Heparin Lock Flush Disease Interactions

Anticoagulants are contraindicated in patients with active major bleeding or those patients at risk for hemorrhage. Hemorrhage due to heparin derivatives may be treated with protamine sulfate 1%. However, protamine sulfate may not completely neutralize the anti- Factor Xa activity.

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The use of certain heparin sodium injections and heparin lock flush solutions is considered by the manufacturers to be contraindicated in premature infants and infants of low birth weight. Some formulations of these drugs contain benzyl alcohol which, in bacteriostatic saline intravascular flush and endotracheal tube lavage solutions, has been associated with fatalities and severe respiratory and metabolic complications in low-birthweight premature infants. Symptoms include a striking onset of gasping respiration, hypotension, bradycardia, and cardiovascular collapse. The manufacturers further recommend that use of these products be avoided in all neonates whenever possible. Neonates requiring heparin lock flush solution should be given a preservative-free formulation. Nevertheless, many experts feel that, in the absence of benzyl alcohol-free equivalents, the amount of the preservative present in these formulations should not necessarily preclude their use if they are clearly indicated. The American Academy of Pediatrics considers benzyl alcohol in low doses (such as when used as a preservative in some medications) to be safe for newborns.

The use of heparin for maintaining patency of umbilical artery catheters may be associated with an increased risk of germinal matrix intraventricular hemorrhage in low-birthweight neonates. Although a definitive causal relationship has not been established, caution may be appropriate when heparin lock flush solutions are used.

Due to the risk of overdose, heparin lock flush solutions containing 100 units/mL should not be used in neonates, particularly those who are premature or have low birthweight.

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The use of heparin is contraindicated in patients with severe thrombocytopenia. Acute thrombocytopenia can occur in patients receiving heparin, with a reported incidence of up to 30%. Platelet counts should be obtained before and periodically during heparin administration, including regular and repeated use of heparin flush solutions if given for longer than 5 days. Mild thrombocytopenia with counts above 100,000/mm3 may remain stable or reverse despite continued heparin administration. However, thrombocytopenia of any degree should be closely monitored. Therapy should be discontinued if the count falls below 100,000/mm3 or if recurrent thrombosis develops, and an alternative, nonheparin anticoagulant (e.g., argatroban, bivalirudin, lepirudin) administered if necessary. Heparin-induced thrombocytopenia (HIT) is a serious antibody-mediated reaction resulting from irreversible aggregation of platelets. HIT may progress to the development of venous and arterial thromboses, a condition referred to as heparin-induced thrombocytopenia and thrombosis (HITT). Thrombotic events may also be the initial presentation for HITT, and may include deep vein thrombosis, pulmonary embolism, cerebral vein thrombosis, limb ischemia, stroke, myocardial infarction, mesenteric thrombosis, renal artery thrombosis, skin necrosis, gangrene of the extremities that may lead to amputation, and possibly death. Both HIT and HITT can occur up to several weeks after the discontinuation of heparin therapy. Patients presenting with thrombocytopenia or thrombosis after discontinuation of heparin should be evaluated for HIT and HITT. Following an episode, any future use of heparin should be avoided, and use of low-molecular weight heparin should consider the potential for cross-reactivity with the HIT antibody and approached with extreme caution, if not otherwise contraindicated.

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