Administration Of Heparin In Patients Research Articles

Hirudin-based anticoagulant strategy during isolated limb perfusion in a patient with heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a rare but potentially fatal complication of heparin therapy. The administration of heparin in patients with HIT causes platelet aggregation, thromboembolism and thrombocytopenia. Therefore, an alternative anticoagulant is recommended in these patients. We describe the use of recombinant hirudin (r-hirudin; Refludan, Pharmion Germany GmbH, Hamburg, Germany) as an anticoagulant in a patient with HIT requiring isolated limb perfusion (ILP) for in-transit metastases of malignant melanoma of the leg; r-hirudin was used in both the extracorporeal and systemic circuits. The coagulation monitoring included the activated partial thromboplastin time (aPTT) and ecarin clotting time (ECT). There were no thrombotic or bleeding complications. The dosage regimen and the strategy of monitoring of the anticoagulant activity are described. It can be concluded that ILP in patients with suspected or confirmed HIT can be safely performed with the use of r-hirudin in both the extracorporeal and systemic circuits. Monitoring of the anticoagulation effect is necessary and should preferably be performed using ECT.

Continuous administration of heparin in patients with deep vein thrombosis can increase plasma levels of diamine oxidase

Besides its anticoagulant activity, the sulfated polysaccharide heparin has numerous other biological effects. Especially the antiinflammatory and immunoregulatory properties of heparin may be associated with its ability to release the histamine-degrading enzyme diamine oxidase (DAO) from tissue-bound sites into the circulation. Whereas DAO activity is at the limits of detection in normal human plasma, the application of heparin leads to a significant increase of plasma DAO activity. However, previously, only the effect of bolus injection of unfractionated heparin (UFH) had been studied. To investigate DAO release during continuous heparin infusion, 28 patients with deep vein thrombosis (DVT) undergoing heparin therapy were analyzed. Whereas continuous heparin infusion did not lead to any increase of plasma DAO activity in 12 patients (43%), 6 patients (21%) showed a single elevated and 10 patients (36%) permanently elevated plasma DAO activity. The groups of patients exhibiting different DAO release responses did not differ in age, sex, body weight, concomitant diseases, heparin infusion rates, coagulation indices, location and extension of thrombosis, or clinical outcome. However, the rate of idiopathic DVT was significantly higher in the group of patients releasing DAO. This study shows, for the first time, that continuous heparin infusion can lead to DAO release and that individuals exhibit considerable differences in their release response. Although the significance of heparin-induced DAO release needs further clarification, our results indicate that postheparin plasma DAO activity could be an interesting parameter correlated with idiopathic DVT.

FDA's role in anesthetic drug development.

FDA's role in anesthetic drug development.

Plasma Tissue Factor Pathway Inhibitor and Tissue Factor Antigen Levels After Administration of Heparin in Patients With Angina Pectoris

The hypercoagulability is associated with expression of tissue factor in patients with angina. Tissue factor pathway inhibitor regulates the extrinsic coagulation pathway mediated by tissue factor. Plasma samples were obtained from 14 patients with angina pectoris and 9 with chest pain syndrome before and 5, 30, 60, and 120 minutes after administration of heparin (50 IU/kg). The tissue factor and prothrombin fragment 1+2 levels before administration were elevated in patients with angina pectoris and were reduced to the levels of chest pain syndrome after the administration. The free tissue factor pathway inhibitor levels after the administration were higher in patients with angina pectoris than in patients with chest pain syndrome. Plasma tissue factor pathway inhibitor levels correlated positively with plasma tissue factor and prothrombin fragment 1+2 levels. We showed that plasma-free TFPI levels after administration of heparin, which may indicate endothelial cell associated TFPI levels, increased in patients with angina pectoris compared with patients with chest pain syndrome. Increased endothelial cell associated TFPI was associated with hypercoagulability in patients with angina pectoris. These may help to explain the reduction in thrombotic risk associated with the use of heparin.

Endogenous Heparin-Like Substances Significantly Impair Coagulation in Patients Undergoing Orthotopic Liver Transplantation

Orthotopic liver transplantation (OLT) is associated with severe bleeding, especially after reperfusion of the grafted liver.Heparin released from the liver graft contributes to postreperfusion coagulopathy. Although patients with liver cirrhosis have increased levels of endogenous heparinoids, the role of these substances during liver transplantation is unclear. Therefore, we performed native and heparinase-modified thrombelastography (TEG) in 72 patients undergoing OLT. TEG was performed at skin incision, 10 min before and 10 min after clamping of the vena cava, 10 min before and 10 min after graft perfusion, and at the end of surgery. Heparinase-modified TEG compared with native TEG demonstrated heparin activity. In contrast to other investigations, we found significant heparin effects before reperfusion, although patients received no exogenous heparin. These heparin effects were greater in patients with cirrhosis compared with patients with cancer as the underlying disease leading to OLT. Administration of coagulation factors is the usual treatment of coagulopathies during OLT. The comparison of native versus heparinase-modified TEG can distinguish between heparin activity or coagulation factor deficiency as a cause of bleeding complications and provides a rational approach to the treatment of bleeding during OLT. Implications: Impaired coagulation function, contributed to by heparin or heparin-like substances, is frequently observed after reperfusion of a transplanted liver. This study demonstrates that a heparinase-modified thrombelastography can identify significant heparin effects in the absence of exogenous heparin administration in patients undergoing liver transplantation. (Anesth Analg 1998;86:691-5)

Time-related anticoagulation after regional and systemic administration of heparin in patients undergoing aortoiliac surgery

Heparin anticoagulation during cardiovascular surgical procedures remains poorly investigated and understood. The objective of this investigation was to assess the effectiveness of three methods of heparin administration. Heparin sulfate (75 IU/kg) administered to patients undergoing aortoiliac surgery was randomised to one of three methods: Group I (n = 9) heparin was injected into a central venous line 5 minutes before infrarenal aortic clamping; Group II (n = 9) heparin was injected into the distal aneurysm immediately after infrarenal aortic clamping; and Group III (n = 8) heparin was injected into a central venous line immediately after infrarenal aortic clamping. Blood samples were analysed for anticoagulant activity from both the upper and lower extremities at 5, 15, 30, 60, and 120 minutes after heparin administration. Anticoagulation, as measured by aPTT, antifactor Xa levels, and ACT, was achieved in all three groups by 5 minutes, but initially with lower heparin activity (measured as antifactor Xa) in the upper extremity (Group II) and lower extremity (Group III), respectively. These differences were also evident in ACT and aPTT determinations. Intravenous heparin administration prior to aortic cross-clamping achieves excellent anticoagulation (anti-factor Xa approximately 1 U/ml) in both upper and lower extremities after 5 minutes. With regional administration, rapid heparin redistribution occurs, but it takes longer to achieve the same level of anticoagulation distant from the site of administration. Nevertheless, from a practical perspective the method of administration does not appear to have a great influence on the eventual achievement of adequate anticoagulation.

Optimal Therapeutic Level of Heparin Therapy in Patients With Venous Thrombosis

Audits of heparin sodium therapy suggest that heparin administration is fraught with difficulty. The literature indicates that the current clinical practice of intuitive ordering of heparin results in inadequate therapy because of fear of bleeding. The importance of exceeding the lower limit of the therapeutic range has been strongly supported by findings of prospective clinical trials. Firm evidence indicates that failure to exceed the lower limit is associated with unacceptably high rates of recurrent venous thromboembolism. By comparison, evidence supporting the risk of exceeding the upper limit of the therapeutic range is weak. The purposes of this study were (1) to validate prospectively an approach designed to minimize the proportion of patients receiving subtherapeutic doses of heparin and (2) to determine the effectiveness and safety of decreasing the heparin dosage infused on the basis of activated partial thromboplastin time (APTT) prolongation reflecting both heparin and warfarin sodium effects. We performed a randomized double-blind study evaluating a prescriptive approach to heparin administration in patients receiving heparin or heparin with warfarin. Thromboembolic and bleeding complications were objectively documented. Only 1% and 2% of patients had subtherapeutic heparin levels for 24 hours or more in the heparin and combined groups, respectively. Recurrent venous thromboembolism occurred infrequently in both groups (7%). Sixty-nine (69%) of 99 patients receiving combined therapy had supratherapeutic values, compared with 24 (24%) of 100 receiving heparin; bleeding complications occurred in 9% and 12%, respectively. Our findings demonstrate that no association exists between supratherapeutic APTT responses and bleeding, which is in direct contrast to the observed association between subtherapeutic APTT responses and recurrent venous thromboembolism.

Optimal therapeutic level of heparin therapy in patients with venous thrombosis

<h3>Background.—</h3> Audits of heparin sodium therapy suggest that heparin administration is fraught with difficulty. The literature indicates that the current clinical practice of intuitive ordering of heparin results in inadequate therapy because of fear of bleeding. The importance of exceeding the lower limit of the therapeutic range has been strongly supported by findings of prospective clinical trials. Firm evidence indicates that failure to exceed the lower limit is associated with unacceptably high rates of recurrent venous thromboembolism. By comparison, evidence supporting the risk of exceeding the upper limit of the therapeutic range is weak. <h3>Objectives.—</h3> The purposes of this study were (1) to validate prospectively an approach designed to minimize the proportion of patients receiving subtherapeutic doses of heparin and (2) to determine the effectiveness and safety of decreasing the heparin dosage infused on the basis of activated partial thromboplastin time (APTT) prolongation reflecting both heparin and warfarin sodium effects. <h3>Methods.—</h3> We performed a randomized double-blind study evaluating a prescriptive approach to heparin administration in patients receiving heparin or heparin with warfarin. Thromboembolic and bleeding complications were objectively documented. <h3>Results.—</h3> Only 1% and 2% of patients had subtherapeutic heparin levels for 24 hours or more in the heparin and combined groups, respectively. Recurrent venous thromboembolism occurred infrequently in both groups (7%). Sixty-nine (69%) of 99 patients receiving combined therapy had supratherapeutic values, compared with 24 (24%) of 100 receiving heparin; bleeding complications occurred in 9% and 12%, respectively. <h3>Conclusions.—</h3> Our findings demonstrate that no association exists between supratherapeutic APTT responses and bleeding, which is in direct contrast to the observed association between subtherapeutic APTT responses and recurrent venous thromboembolism. (<i>Arch Intern Med.</i>1992;152:1589-1595)

Fibrinopeptide A in Urine from Patients with Venous Thromboembolism, Disseminated Intravascular Coagulation and Rheumatoid Arthritis - Evidence for Dephosphorylation and Carboxyterminal Degradation of the Peptide by the Kidney

Urinary fibrinopeptide A immunoreactivity was determined by radioimmunoassay using two anti-fibrinopeptide A sera with a different specificity in patients with venous thromboembolism, disseminated intravascular coagulation and rheumatoid arthritis. Elevated levels were frequently observed with both sera, and intravenous administration of heparin in patients with a thromboembolic disorder resulted in a decline of urinary fibrinopeptide A (FPA) concentrations to normal or nearly normal values. For both sera significant correlations with plasma levels were found although one of the sera reacted significantly better with the material in urine samples from these patients than the other (p less than 0.0001, n = 73). Analysis of urinary fibrinopeptide A immunoreactivity by high performance liquid chromatography (HPLC) provided evidence that A peptide material present in this body fluid was heterogeneous. In view of the characteristics of the antisera used in this study, data suggest that urinary FPA immunoreactivity consists to a large extent of carboxyterminally degraded FPA. Excretion of circulating FPA immunoreactive material through the kidneys apparently involves dephosphorylation and carboxyterminal breakdown of the A peptide. Since both synthetic and native phosphorylated or unphosphorylated fibrinopeptide A appeared to be stable in urine in vitro, an active role of the kidney in degrading the A peptide is likely.