Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

OBJECTIVE: Despite controversy about whether peripheral and central venous catheters should be locked with heparin to prevent catheter-associated clotting, the practice is widespread. We describe a severe side effect of the practice: a case of heparin-induced thrombocytopenia occurring with catheter flushes using unfractionated heparin (UFH) in a 10-month-old boy successfully treated with danaparoid. Patient: A preterm-born patient (33 wks gestational age, birth weight 1200 g) suffering from VACTERL syndrome was repeatedly treated with UFH in the context of several invasive procedures. On day 310 of age, a central venous catheter was inserted to provide total parenteral nutrition. The central catheter was flushed with a continuous infusion of UFH at 100 U/day, and a decrease in platelet counts from 150,000/&mgr;L (on day 310 of age) to 45,000/&mgr;L (on day 319 of age) was observed. Clinically suspected heparin-induced thrombocytopenia (HIT) was serologically confirmed by demonstrating HIT antibodies with platelet factor 4/heparin complex specificity. Main Result: Catheter flushing was switched to low-dose danaparoid sodium as a continuous infusion at 15 anti-factor Xa units per day. Two days later, platelet counts recovered. Neither catheter thrombosis nor systemic thromboembolic complications occurred during the follow up period. CONCLUSIONS: Even continuous infusion of low-dose heparin to provide patency of central venous port catheters may trigger the primary immune response of HIT. Low-dose danaparoid sodium, a heparinoid, can prevent in-catheter thrombus formation and allows normalization of platelet counts in acute HIT.
 ...
PMID:Low-dose danaparoid sodium catheter flushes in an intensive care infant suffering from heparin-induced thrombocytopenia. 1279 78

The objective of this study was to gain deeper insight into the early reasons for saphenous vein graft disease and to find a practical approach to obviate it. Intraoperative storage of freshly explanted venous grafts (45 min, 20 degrees C; n=25 in each case) in saline, saline + 5% albumin, or HTK-solution and also in heparinized autologous blood was poorly tolerated by the endothelium. Large endothelial areas (mostly >75% of total surface) were detached already during brief non-pulsatile flushing just before the transplantation. Contact of deendothelialized areas in graft remnants with defined mixtures of coagulation factors or blood (n=11-17) caused rapid coagulatory processes via expression of tissue factor and assembly of prothrombinase in the subendothelium. Attached platelets and leukocytes accelerated the procoagulatory processes further, and endothelium-dependent anticoagulatory activities were significantly abolished. During pulsatile arterial flow, the resulting blood clots exacerbated the damage of the intima markedly, because they were flushed away tearing off further endothelium. In contrast, storage of venous grafts in a plasma preparation freed from isoagglutinins and coagulation factors preserved the endothelium, which resisted arterial flow and revealed anticoagulatory activity in the presence of antithrombin III and/or protein C. We conclude that gentle preparation and preservation of the vascular endothelium with a suitable storage solution during bypass surgery is a decisive first step to obviate saphenous vein graft disease.
 ...
PMID:Extensive deendothelialization and thrombogenicity in routinely prepared vein grafts for coronary bypass operations: facts and remedy. 1968 84

Of the new direct oral anticoagulants, direct factor Xa inhibitors are limited by the absence of a proven reversal agent. We assessed the safety, tolerability and impact on anticoagulation reversal of ciraparantag (PER977) alone and following a 60 mg dose of the FXa inhibitor edoxaban. Escalating, single IV doses of ciraparantag were administered alone and following a 60 mg oral dose of edoxaban in a double-blind, placebo-controlled fashion to healthy subjects. Serial assessments of the pharmacokinetics and pharmacodynamic effects of ciraparantag were performed. Eighty male subjects completed the study. Following edoxaban (60 mg), a single IV dose of ciraparantag (100 to 300 mg) demonstrated full reversal of anticoagulation within 10 minutes and sustained for 24 hours. Fibrin diameter within clots was restored to normal 30 minutes after a single dose of 100 to 300 mg ciraparantag as determined by scanning electron microscopy and change in fibrin diameter quantified by automated image analysis. Potentially related adverse events were periorbital and facial flushing and cool sensation following IV injection of ciraparantag. Renal excretion of ciraparantag metabolite was the main elimination route. There was no evidence of procoagulant activity following ciraparantag as assessed by D-dimer, prothrombin fragments 1.2, and tissue factor pathway inhibitor levels. In conclusion, ciraparantag in healthy subjects is safe and well tolerated with minor, non-dose limiting adverse events. Baseline haemostasis was restored from the anticoagulated state with doses of 100 to 300 mg ciraparantag within 10-30 minutes of administration and sustained for at least 24 hours.
 ...
PMID:Single-dose ciraparantag safely and completely reverses anticoagulant effects of edoxaban. 2785 9