July 29, 2008
We promised you we’d be discussing a lot more topics from the recently published “Antithrombotic and Thrombolytic Therapy, 8th Ed: ACCP Guidelines”. Our last two Patient Safety Tip of the Week columns had piqued our interest as to the frequency of heparin-induced thrombocytopenia (HIT) after use of heparin flushes. As you might expect, there are no good epidemiological data to provide a good estimate. Many of the patients who developed HIT were receiving heparin therapeutically or for DVT prophylaxis in addition to receiving heparin flushes in attempt to maintain catheter patency. Nevertheless, there clearly are reports of patients developing HIT who only received heparin flushes (Kadidal 1999, Andreescu 2000, Frost 2005, McNulty 2005, Laird 2005). The 1999 paper by Kadidal et al noted 3 cases of HIT related to daily heparin flushes of central venous access devices and found only 29 previously reported cases in a review of the literature. However, the 2005 study by McNulty et al included 23 cases from one institution of HIT related solely to intravascular catheter or filter flush with heparin.
HIT is an immune-mediated disorder characterized by thrombocytopenia and propensity to both venous and arterial thromboses that occurs in patients exposed to heparin products. Other features may include skin lesions at the sites of heparin injections and some patients may suffer an anaphylactoid reaction after an IV bous of heparin. The definition of HIT has varied somewhat in the literature but most include a fall in platelet count of 50% or more from baseline. That assumes one knows the baseline platelet count prior to starting the heparin product. Note that it is possible for the platelet count to still be within the “normal” range at a time when it has already fallen 50%. Diagnosis requires confirmation of HIT antibodies in the serum. The reported incidence of HIT has been as high as 1-3%. However, the incidence depends upon characteristics of both the heparin products and patients themselves. The ACCP guideline “Treatment and Prevention of Heparin-Induced Thrombocytopenia: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)” places the overall incidence of HIT as being anywhere from less than 0.1% to 1-5%. Though the incidence may be lower with low-molecular weight heparins (LMWH) than unfractionated heparin (UFH), HIT does occur with LMWH.
The most typical course of HIT is development of thrombocytopenia 5 to 14 days after starting therapy with a heparin product. However, some patients (particularly those exposed to heparin products within the previous 100 days) may develop a more acute form that appears in the first few days after heparin is started.
Early recognition of HIT is important because of the potentially serious thrombotic complications that may occur. The thrombotic complications usually occur after the fall in platelet count has occurred but in almost 25% of cases the thrombotic complications may precede recognition of a falling platelet count. Early recognition is facilitated by monitoring the platelet count and then confirming serologically the presence of antibodies characteristic of HIT. The ACCP guideline makes its platelet count monitoring recommendations based upon the risk stratification of the patient. High-risk patients (those with risk of 1-5%) include postoperative orthopedic, cardiac and vascular surgery patients who are receiving unfractionated heparin as DVT prophylaxis for 1-2 weeks. They recommend these patients have at least every other day platelet count monitoring between postoperative days 4 to 14 (or until heparin is stopped, whichever occurs first). For patients with lesser risk (0.1% to 1%), such as medical and obstetrical patients receiving prophylactic UFH, or postoperative patients receiving LMWH after first receiving UFH, or post-operative patients receiving heparin flushes, they recommend platelet count monitoring every 2-3 days from day 4 to day 14. For the lowest risk group (risk less than 0.1%), such as medical and obstetrical patients receiving LMWH, they do not recommend routine platelet count monitoring. For patients who are starting either UFH or LMWH but who have been exposed to heparin within the past 100 days and thus are at risk for the rapid-onset type HIT, they recommend getting a baseline platelet count and a repeat within 24 hours of starting heparin. Those who have an anaphylactoid reaction to an IV bolus of heparin should have an immediate platelet count and comparison to recent prior plateley counts. For patients who are on full-dose heparin anticoagulation for treatment of venous or arterial thrombosis, the recommendation is for platelet count monitoring every 2-3 days from day 4 to day 14 (or until heparin is stopped, whichever is sooner). This group seems to be at lower risk than the group of postoperative patients on DVT prophylaxis.
Given the widespread use of heparin products in DVT prophylaxis, plus the use of heparin products for full-dose anticoagulation, plus the use (correctly or incorrectly) of heparin flushes to maintain patency of various catheters and lines, a large hospital may have several hundred patients at risk for HIT at any point in time. It is impractical to think that a physician would remember to order platelet monitoring in each of the above circumstances. A more comprehensive system for screening is desirable. Andreescu et al (Andreescu 2000) developed a pharmacy-based surveillance system to screen for HIT. They had pharmacists do chart reviews on all patients receiving 10,000 units or more of heparin products. They ensured that platelet counts were performed at least every other day on these patients. If they found the platelet count had fallen 50% from baseline or to below 100,000, the staff pharmacist contacted the pharmacist on the anticoagulation service who then coordinated management with the attending physician. Even so, they also identified some patients who were not being monitored that frequently, such as one patient who developed HIT while receiving heparin flushes only. In their study the incidence of definite HIT was 2.0 cases per 1000 heparin courses. If the cases of probable HIT were included, the incidence was 2.5 cases per 1000 heparin courses. If they considered only patients taking heparin for 5 days or more, the incidence was 12.2 cases per 1000 heparin courses. Though they recognized some limitations of their study, they felt that the surveillance program likely improved clinical outcomes and probably did so cost-effectively. In the current computer age, an automated surveillance system (using tools similar to the trigger tools we have previously described in our April 15, 2008 Patient Safety Tip of the Week “Computerizing Trigger Tools”) makes more sense. One would have to identify which patients should have platelet count tracking at the time of physician order entry (note that this is another good reason why even heparin flushes should require a physician order), ensure a baseline platelet count has been obtained, prompt for the appropriate interval for tracking, and then flag for appropriate intervention any case in which the platelet count falls 50% or more (or falls below 100,000).
Of course, there is also a downside to close monitoring for HIT. There are costs associated with the frequent bloodwork, though these are relatively small compared to the costs that might be incurred in managing a case of HIT. But the most important unintended consequence would be in incorrectly identifying a patient with a platelet count that is falling for other reasons and then (while waiting for the serological confirmatory testing for HIT) either stopping the heparin that is beneficial to them or switching them to an alternative anticoagulant that may carry a higher risk of bleeding.
The management of HIT is beyond the scope of this column and we refer you to the ACCP guideline for that. Most important is discontinuation of the heparin and switching to an alternative anticoagulant. Since a high percentage of patients managed with simple discontinuation of the heparin product still develop thrombotic complications, use of alternative anticoagulants is usually recommended. The ACCP guideline does an excellent job of making recommendations for various clinical scenarios.
Kadidal VV, Mayo DJ, Horne MK. Heparin-induced thrombocytopenia (HIT) due to heparin flushes: a report of three cases. Journal of Internal Medicine 1999; 246(3):325-329 http://www.journalofinfusionnursing.com/pt/re/jinfusionnurse/abstract.00004777-199909000-00012.htm;jsessionid=LNlVTvsb6SWprPG8QHySNv0VLx4F89Qd4Q2p51N02wgM5xdZNyCq!1629792715!181195629!8091!-1?nav=reference
McNulty I, Katz E, Kim KY. Thrombocytopenia Following Heparin Flush. Progress in Cardiovascular Nursing 2007; 20 (4):143-147 Published Online: 30 Jan 2007 http://www3.interscience.wiley.com/journal/118701380/abstract
Frost J, Mureebe L, Russo P, Russo J, Tobias JD. Heparin-induced thrombocytopenia in the pediatric intensive care unit population. Case Reports. Pediatric Critical Care Medicine 2005; 6(2):216-219 http://www.pccmjournal.com/pt/re/pccm/abstract.00130478-200503000-00018.htm;jsessionid=LNkVXtyn6N8nQrZ9lTQkSh0dC97K9l8X2gfwVb5GTlfG5nvtp2J4!523807009!181195628!8091!-1
Laird JH, Douglas K, Green R. Heparin-induced thrombocytopenia type II: A rare but significant complication of plasma exchange. Journal of Clinical Apheresis 2005; 21(2): 129-131 Published Online: 8 Dec 2005
Andreescu ACM, Possidente C, Hsieh M, Suchman M. Evaluation of a Pharmacy-Based Surveillance Program for Heparin-Induced Thrombocytopenia. Pharmacotherapy 2000; 20(8): 974-980 http://www.atypon-link.com/PPI/doi/abs/10.1592/phco.20.11.974.35264
Warkentin TE, Greinacher A, Koster A, Lincoff AM. Treatment and Prevention of Heparin-Induced Thrombocytopenia: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008: 340S–380S. DOI 10.1378/chest.08-0677
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