Setting Of Heparin-induced Thrombocytopenia Research Articles

Intra-cardiac thrombosis in the setting of heparin-induced thrombocytopenia.

Key clinical message is to know that HIT is a massive thrombotic storm. Atrial fibrillation cardioversion might not be safe in HIT using the standard 48‐hour cutoff from arrhythmia onset. Also, the case serves as a reminder of how to suspect, diagnose, and treat HIT.

Abstract 15944: Fondaparinux: A Low-hanging Fruit in Heparin-induced Thrombocytopenia

Introduction: Heparin-induced thrombocytopenia (HIT) is a life-threatening disease associated with thromboembolic complications. Therefore, its treatment should comprise non-heparin anticoagulants. As opposed to direct thrombin inhibitors (DTI) and danaparoid, fondaparinux use is generally regarded as off-label. Purpose: To perform a meta-analysis to appraise fondaparinux efficacy and safety in the setting of HIT. Methods: We systematically searched Embase, MEDLINE, Web of Science, Cochrane CENTRAL and Google Scholar databases, using the terms “heparin-induced thrombocytopenia” and “fondaparinux”, form inception to June 1, 2020. Studies targeting thrombotic complications, bleeding events, platelet count and mortality were included. The primary endpoint was a composite of arterial and venous thromboembolism, amputation, gangrene and HIT-related mortality. Therapeutic arms were those of fondaparinux and a standard non-heparin anticoagulant. A random-effects model with Mantel-Haenszel method was performed to calculate pooled odds ratios (OR) and their 95% confidence interval (CI). Results: We encompassed 7 retrospective studies, which accounted for 630 patients, of which 302 were under fondaparinux. The remaining were treated with danaparoid, argatroban, lepirudin or bivalirudin. There were 109 primary endpoint events, 80 hemorrhages, 13 persistent or recurring thrombocytopenia cases and 98 deaths. Fondaparinux was found not only to numerically reduce thromboembolism (6 studies, OR 0.28, 95% CI 0.06-1.20, P 0.09, i 2 45%) but also to significantly lessen primary endpoint events (7 studies, OR 0.26, 95% CI 0.10-0.67, P 0.006, i 2 66%). In parallel, a tendency towards a lower rate of bleeding with fondaparinux use was also unveiled (7 studies, OR 0.78, 95% CI 0.50-1.21, P 0.27, i 2 0%). Likewise, thrombocytopenia cases were less common in the fondaparinux arm (4 studies, OR 0.16, 95% IC 0.05-0.57, P 0.004, i 2 0%). Finally, fondaparinux use was also associated with a survival benefit (6 studies, OR 0.26, 95% IC 0.08-0.90, P 0.03, i 2 54%). Conclusions: Fondaparinux seems to be at least as safe and more effective than other non-heparin anticoagulants, in the setting of HIT. Prospective studies are needed to demonstrate this hypothesis.

Treatment and Outcomes in Heparin-Induced Thrombocytopenia (HIT) in Patients with Neoplasm: A Single Centre Experience

Background: Heparin-induced thrombocytopenia (HIT) is an immune mediated, pro-thrombotic disorder associated with exposure to heparin and a substantial number of patients develop thrombosis (HITT) in the venous, arterial, or microvascular system. Treatment includes cessation of heparin and starting a non-heparin anticoagulant. Patients with cancer are already at high risk of venous thromboembolism (VTE) as well as recurrent VTE despite anticoagulant therapy and are also at higher risk of bleeding compared with patients without cancer. Consequently, cancer patients may not share similar outcomes as patients without cancer in the setting of HIT. We conducted a single-centre, retrospective study to evaluate baseline characteristics, treatments and outcomes in HIT patients with and without cancer. Methods: Medical records of all patients seen at our tertiary centre between November 1, 2006 and December 31, 2016 who tested positive for HIT antibodies and had a 4T score of 4 or higher were reviewed. Patients with cancer were defined as those who had any evidence of cancer, including myeloproliferative neoplasm (MPN), and/or receiving cancer treatment within 6 months prior to HIT diagnosis. Details of treatments and outcomes were captured up to 6 months after start of HIT treatment. Comparative statistics was performed between the cancer and non-cancer cohorts. Results: We identified 95 patients with confirmed HIT, of whom 39 (41%) had cancer and 41 (43%) had HITT as the index event. The mean age was 65 years (standard deviation 16) and 59% were female. Thirty (77%) cancer patients had at least 3 months of available records and 26 (67%) had at least 6 months, while 37 (66%) non-cancer patients had at least 3 months of available records and 27 (48%) had at least 6 months. Baseline demographics including cancer types are summarized in Table 1. The most common malignancy was polycythemia vera (PV), with those with MPN (7 PV, 2 essential thrombocythemia) representing 23% of the patients with cancer. Cancer patients were more likely to have a history of thromboembolic events prior to index heparin exposure and HIT diagnosis (79.5% vs. 53.6%, p=0.02) than those without cancer. Among patients with HITT, the two groups had similar incidences of pulmonary embolism and/or deep vein thrombosis, although a higher proportion of the non-cancer group had clots in other non-classic locations (32.1% vs. 10.3%, p=0.01) such as splanchnic thrombosis. A variety of non-heparin agents were used, including direct oral anticoagulants (Table 2), with most patients receiving either fondaparinux or argatroban followed by warfarin. The cancer group received fondaparinux more often than the non-cancer group (87.2% vs. 64.3%, p=0.02). In those alive with at least 6 months of follow-up, the median duration of non-heparin anticoagulation was 180 days for both cancer patients and non-cancer patients. During follow-up, 16 (17%) patients had a thrombotic event, 15 (16%) had major bleeding and 11 (12%) died among the 95 patients with HIT. The rates of subsequent thrombosis, bleeding events, and death were similar between the two cohorts over the 6-month follow-up period (Table 3). None of the deaths were from thrombotic or bleeding events but the cause of death for one patient with cancer was unknown. Conclusion: Patient outcomes following a diagnosis of HIT appear similar between patients with and without cancer, with high rates of subsequent thrombosis and major bleeding. Patients with MPN might have a higher risk of HIT. Further studies are warranted to confirm these findings and determine if direct oral anticoagulants might be efficacious and safe in patients with HIT. Disclosures Lee: Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria; LEO Pharma: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. OffLabel Disclosure: Direct oral anticoagulants and fondaparinux were used as non-heparin anticoagulants for the treatment of heparin induced thrombocytopenia.

Use of Intravenous Immunoglobulin G in HIT: Impact on Thrombosis and Mortality in a Population-Based Study

Introduction: Heparin-induced thrombocytopenia (HIT) is a severe prothrombotic syndrome with a mortality rate of 10% (Lancet Haematol. 2018 May; 5(5):e220-e231). Case reports show that Intravenous Immunoglobulin G (IVIg) can rapidly and durably counteract HIT antibody-mediated platelet activation in the setting of severe persistent HIT (Chest. 2017 Sep;152(3):478-485 and others). While this data supports use of IVIg in severe HIT, it is well documented that “positive result bias” enhances the likelihood of publication of studies that demonstrate salutary effects of interventions. IVIg has a black box warning for thrombosis which lists a number of potential predisposing states for this complication including hypercoagulable conditions (such as HIT). Thus, one concern is that of new/worsening thrombosis in HIT patients treated with this drug, something that is not evaluable with the limited publications in this area. The Nationwide Inpatient Sample (NIS) is the largest publicly available patient discharge database in the US that includes ~7 million discharges per year representative of discharges from all hospital types in the country. The goal of this study was to evaluate thrombosis, bleeding and mortality outcomes associated with IVIg use in HIT using the NIS database.Methods: Hospital discharges with an ICD-9-CM code for HIT (289.84) in the NIS were used to compare outcomes in adult patients (≥18yrs) who did and did not receive IVIg treatment (ICD-9-CM code 99.14) from October 1, 2008 to December 31, 2014. Discharges with diagnoses suggestive of a history of thrombosis (ICD-9-CM codes V12.51, V12.52, V12.55), idiopathic thrombocytopenic purpura (287.31), or secondary thrombocytopenia (287.4) were excluded. Patient characteristics included age, sex, all patient refined diagnosis related groups (APR-DRG) severity index, and APR-DRG mortality index. Outcomes included arterial thrombosis, venous thrombosis, bleeding, mortality, and a composite of all outcomes. Variables were compared by IVIg treatment status using survey weighted Chi-squared tests for categorical variables and ANOVA for continuous variables. Survey weighted multiple logistic regression was used to model each binary outcome by IVIg treatment status while adjusting for age, gender, APR-DRG severity index and mortality index. A matched analysis was performed as a sensitivity analysis for the multiple logistic regression results. Controls were matched with IVIg cases by exact gender, APRDRG severity index, and mortality index. Five matching controls were selected for each case based on nearest age. Conditional logistic regression was used to analyze each outcome using the matched dataset.Results: HIT patients treated with IVIg and those without were no different in age and sex (Table 1). Consistent with the limited published experience of IVIg use in HIT, those who received IVIg had more severe disease with greater likelihood of dying as indicated by their APR-DRG severity and mortality indices (Table 1). Multiple logistic regression showed that the adjusted odds ratio (aOR) was lower for all outcomes except bleeding in the IVIg-treated group, although this did not reach statistical significance (Fig 1; aOR of 0.766, 0.922, 1.049, 0.685 and 0.703 for arterial thrombosis, venous thrombosis, bleeding, death and composite outcome, respectively). Similar results were obtained in conditional logistic regression of matched data (Fig 2).Conclusions: Use of IVIg was not associated with worse thrombotic outcomes or mortality in HIT. On the contrary, results suggest a possible protective effect on these outcomes, but results did not achieve statistical significance possibly due to small numbers of IVIg-treated patients. The aOR was higher (but not significantly so) for bleeding in IVIg-treated HIT patients, however, this finding is consistent with the possibility that IVIg was used more frequently in patients who had more severe disease (and had already hemorrhaged), as suggested by worse APR-DRG severity and mortality indices in IVIg-treated patients. A prospective randomized treatment study may be necessary to provide conclusive data on IVIg efficacy and risk in HIT. [Display omitted] DisclosuresDhakal:Amgen: Honoraria; Celgene: Consultancy, Honoraria; Takeda: Honoraria. Aster:BloodCenter of Wisconsin: Patents & Royalties. Padmanabhan:Janssen Pharmaceuticals: Consultancy; GE Healthcare: Other: Material support for Clinical Quality Improvement Initiative; Retham Technologies LLC: Equity Ownership, Other: Retham seeks to develop HITDx(TM), a new assay for HIT diagnosis; BloodCenter of Wisconsin: Patents & Royalties: Patent/royalties for HIT diagnostic testing; Veralox Therapeutics: Other: Advisory Board; TerumoBCT: Consultancy.

Bivalirudin for Cardiopulmonary Bypass in the Setting of Heparin-Induced Thrombocytopenia and Combined Heart and Kidney Transplantation—Diagnostic and Therapeutic Challenges

Bivalirudin for Cardiopulmonary Bypass in the Setting of Heparin-Induced Thrombocytopenia and Combined Heart and Kidney Transplantation—Diagnostic and Therapeutic Challenges

Unilateral Adrenal Hemorrhage and the Challenge Of Early Recognition

Adrenal hemorrhage (AH) is a rare condition with an estimated prevalence of 1% among hospital-based autopsies. It is usually discovered incidentally on computed tomography.1 Most cases are associated with the use of anticoagulation, especially in the setting of heparin-induced thrombocytopenia, anti-phospholipid antibody syndrome, trauma, metastatic disease, sepsis, and critical illness.5-7 We report a case of acute unilateral adrenal hemorrhage associated with Escherichia coli pyelonephritis in the context of recent prolonged steroid use.

Warfarin-Induced Skin Necrosis Following Heparin-Induced Thrombocytopenia

Anticoagulants, such as heparin and warfarin, are commonly used in the treatment and prevention of thromboembolic events. The risk of developing warfarin-induced skin necrosis (WISN) with warfarin is reported to be <1%. However, the risk of WISN may be increased with the initiation of warfarin in the setting of heparin-induced thrombocytopenia and thrombosis syndrome (HITT). WISN can lead to catastrophic tissue necrosis requiring amputations and mass debridement. This report describes a case of WISN following HITT and discusses the appropriate medical management of patients with HITT to avoid secondary WISN.

The platelet Fc receptor, FcγRIIa.

Human platelets express FcγRIIa, the low-affinity receptor for the constant fragment (Fc) of immunoglobulin (Ig) G that is also found on neutrophils, monocytes, and macrophages. Engagement of this receptor on platelets by immune complexes triggers intracellular signaling events that lead to platelet activation and aggregation. Importantly these events occur in vivo, particularly in response to pathological immune complexes, and engagement of this receptor on platelets has been causally linked to disease pathology. In this review, we will highlight some of the key features of this receptor in the context of the platelet surface, and examine the functions of platelet FcγRIIa in normal hemostasis and in response to injury and infection. This review will also highlight pathological consequences of engagement of this receptor in platelet-based autoimmune disorders. Finally, we present some new data investigating whether levels of the extracellular ligand-binding region of platelet glycoprotein VI which is rapidly shed upon engagement of platelet FcγRIIa by autoantibodies, can report on the presence of pathological anti-heparin/platelet factor 4 immune complexes and thus identify patients with pathological autoantibodies who are at the greatest risk of developing life-threatening thrombosis in the setting of heparin-induced thrombocytopenia.

Implementation of a Heparin-Induced Thrombocytopenia Management Program Reduces the Cost of Diagnostic Testing and Pharmacologic Treatment in an Academic Medical Center

Abstract Hematologists that are expert in benign hematology are needed to promote safe and cost-effective diagnosis of bleeding and thrombotic disorders in the hospital setting. The Joint Commission has identified anticoagulation as an area that has a high frequency of adverse drug outcomes and needs close supervision. The purpose of this study is to demonstrate the clinical utility of benign hematology expertise to guide use of direct thrombin inhibitors (DTIs) in the setting of heparin-induced thrombocytopenia. Heparin-induced thrombocytopenia represents a serious complication of heparin therapy and requires accurate diagnostic testing and safe and effective anticoagulation to prevent adverse outcomes. In recent years, serologic tests for the presence of heparin–platelet factor 4 antibodies has led to widespread testing and increased use of DTIs to manage thrombocytopenic patients. Patients that have a positive ELISA assay are tested by the serotonin release assay to confirm the presence of the antibody that can trigger thrombosis. The antibody can trigger platelet activation, arterial thrombosis and/or venous thrombosis. The risk of a thrombotic event is high and anticoagulation is recommended to reduce thrombosis that can lead to amputation, stroke, or loss of life. Treatment is recommended with a DTI followed by warfarin therapy. The American Society of Hematology and several expert panels have published guidelines regarding management of heparin-induced thrombocytopenia. Despite these guidelines, medical centers are challenged by regulating the diagnosis and management of this clinical problem. The Medical University of South Carolina Hospital, a 750 bed academic medical center, established an Anticoagulation and Bleeding Management Service led by hematologists and a multidisciplinary team to evaluate the use of diagnostic testing and use of DTIs. In phase one, a review of the testing in the intensive care units at our medical center was retrospectively analyzed. Results demonstrated a high frequency of serologic testing in cases that had low to intermediate 4T score results. In contrast, a very low percentage of ELISA-positive cases were confirmed to be serotonin release assay-positive. Often times DTIs were administered for several days until the SRA assay results were available. In collaboration with nursing, pharmacy, pathology and hematology, a specific set of guidelines were implemented. Prior to submitting an ELISA measurement clinicians were required to perform a 4T score. All positive ELISA assays were reported to the Anticoagulation and Bleeding Management Consult Service and specific treatment guidelines were provided in accordance with published ASH guidelines. We collected and reviewed baseline data regarding the frequency of testing and use of DTIs prior to implementing the protocol. We found that an average of 5.5 cases per month were given DTIs prior to implementation of the protocol. The average number of patients treated with DTI after the implementation of the protocol averaged 1.2 per month . This represented a 78% drop in DTI use. Over the same time period we saw ELISA testing and SRA testing both decline, with ELISA testing reduced by 20% and Serotonin Release Assay testing reduced by 70%. In conclusion, the implantation of a centralized hospital-wide protocol that coordinates testing and treatment of patients suspected of having heparin-induced thrombocytopenia has led to a substantial reduction in use of DTIs and improved management of patients suspect of having this clinical disorder. An Anticoagulation and Bleeding Management Service led by expert benign hematologists can play a major role in developing safe and cost-effective approaches for the diagnosis and treatment of complicated bleeding and thrombotic disorders. Disclosures No relevant conflicts of interest to declare.

Fondaparinux‐associated heparin‐induced thrombocytopenia

Large licensing trials did not find any association between the use of fondaparinux and the development of heparin-induced thrombocytopenia (HIT). Fondaparinux is in fact recommended as an option for the management of HIT. Since the first report of fondaparinux-associated HIT in 2007, additional reports have been published. However, the rarity of these cases, differences in case definition, and lack of larger case series have prevented better understanding of this disease. The objective of this study was to determine the clinical manifestations of fondaparinux-associated HIT, the predictive value of pretest probability (4Ts) scoring system, and the outcomes associated with current management. Using several search terms, we reviewed all cases of fondaparinux-associated HIT reported and indexed in PubMed till May 2013. All references were also checked for additional reports. We categorized the cases of fondaparinux-associated HIT as confirmed, probable, and possible based on our case definition. A total of eight cases of fondaparinux-associated HIT were identified. Fondaparinux-associated HIT occurred in the setting of pro-inflammatory state, prior HIT, or exposure to heparin products. Bilateral adrenal hemorrhage or infarct, reflecting hypercoagulability or disseminated intravascular coagulation, was seen in 25% of patients. The pretest probability (4Ts) scoring system used for HIT appears to correctly risk stratify all the cases. Although functional assays can be used for the diagnosis, in the presence of recent exposure to heparin products, only the demonstration of fondaparinux-dependent platelet activation should be considered confirmatory. Non-heparin anticoagulants are effective therapy; however, one-third of the patients had poor outcomes. The risk of fondaparinux-associated HIT, although low is real, which along with documented cases of fondaparinux failure mandate its cautious use in the management of HIT.

Allograft Coronary Artery Thrombosis: A Case Report of Early Cardiac Allograft Left Ventricular Myocardial Infarction

Cardiac allograft dysfunction is a major cause of morbidity and mortality in the early post-transplantation period. This is a critical condition that requires prompt diagnosis and management. We present the case of a 57-year-old man with ischemic cardiomyopathy who underwent cardiac transplantation and developed a rare case of coronary artery thrombosis in the setting of heparin-induced thrombocytopenia and thrombosis syndrome (HITTS) within the first 2 postoperative weeks. Transmural myocardial infarction (MI) was initially noted on cardiac magnetic resonance (CMR) imaging as regional left ventricular wall motion abnormalities and transmural hyperenhancement after gadolinium administration, prompting further evaluation of the coronary circulation with angiography.

A case of unsuccessful treatment of heparin-induced thrombocytopenia (HIT) with fondaparinux

Heparin-induced thrombocytopenia (HIT) is a rare immune-mediated complication associated with unfractionated heparin and to a lesser extent with low-molecular weight heparins. The American College of Chest Physicians recommends treating patients with suspected HIT with a non-heparin product regardless if thrombosis is present. The direct thrombin inhibitors are the preferred agents for the treatment of acute HIT (lepirudin, argatroban [Grade 1C]). Fondaparinux is also suggested as an alternative with a lower level of evidence (Grade 2C). The evidence supporting the use of fondaparinux in the treatment of HIT is limited, but the evidence of fondaparinux causing HIT is even less. We present a case of a patient who developed complications with fondaparinux when used in the acute setting of HIT.

Successful surgical management of massive pulmonary embolism during the second trimester in a parturient with heparin-induced thrombocytopenia

Cardiopulmonary bypass during pregnancy is associated with a high fetal and maternal mortality. We report a successful pulmonary embolectomy in a woman at the 27th week of pregnancy; we performed surgical pulmonary embolectomy under cardiopulmonary bypass to restore adequate hemodynamic stability and to relieve right ventricle strain. We discuss the decision made for the preferred anticoagulation drug in the setting of heparin-induced thrombocytopenia in the gravida. The pregnancy was carried to term and she delivered a healthy boy at 38weeks of gestation.

Bivalirudin Use During Radiofrequency Catheter Ablation Procedures in Two Patients with a History of Heparin‐Induced Thrombocytopenia

Current guidelines recommend using bivalirudin, a direct thrombin inhibitor,as a preferred alternative to unfractionated heparin in patients with heparin induced thrombocytopenia (HIT) for percutaneous coronary intervention, as well as for cardiac and vascular surgery. Anticoagulation during radiofrequency catheter ablation (RFA) procedures may be another potential use for bivalirudin in the setting of HIT. Radiofrequency catheter ablation procedures involving left atrial or left ventricular access are increasingly employed as a method to treat cardiac arrhythmias. Because stroke risk is a serious complication of RFA, anticoagulation is required during this procedure. We describe the first report, to our knowledge, of successful use of bivalirudin anticoagulation during RFA procedures in two patients with a history of clinically diagnosed HIT that precluded the use of unfractionated heparin or low-molecular-weight heparin. One of the patients underwent RFA for ventricular tachycardia, the other for pulmonary vein isolation for the treatment of atrial fibrillation. In both patients, bivalirudin was administered as a 0.75-mg/kg intravenous bolus, followed by a 1.75-mg/kg/hour infusion.Activated clotting time (ACT) was measured after the initial bolus in each patient. However, no dosage adjustment was made based on the ACT, and the infusion rate of bivalirudin remained fixed during the procedures. Both procedures were completed without any embolic events. No bleeding or clotting events were noted; one patient experienced minor access site oozing that was not felt to be clinically important. Bivalirudin is a therapeutic option for anticoagulation during left-sided catheter RFA procedures in patients with a history of HIT.

Weight-Based Argatroban Dosing Nomogram for Treatment of Heparin-Induced Thrombocytopenia

Manufacturer recommendations for argatroban use in the setting of heparin-induced thrombocytopenia (HIT) state that the dosage should be titrated to a goal activated partial thromboplastin time (aPTT) of 1.5-3 times the baseline aPTT. The lack of a clear dosing strategy with argatroban may result in delayed stabilization of aPTT. There are no published nomograms to guide the dosing of argatroban. To study the anticoagulant effect and incidence of bleeding and thrombotic events in patients receiving argatroban, with doses determined using a weight-based nomogram. Patients with suspected or documented HIT at an 800-bed teaching community hospital were prospectively treated, in a nonrandomized, nonblinded manner, with argatroban; dosage adjustments were made according to 1 of 2 variations of a dosing nomogram: standard or hepatic/critically ill. The primary outcomes were time to aPTT stabilization and percentage of patients whose aPTTs were within the therapeutic range of 45-90 seconds at 6, 12, 24, 48, 72, and 96 hours. Secondary outcomes were the percentage of patients whose aPTTs were subtherapeutic, supratherapeutic, or above the therapeutic threshold of 45 seconds at each time interval; incidence of thrombotic events; number of dosage adjustments to achieve stabilization; and number of major bleeding events. Fifty-one patients were prospectively treated using the standard (n = 34) and hepatic/critically ill (n = 17) nomograms. Mean time to aPTT stabilization was 16.25 hours with the standard nomogram and 27.05 hours with the hepatic/critically ill nomogram. The percentages of patients with aPTTs within the therapeutic range at each time interval were 82.4%, 82.4%, 88.2%, 96.4%, 100%, and 100% with the standard nomogram and 58.8%, 82.4%, 76.5%, 93.3%, 100%, and 90.9% with the hepatic/critically ill nomogram. There were no thrombotic events after the initiation of argatroban. Three cases of major bleeding occurred. The nomogram is an effective dosing tool for achieving and maintaining therapeutic levels of anticoagulation.

Fondaparinux as a Treatment Option for Heparin‐Induced Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is an immune-mediated complication that can occur after exposure to heparin products. Because patients with HIT are at increased risk for thrombosis, anticoagulation is warranted. The direct thrombin inhibitors lepirudin and argatroban are approved by the United States Food and Drug Administration (FDA) for this indication. Bivalirudin, another direct thrombin inhibitor, is approved for use in patients with HIT who must undergo percutaneous coronary intervention. The synthetic pentasaccharide fondaparinux lacks FDA approval for treating patients with HIT; however, a few published reports describe its use. Furthermore, various small-scale, in vitro studies have demonstrated a lack of cross-reactivity between fondaparinux and HIT antibodies. Large, in vivo comparison trials must be performed before fondaparinux can become a standard treatment option in the setting of HIT.

Shock during heparin-induced thrombocytopenia: Look for adrenal insufficiency!

Sir, Heparin-induced thrombocytopenia (HIT) can lead to life-threatening complications. We report a case of shock of unclear origin in a patient, in whom investigations showed adrenal insufficiency induced by adrenal necrosis in the setting of HIT. A 64-year-old man received prophylactic subcutaneous unfractionated heparin therapy after hip replacement. On postoperative day (POD) 7, his platelet count was 76,000/mm3 compared with 339,000/mm3 preoperatively, suggesting HIT. Danaparoid was substituted for heparin, and HIT antibodies were tested. On POD 9, he required ICU admission for cardiovascular collapse, fever, confusion, and abdominal pain. Thrombocytopenia (46,000/mm3) and high urinary sodium were the only abnormal laboratory findings. Abdominal computed tomography showed bilateral adrenal gland enlargement (Fig. 1) consistent with hemorrhagic necrosis. Acute adrenal insufficiency caused by HIT-related thrombosis was suspected. Samples for hormone assays were collected and intravenous hydrocortisone was started immediately. The fever, shock, and norepinephrine requirement resolved within 24 h. The ELISA for HIT antibodies came back strongly positive. Basal plasma cortisol was very low (46 nmol/l) and no rise was noted 60 min after corticotropin stimulation test (42 nmol/l). The patient was discharged to a medicine ward on POD 14 with oral hydrocortisone and fludrocortisone. He recovered uneventfully. Heparin-induced thrombocytopenia occurs in 0.5–5% of patients given heparin, depending on patient characteristics and heparin type [1]. The diagnosis is difficult in ICU patients, who often have thrombocytopenia due to other causes (e. g., sepsis, disseminated intravascular coagulation, bleeding, dilution, and drugs other than heparin), in variable combinations. Similarly, the symptoms of acute adrenal insufficiency are nonspecific and may suggest septic shock in ICU patients. Non-specific yet suggestive features include extravascular fluid loss, unresponsiveness to vasoconstrictors, normolactemia, eosinophilia, hyperkalemia, hyponatremia, hypernatriuresis, and relative hypoglycemia [2]. Recent management of septic shock with systematic adrenal function testing may detect early previously unrecognized cases of adrenal failure [3].

Anticoagulation Strategies for Treatment of Ischemic Stroke and Antiphospholipid Syndrome: Case Report and Review of the Literature

A 49-year-old Caucasian man with antiphospholipid syndrome who experienced an ischemic stroke required multidisciplinary decisions regarding acute and long-term care. The patient first received warfarin and unfractionated heparin, followed by low-molecular-weight heparin. However, he developed complications from these drugs (warfarin-induced necrosis and heparin-induced thrombocytopenia), resulting in thigh necrosis and multiple additional cerebral and peripheral infarcts. His condition improved after warfarin and the heparins were discontinued, and a direct thrombin inhibitor, argatroban, was given intravenously for acute treatment. Argatroban is the only anticoagulant known to be safe in patients who experience an acute ischemic stroke in the setting of heparin-induced thrombocytopenia. For long-term anticoagulation, fondaparinux, an indirect, selective factor Xa inhibitor, was given subcutaneously. The patient received intravenous dexamethasone, later changed to azathioprine, for immunomodulatory treatment. He had significant improvement in his neurologic deficits without recurrent events over the next 18 months. Management of anticoagulation therapy in patients with antiphospholipid syndrome is complex and challenging, and therapeutic strategies need to be evaluated further.

Warfarin-induced skin necrosis and venous limb gangrene in the setting of heparin-induced thrombocytopenia

Warfarin-induced skin necrosis and venous limb gangrene in the setting of heparin-induced thrombocytopenia