History Of Heparin-induced Thrombocytopenia Research Articles

Unlocking the potential of fondaparinux: guideline for optimal usage and clinical suggestions (2023).

Background: Thromboembolic disease is associated with a high rate of disability or death and gravely jeopardizes people's health and places considerable financial pressure on society. The primary treatment for thromboembolic illness is anticoagulant medication. Fondaparinux, a parenteral anticoagulant medicine, is still used but is confusing due to its disparate domestic and international indications and lack of knowledge about its usage. Its off-label drug usage in therapeutic settings and irrational drug use are also common. Objective: The aim of this guideline is to enhance the judicious clinical application of fondaparinux by consolidating the findings of evidence-based research on the drug and offering superior clinical suggestions. Methods: Seventeen clinical questions were developed by 37 clinical pharmacy experts, and recommendations were formulated under the supervision of three methodologists. Through methodical literature searches and the use of recommendation, assessment, development and evaluation grading techniques, we gathered evidence. Results: This guideline culminated in 17 recommendations, including the use of fondaparinux for venous thromboembolism (VTE) prevention and treatment, perioperative surgical prophylaxis, specific diseases, special populations, bleeding and overdose management. For different types of VTE, we recommend first assessing thrombotic risk in hospitalized patients and then administering the drug according to the patient's body mass. In surgical patients in the perioperative period, fondaparinux may be used for VTE prophylaxis, but postoperative use usually requires confirmation that adequate hemostasis has been achieved. Fondaparinux may be used for anticoagulation prophylaxis in patients hospitalized for oncological purposes, in patients with atrial fibrillation (AF) after resuscitation, in patients with cirrhosis combined with portal vein thrombosis (PVT), in patients with antiphospholipid syndrome (APS), and in patients with inflammatory bowel disease (IBD). Fondaparinux should be used with caution in special populations, such as pregnant female patients with a history of heparin-induced thrombocytopenia (HIT) or platelet counts less than 50 × 109/L, pregnant patients with a prethrombotic state (PTS) combined with recurrent spontaneous abortion (RSA), and children. For bleeding caused by fondaparinux, dialysis may partially remove the drug. Conclusion: The purpose of this guideline is to provide all healthcare providers with high-quality recommendations for the clinical use of fondaparinux and to improve the rational use of the drug in clinical practice. Currently, there is a lack of a dedicated antidote for the management of fondaparinux. The clinical investigation of activated prothrombin complex concentrate (APCC) or recombinant activated factor VII (rFⅦa) as potential reversal agents is still pending. This critical gap necessitates heightened scrutiny and research emphasis, potentially constituting a novel avenue for future inquiries into fondaparinux sodium. A meticulous examination of adverse events and safety profiles associated with the utilization of fondaparinux sodium will contribute significantly to a more comprehensive understanding of its inherent risks and benefits within the clinical milieu.

Evaluation of Thrombocytopenia in Patients Receiving Percutaneous Mechanical Circulatory Support With an Impella Device

OBJECTIVES:Evaluate the time course of thrombocytopenia in patients with Impella devices (Abiomed, Danvers, MA).DESIGN:This was a retrospective, multicenter review of electronic medical records at a large hospital system from April 2018 to August 2020.SETTING:Electronic medical records of patients at SSM Health hospitals were reviewed.PATIENTS:Patients 18–89 years old admitted to an SSM Health hospital from April 2018 to August 2020 who received greater than or equal to 24 hours of percutaneous mechanical circulatory support (pMCS) with an Impella device were included. Exclusion criteria were use of other pMCS devices, history of heparin-induced thrombocytopenia (HIT), and presence of device upon transfer from an outside hospital.INTERVENTIONS:None.MEASUREMENTS AND MAIN RESULTS:Ninety-three patients were included. The median duration of pMCS was 63.5 hours. Thrombocytopenia occurred in 86% of patients and was evident 24 hours after device placement. The platelet nadir occurred 84 hours after device placement. Platelet recovery occurred 86.5 hours after device removal. The duration of thrombocytopenia was 156 hours. Signs of hemolysis were present in 44.09% of patients, were evident 12–24 hours after device placement, and resolved after device removal.CONCLUSIONS:Thrombocytopenia occurred in the majority of patients and was evident 24 hours after device placement. The time course of thrombocytopenia mirrored that of hemolysis.

Off-pump coronary artery bypass with heparin in a patient with a history of heparin-induced thrombocytopenia: a case report

BackgroundCardiovascular surgery for patients with a history of heparin-induced thrombocytopenia (HIT) with thrombosis requires careful perioperative anticoagulation therapy. When cardiovascular surgery is required for patients having ‘remote’ HIT, such as those who had a history of HIT and platelet factor-4/heparin antibodies turned out to be negative, it is recommended that re-exposure to heparin should be limited only to the intraoperative phase. However, few case reports have described detailed strategies for perioperative anticoagulation regimens.Case presentationWe present the case of a 76-year-old woman, presenting with unstable angina pectoris and requiring coronary artery bypass grafting. She had a history of cardiac resuscitation and percutaneous coronary intervention for unstable angina pectoris with ventricular tachycardia 7 years prior, which caused HIT with thrombosis resulting in amputation of four fingers. On admission, platelet factor-4/heparin antibodies, biomarkers for HIT were not detected; the platelet count was 18.0 × 104/µl. Off-pump coronary artery bypass grafting was performed using heparin; argatroban infusion was continued until 9 h prior to the operation and restarted 3 h postoperatively, bridged with regular warfarin from 4 days to 3 months postoperatively. Platelet factor-4 /heparin antibodies were detected on postoperative day 8 without any clinical symptoms and became negative by day 91.ConclusionWe consider this anticoagulation strategy is effective especially in countries, where bivalirudin is not available. Re-exposure to heparin in cardiovascular surgery for patients with a history of ‘remote HIT’ is reasonable, and appropriate anticoagulation is important for an uneventful postoperative course.

Argatroban and ultrasound-facilitated thrombolysis with alteplase in a patient with bilateral pulmonary embolism and history of heparin-induced thrombocytopenia: A case report

A 58-year-old female was admitted to the hospital with bilateral pulmonary embolism (PE) with right heart strain. Her medical history included a previous PE resulting in thrombolysis and inferior vena cava filter placement, heparin-induced thrombocytopenia, morbid obesity, and chronic pain that was treated with an epidural injection 2 weeks prior to admission. This case is unusual due to the need for alternative anticoagulation management during thrombolysis in a patient with a heparin allergy who was at increased risk for bleeding. She was initiated on argatroban to achieve therapeutic aPTTs before receiving both mechanical thrombectomy and alteplase through ultrasound-facilitated catheter-directed thrombolysis. The argatroban was reduced to a flat rate of 0.5 mcg/kg/ min during thrombolysis and was subsequently increased to achieve therapeutic aPTTs upon completion of thrombolysis. The patient was transitioned from argatroban to apixaban for lifelong anticoagulation.

Evaluation of a patient specific, targeted-intensity pharmacologic thromboprophylaxis protocol in hospitalized patients with COVID-19.

Patients with COVID-19 are at higher risk of thrombosis due to the inflammatory nature of their disease. A higher-intensity approach to pharmacologic thromboprophylaxis may be warranted. The objective of this retrospective cohort study was to determine if a patient specific, targeted-intensity pharmacologic thromboprophylaxis protocol incorporating severity of illness, weight, and biomarkers decreased incidence of thrombosis in hospitalized patients with COVID-19. Included patients were hospitalized with COVID-19 and received thromboprophylaxis within 48 h of admission. Exclusion criteria included receipt of therapeutic anticoagulation prior to or within 24 h of admission, history of heparin-induced thrombocytopenia, extracorporeal membrane oxygenation, pregnancy, or incarceration. Per-protocol patients received thromboprophylaxis according to institutional protocol involving escalated doses of anticoagulants based upon severity of illness, total body weight, and biomarker thresholds. The primary outcome was thrombosis. Secondary outcomes included major bleeding, mortality, and identification of risk factors for thrombosis. Of 1189 patients screened, 803 were included in the final analysis. The median age was 54 (42–65) and 446 (55.5%) were male. Patients in the per-protocol group experienced significantly fewer thrombotic events (4.4% vs. 10.7%, p = 0.002), less major bleeding (3.1% vs. 9.6%, p < 0.001), and lower mortality (6.3% vs. 11.8%, p = 0.02) when compared to patients treated off-protocol. Significant predictors of thrombosis included mechanical ventilation and male sex. Post-hoc regression analysis identified mechanical ventilation, major bleeding, and D-dimer ≥ 1500 ng/mL FEU as significant predictors of mortality. A targeted pharmacologic thromboprophylaxis protocol incorporating severity of illness, body weight, and biomarkers appears effective and safe for preventing thrombosis in patients with COVID-19.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11239-021-02552-x.

83 Multicenter Evaluation of the Use of Nebulized Heparin for Inhalation Injury (HIHI2 Study)

Abstract Introduction Inhalation injury (IHI) causes significant morbidity and mortality secondary to local compromise of the respiratory system as well as systemic effects limiting perfusion and oxygenation. Nebulized heparin reduces fibrin cast formation and duration of mechanical ventilation in patients with IHI. To date, no study has compared both dosing strategies of 5,000 and 10,000 units to a matched control group. The objective of this study is to compare heparin 5,000 and 10,000 units to a historical control and determine which dosing strategy improves lung function and decreases mechanical ventilation duration. Methods This multicenter, retrospective, case-control study included adult patients with bronchoscopy-confirmed IHI. Each control patient, matched according to age and percent of total body surface area (TBSA), was matched to a patient who received 5,000 units and a patient who received 10,000 units of nebulized heparin, according to each institution’s inhalation injury protocol. Patients were excluded if they were pregnant, incarcerated, died within 72 hours of admission, terminally weaned for reasons other than burn or IHI, had a documented allergy to heparin or history of heparin-induced thrombocytopenia, history of pulmonary hemorrhage within 3 months, or history of a clinically important bleeding disorder. The primary endpoint of the study was total duration of mechanical ventilation (excluding patients who died or were not extubated). Secondary endpoints included 28-day mortality, ventilator-free days in the first 28 days, difference in lung injury scores, length of hospitalization, incidence of bronchoscopy, incidence of ventilator-associated pneumonia, and rate of bleeding events. Results Thirty-five matched patient trios met inclusion criteria. Groups were well-matched for age (p=0.975) and TBSA (p=0.855). When excluding patients who died or were never extubated, patients who received nebulized heparin, either 5,000 or 10,000 units, had 8–11 less days on the ventilator compared to controls (p=0.001). Mortality ranged from 3–14% overall, and no statistical difference was observed between groups. No major or minor bleeding events related to nebulized heparin were reported. Conclusions Mechanical ventilation days were significantly decreased in patients who received 5,000 or 10,000 units of nebulized heparin. There was no statistically significant difference in mortality between groups, supporting that either 5,000 units or 10,000 units of nebulized heparin should be used in IHI treatment. Applicability of Research to Practice To our knowledge, no previously published studies have simultaneously compared dosing strategies of 5,000 and 10,000 units to a control group. These results support the use of nebulized heparin for IHI to reduce the duration of mechanical ventilation.

Dosing of Enoxaparin in Morbidly Obese Patients: A Retrospective Cohort.

Purpose: The purpose of this study was to evaluate odds of major bleeding, thrombosis, and ischemic stroke between different enoxaparin dosage strategies in patients weighing ≥120 kg. Methods: Patients weighing ≥120 kg who received therapeutic anticoagulation with enoxaparin for more than 24 hours were selected for retrospective review. Patients without a baseline weight, serum creatinine, a history of heparin-induced thrombocytopenia, or currently pregnant patients were excluded from the study. Patients with a creatinine clearance (CrCL) <30 mL/min were analyzed separately. The incidence of major bleeding was compared between patients receiving <90% and those receiving ≥90% of the Food and Drug Administration (FDA)-approved dose of enoxaparin, as well as between patients weighing ≥150 kg and those weighing <150 kg. Secondary outcomes included incidence of venous thromboembolism (VTE) and ischemic stroke. Results: A total of 462 patients were included in the primary analysis and 25 patients in the subgroup analysis. No difference in major bleeding was observed between different dosage regimens (P = .12) or weight groups (P = .36). No difference was observed in rates of VTE or ischemic stroke between different dosage regimens (P = .52 and P = .60, respectively) or weight groups (P = .39 and P = .48, respectively). Similar results were observed in the low-CrCL analysis. Results were not altered when patients were propensity matched on baseline characteristics. Conclusion: Reducing the dose of enoxaparin did not reduce the odds of major bleeding or increase the odds of ischemic stroke or VTE.

How I treat patients with a history of heparin-induced thrombocytopenia

AbstractHeparin-induced thrombocytopenia (HIT) is a relatively common prothrombotic adverse drug reaction of unusual pathogenesis that features platelet-activating immunoglobulin G antibodies. The HIT immune response is remarkably transient, with heparin-dependent antibodies no longer detectable 40 to 100 days (median) after an episode of HIT, depending on the assay performed. Moreover, the minimum interval from an immunizing heparin exposure to the development of HIT is 5 days irrespective of the patient's previous heparin exposure status or history of HIT. This means that short-term heparin reexposure can be safely performed if platelet-activating antibodies are no longer detectable at reexposure baseline and is recommended when heparin is the clear anticoagulant of choice, such as for cardiac or vascular surgery. The risk of recurrent HIT 1 to 2 weeks after heparin reexposure is ∼2% to 5% and is attributable to formation of delayed-onset (or autoimmune-like) HIT antibodies that activate platelets even in the absence of pharmacologic heparin. Some studies suggest that longer-term heparin reexposure (eg, for chronic hemodialysis) may also be reasonable. However, for other antithrombotic indications that involve patients with a history of HIT (eg, treatment of venous thromboembolism or acute coronary syndrome), preference should be given to non-heparin agents such as fondaparinux, danaparoid, argatroban, bivalirudin, or one of the new direct-acting oral anticoagulants as appropriate.

Natural history of heparin-induced thrombocytopenia (HIT) in the cancer population.

e18134Background: Cancer patients may be at higher risk of HIT-related complications than the general population, yet there is limited data on the epidemiology and natural history of HIT in cancer....

Heparin Reexposure in Patients With a History of Heparin-Induced Thrombocytopenia.

Patients with a history of heparin-induced thrombocytopenia (HIT), who require subsequent anticoagulation, have limited options. Rechallenge with unfractionated heparin (UFH) has been reported but may be associated with a risk of recurrence of HIT. The objective of this study was to determine the safety of heparin reexposure in patients with a history of HIT. Using several search terms, all cases of heparin reexposure in patients with HIT indexed in MEDLINE (English language only) by June 2014 were reviewed. The bibliography of each relevant article was searched for additional reports. In cases of multiple reexposures, each reexposure was identified as a separate instance of reexposure during analysis. A total of 136 patients with a history of HIT had 141 instances of heparin reexposure. Cardiac (76%) and vascular surgeries (11%) were the most common indications. Antiplatelet factor 4/heparin antibodies were positive in 63% of evaluable cases before reexposure. Preexposure plasma exchange (11%) and postexposure nonheparin anticoagulants (63%) were frequently utilized. Complications with heparin reexposure included recurrence of HIT (2.1%, 95% confidence interval 0.73%-6.07%) and bleeding (2.1%). Intraoperative heparin reexposure in patients with a history of HIT has a small risk of developing HIT recurrence. The use of preexposure plasma exchange in patients with positive antiplatelet factor 4/heparin antibody and postexposure nonheparin anticoagulants arguably may have reduced the risk of recurrence of HIT.

Successful Use of Fondaparinux Early After Mechanical Aortic Valve Replacement in a Patient with a History of Heparin‐Induced Thrombocytopenia

Thromboembolic complications such as systemic embolization and valve thrombosis are a major concern early after mechanical valve replacement; however, the benefit of anticoagulation must be weighed against the risk of early postoperative bleeding complications. Thromboembolic risk is also higher in the early postoperative period (less than 6 mo) compared with the risk in the late postoperative period. Current evidence supports the use of unfractionated heparin or low-molecular-weight heparin early after valve replacement to prevent valve thrombosis or systemic embolization but provides no recommendations for the management of patients with a history of heparin-induced thrombocytopenia (HIT), in which heparin products are contraindicated. We describe the use of fondaparinux early after aortic mechanical valve replacement in a 63-year-old, 95-kg woman with a history of HIT. Fondaparinux was initiated on postoperative day 2 at a prophylactic dose of 2.5 mg subcutaneously daily; the dose was increased to a therapeutic weight-based dose of 7.5 mg subcutaneously daily on postoperative day 3. Warfarin was initiated on postoperative day 1, and fondaparinux was continued until a therapeutic international normalized ratio was achieved. The patient was discharged from the hospital receiving warfarin alone on postoperative day 6. No signs or symptoms of thrombosis or bleeding were noted during or after fondaparinux therapy or at hospital follow-up visits. To our knowledge, this is the first case report to describe the use of fondaparinux within the first 48 hours after mechanical valve replacement in a patient with a history of HIT. This case suggests that fondaparinux may be a safe and effective option to prevent thromboembolic complications early after mechanical valve replacement when heparin products are contraindicated.

CASE 4—2014Ascending Aortic Pseudoaneurysm Repair With Deep Hypothermic Circulatory Arrest in an Adult Congenital Heart Disease Patient With Heparin-Induced Thrombocytopenia

A NUMBER OF FACTORS can complicate the management of perioperative coagulation. Preexisting patient factors, including the presence of mechanical prosthetic valves, chronic therapeutic anticoagulation, and a history of heparin-induced thrombocytopenia (HIT) require evaluation and preparation before surgery and may require alterations to standard intraoperative management (eg, bridging of anticoagulation, the use of unfractionated heparin, etc). Factors related to surgery that add complexity to the demands of coagulation management include the presence of congenital heart disease with multiple prior sternotomies that make the reentry sternotomy high risk, aortic pathology that requires hypothermic circulatory arrest for successful surgical repair, and prolonged cardiopulmonary bypass time. The authors present for discussion a complex case involving all of these elements.

Inferior vena cava thrombectomy in a patient with heparin-induced thrombocytopenia via inflow occlusion technique on beating heart

Anticoagulation management of a patient complicated by heparin-induced thrombocytopenia is one of the challenging situations in open heart surgery. A 40-year old male receiving warfarin for anticoagulation was admitted to our clinic with a history of heparin-induced thrombocytopenia and a diagnosis of inferior caval thrombosis. He was scheduled for inferior vena cava thrombectomy via the inflow occlusion technique on the beating heart. Warfarin sodium was stopped three days prior to the operation while fondaparinux sodium was begun twice a day. The operation was successfully performed and no postoperative complications were observed.

Standard subcutaneous dosing of unfractionated heparin for venous thromboembolism prophylaxis in surgical ICU patients leads to subtherapeutic factor Xa inhibition

To assess coagulation status and factor Xa inhibition in surgical intensive care unit (ICU) patients administered prophylactic unfractionated heparin for venous thromboembolism (VTE) prophylaxis. We conducted a randomized, single-blind study at a tertiary academic medical center. Included were patients 18 years and older admitted to the surgical ICU directly after major abdominal surgery. Exclusion criteria included significant bleeding risk, preoperative anticoagulation, or history of heparin-induced thrombocytopenia. Patients were randomized to two regimens for VTE prophylaxis: standard of care unfractionated heparin, 5,000 units subcutaneously three times daily (SQH) versus unfractionated heparin via intravenous infusion, titrated to an activated partial thromboplastin time of 40-45 s (IVH). Blood samples were taken prior to surgical incision on day 0 and daily for 5 days after surgery. Samples were analyzed for factor Xa inhibition and viscoelastic whole blood clotting parameters (Sonoclot analyzer). A total of 50 patients were randomized to either SQH or IVH. The majority of patients had cancer. Patients in the SQH group had no detectable peak anti-factor Xa (aFXa) activity for 5 days after surgery, while patients in the IVH group had statistically elevated levels compared to the SQH group on days 3-5. SQH patients demonstrated a hypercoagulable profile on Sonoclot, while IVH patients displayed a normal profile. Standard of care subcutaneous dosing of unfractionated heparin for VTE prophylaxis in surgical ICU patients leads to subtherapeutic levels of factor Xa inhibition.

Use of Argatroban as a Procedural and Bridging Anticoagulant in a Patient Undergoing Carotid Endarterectomy with Concomitant Atrial Fibrillation

To describe the use of argatroban as a procedural and bridging anticoagulant in a patient with a previous history of heparin allergy and atrial fibrillation undergoing carotid endarterectomy. A 78-year-old female with a history of heparin-induced thrombocytopenia (HIT) and multiple medical comorbidities, including atrial fibrillation requiring chronic anticoagulation with warfarin, was found to have greater than 70% stenosis of her left carotid artery by standard duplex imaging. Her warfarin therapy was discontinued as an outpatient approximately 48 hours prior to an elective left carotid endarterectomy and she was started on argatroban 2 μg/kg/min for bridging therapy. The endarterectomy was successfully performed while the patient was maintained on a continuous argatroban infusion. The dose was adjusted by 0.25-μg/kg/min intervals to achieve and maintain an activated clotting time of greater than 200 seconds during the procedure. Her postoperative course was unremarkable and she was transitioned back to warfarin and subsequently discharged home. HIT poses a challenge for patients in need of vascular surgery. Optimally, one would postpone any surgical intervention until the heparin antibodies are cleared from circulation, which on average takes about 100 days. In theory, it is safe to reexpose these patients to heparin products upon clearance of the antibody; however, there is scant literature available to show its safety. Current guidelines recommend limiting heparin exposure in any patients with a history of HIT, but the optimal alternative anticoagulant in this setting is unclear. There are several direct thrombin inhibitors available, but argatroban seemed to be a logical choice for our patient, especially in the setting of renal insufficiency, given its favorable pharmacokinetics and ease of monitoring with readily available coagulation tests. To our knowledge, this is the second reported case of the systemic use of argatroban in carotid endarterectomy in a patient with a previous history of HIT. Argatroban may be an effective anticoagulant during carotid endarterectomy in patients with underlying chronic renal disease and a history of HIT. Additional research is needed to determine the ideal anticoagulant in vascular surgery when heparin cannot be utilized.

Is there a role for fondaparinux in perioperative bridging?

A possible role for fondaparinux as a bridging agent in the perioperative setting is explored. Anticoagulation guidelines provide minimal direction on the perioperative use of fondaparinux. Fondaparinux's extended half-life of 17-21 hours complicates its use as a perioperative bridging therapy. The ideal time for discontinuation before surgery is an issue, particularly in surgeries with a high bleeding risk or in which neuraxial anesthesia is used. Guidance for perioperative bridging with fondaparinux must be derived from pharmacokinetic data, surgical prophylaxis trials, case reports, and anesthesia guidelines. Published trials used fondaparinux sodium 2.5 mg daily for venous thromboembolism prophylaxis in surgical patients, and the majority avoided its use before surgery in patients receiving neuraxial anesthesia. Three case reports cited the use of fondaparinux sodium as perioperative bridge therapy; one used a 2.5-mg dose, and the other two used a full treatment dose of 7.5 mg. Furthermore, professional anesthesia guidelines conflict in their recommendations regarding the timing of drug administration with neuraxial catheter use. For these reasons, it may be optimal to avoid fondaparinux use before surgery. In some instances, the use of low-molecular-weight heparin or inpatient use of i.v. unfractionated heparin is not possible, is contraindicated, or has limited efficacy, such as a patient with history of heparin-induced thrombocytopenia or antithrombin III deficiency. Fondaparinux may have a role in bridge therapy for these patients. The role of fondaparinux in perioperative bridge therapy has not been established, and there are some important limitations to its use as a routine bridging agent.

Successful use of fondaparinux in a patient with a mechanical heart valve replacement and a history of heparin-induced thrombocytopenia

The development of heparin-induced thrombocytopenia (HIT) is an antibody-mediated clinicopathologic syndrome. The resultant thrombocytopenia and thrombosis can be severe and life-threatening. Fondaparinux is a parenteral factor Xa inhibitor used for venous thromboembolism prevention and treatment. Fondaparinux has minimal affinity for platelet factor 4, making it an alternative agent to unfractionated heparin (UFH) and low-molecular weight heparin (LMWH) and a plausible consideration for patients with a history of HIT. The use of fondaparinux in patients with mechanical heart valve replacement and a history of HIT has never been discussed in the literature. We report on the case of a patient with a mechanical aortic heart valve replacement and a history of HIT who was successfully bridged postoperatively with fondaparinux. While there is currently no literature to support the use of fondaparinux in patients with mechanical heart valves, this drug may offer an option for management of such patients who cannot use heparin products. However, further clinical investigations are warranted to confirm both the safety and efficacy of this agent in the mechanical heart valve population.

Issues in assessing and reducing the risk for venous thromboembolism

To describe issues and challenges associated with venous thromboembolism (VTE) risk assessment and the use of drug therapies for VTE prophylaxis. Patients at risk for VTE are a heterogeneous group. Systems for scoring VTE risk have been developed to identify patients who warrant prophylaxis, but most risk-scoring systems are complex and have not been validated. The optimal drug therapies and dosing strategies for reducing VTE risk are not well defined for many clinical situations, despite the availability of evidence-based guidelines from authoritative sources. Patient characteristics can influence the agent selected, dosing, timing of initiation, and duration of drug therapy. Individualized approaches to prophylaxis in patients undergoing major orthopedic surgery should take into account the presence of severe renal impairment, critical illness, morbid obesity, epidural catheters, and history of heparin-induced thrombocytopenia. To provide safe, effective VTE prophylaxis, clinicians, including health-system pharmacists, should collaborate in developing management plans tailored to patients' needs. Preventing VTE is a challenge that can be addressed by gaining an understanding of the issues involved in patient assessment and prophylactic drug therapy and using a team approach to optimize patient outcomes.

Coronary arterial bypass surgery with beating heart in a patient with heparin-induced thrombocytopenia: Usage of thrombin inhibitor (Lepirudin; r-hirudin)

Abstract One of the most important adverse drug reactions that physicians encounter is the life-threatening prothrombotic syndrome known as heparin-induced thrombocytopenia (HIT). In patients with a history of heparin-induced thrombocytopenia and coronary arterial disease, alternative anticoagulatory regimens are needed during cardiac surgery for prevention of thrombosis. Treatment options for such patients now generally include the use of alternative anticoagulants such as lepirudin, bivalirudin, argatroban or danaparoid. In this article, we present a case where heparin-induced thrombocytopenia was properly performed coronary arterial bypass grafting by using lepirudin. (This sentence is confusing)

Prolonged elevation of plasma argatroban in a cardiac transplant patient with a suspected history of heparin‐induced thrombocytopenia with thrombosis

Direct thrombin inhibitors (DTIs) provide an alternative method of anticoagulation for patients with a history of heparin-induced thrombocytopenia (HIT) or HIT with thrombosis (HITT) undergoing cardiopulmonary bypass (CPB). In the following report, a 65-year-old critically ill patient with a suspected history of HITT was administered argatroban for anticoagulation on bypass during heart transplantation. The patient required massive transfusion support (55 units of red blood cells, 42 units of fresh-frozen plasma, 40 units of cryoprecipitate, 40 units of platelets, and three doses of recombinant Factor VIIa) for severe intraoperative and postoperative bleeding. Plasma samples from before and after CPB were analyzed postoperatively for argatroban concentration using a modified ecarin clotting time (ECT) assay. Unexpectedly high concentrations of argatroban were measured in these samples (range, 0-32 microg/mL), and a prolonged plasma argatroban half life (t(1/2)) of 514 minutes was observed (published elimination t(1/2) is 39-51 minutes [< or = 181 minutes with hepatic impairment]). Correlation of plasma argatroban concentration versus the patient's coagulation variables and clinical course suggest that prolonged elevated levels of plasma argatroban may have contributed to the patient's extended coagulopathy. Because DTIs do not have reversal agents, surgical teams and transfusion services should remain aware of the possibility of massive transfusion events during anticoagulation with these agents. This is the first report to measure plasma argatroban concentration in the context of CPB and extended coagulopathy.