Prior Heparin Exposure Research Articles

The incidence of heparin-induced antibodies in patients undergoing vascular surgery: A prospective study

Purpose: This study prospectively assessed the incidence of heparin-induced antibodies in patients undergoing peripheral vascular surgery and determined whether the incidence is influenced by previous heparin exposure. Methods: Fifty-four hospitalized patients (36 men and 18 women) undergoing peripheral vascular surgery and receiving intraoperative heparin anticoagulation were studied. Unfractionated porcine heparin was given for intraoperative anticoagulation and was not continued postoperatively. Carotid endarterectomy was performed in 36 patients, aortic reconstruction in 11 patients, and infrainguinal bypass in 7 patients. Plasma was tested before and after (14 ± 7.5 [SD] days) surgery for IgG antibodies to the complex of heparin/platelet factor 4, using a standardized, validated enzyme-linked immunosorbent assay (ELISA). Results are expressed as an optical density ratio (ODR) of patient plasma to normal plasma, with the threshold for a positive result of ≥1.8. Platelet counts and clinical outcomes were also assessed. Results: The mean patient age was 67.2 ± 9.7 years. A prior exposure to heparin was documented in 41% of patients. The mean intraoperative heparin dose was 9089 ± 3607 units. Only 1 patient converted from a negative antibody status to a positive status (1.9%, 95% CI = 0.10% – 11.18%). The change in the ELISA ODR after surgery was not significantly different for patients with (+0.042 ± 0.272) and without (-0.022 ± 0.299, P = 0.57) prior heparin exposure. Postoperatively, the platelet counts dropped from 227,620 ± 78,308 μL, to 185,706 ± 80,842 μL (P < .001). The decrease in platelet count was the same in patients with prior heparin exposure (–23.0 ± 18.0%) and without (–18.0 ± 14.0%, P = .46). One thrombotic complication occurred, a femorotibial bypass graft occlusion in a patient who tested negative for antibodies. Conclusion:Heparin-induced antibodies occur infrequently after peripheral vascular surgery. The commonly observed, mild degree of postoperative thrombocytopenia does not appear to be caused by heparin-induced antibodies. These results indicate that a standard dose of heparin for intraoperative anticoagulation during vascular surgery is not associated with a significant risk of heparin-induced thrombocytopenia and thrombosis. (J Vasc Surg 1998;28:439-45.)

Anticoagulant effects of protamine sulfate in a canine model

Protamine sulfate is considered a weak anticoagulant, yet little is known concerning the mechanism of this effect or its relation to prior heparin exposure. This investigation defined the influence of increasing doses of protamine, with and without prior heparin anticoagulation, on the activated clotting time (ACT), thrombin clotting time (TCT), prothrombin time (PT), partial thrombosplastin time (PTT), fibrinogen level, platelet count, and platelet aggregation to ADP in dogs ( n = 8). Four doses of intravenous protamine sulfate (1.5, 3.0, 6.0, and 15.0 mg/kg) were studied in each animal, with at least 5 days between individual studies. Four dogs received heparin, 150 IU/kg 10 min prior to protamine sulfate administration, and four dogs received protamine sulfate alone. Protamine sulfate caused anticoagulation, both in the presence and absence of heparin, with significant changes occurring in the ACT, PTT, platelet count, and platelet aggregation. Relevant changes did not occur in the TCT, PT, or fibrinogen levels. Platelet effects were capable of causing bleeding with standard or excess use of protamine sulfate, especially if platelet numbers were already decreased, as might occur in surgical procedures where thrombocytopenia commonly accompanies major blood loss and replacement. The ACT, reflecting both the coagulation cascade and platelet function, was the test most profoundly affected by protamine overdosage, and therefore may be misleading as a measure of protamine reversal of heparin. The TCT, which is sensitive to heparin anticoagulation but not protamine-induced anticoagulation, should be more accurate in differentiating inadequate heparin reversal from the effects of excess protamine.

The effects of heparin on the adherence of five species of urinary tract pathogens to urinary bladder mucosa.

Previous studies performed in our laboratory have indicated that the primary antibacterial defense mechanism of the rabbit urinary bladder is the antiadsorptive action of the surface mucopolysaccharide. Removal of this layer with an acid rinse increases bacterial adherence up to 100 fold. Exogenous mucopolysaccharide (heparin) has been shown to restore Escherichia coli adherence to control levels. To determine whether this antiadherence action of heparin is species specific, we compared the adherence of 5 common urinary tract pathogens (Escherichia coli, Klebsiella ozonae, Proteus mirabilis, Pseudomonas aeruginosa, and Streptococcus fecalis) to both mucin intact and mucin deficient rabbit bladders with and without prior heparin exposure. Bacteria were radiolabeled by addition of 3H-adenine to the culture broth so that the number of bacteria adhering to the bladder could be determined using liquid scintillation spectrophotometry. Results were as follows: Acid removal of the mucin layer significantly increased the adherence approximately 10 fold for all 5 species tested. Briefly exposing the mucin deficient bladders to heparin decreased the adherence of all species tested except Pseudomonas to mucin intact control levels. Heparin treatment of mucin intact bladders slightly decreased adherence of all species except Pseudomonas below mucin intact controls, however, results were not statistically significant. The magnitude of Klebsiella adherence was nearly 20 fold greater than all other species tested. While this non-species specific adherence inhibition of heparin may prove useful in the clinical setting, it appears to be less effective against Pseudomonas.