A Difficult Task: Determining Oral Anticoagulation Efficacy (OAC) in Patients with HIT Type II

Abstract

Since 1937, heparin has remained the anticoagulant of choice for a wide variety of clinical scenarios. There remains a relatively high prevalence of heparin-induced thrombocytopenia (HIT), an immune-mediated syndrome in which antibodies (most frequently IgG) bind to a complex of heparin and platelet factor IV, resulting in platelet destruction and the release of prothrombotic platelet derived microparticles. Serious complications include thrombocytopenia (usually occurring between 6-12 days after initiating therapy) and thrombosis. The risk of thrombosis in patients with HIT is estimated at 30% and mortality rates have been reported as high as 20-30%. In cases of HIT type II when patients require continuous anticoagulation, such as following implantation of mechanical heart valves, alternative anticoagulants such as direct thrombin inhibitors can be used. The difficulty of using drugs such as argatroban for bridging therapy to warfarin is that they have been found to elevate both the aPTT as well as INR. Therefore, is it difficult to assess whether patients will maintain therapeutic INRs when argatroban is held and they are continued on warfarin monotherapy. The standard treatment regimen calls for argatroban to be started until INR reaches some therapeutic level at which time argatroban is held and INR is rechecked 4-6 hours later. The risk of major bleeding associated with supra-therapeutic INR's is substantial, and as such patients should be continued on bridging therapy to the lowest INR level that is still found to be therapeutic once argatroban is held. Previous research has examined the efficacy of transitioning from argatroban to warfarin in patients with HIT type II. This case report reviews the care of a patient following a diagnosis of HIT, the methods used to measure the efficacy of oral anticoagulation (OAC), and the complications that arose with management. The patient is a 51-year-old woman who received a mechanical mitral valve replacement for mitral valve regurgitation. Two weeks later, she returned to the hospital with lower extremity swelling. On admit, the patient's INR was sub-therapeutic at 1.2. Enoxaparin was initiated with plans to bridge to warfarin until the INR reached 2.5-3.5. Within four days of enoxaparin initiation, platelets decreased from 238,000/uL to 114,000/uL. On day four, a new non-occlusive right internal jugular thrombus was found. A serotonin release assay (SRA) and HIT antibody with reflex were ordered. While labs were in process, enoxaparin was held and argatroban initiated. The PTT was checked and found to be 62.6 seconds, and it was determined that the patient was adequately anticoagulated. A 4-T score of 6 indicated a ~64% probability of HIT with the patient requiring indefinite anticoagulation due to the mechanical mitral valve. When the patient's INR reached 2.5 argatroban was held, however the following INR was found to be subtherapeutic at 1.3. Argatroban was restarted with plans to continue argatroban therapy until INR>4, at which time argatroban was to be held and INR rechecked in 4-6 hrs. If the INR remained therapeutic off argatroban then it was determined that the patient was appropriately anticoagulated. When the INR reached 4.9 and argatroban was held, the recheck 5 hours later was 3.1. Using this algorithm, the patient ultimately achieved a therapeutic INR with platelet counts of >300,000/uL at time of discharge without any major bleeding events or other serious complications. For patients in whom HIT is diagnosed, immediate discontinuation of heparin infusions and elimination of heparin from all flushes and ports is a necessity as the first step of treatment. Argatroban may be used as a bridging agent, but OAC efficacy cannot be monitored solely using the parameter of INR due to argatroban's INR-elevating effect. By trending the aPTT to monitor anticoagulation status and only utilizing the INR once argatroban therapy was removed, we ensured that the patient had achieved OAC efficacy prior to discharge. In our patient an INR of 5 did not result in any major bleeding incident; however, by initially discontinuing prematurely at an INR of 2.5, the patient's hospital stay was extended. The chromogenic factor X assay has shown some accuracy in predicting INR free of argatroban influence by measuring the amount of vitamin x, but further studies are warranted to establish an optimal method by which to convert patients from argatroban to warfarin. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal