Subacute Heparin-induced Thrombocytopenia Research Articles

Epoprostenol Therapy for a Pediatric Patient With Subacute Heparin-Induced Thrombocytopenia and a Ventricular Assist Device Undergoing Heart Transplant: A Case Report

Concerns remain regarding the use of direct thrombin inhibitors for cardiopulmonary bypass anticoagulation in pediatric patients with heparin-induced thrombocytopenia undergoing complex cardiac surgery. We describe the safe and effective use of epoprostenol sodium as an alternative therapy before heparin exposure for a pediatric patient with subacute heparin-induced thrombocytopenia and a ventricular assist device undergoing heart transplant.

The use of cangrelor with heparin for left ventricular assist device implantation in a patient with acute heparin-induced thrombocytopenia

BackgroundOptimal anticoagulation strategy for cardiopulmonary bypass (CPB) in end-stage heart failure patients with heparin-induced thrombocytopenia (HIT) requiring left ventricular assist device (LVAD) implantation remains uncertain. Presently, there are no large-scale randomized studies comparing outcomes of alternative anticoagulation strategies for CPB in this patient population. A novel antiplatelet agent – cangrelor, which is a potent P2Y12 inhibitor with robust antiplatelet efficacy, rapid reversibility, and measurable drug effect, has become available since 2015. Intraoperative anticoagulation for CPB using cangrelor with heparin has not been reported before.Case presentationWe report the case of a 47-year-old male with ischemic cardiomyopathy and acute HIT, who underwent an urgent LVAD implantation using cangrelor with heparin for anticoagulation on CPB. This novel strategy resulted in satisfactory anticoagulation for CPB without perioperative thromboembolic events or major bleeding requiring reoperation.ConclusionsCangrelor with heparin was an effective anticoagulation strategy for CPB in this critically ill patient with acute HIT requiring an urgent LVAD implantation. Further studies are warranted to evaluate its efficacy and replicability in other patients with acute or subacute HIT who require urgent cardiac surgery.

Management of the multiple phases of heparin-induced thrombocytopenia.

The clinical course of heparin-induced thrombocytopenia (HIT) may be separated into five sequential phases: 1. suspected HIT, 2. acute HIT, 3. subacute HIT A, 4. subacute HIT B, and 5. remote HIT. Each phase confronts the clinician with a unique set of management questions. In this review, the phases of HIT are defined and key management questions associated with each phase are discussed. Among patients with Suspected HIT, I use the 4Ts score to determine which patients have a sufficiently high probability of HIT to justify discontinuation of heparin and initiation of a non-heparin parenteral anticoagulant. An algorithm for selecting an appropriate non-heparin anticoagulant based on the patient's clinical stability, renal and hepatic function, drug availability, and physician comfort is provided. In patients with Acute HIT, I generally avoid prophylactic platelet transfusion and inferior vena cava filter insertion because of a potential increased risk of thrombosis. I perform 4-limb screening compression ultrasonography. In patients with symptomatic thromboembolism or asymptomatic proximal deep-vein thrombosis, I treat with anticoagulation for three months. In patients without thrombosis, I discontinue anticoagulation upon platelet count recovery. I do not transition patients to an oral anticoagulant until platelet count recovery (i. e. Subacute HIT A). I increasingly choose direct oral anticoagulants over vitamin K antagonists in this setting because of their greater convenience and safety. In Subacute HIT B and Remote HIT, I use heparin for cardiovascular surgery, whereas I use bivalirudin in patients with Acute HIT and Subacute HIT A in whom surgery cannot be delayed.

Cardiopulmonary Bypass Without Heparin.

Due to familiarity, short half-life, ease of monitoring, and the availability of a reversal agent, heparin remains the anticoagulant of choice for cardiac operations requiring cardiopulmonary bypass (CPB). However, occasionally patients require CPB but should not receive heparin, most often because of acute or subacute heparin-induced thrombocytopenia (HIT). In these cases, if it is not feasible to wait for the disappearance of HIT antibodies, an alternative anticoagulant must be selected. A number of non-heparin anticoagulant options have been explored. However, current recommendations suggest the use of a direct thrombin inhibitor such as bivalirudin. This review describes the use of heparin alternatives for the conduct of CPB with a focus on the direct thrombin inhibitors.

Plasma exchange to remove HIT antibodies: dissociation between enzyme-immunoassay and platelet activation test reactivities

AbstractRepeated therapeutic plasma exchange (TPE) has been advocated to remove heparin-induced thrombocytopenia (HIT) IgG antibodies before cardiac/vascular surgery in patients who have serologically-confirmed acute or subacute HIT; for this situation, a negative platelet activation assay (eg, platelet serotonin-release assay [SRA]) has been recommended as the target serological end point to permit safe surgery. We compared reactivities in the SRA and an anti-PF4/heparin IgG-specific enzyme immunoassay (EIA), testing serial serum samples in a patient with recent (subacute) HIT who underwent serial TPE precardiac surgery, as well as for 15 other serially-diluted HIT sera. We observed that post-TPE/diluted HIT sera—when first testing SRA-negative—continue to test strongly positive by EIA-IgG. This dissociation between the platelet activation assay and a PF4-dependent immunoassay for HIT antibodies indicates that patients with subacute HIT undergoing repeated TPE before heparin reexposure should be tested by serial platelet activation assays even when their EIAs remain strongly positive.

Treatment and Prevention of Heparin-Induced Thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

Heparin-induced thrombocytopenia (HIT) is an antibody-mediated adverse drug reaction that can lead to devastating thromboembolic complications, including pulmonary embolism, ischemic limb necrosis necessitating limb amputation, acute myocardial infarction, and stroke. The methods of this guideline follow the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. Among the key recommendations for this article are the following: For patients receiving heparin in whom clinicians consider the risk of HIT to be > 1%, we suggest that platelet count monitoring be performed every 2 or 3 days from day 4 to day 14 (or until heparin is stopped, whichever occurs first) (Grade 2C). For patients receiving heparin in whom clinicians consider the risk of HIT to be < 1%, we suggest that platelet counts not be monitored (Grade 2C). In patients with HIT with thrombosis (HITT) or isolated HIT who have normal renal function, we suggest the use of argatroban or lepirudin or danaparoid over other nonheparin anticoagulants (Grade 2C). In patients with HITT and renal insufficiency, we suggest the use of argatroban over other nonheparin anticoagulants (Grade 2C). In patients with acute HIT or subacute HIT who require urgent cardiac surgery, we suggest the use of bivalirudin over other nonheparin anticoagulants or heparin plus antiplatelet agents (Grade 2C). Further studies evaluating the role of fondaparinux and the new oral anticoagulants in the treatment of HIT are needed.

Plasmapheresis and Heparin Reexposure as a Management Strategy for Cardiac Surgical Patients with Heparin-Induced Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) complicates the management of patients presenting for cardiac surgery, because high-dose heparin anticoagulation for cardiopulmonary bypass is contraindicated in these patients. Alternative anticoagulants are available, but there are concerns about dosing, efficacy, monitoring, thrombosis, and hemorrhage. A retrospective chart review between November 2004 and March 2008 retrieved perioperative clinical and laboratory data for 11 adult cardiac surgical patients with a preoperative history of HIT and a current positive antiheparin/platelet factor 4 (anti-HPF4) antibody titer, who were managed with plasmapheresis and heparin anticoagulation. The median (interquartile range) preoperative anti-HPF4 antibody titer was 0.8 (0.7-2.2). Three of the 11 patients (27%) died of causes unrelated to HIT and 1 of these patients (9%) developed an ischemic foot, in the setting of cardiogenic shock, not thought to be HIT-related. A single plasmapheresis treatment reduced titers by 50%-84%, and 6 patients had negative titers after treatment; none of the 3 patients with reduced titers developed clinical HIT. This case series describes an alternative management strategy using intraoperative plasmapheresis for patients presenting for cardiac surgery with acute or subacute HIT. Reducing antibody load can potentially decrease the thrombotic risk associated with high anti-HPF4 titers and decrease the urgency to initiate postoperative anticoagulation in this patient group at high risk of postoperative bleeding.

Anticoagulation management in patients with subacute heparin-induced thrombocytopenia scheduled for heart transplantation

Objective: Short-term use of unfractionated heparin (UFH) for cardiopulmonary bypass (CPB) surgery, with restriction of UFH to the surgery itself, is safe and effective in patients with a history of heparin-induced thrombocytopenia (HIT) provided that circulating anti-platelet factor 4 (PF4)/heparin antibodies are no longer detectable. However, optimal management of patients with subacute HIT in whom platelet counts have normalized, but in whom anti-PF4/heparin immunoglobulin (Ig) G antibodies are still detectable by enzyme-immunoassay (EIA), remains uncertain.

Management of anticoagulation in patients with subacute heparin-induced thrombocytopenia scheduled for heart transplantation

AbstractAnticoagulation management of patients with recent heparin-induced thrombocytopenia (HIT) requiring cardiopulmonary bypass (CPB) surgery is a serious challenge, and especially difficult in patients requiring urgent heart transplantation. As nonheparin anticoagulants during CPB bear a high risk of major bleeding, these patients are at risk of being taken off the transplant list. Short-term use of unfractionated heparin (UFH) for CPB, with restriction of UFH to the surgery itself, is safe and effective in patients with a history of HIT who test negative for antiplatelet factor 4 (PF4)/heparin antibodies. We present evidence that it is safe to expand the concept of UFH reexposure to patients with subacute HIT (ie, those patients with recent HIT in whom the platelet count has recovered but in whom anti-PF4/heparin IgG antibodies remain detectable) requiring heart transplantation, if they test negative by a sensitive functional assay using washed platelets. This can be lifesaving in patients with end-stage heart failure.

Successful Use of Argatroban for Abdominal Aortic Surgery in Subacute Heparin-Induced Thrombocytopenia

亜急性期ヘパリン起因性血小板減少症 (HIT) 患者に対する腹部大動脈人工血管置換術の周術期抗凝固管理を行った. 患者はワルファリン単剤で良好に抗凝固管理されていたが, 腹部大動脈血栓の融解は得られず手術となった. ワルファリンは術当日まで継続しPT-INRは2.58と高値であったが, 大動脈遮断前の抗凝固能としては不十分であったため, アルガトロバンを持続投与することで無事管理ができた. 術中の臨床的な抗凝固レベルはACTの推移と比較的よく合致していたが, PT-INRのみを指標として抗凝固の調節をするのは困難であった. 亜急性期HIT患者の抗凝固管理においては凝固能検査値の適切な解釈と判断が重要である.

Bivalirudin Use in Carotid Endarterectomy in a Patient with Heparin-Induced Thrombocytopenia

To describe the successful use of bivalirudin as the primary procedural anticoagulant in a patient with suspected heparin-induced thrombocytopenia (HIT) undergoing carotid endarterectomy (CEA). A 73-year-old white man presented for an elective CEA 3 weeks after emergent, on-pump coronary artery bypass grafting. Bivalirudin was used for procedural anticoagulation because of seropositivity for heparin-PF4 antibodies and a clinical history consistent with HIT. The dose was administered as a 0.75 mg/kg bolus and 1.75 mg/kg/h infusion as reported in percutaneous coronary intervention, based on review of the available bivalirudin literature. The dosage was adjusted for the patient's renal dysfunction. The outcome was successful, with the patient discharged home in 8 days without significant complications. During active HIT, when thrombocytopenia and heparin-PF4 antibodies are present, heparin therapy must be avoided. In patients with subacute HIT, when platelet counts have recovered but HIT antibodies are still present, it is also prudent to avoid heparin administration. In the case of a patient in whom anticoagulation is necessary but heparin use is contraindicated, a direct thrombin inhibitor, such as bivalirudin, may offer a viable alternative. Bivalirudin is not immunogenic and does not cross-react with the heparin-PF4 antibodies associated with HIT. To our knowledge, as of January 20, 2006, this is the first report of the use of bivalirudin for procedural anticoagulation during CEA in a patient with HIT antibodies and recent exposure to heparin. Further investigation is warranted to clarify the clinical benefits of bivalirudin for patients undergoing vascular surgery of the carotids, including potential advantages for vulnerable patient populations such as those with diagnosed or suspected HIT as well as those with renal dysfunction.

New Concepts in Heparin-Induced Thrombocytopenia: Diagnosis and Management

Heparin-induced thrombocytopenia (HIT) is a clinicopathologic condition and adverse drug reaction caused by immunoglobulin G (IgG) antibodies directed against the heparin-platelet factor 4 complex. In most patients, the onset of thrombocytopenia begins while the patient is receiving heparin. In less than 5% of patients, the onset of thrombocytopenia begins several days following heparin discontinuation and has been termed "delayed-onset" HIT. This review summarizes the presentation and clinical course of published reports of delayed-onset HIT occurring in 30 patients. The diagnosis of delayed-onset HIT should be considered in all patients presenting with venous thromboembolism (VTE) and all patients with recent heparin exposure (within the past 14 days) who present with a low platelet count. Most patients with HIT are treated with direct thrombin inhibitors and transitioned to warfarin oral anticoagulation. Administration of direct thrombin inhibitors requires close monitoring for bleeding, dose adjustments based upon coagulation monitoring and is costly. Fondaparinux, a synthetic pentasaccharide and indirect-acting factor-Xa inhibitor, has little to no cross-reactivity with the heparin-platelet factor 4 antibody in in vitro testing. This review summarizes dosing, monitoring and outcomes of preliminary reports of fondaparinux successfully administered to 13 patients with subacute HIT and 22 patients with acute HIT. While several reports have described the treatment and prophylaxis of thrombosis in patients with HIT using fondaparinux, clinical trials should be conducted and reported before fondaparinux becomes a therapy of choice for HIT.

Update on Heparin-Induced Thrombocytopenia and Cardiovascular Interventions

Although heparin/protamine has been the standard anticoagulation regimen in cardiac surgery for decades, it induces negative reactions within the vasculature. Heparin-induced thrombocytopenia (HIT) is a highly prothrombotic immune reaction to heparin that may result in death, limb ischemia leading to amputation, graft occlusion, and other severe thrombotic events. Patients undergoing cardiac surgery are at high risk for HIT antibody seroconversion and at risk for clinical HIT. For patients with acute or subacute HIT and needing urgent cardiac surgery, accepted protocols for alternative, non-heparin anticoagulation are needed. The direct thrombin inhibitor bivalirudin offers promise in this area and is currently being evaluated in multicenter trials as an alternative for heparin/protamine in patients with HIT undergoing cardiac surgery.

The Management of Patients With Heparin-Induced Thrombocytopenia Who Require Anticoagulant Therapy

For patients with heparin-induced thrombocytopenia (HIT), reexposure to heparin is generally not recommended. However, these patients are likely to require anticoagulation therapy at some point in the future. During acute HIT, when thrombocytopenia and anti-heparin-platelet factor 4 antibodies (or HIT antibodies) are present, therapy with heparin must be avoided. In patients with subacute HIT, when platelets have recovered but HIT antibodies are still present, therapy with heparin should be avoided. In patients with a remote history of HIT, when HIT antibodies have cleared, heparin reexposure may be safe, although recurrent HIT has been described in some patients. For all of these patients, the use of alternate anticoagulant agents, including direct thrombin inhibitors and anti-Xa agents, is preferable. There is an increasing amount of data supporting the use of these alternative agents in a wide variety of clinical circumstances, including thromboprophylaxis and treatment of acute thrombosis. Except for a few clinical situations, it is generally possible to avoid heparin reexposure in patients with a history of HIT.