Life-threatening Hemorrhagic Complications Research Articles

The substantial burden of iatrogenic vascular injury on the vascular surgery workforce at an academic medical center

ObjectiveVascular surgeons are often called upon to provide emergent surgical assistance to other specialties for iatrogenic complications, both intraoperatively and in the inpatient setting. The management of iatrogenic vascular injury remains a critical role of the vascular surgeon, especially in the context of the increasing adoption of percutaneous procedures by other specialties. This study aims to characterize consultation timing, management, and outcomes for iatrogenic vascular injuries. MethodsThis study identified patients for whom vascular surgery was consulted for iatrogenic vascular complications from February 1, 2022, to May 12, 2023. Patient information, including demographic information, injury details, and details of any operative intervention, was retrospectively collected from February 1, 2022, to October 13, 2022, and prospectively collected for the remainder of the study period. Analyses were performed with R (version 2022.02.03). ResultsThere were 87 patients with consultations related to iatrogenic vascular injury. Of these, 42 (46%) were female and the mean age was 59 years (±18 years). The most common consulting services were cardiology (32%), cardiothoracic surgery (26%), general surgery (8%), and neurointerventional radiology (10%). Reasons for consultation included hemorrhage (36%), limb ischemia (36%), and treatment of pseudoaneurysm (23%). A total of 24% of consults were intraoperative, 20% of consults related to extracorporeal membrane oxygenation cannulation, and 16% of consults related to ventricular assist devices including left ventricular assist device and intra-aortic balloon pump. The majority of these consult requests (60%) occurred during evening and night hours (5 PM to 7 AM). Emergent intervention was required in 62% of cases and consisted of primary open surgical repair of arterial injury (54%), endovascular intervention (21%), and open thromboembolectomy (15%). Overall, in-hospital mortality for the patient cohort was 20% and the reintervention rate was 23%, reflecting the underlying complexity of the illness and nature of the vascular injury in this patient group. ConclusionsVascular surgeons play an essential role in managing emergent life-threatening hemorrhagic and ischemic iatrogenic vascular complications in the hospitalized setting. The complications require immediate bedside or intraoperative consult and often emergent open surgical or endovascular intervention. Furthermore, many of these require urgent management in the evening or overnight hours, and therefore the high frequency of these events represents a potential significant resource utilization and workforce issue to the vascular surgery workforce.

Hereditary hemorrhagic telangiectasia may be the most morbid inherited bleeding disorder in women

AbstractHereditary hemorrhagic telangiectasia (HHT) is the second-most common inherited bleeding disorder (BD) worldwide and remains without approved therapies. HHT causes serious mucosal bleeding resulting in severe iron-deficiency anemia, major psychosocial complications, and visceral arteriovenous malformations in the brain, lung, and liver, which can cause life-threatening hemorrhagic complications. No study has examined the relative morbidity of HHT and von Willebrand disease (VWD), which is the most common inherited BD in women. We performed an observational cohort study of women with HHT or VWD, comparing a representative sample of 100 randomly selected women with HHT to 100 randomly selected age-matched women with VWD. In HHT vs VWD, recurrent epistaxis and gastrointestinal bleeding were more likely (odds ratio [OR], 32.73 [95% confidence interval, 13.81-71.80]; P < .0001 and 5.69 [2.59-12.89]; P < .0001) and heavy menstrual bleeding was less likely (OR, 0.32 [0.18-0.57]; P < .0001). Iron-deficiency anemia was significantly more likely, and the lowest hemoglobin was significantly lower in HHT than in VWD. The odds of iron infusion dependence, requirement for red cell transfusion, and hemostatic surgical procedures were significantly higher—17-fold, threefold, and eightfold higher, respectively—and hospital admissions to manage disease complications were both ∼14 times more frequent in women with HHT vs those with VWD. In conclusion, much higher disease-related morbidity, mortality, and health care use were observed in women with HHT vs VWD, providing evidence that HHT may be the most clinically significant inherited BD in women. Given the vast gap in research funding for HHT compared with both hemophilia (a disease primarily of men) and VWD, these findings have significant implications for gender equity in hematology.

Disseminated Intravascular Coagulation With Excessive Fibrinolysis (DIC-XFL) A Rare Association of Metastatic Prostate Adenocarcinoma: A Case Report

We present disseminated intravascular coagulation (DIC) with excessive fibrinolysis (XFL) as an unusual presenting manifestation of metastatic prostate cancer (PC), which was successfully treated with chemotherapy with Docetaxel which not only controlled the disease but also reversed the patient’s coagulopathy within seven days effectively. Thus highlighting rare and life-threatening haemorrhagic complications of prostate cancer along with its satisfactory management option.

Impact of Covid-19 on risk of severe maternal morbidity

BackgroundWe examined the risk of severe life-threatening morbidity in pregnant patients with Covid-19 infection.MethodsWe conducted a population-based study of 162,576 pregnancies between March 2020 and March 2022 in Quebec, Canada. The main exposure was Covid-19 infection, including the severity, period of infection (antepartum, peripartum), and circulating variant (wildtype, alpha, delta, omicron). The outcome was severe maternal morbidity during pregnancy up to 42 days postpartum. We estimated risk ratios (RR) and 95% confidence intervals (CI) for the association between Covid-19 infection and severe maternal morbidity using adjusted log-binomial regression models.ResultsCovid-19 infection was associated with twice the risk of severe maternal morbidity compared with no infection (RR 2.02, 95% CI 1.76–2.31). Risks were elevated for acute renal failure (RR 3.01, 95% CI 1.79–5.06), embolism, shock, sepsis, and disseminated intravascular coagulation (RR 1.35, 95% CI 0.95–1.93), and severe hemorrhage (RR 1.49, 95% CI 1.09–2.04). Severe antepartum (RR 13.60, 95% CI 10.72–17.26) and peripartum infections (RR 20.93, 95% CI 17.11–25.60) were strongly associated with severe maternal morbidity. Mild antepartum infections also increased the risk, but to a lesser magnitude (RR 3.43, 95% CI 2.42–4.86). Risk of severe maternal morbidity was around 3 times greater during circulation of wildtype and the alpha and delta variants, but only 1.2 times greater during omicron.ConclusionsCovid-19 infection during pregnancy increases risk of life-threatening maternal morbidity, including renal, embolic, and hemorrhagic complications. Severe Covid-19 infection with any variant in the antepartum or peripartum periods all increase the risk of severe maternal morbidity.

The Significant Burden of Iatrogenic Vascular Injury on the Vascular Surgery Workforce at an Academic Medical Center

The treatment of iatrogenic vascular injury remains a critical role of the vascular surgeon, especially in the context of the increasing adoption of percutaneous procedures by other inpatient services. Vascular surgeons are called upon to provide emergent surgical assistance to other specialties for iatrogenic complications, both intraoperatively and at the bedside. This study aims to characterize consultation timing, management, and outcomes for iatrogenic vascular injuries. This study identified patients for whom vascular surgery was consulted for iatrogenic vascular complications from February 1, 2022, to January 8, 2023. Patient information, including demographic information, injury details, and details of any operative intervention, were retrospectively collected from February 1 to October 13 and prospectively collected for the remainder of the study period. Analyses were performed with R version 2022.02.03. There were 63 patients with consultations related to iatrogenic vascular injury. Of these, 29 (46%) were female and the mean age was 59 ± 18 years. The most common consulting services were cardiology (32%), cardiothoracic surgery (27%), and neurointerventional radiology (10%). Reasons for consultation included hemorrhage (38%), limb ischemia (32%), and treatment for pseudoaneurysm (27%). Of the consults, 25% were intraoperative, 19% related to ECMO cannulation, and 19% related to ventricular assist devices including left ventricular assist devices and intra-aortic balloon pumps. The majority of consult requests occurred during evening and night hours (5 pm to 7 am) (60%) (Figure). Emergent intervention was required in 75% of cases and consisted of: primary open surgical repair of arterial injury (50%), endovascular intervention (15%), and open thromboembolectomy (13%). Overall, in-hospital mortality for the patient cohort was 18% and the reintervention rate was 21%, reflecting the underlying complexity of the illness and nature of the vascular injury in this patient group. Vascular surgery plays an essential role in managing emergent life-threatening hemorrhagic and ischemic iatrogenic vascular complications in the hospitalized setting. These consults and complications require immediate bedside or intraoperative consultation and often emergent open surgical or endovascular intervention. Furthermore, many of these require urgent management in the evening or overnight hours, and therefore the high frequency of these events represents a potential significant resource utilization and workforce issue to vascular surgeons.

Recurrent Disseminated Intravascular Coagulation in Metastatic Castration-Resistant Prostate Cancer: A Case Report.

Disseminated intravascular coagulation (DIC) is a systemic disease characterized by simultaneous thrombosis, bleeding, and partially excessive fibrinolysis. Systemic shock, trauma, bacterial toxins, and procoagulants-expressing solid and hematologic malignancies are common causes of this life-threatening hemorrhagic complication and often require treatment in intensive care units. We describe a case of an elderly man with recurrent severe bleeding events in the cause of DIC, including epistaxis, hemoptysis, hematuria, and gastrointestinal bleeding. Laboratory investigations revealed elevated prostate-specific antigen (PSA), suggesting an underlying prostate cancer. Despite intensified coagulatory therapy, the coagulation disorder could not be stabilized. A single injection of degarelix, a gonadotropin-releasing hormone (GnRH) receptor antagonist, led to rapid stabilization of the coagulation and decreased PSA within days. One year after initiating androgen-deprivation therapy, there were recurrent transfusion-requiring bleeding events, and a concomitant PSA increase occurred, suggesting metastatic castration-resistant disease associated with DIC. This case emphasizes DIC as a possible primary phenomenon and indicator for the progression of the underlying malignancy, as well as the importance of etiological therapies in the management of DIC.

Massive haemorrhagic complications of ruptured pulmonary arteriovenous malformations: outcomes from a 12\xa0years\u2019 retrospective study

BackgroundThe life-threatening haemorrhagic complications of pulmonary arteriovenous malformations (PAVMs) are extremely rare, and only described in isolated cases. This study was designed to comprehensively investigate management of ruptured PAVMs.MethodsWe retrospectively assessed clinical and imaging data of ruptured PAVMs to summarize incidence, clinical characteristics, and outcomes following embolisation between January 2008 and January 2021.ResultsEighteen of 406 (4.4%) patients with PAVMs developed haemorrhagic complications. Twelve of 18 patients were clinically diagnosed with hereditary haemorrhagic telangiectasia (HHT). Haemorrhagic complications occurred with no clear trigger in all cases. Eight of 18 patients (44.4%) were initially misdiagnosed or had undergone early ineffective treatment. 28 lesions were detected, with 89.3% of them located in peripheral lung. Computed tomography angiography (CTA) showed indirect signs to indicate ruptured PAVMs in all cases. Lower haemoglobin concentrations were associated with the diameter of afferent arteries in the ruptured lesions. Successful embolotherapy was achieved in all cases. After embolotherapy, arterial oxygen saturation improved and bleeding was controlled (P < 0.05). The mean follow-up time was 3.2 ± 2.5 years (range, 7 months to 10 years).ConclusionsLife threatening haemorrhagic complications of PAVMs are rare, they usually occur without a trigger and can be easily misdiagnosed. HHT and larger size of afferent arteries are major risk factors of these complications. CTA is a useful tool for diagnosis and therapeutic guidance for ruptured PAVMs. Embolotherapy is an effective therapy for this life-threatening complication.

Placenta praevia і Placenta accreta: сучасні методи діагностики і розродження

The article presents data from recent randomized trials and published in 2018 two guidelines from the Royal College of Obstetricians and Gynecologists of Great Britain on epidemiology, risk factors, modern diagnostic methods, modern algorithms and innovative surgical methods in cases of placenta (pl. praevia/accreta). From the point of view of evidence-based medicine, the relevance of the problem in the aspect of antenatal diagnosis of placental pathology for prediction and prevention of life-threatening hemorrhagic complications is highlighted. Data are presented indicating the need for a multidisciplinary approach to pregnancy in the case of diagnosis of placenta percreta with cesarean section and hysterectomy without attempting to separate the placenta. The given data will be useful for practitioners of obstetrician-gynecologists for the purpose of optimal management and delivery of pregnant women with this difficult obstetric pathology. Key words: placenta previa, abnormal invasive placenta, placenta accreta, placenta accreta spectrum disorders, increta/percreta.

Local low-dose urokinase thrombolysis for the management of haemodynamically stable pulmonary embolism with right ventricular dysfunction.

The aim of this study was to evaluate the effectiveness of local low-dose urokinase thrombolysis (LLDUT) in haemodynamically stable pulmonary embolism with right ventricular dysfunction (RVD). This was a prospective study. LLDUT with a 200,000 IU bolus followed by a 100,000 IU/hr infusion was given. Treatment duration was determined through radiological control performed 48-72 hrs into treatment. A follow-up echocardiogram was performed within seven days after LLDUT completion. Evolution of thrombus burden, pulmonary artery pressures (PAP) and RVD were studied, and haemorrhagic complications and mortality were recorded. Eighty-seven patients were included (62.5±16.5 years). In 67 patients (77%), the baseline echocardiogram showed mild-to-severe RVD, a dilated right ventricle (diameter: 44.4±6.2 mm) and a decreased tricuspid annular plane systolic excursion (14 mm [12-17]). Seventy-six patients (87.4%) experienced radiological improvement. Initially high PAP (mmHg) decreased after LLDUT: systolic 52.4 vs. 35.2 (17.2 [95% CI: 14.5-19.9]; p<0.0001), mean 34.2 vs. 23.5 (10.7 [95% CI: 9.0-12.5]; p<0.0001) and diastolic 23.9 vs. 16.0 (7.9 [95% CI: 6.1-9.7]; p<0.0001). Follow-up echocardiography showed overall improvement of RVD. No life-threatening haemorrhagic complications were reported. Six-month survival was 96.5%. LLDUT rapidly decreased thrombus burden and PAP, improving right ventricular function, and was not associated with any life-threatening complications or pulmonary embolism (PE)- or treatment-related mortality.

Hypoprothrombinemia and severe perioperative haemorrhagic complications in cardiac surgery patients treated with high-dose cefazolin for infective endocarditis

Endocarditis is a serious and common disease that requires prolonged antimicrobial therapy. The recent shortage of oxacillin has led to the use of other antimicrobial agents such as cefazolin to treat endocarditis due to methicillin-sensitive Staphylococcus aureus. We describe four cases of life-threatening haemorrhagic complications (fatal in two cases) in patients treated with high-dose cefazolin. All of these patients with major bleeding presented with hypoprothrombinemia secondary to hypovitaminosis K. This adverse event may be due to inhibition of vitamin K epoxide reductase and/or gamma-glutamyl-carboxylase by the 2-methyl-1,2,3-thiadiazol-5-thiol group of cefazolin. This inhibition may result in hypoprothrombinemia by altering the synthesis of vitamin K-dependent coagulation factors. The increasing use of cefazolin, especially at a high dose and for a prolonged period of time, should be accompanied by regular monitoring of coagulation, including prothrombin index, and vitamin K supplementation.

Close: Closure of patent foramen ovale, oral anticoagulants or antiplatelet therapy to prevent stroke recurrence: Study design.

Currently available data do not provide definitive evidence on the comparative benefits of closure of patent foramen ovale, oral anticoagulants and antiplatelet therapy in patients with patent foramen ovale-associated cryptogenic stroke To assess whether transcatheter patent foramen ovale closure plus antiplatelet therapy is superior to antiplatelet therapy alone and whether oral anticoagulant therapy is superior to antiplatelet therapy, for secondary stroke prevention in patients aged 16 to 60 years with a large patent foramen ovale or a patent foramen ovale associated with an atrial septal aneurysm, and an otherwise unexplained ischaemic stroke or retinal ischaemia. Six hundred and sixty-four patients were included in the study. CLOSE is an academic-driven, multicentre, randomized, open-label, three-group, superiority trial with blinded adjudication of outcome events. The trial has been registered with Clinical Trials Register (Clinicaltrials.gov, NCT00562289). Patient recruitment started in December 2007. Patient follow-up will continue until December 2016. Expected mean follow-up = 5.6 years. The primary efficacy outcome is the occurrence of fatal or nonfatal stroke. Safety outcomes include fatal, life-threatening or major procedure- or device-related complications and fatal, life-threatening or major haemorrhagic complications. CLOSE is the first specifically designed trial to assess the superiority of patent foramen ovale closure over antiplatelet therapy alone and the superiority of oral anticoagulants over antiplatelet therapy to prevent stroke recurrence in patients with patent foramen ovale-associated cryptogenic stroke.

Source and Purity of Dengue-Viral Preparations Impact Requirement for Enhancing Antibody to Induce Elevated IL-1β Secretion: A Primary Human Monocyte Model.

Dengue virus is a major global health threat and can lead to life-threatening hemorrhagic complications due to immune activation and cytokine production. Cross-reactive antibodies to an earlier dengue virus infection are a recognized risk factor for severe disease. These antibodies bind heterologous dengue serotypes and enhance infection into Fc-receptor-bearing cells, a process known as antibody-dependent enhancement of infection. One crucial cytokine seen elevated in severe dengue patients is IL-1β, a potent inflammatory cytokine matured by the inflammasome. We used a highly-physiologic system by studying antibody-dependent enhancement of IL-1β in primary human monocytes with anti-dengue human monoclonal antibodies isolated from patients. Antibody-enhancement increased viral replication in primary human monocytes inoculated with supernatant harvested from Vero cells infected with dengue virus serotype 2 (DENV-2) 16681. Surprisingly, IL-1β secretion induced by infectious supernatant harvested from two independent Vero cell lines was not enhanced by antibody. Secretion of multiple other inflammatory cytokines was also independent of antibody signaling. However, IL-1β secretion did require NLRP3 and caspase-1 activity. Immunodepletion of dengue virions from the infectious supernatant confirmed that virus was not the main IL-1β-inducing agent, suggesting that a supernatant component(s) not associated with the virion induced IL-1β production. We excluded RNA, DNA, contaminating LPS, viral NS1 protein, complement, and cytokines. In contrast, purified Vero-derived DENV-2 16681 exhibited antibody-enhancement of both infection and IL-1β induction. Furthermore, C6/36 mosquito cells did not produce such an inflammatory component, as crude supernatant harvested from insect cells infected with DENV-2 16681 induced antibody-dependent IL-1β secretion. This study indicates that Vero cells infected with DENV-2 16681 may produce inflammatory components during dengue virus propagation that mask the virus-specific immune response. Thus, the choice of host cell and viral purity should be carefully considered, while insect-derived virus represents a system that elicits antibody-dependent cytokine responses to dengue virus with fewer confounding issues.

Anticoagulation reversal in the era of the non-vitamin K oral anticoagulants.

In recent years, non-vitamin K oral anticoagulants (NOACs) have emerged as an alternative to warfarin for the prevention and treatment of thrombo-embolic disease. Large randomized trials have demonstrated that these agents, which act by directly targeting thrombin (dabigatran) and factor Xa (rivaroxaban, apixaban, and edoxaban), are at least as effective as warfarin, with lower rates of bleeding and fewer interactions with food and drugs. In addition, NOACs have a more predictable anticoagulant effect, allowing a fixed dose regimen and obviating the need for routine anticoagulation monitoring. Since the introduction of NOACs, one of the major concerns for clinicians has been the lack of specific agents to reverse their anticoagulant effect in case of life-threatening haemorrhagic complications or emergency surgery, which have limited their use in patients deemed at a higher risk of bleeding. New specific antidotes (e.g. idarucizumab, andexanet alfa, and ciraparantag) show promising data, and may soon become available for clinical use. In this article, we review the pharmacology of these agents, the incidence and outcomes of haemorrhagic complications, the available strategies for anticoagulation reversal, and the more recent advances for the development of specific antidotes.

A Tough Pill to Swallow- Spontaneous Retropharyngeal Hematoma: A Rare and Unusual Complication of Rivaroxaban Therapy

Aims: We present the first case of a patient that developed a spontaneous retropharyngeal hematoma as a complication of rivaroxaban therapy. Case Presentation: A 49-year-old Caucasian male with chronic atrial fibrillation on rivaroxaban presented to the hospital with a rapidly expanding spontaneous retropharyngeal hematoma. He required emergent intubation for airway protection and subsequently was treated with catheterdirected embolization and surgical evacuation. Discussion: Our report presents a case of a spontaneous retropharyngeal hematoma on rivaroxaban therapy. Unfortunately, most patients with this complication typically present with insidious symptoms including mild neck pain and ear ache, and as a result the diagnosis can easily be overlooked. Therefore, it is of utmost importance that physicians maintain a high index of suspicion, as early recognition and appropriate therapy can reduce morbidity and mortality. Conclusion: This case highlights a rare but life-threatening hemorrhagic complication of rivaroxaban therapy. Case Study Naqvi et al.; CA, 4(4): 156-159, 2015; Article no.CA.2015.039 157

Thrombomodulin alfa treatment in patients with acute promyelocytic leukemia and disseminated intravascular coagulation: A retrospective analysis of an open-label, multicenter, post-marketing surveillance study cohort

IntroductionPatients with acute promyelocytic leukemia (APL) can develop disseminated intravascular coagulation (DIC) that results in life-threatening hemorrhagic complications. Studies regarding the safety and efficacy of thrombomodulin alfa (TM-α; recombinant human soluble thrombomodulin) in patients with APL and DIC are limited. Materials and methodsA retrospective evaluation was performed on a cohort of 172 patients with APL from an open-label, multicenter, post-marketing surveillance study of TM-α. ResultsOf the 172 patients, 31 were relapse/refractory APL patients, and 141 were newly diagnosed APL patients. Within the first 30days, 24 patients (14.0%) died, and six of those deaths (3.5%) were due to hemorrhage. In total, 12 patients (7.0%) had severe hemorrhagic complications. Both the early death rate due to hemorrhage as well as the severe hemorrhage rate did not exceed those in some recent population-based studies of patients with APL. Forty-nine patients received TM-α prior to the initiation of antileukemic treatment, and one patient experienced hemorrhagic early death (ED), suggesting that early TM-α treatment appeared to result in a reduction in the hemorrhagic ED rate. Moreover, TM-α improved coagulopathy regardless of concomitant all-trans retinoic acid treatment. ConclusionsThis study confirmed the safety and efficacy of TM-α in daily clinical practice for patients with APL and DIC. TM-α appeared to reduce hemorrhagic early deaths due to DIC in patients with APL who were receiving antileukemic treatment.

Unusual complications of spinal surgery: A report of life-threatening vascular injury

Kyphoplasty and lumbar spine fusion are rarely associated with significant vascular damage and internal bleeding. However, anaesthesiologists must maintain vigilance in order to detect rare, but potentially lifethreatening haemorrhagic complications of these procedures which may present intra-operatively or in the immediate post-operative period. We present two cases of life-threatening haemorrhagic complications of spine surgery, one from T12 kyphoplasty and the other from a redo lumbar laminectomy and fusion. In both cases, prompt recognition of vascular injuries with internal or covert bleeding which presented shortly after surgery allowed timely and life-saving treatment.

Management of antithrombotic therapy in patients undergoing implantation or replacement of cardiac implantable electronic devices

In Italy tens of thousands of patients undergo implantation or replacement of cardiac implantable electronic devices (CIEDs) annually, and up to 50% of these subjects receive antiplatelet agents or oral anticoagulants. The rate of CIED-related complications, mainly infective, has also significantly increased, so that transvenous lead extraction procedures are often required. CIED surgery is peculiar and portends specific intrinsic risks of developing life-threatening hemorrhagic complications; on the other hand periprocedural discontinuation of antithrombotic therapy in patients at high thromboembolic risk may have catastrophic consequences. Accordingly, the management of candidates to CIED surgery who receive concomitant antithrombotic therapy is of great clinical relevance, though controversial and only partially, if not at all, adequately addressed in current evidence-based guidelines. Although for many procedures the administration of aspirin alone or continuation of anticoagulant therapy seems reasonably safe, with use of bridging therapy with parenteral heparins restricted to selected cases, there are multiple variables that may make therapeutic choices challenging. The aim of the present position paper is to provide practical recommendations for the management of antithrombotic therapy in patients undergoing CIED surgery by defining indications for a systematic approach integrating general technical considerations with patient-specific elements based on a careful evaluation of the balance between hemorrhagic and thromboembolic risk. The decision-making process applied in this document relies on the stratification of the procedural hemorrhagic risk and of the risk deriving from discontinuation of antiplatelet or anticoagulant therapy combined to produce different clinical scenarios with specific indications for optimal management of periprocedural antithrombotic therapy.

Thrombomodulin Alfa Treatment For Disseminated Intravascular Coagulation In Acute Promyelocytic Leukemia: A Retrospective Analysis Of The Open-Label, Multicenter Study Cohort

BackgroundPatients with acute promyelocytic leukemia (APL) patients present disseminated intravascular coagulation (DIC) that can result in life-threatening hemorrhagic complications. In 2008, the anticoagulant thrombomodulin alfa (TM-α, recombinant human soluble thrombomodulin) was approved for the treatment of DIC in Japan. After commercial launch, only small case series have been described in APL patients, and data from larger patients cohort are awaited. We accessed the clinical safety and beneficial effects of TM-α treatment in DIC patients with APL, by evaluating data on the open-label, multicenter, post-marketing surveillance study cohort.Patients andMethodsA retrospective evaluation was carried out on a cohort of 172 patients with APL from the open-label, multicenter, post-marketing surveillance study of TM-α in Japan. Of all 172 patients, 31 were relapse/refractory APL patients and 141 were newly diagnosed. The newly diagnosed APL patients were generally received all-trans retinoic acid (ATRA) and anthracycline-containing induction therapy followed by consolidation therapy as previously reported by the Japan Adult Leukemia Study Group (Yanada et al, Eur. J. Haematol. 2007). The relapse/refractory APL patients were received arsenic trioxide, tamibarotene, and/or gemtuzumab ozogamicin. Early death (death within 30 days from the start of antileukemic treatment), severe hemorrhagic events, and the improvement of coagulopathy were analyzed. ResultsThe study population consisted of 97 males and 75 females, with a median age of 58 (range 10 - 88). TM-α was administration by 380 ± 52.5 U/kg/day and the duration of dosing was 7.0 ± 6.3 days. In most patients (81 %), TM-α was started on or before the start of antileukemic treatment. Within the first 30 days, 12 patients (7 %) had severe hemorrhage and there were 24 (14 %) early deaths. Six of those (3.5% of 172 patients) were due to hemorrhage. TM-α treatment rapidly and significantly improved coagulopathy regardless of concomitant ATRA treatment (Table 1). ConclusionsAlthough anticoagulation therapy during APL chemotherapy may induce severe hemorrhagic complication, our findings suggest that supportive care with TM-α ameliorates coagulopathy and reduces the risk of hemorrhagic early deaths in patients with APL. Disclosures:Watanabe:Asahi Kasei Pharma Corporation: Employment. Honda:Asahi Kasei Pharma Corporation: Employment.

Minimally Invasive Treatment of a Life-threatening Hemorrhagic Complication of Drain Removal

Minimally Invasive Treatment of a Life-threatening Hemorrhagic Complication of Drain Removal

Safety and Efficacy of Intense Antithrombotic Treatment and Percutaneous Coronary Intervention Deferral in Patients With Large Intracoronary Thrombus

The optimal management of a large intracoronary thrombus in patients with acute coronary syndromes without an urgent need of revascularization is unclear. We investigated whether deferring percutaneous coronary intervention (PCI) after a course of intensive antithrombotic therapy (ATT) (glycoprotein IIb/IIIa inhibitors, enoxaparin, aspirin, and clopidogrel) improves the outcomes compared with immediate PCI. We studied 133 stable patients with ACS and a large intracoronary thrombus and without an urgent need for revascularization at angiography. The angiographic and in-hospital outcomes of a prospective cohort of 89 patients who had undergone deferred angiography with or without PCI after ATT (d-PCI) were compared with a historical cohort of 44 patients who had undergone immediate PCI, matched for age, gender, and Thrombolysis In Myocardial Infarction thrombus grade. The absolute thrombus volume was measured before and after ATT using dual quantitative coronary angiography. All d-PCI patients remained stable during ATT (60.0 ± 30.8 hours). A significant reduction in the Thrombolysis In Myocardial Infarction thrombus grade (4, range 4 to 5, vs 3, range 2 to 4; p <0.001), thrombus volume (51.1, range 32.1 to 83, vs 38.1, range 21.7 to 50.7 mm(3); p <0.001), stenosis severity (73.8 ± 25.8% vs 60.3 ± 32.5%; p <0.001) and better Thrombolysis In Myocardial Infarction flow (2, range 0 to 3, vs 3, 1.5 to 3; p <0.001) were noted after ATT. PCI, stenting, and thrombus aspiration were performed less frequently in the d-PCI group (76.4% vs 100%, p <0.001; 70.8% vs 93.2%, p = 0.003; and 21% vs 100%, p <0.001, respectively). However, distal embolization and slow and/or no-reflow were more common during immediate PCI (31.8% vs 9%; p = 0.001). No life-threatening or severe hemorrhagic complications were observed, although the rate of mild and/or moderate bleeding was similar between the 2 groups (6.8% in immediate PCI vs 7.9% in d-PCI; p = 0.829). In conclusion, compared with immediate PCI, d-PCI after ATT in selected, stabilized patients with ACS and a large intracoronary thrombus and without an urgent need for revascularization is probably safe and associated with a reduction in thrombotic burden, angiographic complications, and the need of revascularization. These benefits were observed without an increase in hemorrhagic complications.