Drug General Information (ID: DDIYIOE6R4)
Drug Name			Alteplase		Drug Info		Heparin		Drug Info
Drug Type		Protein/peptide				Small molecule
Therapeutic Class		Thrombolytics				Anticoagulants

Mechanism of Alteplase-Heparin Interaction (Severity Level: Major)
Increased risk of bleeding Click to Show/Hide Mechanism Graph
Drug Name		Alteplase				Heparin
Mechanism		Risk of bleeding Thrombolytic agent				Risk of bleeding Anticoagulant
Key Mechanism Factor 1
		Factor Name		Bleeding
		Factor Description		Patients may be at risk for bleeding when the outcome of a disease or disease treatment confounds the standard mechanisms for maintaining hemostasis. Signs or symptoms of abnormal bleeding include: bleeding that takes a long time to stop (including nosebleeds, bleeding gums, bleeding from cuts and abrasions, and menstrual bleeding); severe unexplained bruising, or bruising that becomes larger; blood in the urine or stool, etc.
Mechanism Description		Increased risk of bleeding by the combination of Alteplase and Heparin

Recommended Action
Management		Alteplase is contraindicated in patients with acute ischemic stroke who have received heparin within the last 48 hours and have an elevated activated partial thromboplastin time (aPTT). Patients who are to receive a thrombolytic plus heparin for other indications should be carefully selected according to recommended eligibility criteria. The heparin dosage should be adjusted as appropriate to maintain therapeutic aPTT values. Patients should be closely monitored for signs of bleeding, especially at arterial puncture sites. Thrombolytic and/or anticoagulation therapy should be discontinued immediately if serious or uncontrollable bleeding occurs.

References
1	Deboer A, Vangriensven JM "Drug interactions with thrombolytic agents: current perspectives." Clin Pharmacokinet 28 (1995): 315-26. [PMID: 7648759]
2	Harder S, Klinkhardt U "Thrombolytics: drug interactions of clinical significance." Drug Saf 23 (2000): 391-9. [PMID: 11085346]
3	Hirsch J, Dalen J, Guyatt G, American College of Chest Physicians "The sixth (2000) ACCP guidelines for antithrombotic therapy for prevention and treatment of thrombosis. American College of Physicians." Chest 119(1 Suppl) (2001): 1S-2S. [PMID: 11157638]
4	Lam XM, Ward CA, Dumee CPRD "Stability and activity of alteplase with injectable drugs commonly used in cardiac therapy." Am J Health Syst Pharm 52 (1995): 1904-9. [PMID: 8528854]
5	Product Information. Abbokinase (urokinase). Abbott Pharmaceutical, Abbott Park, IL.
6	Product Information. Activase (alteplase). Genentech, South San Francisco, CA.
7	Product Information. Retavase (reteplase). Boehringer Mannheim, Gaithersburg, MD.
8	Product Information. Streptase (streptokinase). Astra USA, Westborough, MA.
9	Product Information. TNKase (tenecteplase) Genentech, South San Francisco, CA.
10	Sheiman RG, Phillips DA "Combined effects of urokinase and heparin on PTT values during thrombolytic therapy." Angiology 44 (1993): 114-22. [PMID: 8434804]
11	Zahger D, Maaravi Y, Matzner Y, Gilon D, Gotsman MS, Weiss AT "Partial resistance to anticoagulation after streptokinase treatment for acute myocardial infarction." Am J Cardiol 66 (1990): 28-30. [PMID: 2360532]
12	Gore JM, Sloan M, Price TR, Randall AM, Bovill E, Collen D, Forman S, Knatterud GL, Sopko G, Terrin ML "Intracerebral hemorrhage, cerebral infarction, and subdural hematoma after acute myocardial infarction and thrombolytic therapy in the Thrombolysis in Myocardial Infarction Study. Thrombolysis inMyocardial Infarction, Phase II, pilot and clinical trial." Circulation 83 (1991): 448-59. [PMID: 1899364]