): 48–55. http://dx.doi.org/10.1016/j.bjps.2013.09.003.

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SOMERVILLE, PATRICIA, PAUL E. WEISS, and JOHN L. GHERTNER. "Abdominal Wall Uptake of Tc-99m MDP Secondary to Subcutaneous Heparin Injection." Clinical Nuclear Medicine 21, no. 2 (February 1996): 152–53. http://dx.doi.org/10.1097/00003072-199602000-00020.

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Wilson, R., D. Gordon, R. V. Johnstone, P. Johnstone, G. H. Beastall, and J. A. Thomson. "The Parallel Effects of a Very Low Molecular Weight Heparin (CY222) on anti Xa Activity and Thyroid Hormone Levels in Blood." Scottish Medical Journal 32, no. 3 (June 1987): 76–78. http://dx.doi.org/10.1177/003693308703200306.

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A very low molecular weight heparin fragment (CY222) was administered by subcutaneous injection to a group of normal volunteers. This drug caused increased anti Xa activity with peak levels being observed two hours after injection. This coincided with changes in thyroid hormone levels especially with a fall in red cell thyroxine levels. Larger doses of CY222 caused a fall in serum total thyroxine and triiodothyronine, a rise in free thyroxine and a fall in TSH levels. It was thought that these findings may be due to the production of a circulating inhibitor of cellular uptake of thyroxine and that this might be related to the elevated levels of serum free fatty acids produced by the heparin.

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Duncumb, Joseph W., Kana Miyagi, Parto Forouhi, and Charles M. Malata. "Successful Deep Inferior Epigastric Perforator Flap Harvest despite Preoperative Therapeutic Subcutaneous Heparin Administration into the Abdominal Pannus." Case Reports in Surgery 2016 (2016): 1–4. http://dx.doi.org/10.1155/2016/9168154.

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Abdominal free flaps for microsurgical breast reconstruction are most commonly harvested based on the deep inferior epigastric vessels that supply skin and fat via perforators through the rectus muscle and sheath. Intact perforator anatomy and connections are vital for subsequent optimal flap perfusion and avoidance of necrosis, be it partial or total. The intraflap vessels are delicate and easily damaged and it is generally advised that patients should avoid heparin injection into the abdominal pannus preoperatively as this may compromise the vascular perforators through direct needle laceration, pressure from bruising, haematoma formation, or perforator thrombosis secondary to external compression. We report three cases of successful deep inferior epigastric perforator (DIEP) flap harvest despite patients injecting therapeutic doses of low molecular weight heparin into their abdomens for thrombosed central venous lines (portacaths™) used for administering primary chemotherapy in breast cancer.

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Jouault, S. Colliec, S. Mauray, J. Theveniaux, C. Sternberg, Boisson Vidal, A. M. Fischer, and J. Millet. "Antithrombotic and Anticoagulant Activities of a Low Molecular Weight Fucoidan by the Subcutaneous Route." Thrombosis and Haemostasis 81, no. 03 (1999): 391–95. http://dx.doi.org/10.1055/s-0037-1614484.

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SummaryFucoidans (high-molecular-weight sulfated polysaccharides extracted from brown seaweeds) have anticoagulant and antithrombotic effects. They inhibit thrombin by catalyzing both serpins (antithrombin and heparin cofactor II) according to their chemical structures and origins. In this study, a low-molecular-weight (LMW) fucoidan of 8 kDa was obtained by chemical degradation of a high-molecular-weight fraction. The antithrombotic and anticoagulant activities of this new compound were compared to those of a low-molecular-weight heparin (LMWH), dalteparin, following subcutaneous administration to rabbits. This LMW fucoidan exhibited dose-related venous antithrombotic activity, with an ED80 of about 20 mg/kg, 2 h after a single subcutaneous injection. Its activity was comparable to that of dalteparin (close to 200 anti-Xa IU/kg) and was maximal 30 min after a single subcutaneous injection. The activity remained stable (about 70%) from 1 to 4 h after injection, but disappeared by 8 h. The antithrombotic activity was not associated with either a prolongation of the thrombin clotting time (TCT) or an increase in anti-Xa activity, contrary to dalteparin. A slight prolongation of APTT occurred with both compounds. This venous antithrombotic activity was associated with a decrease in ex vivo thrombin generation and with a significant increase in the lag phase in a thrombin generation test. LMW fucoidan thus has potent antithrombotic activity and a potentially weaker haemorrhagic effect (i.e. a smaller effect on coagulation tests and a smaller prolongation of the bleeding time) than dalteparin.

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42

Fiessinger, J. N., M. Lopez-Fernandez, E. Gatterer, S. Granqvist, A. Kher, C. G. Olsson, and K. Söderberg. "Once-daily Subcutaneous Dalteparin, a Low Molecular Weight Heparin, for the Initial Treatment of Acute Deep Vein Thrombosis." Thrombosis and Haemostasis 76, no. 02 (1996): 195–99. http://dx.doi.org/10.1055/s-0038-1650553.

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SummaryThe aim of the study was to compare the efficacy and safety of once-daily subcutaneous injection of dalteparin, a low molecular weight heparin, with that of intravenous unfractionated heparin in the treatment of deep venous thrombosis (DVT). Patients were included if they had deep venous thrombosis distal to inguinal ligament and were randomised either before, if it was considered necessary, or after phlebographic verification of the diagnosis. There was no pre-inclusion treatment with unfractionated heparin. One hundred and twenty patients received dalteparin, administered subcutaneously once-daily at a fixed dose of 200 IU anti-factor Xa/kg, and 133 patients received a continuous intravenous infusion of unfractionated heparin (UFH). Oral anticoagulation was started on the first or second day, and initial treatment with dalteparin or UFH discontinued when the prothrombin time was in the therapeutic range (2<INR<3) on two consecutive days. Control phlebograms were taken within 4 days, thereafter. There were no significant differences between the two initial treatment groups in improvements in Marder score. Two major bleeding events occurred in the UFH group versus none in the dalteparin group. One patient in each group experienced clinically significant pulmonary embolism. During a mean follow-up period of 6.9 ± 1.5 months, recurrent DVT occurred in four patients in the dalteparin group and in two of the UFH group. These results confirm those of a previous study on dalteparin in the initial treatment of DVT, and suggest that dalteparin administered once-daily at a fixed dose of 200 UI/kg is as effective and well-tolerated as UFH in patients with DVT below the inguinal ligament. The present study also demonstrates that dalteparin can be started as soon as the diagnosis of DVT is suspected and without pre-treatment with UFH. Given that the administration of once-daily subcutaneous injections needs not require a patient to be hospitalised, studies to investigate the possibility of using dalteparin for the initial treatment of DVT in the outpatient setting are warranted.

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Dawes, J., C. V. Prowse, and D. D. Pepper. "The Measurement of Heparin and Other Therapeutic Sufphated Polysaccharides in Plasma, Serum and Urine." Thrombosis and Haemostasis 54, no. 03 (1985): 630–34. http://dx.doi.org/10.1055/s-0038-1660086.

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SummaryThe competitive binding assay described will specifically and accurately measure concentrations of administered heparin in biological fluids with a sensitivity of 60 ng ml-1. Neither endogenous glycosaminoglycans, nor plasma proteins such as ATIII and PF4 interfere in the assay. Semi-synthetic highly sulphated heparinoids and LMW heparin can also be measured. Using this assay heparin clearance followed simple first-order kinetics over the dose range 100-5,000 units, but the half-life was strongly dose-dependent. There was good correlation with heparin activity measurements by APTT and anti-Xa clotting assays. Plasma concentrations were measurable for at least 5 h following subcutaneous injection of 10,000 units of heparin. Excretion in the urine could be followed after all but the lowest intravenous dose. This assay, used in conjunction with measurements of heparin anticoagulant activity, will be valuable in the elucidation of mechanisms of action of heparin and the heparinoids, and in the assessment and management of problems related to heparin therapy.

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Nandy, U., GI Varughese, N. Iqbal, and TJ Constable. "Picture Quiz (Answer)." Acute Medicine Journal 4, no. 2 (April 1, 2005): 75. http://dx.doi.org/10.52964/amja.0105.

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Subcutaneous low molecular weight heparins are widely used in hospitalised patients for the treatment of DVT, pulmonary embolism and acute coronary syndromes, as well as for thromboprophylaxis. Rectus sheath hematoma is a recognised, but sometimes misdiagnosed, complication of treatment with anticoagulant therapy,1 including full and prophylactic doses of low molecular weight heparin.2 Studies have shown that the most frequent location of a haematoma is in the lower part of the abdomen. The explanation for this lies in the anatomy of the abdominal wall.3 The rectus abdominis muscle lies between the aponeuroses of the transverse and oblique muscles, which form the so-called rectus sheath. In this lower aspect of the muscle the perforating branches of the inferior epigastric artery running in the preperitoneal fat may rupture causing a large haematoma widely spreading in this loose space. Care should be taken to avoid this area for injection of heparin, particularly in thin patients where inadvertent intramuscular.

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Gastpar, Robert, and Susanne Alban. "Plasma Levels of Total and Free Tissue Factor Pathway Inhibitor (TFPI) as Individual Pharmacological Parameters of Various Heparins." Thrombosis and Haemostasis 85, no. 05 (2001): 824–29. http://dx.doi.org/10.1055/s-0037-1615755.

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SummaryThe release of circulating tissue factor pathway inhibitor (TFPI) into plasma by heparins is thought to contribute to their overall anti-thrombotic activity. In the presented study in healthy volunteers, we measured the heparin-induced increase of circulating total and free TFPI antigen and the aXa- and aIIa activity after subcutaneous (s.c.) injection of 9000 aXa-U of four different heparins: unfractionated heparin (UFH) (13.0 kDa), a medium molecular weight (MW) heparin with a narrow MW range (HF) (10.5 kDa), certoparin (6.0 kDa) and enoxaparin (4.5 kDa). Based on the administration of equi-active aXa doses, certoparin induced the highest increase in total TFPI determined as AUC (p <0.01). The lowest effect was observed for UFH (p <0.0001). However, the AUC of released free TFPI significantly increased in the order: enoxaparin < UFH < certoparin < HF, showing MW dependency with the exception of UFH. Comparing the effects of equi-gravimetric heparin doses, the MW dependency becomes even more pronounced. The mismatch of UFH may be due to its poor bioavailability, which becomes obvious from its low ex vivo aXa activity. In contrast to the TFPI releasing potency, the ex vivo aXa activity continuously decreased with increasing MW. Although the ex vivo aIIa activity of the heparins increased in the same order like the release of free TFPI, there was no clear correlation. This is attributed to the fact that the aIIa activity of heparin is not only dependent on the MW, but, in contrast to its TFPI releasing effect, also on the percentage of material with high affinity to AT. In conclusion, besides the aXaand aIIa activity, the TFPI releasing effect of heparins is an additional parameter of their individual pharmacological profile.

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Ghaleb, Mervat, Mervat Abdel Fatah, and Neema Abou Shady. "Evaluation of Bruises and Induration Formation after Two Techniques of Subcutaneous Heparin Injection." Journal of High Institute of Public Health 33, no. 2 (April 1, 2003): 329–36. http://dx.doi.org/10.21608/jhiph.2003.196608.

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47

Koppenhagen, K., J. Adolf, M. Matthes, E. Tröster, J. D. Roder, S. Haas, H. M. Fritsche, and H. Wolf. "Low Molecular Weight Heparin and Prevention of Postoperative Thrombosis in Abdominal Surgery." Thrombosis and Haemostasis 67, no. 06 (1992): 627–30. http://dx.doi.org/10.1055/s-0038-1648513.

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SummaryIn a prospective, double-blind, randomized multicenter trial the efficacy and safety of low molecular weight heparin and unfractionated heparin were compared for the prevention of postoperative deep vein thrombosis in patients undergoing abdominal surgery. Six hundred and seventy-three patients were randomly allocated to the two prophylaxis groups; 20 of these, however, did not undergo surgery and did not receive any prophylaxis. Of the remaining 653 patients 323 received one subcutaneous injection of 3,000 anti-Xa units of low molecular weight heparin and 330 received subcutaneously 5,000 U heparin three times a day. Treatment was initiated 2 h preoperatively and continued for 7 to 10 days. The occurrence of DVT was determined by the 125I-labelled fibrinogen uptake test and phlebography. Venous thrombosis was diagnosed in 24 of 323 patients (7.4%) treated with low molecular weight heparin and in 26 of 330 patients (7.9%) treated with low-dose heparin. DVT of proximal veins was detected in four patients of the low molecular weight heparin group and in three patients of the low-dose heparin group. During the observation period three pulmonary emboli - one fatal and two non-fatal - occurred in patients receiving prophylaxis with low-dose heparin. No pulmonary embolism was found in patients treated with low molecular weight heparin. Both prophylactic schemes were well tolerated. Intra-and postoperative blood loss, incidence of wound hematoma, frequency and volume of intra- and postoperative blood transfusion were similar in both groups with a slight advantage for the low molecular weight heparin group. The results of this trial show that the investigated low molecular weight heparin is at least as effective and safe as low-dose heparin in preventing deep vein thrombosis in patients undergoing elective abdominal surgery.

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Kristensen, Hanne I., Per B. Østergaard, Ole Nordfang, Ulrich Abildgaard, and Anne Karin Lindahl. "Effect of Tissue Factor Pathway Inhibitor (TFPI) in the HEPTEST® Assay and in an Amidolytic Anti Factor Xa Assay for LMW Heparin." Thrombosis and Haemostasis 68, no. 03 (1992): 310–14. http://dx.doi.org/10.1055/s-0038-1656371.

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SummaryBoth the HEPTEST® and amidolytic anti factor Xa assays are currently being used for heparin activity detection in plasma from patients receiving standard heparin or low molecular weight heparin (LMWH). In this study we have investigated the influence of recombinant and endogenous Tissue Factor Pathway Inhibitor (TFPI) on these assays. The HEPTEST® determinations were performed on an ACL 300 R Clottimer using the APTT program which resulted in a longer incubation time with factor Xa than recommended by the manufacturer. rTFPI added to plasma prolonged the HEPTEST® clotting time markedly, but had only a little effect in the amidolytic assay. Antibodies against TFPI (anti-TFPI) abolished these effects. The effect of adding rTFPI and Logiparin® was additive. When anti-TFPI IgG was added to samples of normal plasma, a statistically significant shortening of the HEPTEST® clotting time was seen. When anti-TFPI was added to plasma samples from volunteers who had received Logiparin® by subcutaneous or intravenous injection, then the HEPTEST® clotting time was shortened considerably. For some samples the clotting time was halved. These experiments show that the HEPTEST® clotting time is prolonged not only by heparin-antithrombin III, but also by TFPI released by heparin injection.

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Gori, A. M., G. Pepe, M. Attanasio, M. Falciani, R. Abbate, D. Prisco, S. Fedi, et al. "Tissue Factor Reduction and Tissue Factor Pathway Inhibitor Release after Heparin Administration." Thrombosis and Haemostasis 81, no. 04 (1999): 589–93. http://dx.doi.org/10.1055/s-0037-1614530.

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SummaryElevated plasma levels of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) and large amounts of monocyte procoagulant activity (PCA) have been documented in unstable angina (UA) patients. In in vitro experiments heparin is able to blunt monocyte TF production by inhibiting TF and cytokine gene expression by stimulated cells and after in vivo administration it reduces adverse ischemic outcomes in UA patients. TF and TFPI plasma levels and monocyte PCA have been investigated in 28 refractory UA patients before and during anticoagulant subcutaneous heparin administration (thrice daily weight- and PTT-adjusted for 3 days) followed by 5000 IU × 3 for 5 days. After 2-day treatment, immediately prior to the heparin injection, TF and TFPI plasma levels [(median and range): 239 pg/ml, 130-385 pg/ ml and 120 ng/ml, 80-287 ng/ml] were lower in comparison to baseline samples (254.5 pg/ml, 134.6-380 pg/ml and 135.5 ng/ml, 74-306 ng/ml). Four h after the heparin injection TF furtherly decreased (176.5 pg/ml, 87.5-321 pg/ml; -32.5%, p<0.001) and TFPI increased (240.5 ng/ml, 140-450 ng/ml; +67%, p<0.0001).After 7-day treatment, before the injection of heparin, TF and TFPI plasma levels (200 pg/ml, 128-325 pg/ml and 115 ng/ml, 70-252 ng/ml) significantly decreased (p<0.05) in comparison to the pre-treatment values. On the morning of the 8th day, 4 h after the injection of heparin TF plasma levels and monocytes PCA significantly decreased (156.5 pg/ml, 74-259 pg/ml and from 180 U/105 monocytes, 109-582 U/105 monocytes to 86.1 U/105 monocytes, 28-320 U/105 monocytes; - 38% and -55% respectively) and TFPI increased (235.6 ng/ml, 152-423 ng/ ml; +70%, p<0.001). In conclusion, heparin treatment is associated with a decrease of high TF plasma levels and monocyte procoagulant activity in UA patients. These actions of heparin may play a role in determining the antithrombotic and antiinflammatory properties of this drug.

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Bendetowicz, Ana Victoria, Suzette Béguin, H. Caplain, and H. Coenraad Hemker. "Pharmacokinetics and Pharmacodynamics of a Low Molecular Weight Heparin (Enoxaparin) after Subcutaneous Injection, Comparison with Unfractionated Heparin – A Three Way Cross Over Study in Human Volunteers." Thrombosis and Haemostasis 71, no. 03 (1994): 305–13. http://dx.doi.org/10.1055/s-0038-1642435.

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SummaryWe determined, in volunteers, the plasma levels of heparin above and below the critical chainlength necessary for thrombin inhibition (ACLM and BCLM), from 1 to 24 h after subcutaneous injection of 5000IU unfractionated heparin (UFH), 40 mg enoxaparin and 1 mg/kg body weight of enoxaparin (LMWH) (n = 12 for each dose). The levels were calculated from the antithrombin- and anti-Xa activities using the specific activities of the materials injected. We also determined the course of thrombin- and of factor Xa generation after triggering the extrinsic system in the same samples. From the thrombin generation curves, we calculated the course of prothrombinase activity.When the ACLM and BCLM plasma-levels are plotted against the inhibition of thrombin- and factor Xa generation, it appears that:a) There is a unique dose response relationship between ACLM level and the inhibition of thrombin generation, independent of whether the ACLM is derived from UFH or LMWH. This relationship is not significantly altered by the BCLM appearing after LMWH injection.b) There is a similar unique relationship between ACLM level and the inhibition of factor Xa generation, again independent of BCLM.c) Inhibition of prothrombin activation hardly contributes to the overall effect on thrombin formation and is again independent of the source of ACLM.d) ACLM levels were significantly higher after injection of LMWH than after UFH injection, even though the amounts of ACLM injected with the highest dose of LMWH were smaller than those administered in the UFH injection.We conclude that the only functional difference between LMWH and UFH is the much higher bioavailability of the former. We surmise that, from the UFH injected, only the lower molecular weight species reach the circulation, i. e. a fraction similar to the ACLM injected with enoxaparin.

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Journal articles on the topic 'Subcutaneous heparin injection'

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