Heparin treatment

Einhaupl KM, Villringer A, Meister W, Mehraein S, Garner C, PeUkofer M, Haberl RL, Pfister HW, Schiedek P. Heparin treatment in sinus venous thrombosis. Lancet 1991 338 597-600. 

Handeland G. F., Abildgaard U., Holm H. A Arresen E. Dose adjusted heparin treatment of deep venous thrombosis a comparison to unfractionated and low molecular weight heparin. Eur J Clin Pharmacol 1990 39, 107-12. 

Heparin may also produce a decrease in platelets (thrombocytopenia) in some patients.13,84 This condition, known commonly as heparin-induced thrombocytopenia (HIT), is less common with LMWHs versus unfractionated heparin, but HIT can occur with any type of heparin treatment.101,145... 

Glyceryl trinitrate overdose should be treated with the patient s head lowered. Other measures include respiration maintenance, use of plasma expanders, and electrolyte balance. Withdrawal of heparin treatment or dose reduction should be performed with the overdose of heparin. Protamine sulfate may be used to reduce severe bleeding. Heparin should be used with caution with glyceryl trinitrate, aprotinine, alcohol, tobacco, and ACE inhibitors. Nifedipine should be used with care when coadministering with immunosuppressants, magnesium salts, tobacco, digoxin, antineoplastics, calcium channel blockers, antihistamines, antifungals, antiepileptics, antiarrhythmics, and alcohol. 

Aprotinin administration during surgery should follow heparin treatment to avoid any risk. Patients under the treatment of antifibrinolytic therapy should be treated cautiously when coadministering drugs affecting hemostasis and estrogens.229 Accumulation of albumin may occur in patients with impaired renal function if large volumes of albumin solutions are administered. 

Heparin acts by binding to anti thrombin III, which serves as a major inhibitor of serine protease clotting enzymes. Abruptly ending heparin treatment can be hazardous because of reduced levels of antithrombin III. Coumarins, typified by warfarin, are structurally similar to vitamin K, which plays an important role in blood coagulation. By interfering with the function of vitamin K, vitamin K-dependent proteins such as clotting factors VII, IX, X and prothrombin are reduced. 

Corticosteroids, heparin treatment, particularly if used during pregnancy, and anticonvulsants have all been implicated in the development of osteoporosis. 

Minor increases in serum transaminases without evidence of liver dysfunction are common in patients receiving standard heparin or low molecular weight heparin given therapeutically or prophylactically (60,61). This rise is more pronounced for alanine transaminase than for aspartate transaminase and occurs after 5-10 days of heparin treatment (61). The source of heparin has no relation to the development of raised transaminases. After withdrawal of heparin and sometimes even in spite of continued treatment (60,61), the transaminases return to normal (62,63). The mechanism of these increases has not been elucidated. A concomitant increase in gamma-glutamyl transpeptidase activity has been described in some patients (64). 

Erythematous nodules or infiltrated and sometimes eczema-hke plaques at the site of injection are common adverse effects of subcutaneous standard heparin 3-21 days after starting heparin treatment. They are probably delayed-type hypersensitivity reactions and are also seen with low molecular weight heparin (65-69). There can be cross-reactivity between standard heparin and low molecular weight heparin (69). 

The maternal rate of bleeding comphcations during heparin treatment is about 2%. This is consistent with the reported rates of bleeding associated with heparin therapy in non-pregnant women, and in warfarin therapy when used for the treatment of venous thrombosis (95). Subcutaneous heparin given just before labor can also cause a persistent anticoagulant effect at the time of delivery the mechanism of this prolonged effect is unclear (96). 

Artefactual increases of as much as 50% in total thyroxine, estimated by a competitive protein-binding assay, and of as much as 30% in triiodothyronine resin uptake are probably due to rapid and continuing lipolytic hydrolysis of triglycerides after blood has been drawn (126). Thyroid function tests should therefore always be performed on blood samples taken before (or a sufficient time after) heparin treatment (127). An increase in serum-free thyroxine concentrations has also been reported after low molecular weight heparin, by up to 171% in specimens taken 2-6 hours after injection. When specimens were obtained 10 hours after injection, the effects were smaller, but with concentrations still up to 40% above normal the results can still cause errors of interpretation (128). 

Dahlman T, Lindvall N, Hellgren M. Osteopenia in pregnancy during long-term heparin treatment a radiological study post partum. Br J Obstet Gynaecol 1990 97(3) 221-8. 

Stevenson HP, Archbold GP, Johnston P, Young IS, Sheridan B. Misleading serum free thyroxine results during low molecular weight heparin treatment. Clin Chem 1998 44(5) 1002-7. 

Heparin treatment After resection of aldosterone-producing adenoma... 

B16. Bounameaux, H., Marbet, G. A., Lammle, B., Eichlisberger, R., and Duckert, F., Monitoring of heparin treatment. Comparison of thrombin time, activated partial thromboplastin time and plasmin heparin concentration and analysis of the behavior of antithrombin III. Am. J. Clin. Pathol. 74, 68-73 (1980). 

The total synthesis of a series single glyco-mimetics of heparin was recently announced (169). One structurally optimized oligosaccharide heparin mimetic is 10 times more potent in vivo than both standard heparin and low molecular weight heparins and is also devoid of the undesired side effect, thrombocytopenia, that is associated with heparin treatment. Thus, chemical synthesis was employed to optimize the length and the charge of the synthetic oligosaccharides. 

LPL can be dissociated from capillary walls by treatment with heparin (a gly-cosaminoglycan). Measurements can be made on blood after heparin treatment to determine whether LPL levels are abnormal. 

Using concentrations of heparin, that are inhibitory to SMC proliferation, causes SM-type a-actin expression to be up-regulated [295,296]. In plasma-derived serum however, heparin is not able to modify a-actin expression, indicating that its action is related to an antiproliferative action [296]. Barzu et al. [297], have isolated in vitro a subpopulation of rat aortic SMC that is heparin-resistant in terms of growth inhibition, but differentiation responsive (increased SM-type a-actin expression) to heparin treatment. This finding is in line with the theory that heparin acts on SMC differentiation and proliferation through distinct pathways. 

Barzu T, Hereber I-M, Desmouli re A, Carayon P, Pascal M (1994) Characterization of rat aortic smooth muscle cells resistant to the antiproliferative activity of heparin following long-term heparin treatment. J Cell Physiol 160 239-248... 

Heparin surface modification and heparin treatments of lenses may reduce the incidence of postoperative endophthalmitis and intraocular inflammation. Significantly fewer Staphylococcus epidermidis attached to heparin surface-modified intraocular lenses and to regular poly(methyl methacrylate) intraocular leuses treated with heparin than to untreated poly(methyl methacrylate) intraocular lenses (104). When heparin was added to the medium, the numbers of Pseudomonas aeruginosa adhering to the contact lenses were significantly lower than those adhering to the control lenses (105). 

The reduced effect of warfarin with dicloxacillin and nafcillin appears to be established. If these penicillins are used, increase monitoring of the INR and anticipate the need to increase the warfarin dose. Some patients taking nafcillin have been warfarin resistant, and needed heparin treatment. 

Mattioli AV, Bonetti L, Zennaro M, Ambrosio G, Mattioli G. Heparin/PF4 antibodies formation after heparin treatment temporal aspects and long-term follow-up. Am Heart J 2009 157(3) 589-95. 

GoSb V, Strotz V, Verdet M, Le Loet X, Vittecoq O. Post-partum sacral fracture associated with heparin treatment. Clin Rheumatol 2008 27(Suppl 2) S51-3. 

A fall in ) -lipoprotein and, particularly. TG concentrations in hyperlipaemic patients with frequent increase of a-lipoprotein is observed after heparin treatment at doses activating lipoprotein lipase, an enzyme which catalyses the hydrolysis of TG. 

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