Heparin-induced Precipitation Research Articles

Precipitating Plasma.

An adult female diagnosed with granulomatosis with polyangiitis was admitted for treatment with immunosuppressive medication. When a stored lithium-heparin tube was retrieved for additional testing, the plasma was found to contain a precipitate that dissolved upon heating to 37°C. Cryoprecipitate testing on fresh serum and plasma collected in prewarmed tubes with prewarmed needles was performed. Visual precipitates and immunofixation results are shown in Fig. 1. ... ... The answers are below. Cryoprecipitation in plasma, but not serum, is consistent with cryofibrinogenemia (1, 2). The heparin plasma cryoprecipitate mainly consisted of fibrinogen and fibronectin. Part of the cryofibrinogen observed in this patient was caused by a heparin-precipitable fraction as the citrate plasma cryoprecipitate was significantly smaller (3–5). Cryofibrinogenemia may be primary or secondary to autoimmunity, infection, or malignancy (1, 2). Its association with skin-lesions and systemic thrombosis is strongest when observed in citrate plasma as this distinguishes cryofibrinogenemia from heparin-induced precipitation (1–5).

Lipid apheresis techniques: current status in Germany

For long-term lipid apheresis therapy, several different technical systems have been developed which enable effective reduction of LDL cholesterol and other atherogenic lipoproteins, such as Lp(a), with sufficient selectivity and good clinical tolerance. Suitable techniques include whole blood adsorption with polyacrylamide and dextran sulfate cellulose, while primary plasma separation is used for cascade filtration, heparin-induced precipitation, immunoadsorption, silicate gel adsorption, and dextran sulfate cellulose (both techniques).The technical features are described. Only intensive training and experience of the medical personnel guarantees reliable treatment safety of all systems at a very low rate of minor side effects.

Extracorporeal LDL-Cholesterol Elimination in the Treatment of Severe Familial Hypercholesterolemia

The extracorporeal elimination of LDL-cholesterol could be performed using the classic non-selective centrifuge or membrane plasmapheresis. The modern methods are more selective and effective. The atherogenic particules are removed from plasma by active colon or capsula. The methods include: cascade filtration, imunoadsorbtion, heparin-induced precipitation of LDL, thermofiltration, dextran-induced precipitation of LDL and direct adsorption of lipids (DALI). The regular LDL-apheresis is the life-saving technique in the treatment of homozygous familial hypercholesterolaemia. It is used in heterozygous familial hypercholesterolaemia when the patients do not respond to diet and drugs therapy, too. The regular LDL-apheresis treatment may be followed by the decreased frequency of angina pain episodes, the reduction of ECG changes during the bicycle ergometry and significant disappearance of tendinous xantomas. Some prospective randomised studies has shown even in this group of patients, resistant to conventional treatment, a significant regression of atherosclerotic changes.

Low factor XIIIA levels are associated with increased blood loss after coronary artery bypass grafting

Current hematologic approaches to minimize postoperative bleeding have focused principally on antifibrinolytic agents. To explore whether a need might exist to promote clot stabilization independent of steps that might be taken to prevent lysis, we followed levels of the functional A-chain of factor XIII (fibrin stabilizing factor) immunologically in 19 patients undergoing coronary artery bypass grafting. The levels of factor XIIIA together with alterations in fibrinogen were followed at five stages of operation: (1) initial catheter placement (control), (2) heparinization, (3) initiation of cardiopulmonary bypass, (4) discontinuation of cardiopulmonary bypass, and (5) heparin neutralization with protamine sulfate. Significant (p < 0.05) inverse correlations were observed between postoperative chest-tube drainage volumes and levels of XIIIA at stages 1 through 3, and borderline associations (p < 0.1) were observed for stages 4 and 5. Pronounced losses of factor XIIIA accompanied initiation of cardiopulmonary bypass, when levels fell to 43% +/- 12% (standard deviation) of the control value, significantly below the 59% +/- 9% of the control value expected from hemodilution. By comparison, fibrinogen concentrations fell only to the extent attributable to hemodilution, unaccompanied by substantial degradation as indicated by electrophoretic, functional, and immunologic assays. There was a reversible heparin-induced precipitation of fibrin complexes and fibrinogen dimers from the blood on initiation of hypothermia, but these components returned to the circulation on restoration of normothermia. This precipitation was unrelated to losses of factor XIIIA. The findings warrant inference that XIIIA supplementation in deficient states should be considered as an adjunct to other therapies for postoperative bleeding.

Pharmacokinetics of Doxorubicin in the Heparinized Perfusate during Isolated Hyperthermic Limb Perfusion

Background: Hyperthermic isolated limb perfusion (HILP) is a standardized technique for treatment of malignant melanoma (MM) and soft-tissue sarcoma (SA). Doxorubicin (DOX) has proved to be effective in HILP chemotherapy. DOX levels in the perfusate can be influenced by various factors. Particularly heparin-induced precipitation and adhesion to plastics have been discussed to modify bioavailability of the drug to the treated tumor. Peripheal DOX pharmacokinetics in the perfusate were investigated to clarify if DOX levels are compromised by the artificial conditions during HILP. Data should also contribute to a further improvisation of DOX dosage during the procedure. Material and Methods: DOX pharmacokinetics were analyzed in 7 patients with MM and SA during clinical HILP of the upper/lower extremity after bolus administration of 10 or 20 mg DOX. Influence of high heparin dosage (10/25 IU/ml heparin) on DOX pharmacokinetics and adhesion to plastics was additionally evaluated during experimental perfusate recirculation without patient contact. For the detection and quantification of DOX and metabolites a high-performance liquid chromatography assay was used. Results: All patients had measurable values of DOX during the total perfusion period. Metabolites, particularly the 7-deoxyaglycones, could be detected in low concentrations. DOXol is the major metabolite of DOX in the perfusate. This implicates that an aldo-keto-reductase, which is responsible for this metabolism, must be present in peripheral tissues. Mean half-life of DOX was 27.3 + 5,6 min, mean plasma clearance was 77.8 + 41.6 ml/min. Peripheral DOX metabolism appeared to be 10-fold reduced, when compared with the systemic metabolism. i We conclude that the continuous decrease of the DOX perfusate concentration during clinical HILP seems to be mostly a function of DOX tissue absorption. This is supported by the finding that neither relevant heparin-induced DOX precipitation nor a significant loss due to adhesion to plastics was noted in the experimental setting.

Treatment of severe hypercholesterolemia with heparin-induced LDL apheresis

Five patients with familial heterozygous hypercholesterolemia underwent low-density lipoprotein (LDL) apheresis using heparin-induced precipitation without concomitant lipid-lowering drug therapy for one year. Compared with the effects of combined lipid-lowering drug therapy, LDL apheresis produced a greater decrease in mean LDL cholesterol (7.36 ± 0.42 mmol/L vs 4.09 ± 0.05 mmol/L). High-density lipoprotein (HDL) cholesterol levels increased by 11%, and the LDL:HDL cholesterol ratio decreased from 7.9 to 3.9. Other cardiovascular risk factors, including lipoprotein(a), fibrinogen, plasma and whole blood viscosity, and erythrocyte aggregation, were also improved by a single treatment and over time. Serum proteins, hemostasis parameters, and safety parameters were not adversely affected. After 1 year, an improvement in clinical status, especially a reduction in the frequency of angina pectoris, was obtained. LDL apheresis should be used in conjunction with lipid-lowering drugs; the addition of HMG-CoA-reductase inhibitors to the LDL apheresis treatment decreased mean LDL cholesterol levels by 1.5 mmol/L.

Blood Rheology After LDL Apheresis Using Dextran Sulfate Cellulose Absorption—A Case Report

The authors describe a thirty-eight-year-old woman with familial hypercholesterolemia treated by dextran sulfate cellulose adsorption apheresis. This technique and the selective extracorporeal LDL cholesterol elimination by immunoabsorption or heparin-induced precipitation not only dramatically decrease blood lipids but also result in a marked improvement in the rheologic profile. It is suggested that the amelioration of blood rheology by LDL apheresis may represent the cause for the early clinical improvement felt by most patients with severe coronary heart disease and hypercholesterolemia.

Distribution of plasma fibronectin (cold-insoluble globulin) and components of the factor VIII complex after heparin-induced precipitation of plasma

Factor VIII procoagulant (VIII:C) activity, factor VIII coagulant antigen (VIII:CAg), von Willebrand ristocetin cofactor (VIIIR:RC) activity, factor VIII-related antigen (VIIIR:Ag), and plasma fibronectin (CIg; cold-insoluble globulin) were measured in the heparin precipitable fraction (HPF) and heparin supernatant fraction (HS) of normal human plasma. Following heparin induced precipitation, most measurable VIII:C activity (77% +/- 24%) was recovered in the HS. Although there was little VIII:C activity (less than 1%) in the HPF, 20% +/- 6.5% VIII:CAg was present as well as CIg (81% +/- 5.6%). VIIIR:RC activity (72% +/- 12%), and VIIIR:Ag (34 +/- 5.2%). As assessed by Na dodecyl SO4 glyoxyl agarose electrophoresis, the multimeric forms of plasma VIIIR:Ag could be resolved into a series of bands. Larger multimers tended to precipitate with the HPF whereas the smaller multimers tended to remain supernatant. Plasma from a subject with congenital afibrinogenemia was also studied. Although the afibrinogenemic HPF contained CIg, neither VIIIR:RC activity nor VIIIR:Ag was precipitated. However, both were present in the HPF from afibrinogenemic plasma to which fibrinogen had been added, suggesting that they are incorporated in this precipitate because of an affinity for fibrinogen. The ability of heparin to induce precipitation of CIg while leaving most VIII:C activity in the supernatant plasma may be useful in the preparation of procoagulant-rich plasma subfractions, since VIII:C can subsequently be recovered in good yield by cryoprecipitation.