Coagulation and Aging: Implications for the Anesthesiologist

Purpose of Review This narrative review focuses on aging-related modifications in coagulation resulting in increased thromboembolic and hemorrhagic risk of the elderly. We further discuss the current evidence and emerging data relating the perioperative treatment of elderly patients with antithrombotic therapy. Recent Findings Relevant changes in all elements of the Virchow’s triad can be found with aging. Increased blood stasis due to immobility, progressive endothelial dysfunction with altered microcirculation, elevated concentrations of several coagulation factors, and increased platelet reactivity all lead to a procoagulant state. Elderly people are, therefore, commonly treated with oral anticoagulation and antiplatelet drugs. This antithrombotic therapy might be essentially causative for their increased bleeding risk. Summary Elderly patients are at increased risk for thromboembolism due to changes in the hemostatic system in combination with frailty and multimorbidity. Both the thromboembolic due to aging and bleeding risk due to antithrombotic therapy need special attention in the elderly surgical patients.

Fatal hemorrhagic complication after coil embolization of a petrosal arteriovenous shunt

Background Cerebello-pontine AVMs (CPAVMs) and petrous apex dural arteriovenous fistulae (DAVFs) are rare and sometimes difficult to distinguish. We report a fatal hemorrhagic complication after coil embolization of the petrosal vein draining a trigeminal AVM misdiagnosed as a DAVF. Case presentation A 73-year-old woman with a petrous apex arteriovenous shunt with dual dural and pial arterial supply presented with posterior fossa hemorrhage. The draining petrosal vein was catheterized and coiled via the superior petrosal sinus. Two episodes of contrast extravasation occurred during coiling, but the lesion was completely occluded at the end of the procedure. The patient developed a fatal posterior fossa hemorrhage in the recovery room. Microscopic pathology revealed numerous dilated vessels within the trigeminal nerve. Conclusion CPAVMs and DAVFs with pial drainage should be distinguished pre-operatively. Occlusion of a pial vein (as opposed to a sinus) in the treatment of an arteriovenous shunt carries hemorrhagic risk if a liquid embolic agent is not used to completely occlude all pathological vessels.

Current Therapeutic Approach to Acute Myocardial Infarction in Patients with Congenital Hemophilia

Advances in the treatment of hemophilia have made the life expectancy of hemophiliacs similar to that of the general population. Physicians have begun to face age-related diseases not previously encountered in individuals with hemophilia. Treatment of acute myocardial infarction (AMI) is particularly challenging because the therapeutic strategies influence both the patient’s thrombotic and hemorrhagic risk. As progress has been made in the treatment of AMI over the last decade, we performed an in-depth analysis of the available literature, highlighting the latest advances in the therapy of AMI in hemophiliacs. It is generally accepted that after the optimal substitution therapy has been provided, patients with hemophilia should be treated in the same way as those in the general population. New-generation stents that allow short dual antiplatelet therapy and potent P2Y12 receptor inhibitors have begun to be successfully used. At a time when specific recommendations and relevant data are scarce, our study provides up-to-date information to physicians involved in the treatment of AMI in hemophiliacs.

Torsion of the Ovary in Infancy, a Rare Emergency; A Case Report

Torsion of the ovary is a rare condition whose diagnosis remains difficult given the non-specificity of the clinical picture as well as the difficulty of clinical evaluation, especially in young girls. It is a surgical emergency because it involves the vital prognosis by the hemorrhagic risk, and functional prognosis by the risk of infertility. The clinical picture is dominated by acute abdominal pain. Our work reports the case of a 2-year-old girl in whom the diagnosis of ovarian torsion was made in front of an atypical clinical picture. Laparoscopy is the method of choice for making a positive diagnosis and performing a conservative procedure as described in this work.

Immune Thrombocytopenia in Antiphospholipid Syndrome: Is It Primary or Secondary?

Antiphospholipid syndrome (APS) is frequently associated with thrombocytopenia, in most cases mild and in the absence of major bleedings. In some patients with a confirmed APS diagnosis, secondary immune thrombocytopenia (ITP) may lead to severe thrombocytopenia with consequent major bleeding. At the same time, the presence of antiphospholipid antibodies (aPL) in patients with a diagnosis of primary ITP has been reported in several studies, although with some specific characteristics especially related to the variety of antigenic targets. Even though it does not enter the APS defining criteria, thrombocytopenia should be regarded as a warning sign of a “high risk” APS and thus thoroughly evaluated. The presence of aPL in patients with ITP should be assessed as well to stratify the risk of paradoxical thrombosis. In detail, besides the high hemorrhagic risk in secondary thrombocytopenia, patients with a co-diagnosis of APS or only antibodies are also at risk of arterial and venous thrombosis. In this narrative review, we discuss the correlation between APS and ITP, the mechanisms behind the above-reported entities, in order to support clinicians to define the most appropriate treatment strategy in these patients, especially when anticoagulant or antiplatelet agents may be needed.

Clinical Management of Moyamoya Patients

Moyamoya angiopathy (MMA) is a peculiar cerebrovascular condition characterized by progressive steno-occlusion of the terminal part of the internal carotid arteries (ICAs) and their proximal branches, associated with the development of a network of fragile collateral vessels at the base of the brain. The diagnosis is essentially made by radiological angiographic techniques. MMA is often idiopathic (moyamoya disease-MMD); conversely, it can be associated with acquired or hereditary conditions (moyamoya Syndrome-MMS); however, the pathophysiology underlying either MMD or MMS has not been fully elucidated to date, and this poor knowledge reflects uncertainties and heterogeneity in patient management. MMD and MMS also have similar clinical expressions, including, above all, ischemic and hemorrhagic strokes, then headaches, seizures, cognitive impairment, and movement disorders. The available treatment strategies are currently shared between idiopathic MMD and MMS, including pharmacological and surgical stroke prevention treatments and symptomatic drugs. No pharmacological treatment able to reverse the progressive disappearance of the ICAs has been found to date in both idiopathic and syndromic cases. Antithrombotic agents are usually prescribed in ischemic MMA, although the coexisting hemorrhagic risk should be considered. Surgical revascularization techniques, which are currently the best available treatment in symptomatic MMA, are associated with good long-term outcomes and reduced ischemic and hemorrhagic risks. Given the lack of dedicated randomized clinical trials, current treatment is mainly based on observational studies and physicians’ and surgeons’ expertise.

Evaluation of the diagnostic possibility of hemorrhagic risk in pregnant women with severe preeclampsia by rotational thromboelastography

AIM: The aim of this study was to determine the risk of hemorrhagic complications in pregnant women with severe preeclampsia using rotational thromboelastometry (ROTEM) in two screening tests EXTEM and INTEM. MATERIALS AND METHODS: We examined 30 pregnant women with severe preeclampsia, who were observed in the intensive care unit, the Department of Obstetrics and Perinatology, the Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott, Saint Petersburg. The control group consisted of 10 patients with normal pregnancy, delivered by caesarean section for reasons not related to obstetric complications. RESULTS: When interpreting the ROTEM results, the reference intervals for pregnant women in the third trimester were used, as determined in the study by J. Lee et al. (2019). According to the analysis of thromboelastograms of pregnant women with severe preeclampsia, 9 (30%) of them had a tendency towards hypocoagulation. Of these, 3 thromboelastograms had deviations via the intrinsic coagulation pathway (in the INTEM tests), 3 thromboelastograms via the extrinsic coagulation pathway (in the EXTEM tests), and the rest combined both options. Two patients with severe preeclampsia developed a complication in the form of HELLP syndrome, and the phenomena of hypocoagulation, according to the results of ROTEM performed before delivery, were observed in only one patient. A comparative analysis of ROTEM parameters among pregnant women with severe preeclampsia and normal pregnancy did not reveal statistically significant differences. CONCLUSIONS: The use of the ROTEM method with the main screening tests (EXTEM and INTEM) did not show diagnostic value in assessing the risk of hemorrhagic complications of severe preeclampsia.

Real-world use of thrombopoietin receptor agonists in elderly patients with primary immune thrombocytopenia

The efficacy and safety of thrombopoietin-receptor agonists (TRAs) in elderly patients with primary immune thrombocytopenia (ITP) is uncertain. In 384 ITP patients treated with TRAs when aged ≥60 years, we investigated TRAs response and switch, thrombotic/hemorrhagic risk, and sustained responses off-treatment (SROT). After 3 months, 82.5% and 74.3% of eltrombopag and romiplostim-treated patients achieved a response, respectively (p=0.09); 66.7% maintained the response (median follow-up: 2.7 years). Eighty-five (22.2%) patients switched to the alternative TRA; while no cross-toxicity was observed, 83.3% of resistant patients had a response after the switch. During TRA, 34 major thromboses (3 fatal) and 14 major hemorrhages (none fatal) occurred in 18 and 10 patients, respectively, and were associated with thrombosis history (SHR: 2.04, p=0.05) and platelet count <20x109/L at TRA start (SHR: 1.69, p=0.04), respectively. A recurrent event occurred in 15.6% of patients surviving thrombosis, in all cases but one during persisting TRA treatment (incidence rate: 7.7 per 100 patient-years). All recurrences occurred in the absence of adequate antithrombotic secondary prophylaxis. Sixty-two (16.5%) responding patients discontinued TRA; 53 (13.8%) patients maintained SROT, which was associated with TRA discontinuation in complete response (p<0.001). Very old age (≥75, 41.1%) was associated with more frequent TRAs start in persistent/acute phase but not with response or thrombotic/hemorrhagic risk. TRAs are effective in elderly ITP patients, with no fatal haemorrhages and with SROT in a significant portion of patients; in patients with thrombosis history caution is warranted and a careful risk/benefit balance should be carried out.

Anticoagulation in Patients with Platelet Disorders

Platelet disorders comprise heterogeneous diseases featured by reduced platelet counts and/or impaired platelet function causing variable bleeding symptoms. Despite their bleeding diathesis, patients with platelet disorders can develop transient or permanent prothrombotic conditions that necessitate prophylactic or therapeutic anticoagulation. Anticoagulation in patients with platelet disorders is a matter of concern because the bleeding risk could add to the hemorrhagic risk related to the platelet defect. This review provides an overview on the evidence on anticoagulation in patients with acquired and inherited thrombocytopenia and/or platelet dysfunction. We summarize tools to evaluate and balance bleeding— and thrombotic risks and describe a practical approach on how to manage these patients if they have an indication for prophylactic or therapeutic anticoagulation.