Anticoagulant-associated

Heparin is a carbohydrate-based (glycosaminoglycan) anticoagulant associated with many tissues, but mainly found stored intracellularly as granules in mast cells that line the endothelium of blood vessels. Upon release into the bloodstream, heparin binds to and thereby activates an additional plasma protein, namely antithrombin. The heparin-antithrombin complex then binds a number of activated clotting factors (including Ha, IXa, Xa, XIa and Xlla), thereby inactivating them. The heparin now disassociates from the complex and combines with another antithrombin molecule, thereby initiating another turn of this inhibitory cycle. 

Prevention of recurrence of coumarin necrosis in patients with protein C deficiency, if treatment is necessary, could consist of transient simultaneous infusion of fresh frozen plasma (leading to a constant concentration of protein C) and heparin both before and at the first time of administration of an oral anticoagulant, associated or not with protein C concentrate (65,66). 

Grebe HB, Gregory PJ. Inhibition of warfarin anticoagulation associated with chelation therapy. Pharmacotherapy 2002 22(8) 1067-9. 

Horne MK 3rd, Stein CA, LaRocca RV, Myers CE. Circulating glycosaminoglycan anticoagulants associated with suramin treatment. Blood 1988 71(2) 273-9. 

Joss JD, LeBlond RF. Potentiation of warfarin anticoagulation associated with tq>ical methyl salicylate Ann Phamacother (2000) 34, 729-33. 

Routledge PA, Shetty HG, White JP, Collins P (1998) Case studies in therapeutics warfarin resistance and inefficacy in a man with recurrent thromboembolism, and anticoagulant-associated priapism. Br J Clin Pharmacol 46 343-346... 

Clinically, the patients present with a rod-like painful induration in the dorsal aspect of the shaft. Clinical signs and symptoms suggestive for throm-bophebitis, such as fever and local pain, can be present. The disease is usually treated with fibrinolytics and anticoagulation, associated with discontinuance of sexual activity. Spontaneous resolution usually occurs within 6-8 weeks. 

The disease is usually treated with fibrinolytics and anticoagulation, associated with discontinuance of sexual activity. Spontaneous resolution usually occurs within 6-8 weeks. 

Pharmacogenetics the responses to dmgs may be significantiy different according to heritable factors that can modulate pharmacodynamic or pharmacogenetic factors (118). Atypical cholinesterase occurs in about 1 in 2000 Caucasians and is associated with a markedly reduced sensitivity to hydrolysis of the muscle-relaxant cholinesterase. Similarly, the reduced sensitivity to the anticoagulant warfarin is associated with a reduced receptor affinity. 

Dicoumarol [66-76-2] (5) was isolated from spoiled sweet clover hay. It is prepared synthetically by reaction of 4-hydroxycoumarin with formaldehyde (85). It is used in anticoagulant therapy often associated with heparin. 

The LMWHs cause fewer adverse reactions tiian heparin. Bleeding related to die LMWHs is possible but has generally been low. See die Summary Drug Table Anticoagulants for additional adverse reactions associated widi die LMWHs. 

This was largely influenced by the high-dose UFH group in 1ST (OR 1.38, 95% Cl 1.05-1.82). An interaction by UFH dose (p = 0.01) on recurrent stroke risk with combination UFH-aspirin therapy compared to aspirin monotherapy was observed, with a trend toward increased risk of recurrent stroke with high-dose UFH + aspirin (OR 1.22, 95% Cl 0.92-1.62) and a trend toward reduced risk with low-dose UFH + aspirin (OR 0.75, 95% Cl 0.56-1.03), equivalent to 10 fewer (95% Cl 0-20 fewer) recurrent strokes per 1000 patients treated. They found a small, but significant beneht of LMWH over aspirin in the prevention of symptomatic DVT, equivalent to 10 (95% Cl 0-30) fewer DVTs per 1000 patients treated. Compared with aspirin, anticoagulants were associated with nonsignificantly fewer symptomatic PEs (OR 0.85, 95% Cl 0.55-1.32). There were fewer PEs with the combination of UEH and aspirin (OR 0.58, 95% Cl 0.34—1.00), equivalent to 5 fewer (Cl 0-10) PEs per 1000 patients treated. However, the overall incidence of symptomatic DVT and PE was low (1.1% and 0.7%). 

Overall no evidence was found to support the claim that anticoagulants offer a net advantage over aspirin in patients with acute ischemic stroke. There was evidence, however, to suggest that combination anticoagulant and aspirin therapy was associated with a small increase in the number of deaths at the end of follow-up, equivalent to 20 more deaths per 1000 patients treated. This adverse effect can probably be attributed partly to the 10 extra sICHs, and the 5 extra major extracranial hemorrhages per 1000 patients treated with combination anticoagulant/ aspirin therapy. 

Acute Anticoagulation for AF-associated Stroke HAEST and 1ST provided valuable data on relatively large numbers (449 in HAEST, 3169 in 1ST) of patients with AF-associated ischemic stroke treated with acute anticoagulation (danaparoid in HAEST, UFH in 1ST). HAEST found no reduction in early stroke recurrence or effect on late functional outcome in the LMWH arm. In contrast, 1ST found a dose-dependent reduction in early recurrence rates, but no late functional benefit associated with UFH. However, this was offset by an increase in rates of sICH among patients with AF receiving UFH, with no net benefit in the composite outcome of recurrence stroke and sICH combined. The reasons for the discrepancy between trials is unclear. 

Many patients have a rhythm that varies between atrial flutter and AF. Atrial flutter is associated with a 40% higher risk of stroke. Given that the concordance of the AF and atrial flutter is high, anticoagulation should be considered in patients with atrial flutter and coexisting cardiac pathology predisposing to left atrial thrombus. 

Heparin-induced thrombocytopenia (HIT) is a very serious adverse effect associated with UFH use. Platelet counts should be monitored every 2 to 3 days dining the course of UFH therapy.5 HIT should be suspected if the platelet count drops by more than 50% from baseline or to below 120,000. In patients with contraindications to anticoagulation therapy, UFH should not be administered (Table 7-7). 

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