Heparin administration

A complete blood count, platelets, and stools for occult blood may be ordered periodically throughout therapy. Thrombocytopenia may occur during heparin administration. A mild, transient thrombocytopenia may occur 2 to 3 days after heparin therapy is begun. This early development of thrombocytopenia tends to resolve itself despite continued tiierapy. The nurse reports a platelet count of less than 100,000 mm3 immediately because die primary care provider may choose to discontinue die heparin therapy. 

Discuss the use of laboratory tests in monitoring heparin administration. 

The present chapter deals with different calculations associated with parenteral medications which include rate of flow of intravenous fluids, parenteral insulin and heparin administration, reconstitution of powdered medications, and milliequivalent and milliosmole calculations pertinent to injectable medications. 

Whereas LPL predominantly hydrolyzes triglycerides in chylomicrons and VLDL, it has been shown that HL primarily hydrolyzes triglycerides and phospholipids from small VLDL, IDL, and HDL [82]. Like LPL, HL binds to the endothelium through heparan sulfate proteoglycans and is released upon heparin administration because of its higher affinity for heparin than for the endogenous heparan sulfate proteoglycans. Intravenous injection of a heparin bolus displaces the HL enzyme into postheparin plasma, where its activity can be quantified. 

During the past few decades, a number of important studies were published on the effect of cholic acid derivatives on the absorption of macromolecules [81]. Guarini and Ferrari [84—86] compared simultaneous oral dosing of NaDOC and heparin to pretreatment with NaDOC by oral gavage in dogs followed by oral heparin administration at a 0.5-24-h interval. In all pretreatment regimens, NaDOC enhanced heparin absorption, with the maximum effect observed when heparin was administered 1 h after NaDOC. 

The indications for the use of heparin are described in the section on clinical pharmacology. A plasma concentration of heparin of 0.2-0.4 unit/mL (by protamine titration) or 0.3-0.7 unit/mL (anti-Xa units) usually prevents pulmonary emboli in patients with established venous thrombosis. This concentration of heparin will prolong the activated partial thromboplastin time (aPTT) to 2-2.5 times that of the control value. This degree of anticoagulant effect should be maintained throughout the course of continuous intravenous heparin therapy. When intermittent heparin administration is used, the aPTT should be measured 6 hours after the administered dose to maintain prolongation of the aPTT to 2-2.5 times that of the control value. 

Anti-Xa activity has been used extensively for monitoring heparin administration to patients, and remains a necessary feature of the current heparin dose-adjustment paradigm [35]. Moreover, anti-Xa and anti-IIa activity have been used successfully in the exploration of patient covariates which may suggest regimen modifications for certain disease states [35, 36] and subpopulations [37, 38]. These parameters also appear to be sufficient to judge the in-vivo performance of such agents. One reason for the lack of predictability of anti-Xa and anti-IIa activity... 

The TFPI pool bound to the endothelium has been shown to be heparin releasable in a number of studies (104,106), Venous occlusion and agents such as I-deamino-8-D-arginine vasopressin (DDAVP) that induce exocytosis of endothelial granular proteins do not cause the release of TFPI (106). Repeated heparin administration is observed to release... 

Ellis SG, Roubin GS, WilentzJ, Douglas JSJr, King SB III. Effect of I 8- to 24-hour heparin administration for prevention of restenosis after uncomplicated coronary angioplasty. Am Heart J 1989 I 17(4) 777-782. 

Desmond PV, Roberts RK, Wood AJ, Dunn GD, Wilkinson GR, Schenker S. Effect of heparin administration... 

Berkowitz, S.D. Marder, V.J. Kosutic, G. Baughman, R.A. Oral heparin administration with a novel drug delivery agent (SNAC) in healthy volunteers and patients undergoing elective total hip arthroplasty. J. Thromb. Haemost. 2003, 1 (9), 1914-1919. 

Two types of heparin-induced thrombocytopenia have been defined. Type I (mild) occurs within the first few days of heparin administration, while type II (severe), which is less common, is generally seen after a week or more of treatment and is often complicated by the recurrence of thromboembolic events. 

Type I heparin-induced thrombocytopenia is common and is characterized by a mild transient thrombocytopenia (with platelet counts that usually do not fall below 50 X 10 /1) the thrombocytopenia occurs on the first few days of heparin administration (usually 1-5 days) and requires careful monitoring but not usually withdrawal of heparin. Type I thrombocytopenia is generally harmless and very probably results from direct heparin-induced platelet aggregation. Thrombocjdopenia is most common when large doses of heparin are used, or in some particular circumstances, such as after thrombolytic therapy (35) or in the early orthopedic postoperative period (36) it can abate in spite of continued therapy. Tjrpe I thrombocytopenia is a non-immune reaction, probably due to a direct activating effect of heparin on platelets. 

Conversely, some methods give artifactually high results in some circumstances, such as IV heparin administration. 

FT4 assays based on direct equilibrium dialysis or ultrafiltration measure free hormone without the need for total hormone measurements. These methods are unaffected by either variations in serum binding proteins or thyroid hormone autoantibodies. However, IV heparin administration can cause spurious elevations m FT4 determined by these techniques as a consequence of in vitro generation of free fatty acids. Mean values obtained in euthyroid healthy subjects are reported to be slightly higher when using ultrafiltration methods than when using equilibrium dialysis. Analytical performance goals have been recommended for free thyroid hormone assays.When an FT4 assay... 

There are currently no published data regarding EL mass or activity levels in human plasma. Indeed, there has been relatively little study of phosphohpase activity in human plasma. Phospholipase activity increases after administration of heparin [24]. Some of the phospholipase activity in human plasma [25] has been attributed to lecithin-cholesterol acyltransferase (LCAT) [26] and hepatic lipase [27]. In the presence of inflammation, the secretory phospholipase A2 (sPLA2) may account for some of the plasma phosphohpase achvity and is also increased after heparin administration [28]. The contribuhon of endofhehal hpase to plasma phospholipase activity is unknown, but fhe decrease in post-heparin phosphohpase activity in EL knockout mice suggests that EL may contribute substantiaUy to plasma phosphohpase activity in humans. 

To circumvent many of these undesired side effects associated with systemic heparin administration, many investigators have endeavored to immobilize heparin to blood-contacting polymers to form thromboresistant surfaces. Considering that heparin binds to the endothelium following systemic injection (I), this approach appears attractive. 

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