Surgical Emergencies in Patients with Hemophilia A-What to Expect.

Surgical emergencies in patients with hemophilia A represent a major risk of mortality without proper multidisciplinary management and require prompt and effective treatment to prevent complications and improve patient outcomes. We present a short number of cases that were hospitalized in the I-II Surgery Clinic of the Emergency County Hospital "St. Spiridon" from Iasi, Romania, with hemophilia A requiring surgical emergencies. The timing of surgical intervention is very important, so the indication for surgical intervention must be made judiciously and without delay. Consequently, it is vital to ensure access to hemostatic support so surgery can be performed on these patients, ultimately saving their lives.

Modern Treatment of Valvulopathies in Patients with Congenital Hemophilia.

Hemophiliacs can develop cardiovascular diseases, including valvulopathies of various etiologies and severities. Some require surgical treatment. Performing cardiac surgery in hemophiliacs is a challenge because they maintain an increased risk of bleeding throughout their lives. Our review shows that with a multidisciplinary team and careful planning, cardiac surgery can be safely performed in these patients. Valve repair and bioprosthetic valves should be preferred over mechanical valves to avoid life-long anticoagulation. In patients who cannot receive a bioprosthetic valve, the use of the On-X mechanical valve might be considered because it requires less intensive anticoagulation after 3 months of treatment. Antithrombotic treatment is feasible in hemophiliacs only if the coagulation factor level is kept constantly above a specific trough limit. Our review is valuable because, for the first time, the available data on the modern surgical treatment of valvular disease in hemophiliacs have been synthesized and systematized.

Thrombotic Disease in Hemophilic Patients: Is This a Paradox in a State of Hypocoagulability?

Hemophilia patients have a deficiency in or dysfunction of clotting factors, which can lead to a bleeding tendency. However, paradoxically, some hemophilia patients may also be at an increased risk of developing thrombotic events such as deep vein thrombosis or pulmonary embolism. The pathophysiology of thrombosis in hemophilia patients is not fully understood, but it is thought to involve a complex interplay of various factors, including the severity of the hemophilia, the presence of other risk factors such as obesity, smoking, or the use of hormonal therapies, and the presence of certain genetic mutations that increase the risk of thrombosis. In addition, it has been suggested that the use of clotting factor replacement therapy, which is a standard treatment for hemophilia, may also contribute to the development of thrombosis in some cases.

Atherosclerosis in Patients with Congenital Hemophilia: A Focus on Peripheral Artery Disease.

Advances in the treatment of hemophilia have increased the life expectancy of this population and we are currently facing diseases associated with aging, including cardiovascular ones. Coronary atherosclerosis, with acute myocardial infarction as the most severe form of manifestation, has been recognized as part of the comorbidities of hemophiliacs. However, little is known about peripheral artery disease. Available data show that hemophiliacs have cardiovascular risk factors and atherosclerosis similar to the general population. Impaired thrombus formation and phenotype of atheroma plaque rather than the burden of atherosclerosis explains their lower cardiovascular mortality. Since the effect of traditional cardiovascular risk factors overpowers that of decreased coagulability and promotes the onset and progression of atherosclerotic lesions, screening for traditional cardiovascular risk factors and peripheral artery disease should be integrated into standard hemophilia care. There is evidence that invasive treatments and long-term antithrombotic therapy are generally safe, provided that coagulation factor levels are taken into account and replacement therapy is given when necessary.

Large Intron Inversions in Romanian Patients with Hemophilia A-First Report.

Background and Objectives: Despite the vast heterogeneity in the genetic defects causing hemophilia A (HA), large intron inversions represent a major cause of disease, accounting for almost half of the cases of severe HA worldwide. We investigated the intron 22 and intron 1 inversion status in a cohort of Romanian unrelated patients with severe HA. Moreover, we evaluated the role of these inversions as relative risk factors in inhibitor occurrence. Materials and Methods: Inverse shifting-a polymerase chain reaction method was used to detect the presence of intron 22 and intron 1 inversions in 156 Romanian patients with HA. Results: Intron inversion 22 was found in 41.7% of the patients, while intron 1 inversion was detected in 3.2% of the patients. Overall, large intron inversions represented the molecular defect in 44.9% of the studied patients. Our findings are in accord with previously published reports from Eastern Europe countries and with other international studies. The risk of inhibitor development was higher in patients with inversion 1 compared to the patients with HA without any inversion detected. Conclusions: The current study demonstrates the major causative role of large intron inversions in severe HA in Romanian patients. Moreover, our study confirms the contribution of intron 1 inversion in inhibitor development.

Severe Acute Pancreatitis Treated with Negative Pressure Wound Therapy System: Influence of Laboratory Markers.

(1) Background: An open abdomen is a serious medical condition that requires prompt and effective treatment to prevent complications and improve patient outcomes. Negative pressure therapy (NPT) has emerged as a viable therapeutic option for temporary closure of the abdomen, offering several benefits over traditional methods. (2) Methods: We included 15 patients with pancreatitis who were hospitalized in the I-II Surgery Clinic of the Emergency County Hospital "St. Spiridon" from Iasi, Romania, between 2011-2018 and received NPT. (3) Results: Preoperatively, the mean IAP level was 28.62 mmHg, decreasing significantly postoperatively to 21.31 mmHg. The mean level of the highest IAP value recorded in pancreatitis patients treated with VAC did not differ significantly by lethality (30.31 vs. 28.50; p = 0.810). In vacuum-treated pancreatitis patients with a IAP level > 12, the probability of survival dropped below 50% during the first 7 days of stay in the ICU, so that after 20 days the probability of survival was approximately 20%. IAP enters the determinism of surgery with a sensitivity of 92.3% and a specificity of 99%, the cut-off value of IAP being 15 mmHg. (4) Conclusions: The timing of surgical decompression in abdominal compartment syndrome is very important. Consequently, it is vital to identify a parameter, easy to measure, within the reach of any clinician, so that the indication for surgical intervention can be made judiciously and without delay.

Clostridium difficile Infections in an Emergency Surgical Unit from North-East Romania.

Background and Objectives: Colitis with Clostridium difficile is an important health problem that occurs with an intensity that varies between mild and severe. Surgical interventions are required only in fulminant forms. There is little evidence regarding the best surgical intervention in these cases. Materials and Methods: Patients with C. difficile infection were identified from the two surgery clinics from the 'Saint Spiridon' Emergency Hospital Iași, Romania. Data regarding the presentation, indication for surgery, antibiotic therapy, type of toxins, and post-operative outcomes were collected over a 3-year period. Results: From a total of 12,432 patients admitted for emergency or elective surgery, 140 (1.12%) were diagnosed with C. difficile infection. The mortality rate was 14% (20 cases). Non-survivors had higher rates of lower-limb amputations, bowel resections, hepatectomy, and splenectomy. Additional surgery was necessary in 2.8% of cases because of the complications of C. difficile colitis. In three cases, terminal colostomy was performed and as well as one case with subtotal colectomy with ileostomy. All patients who required the second surgery died within the 30-day mortality period. Conclusions: In our prospective study, the incidence was increased both in cases of patients with interventions on the colon and in those requiring limb amputations. Surgical interventions are rarely required in patients with C. difficile colitis.

Molecular and Cellular Mechanisms Involved in Aortic Wall Aneurysm Development.

Aortic aneurysms represent a very common pathology that can affect any segment of the aorta. These types of aneurysms can be localized on the thoracic segment or on the abdominal portion, with the latter being more frequent. Though there are similarities between thoracic and abdominal aortic aneurysms, these pathologies are distinct entities. In this article, we undertook a review regarding the different mechanisms that can lead to the development of aortic aneurysm, and we tried to identify the different manners of treatment. For a long time, aortic wall aneurysms may evolve in an asymptomatic manner, but this progressive dilatation of the aneurysm can lead to a potentially fatal complication consisting in aortic rupture. Because there are limited therapies that may delay or prevent the development of acute aortic syndromes, surgical management remains the most common manner of treatment. Even though, surgical management has improved much in the last years, thus becoming less invasive and sophisticated, the morbi-mortality linked to these therapies remains increased. The identification of the cellular and molecular networks triggering the formation of aneurysm would permit the discovery of modern therapeutic targets. Molecular and cellular mechanisms are gaining a bigger importance in the complex pathogenesis of aortic aneurysms. Future studies must be developed to compare the findings seen in human tissue and animal models of aortic aneurysm, so that clinically relevant conclusions about the aortic aneurysm formation and the pharmacological possibility of pathogenic pathways blockage can be drawn.

Cardiovascular Risk Factors in Patients with Congenital Hemophilia: A Focus on Hypertension.

Aging hemophiliacs face cardiovascular disease. Lots of evidence has been gathered that hemophiliacs have a more unfavorable cardiovascular profile than the general population does, especially due to the increased prevalence of hypertension (HTN). Among the existing scattered evidence, our study provides the most comprehensive and systematized analysis of the determinants of HTN in hemophiliacs. We discussed the contribution to the HTN substrate of hemophilia-specific factors, such as type, severity and the presence of inhibitors. The complex mechanism of kidney dysfunction in relation to hematuria and viral infections was meticulously addressed. Furthermore, we highlighted the new pathogenic concepts of endothelial dysfunction and the association between HTN and hemophilic arthropathy. The clustering of cardiovascular risk factors is common in hemophiliacs, and it enhances the negative vascular effect of HTN and aggravates HTN. It usually leads to an increased risk for coronary and cerebrovascular events. Our work provides reliable evidence to guide and improve the management of HTN in hemophiliacs.

Hemoperitoneum as a Life-Threatening Complication of an Acute Cholecystitis in a Patient with Hemophilia A with Inhibitors: A Case Report.

We present the case of a 52-year-old male with severe hemophilia A with inhibitors, who was diagnosticated with acute lithiasic cholecystitis that required surgical intervention due to lack of favorable response to conservatory treatment. During surgery, hemostatic support was performed with activated recombinant factor VII (rFVIIa, NovoSeven®). The surgery was performed first laparoscopically with adhesiolysis, followed by subcostal laparotomy and cholecystectomy because of the findings of a pericholecystic plastron with abscess and massive inflammatory anatomical modifications. The patient presented postoperative complications, requiring a second surgical intervention, due to the installation of a hemoperitoneum. Hemostatic treatment with rFVIIa was given for a further 3 weeks postoperatively, and the patient was discharged in safe condition. A surgical intervention increases the risk of bleeding in hemophilic patients, which may have vital complications in the absence of adequate hemostatic support and the support of a multidisciplinary team with experience in hemophilic surgery.

Myocardial Ischemia Related to Common Cancer Therapy-Prevention Insights.

Modern antineoplastic therapy improves survival and quality of life in cancer patients, but its indisputable benefits are accompanied by multiple and major side effects, such as cardiovascular ones. Endothelial dysfunction, arterial spasm, intravascular thrombosis, and accelerated atherosclerosis affect the coronary arteries, leading to acute and chronic coronary syndromes that negatively interfere with the oncologic treatment. The cardiac toxicity of antineoplastic agents may be mitigated by using adequate prophylactic measures. In the absence of dedicated guidelines, our work provides the most comprehensive, systematized, structured, and up-to-date analyses of the available literature focusing on measures aiming to protect the coronary arteries from the toxicity of cancer therapy. Our work facilitates the implementation of these measures in daily practice. The ultimate goal is to offer clinicians the necessary data for a personalized therapeutic approach for cancer patients receiving evidence-based oncology treatments with potential cardiovascular toxicity.

Hereditary Thrombophilia in the Era of COVID-19.

Thrombophilia, also called hypercoagulability or prothrombotic condition, usually reflects a certain imbalance that occurs either in the coagulation cascade or in the anticoagulation/fibrinolytic system. A similar imbalance may be induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thrombotic complications are associated with multiorgan failure and increased mortality. In this context, activation of coagulation and thrombocytopenia appeared as prognostic markers in COVID-19. Our work provides a structured and updated analysis of inherited thrombophilia and its involvement in COVID-19, emphasizing the importance of diagnosing and initiating thromboprophylaxis. Since the state of hypercoagulation is directly correlated with COVID-19, we consider that studies on the genetic profiles of proteins involved in thrombophilia in patients who have had COVID-19 and thrombotic events are of great importance, both in treating and in preventing deaths due to COVID-19.

Current Therapeutic Approach to Atrial Fibrillation in Patients with Congenital Hemophilia.

Cardiovascular disease in hemophiliacs has an increasing prevalence due to the aging of this population. Hemophiliacs are perceived as having a high bleeding risk due to the coagulation factor VIII/IX deficiency, but it is currently acknowledged that they also have an important ischemic risk. The treatment of atrial fibrillation (AF) is particularly challenging since it usually requires anticoagulant treatment. The CHA2DS2-VASc score is used to estimate the risk of stroke and peripheral embolism, and along with the severity of hemophilia, guide the therapeutic strategy. Our work provides the most complete, structured, and updated analysis of the current therapeutic approach of AF in hemophiliacs, emphasizing that there is a growing interest in therapeutic strategies that allow for short-term anticoagulant therapy. Catheter ablation and left atrial appendage occlusion have proven to be efficient and safe procedures in hemophiliacs, if appropriate replacement therapy can be provided.

Osteonecrosis of the Jaws in Patients with Hereditary Thrombophilia/Hypofibrinolysis-From Pathophysiology to Therapeutic Implications.

Osteonecrosis of the jaws (ONJ) usually has a clear etiology. Local infection or trauma, radiotherapy and drugs that disrupt the vascular supply or bone turnover in the jaws are its major contributors. The thrombotic occlusion of the bone's venous outflow that occurs in individuals with hereditary thrombophilia and/or hypofibrinolysis has a less known impact on jaw health and healing capability. Our research provides the most comprehensive, up-to-date and systematized information on the prevalence and significance of hereditary thrombophilia and/or hypofibrinolysis states in ONJ. We found that hereditary prothrombotic abnormalities are common in patients with ONJ refractory to conventional medical and dental treatments. Thrombophilia traits usually coexist with hypofibrinolysis traits. We also found that frequently acquired prothrombotic abnormalities coexist with hereditary ones and enhance their negative effect on the bone. Therefore, we recommend a personalized therapeutic approach that addresses, in particular, the modifiable risk factors of ONJ. Patients will have clear benefits, as they will be relieved of persistent pain and repeated dental procedures.

SARS-CoV-2 Infection: What Is Currently Known about Homocysteine Involvement?

Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly throughout the world causing health, social and economic instability. The severity and prognosis of patients with SARS-CoV-2 infection are associated with the presence of comorbidities such as cardiovascular disease, hypertension, chronic lung disease, cerebrovascular disease, diabetes, chronic kidney disease, and malignancy. Thrombosis is one of the most serious complications that can occur in patients with COVID-19. Homocysteine is a non-proteinogenic α-amino acid considered a potential marker of thrombotic diseases. Our review aims to provide an updated analysis of the data on the involvement of homocysteine in COVID-19 to highlight the correlation of this amino acid with disease severity and the possible mechanisms by which it intervenes.

Thromboembolic Disease in Haemophilic Patients Undergoing Major Orthopaedic Surgery: Is Thromboprophylaxis Mandatory?

Haemophilia is a rare genetic disorder, that results from various degrees of deficiency of coagulation factor VIII (haemophilia A), or factor IX (haemophilia B), with an X-linked transmission. The patients affected are in the majority of cases males (who inherit the affected X-chromosome from the maternal side), with rare cases of females with haemophilia (FVIII or FIX < 40 IU/dL), situations in which both X-chromosomes are affected, or one is affected, and the other one is inactive (known as carrier). The hypocoagulable state due to the deficiency of clotting factors, manifests as an excessive, recurrent tendency to bleeding, which positively correlates with plasmatic levels. Severe haemophilia results in hemarthrosis, although recent data have shown that moderate or even mild disease can lead to joint bleeding. Recurrent episodes of haemorrhages, usually affecting large joints such as knees, elbows, or ankles, lead to joint remodelling and subsequent haemophilic arthropathy, which may require arthroplasty as a last therapeutic option. Orthopaedic patients have the highest risk among all for deep vein thrombosis (DVT) and venous thromboembolism (VTE) with morbid and potentially fatal consequences. While for the rest of the population thromboprophylaxis in orthopaedic surgery is efficient, relatively safe, and widely used, for patients with haemophilia who are considered to have a low thromboembolic risk, there is great controversy. The great heterogeneity of this particular population, and the lack of clinical trials, with only case reports or observational studies, makes thromboprophylaxis in major orthopaedic surgery a tool to be used by every clinician based on experience and case particularities. This review aims to briefly summarise the latest clinical data and to offer an insight into the current recommendations that readers would find useful in daily practice.

Prediction of bleeding events using the VTE-BLEED risk score in patients with venous thromboembolism receiving anticoagulant therapy (Review).

Venous thromboembolism (VTE) is a major healthcare problem due to its high incidence, significant mortality rate from pulmonary embolism, high recurrence rate and morbidity from long-term complications. After a first episode of VTE all patients must receive anticoagulant treatment for 3 months. Further anticoagulation is recommended in patients without transient risk factors for VTE or patients with active cancer, if they are not at a high risk for bleeding. The VTE-BLEED risk score was created with the purpose of enabling a better stratification of the bleeding risk during stable anticoagulation after a first VTE. Currently, it is the most validated risk score in VTE settings (selected and non-selected cohorts). It has a good prediction power for major bleeding events in patients receiving any of the currently available classes of oral anticoagulants, and it can identify patients at risk of intracranial and fatal bleeding events. The aim of our review was to highlight the strengths of the VTE-BLEED risk score, to acknowledge its weak points and to properly position its use in current medical practice.

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.

Immune thrombocytopenia, severe hematological consequence in a patient with COVID-19: A case report.

Since the first appearance of coronavirus disease 2019 (COVID-19), multiple studies have focused on this novel coronavirus. Within a few months, the clinical and paraclinical manifestations and the mechanisms by which these changes are induced were elaborated. Clinically, the virus mainly causes the common cold, but can also result in severe or fatal pneumonia/acute respiratory syndrome. Regarding the biological changes, similar to any other virus, it can lead to a reduced lymphocyte count. The second most common change is represented by a reduced thrombocyte count. Furthermore, most patients have blood clotting abnormalities, inflammatory syndrome, raised D-dimer and lactate dehydrogenase levels. Detection of immune thrombocytopenia in asymptomatic patients who tested positive for COVID-19 justifies the need to perform differential diagnosis and testing for COVID-19. Typically, patients with severe forms of COVID-19 develop mild thrombocytopenia, while severe thrombocytopenia is rarely reported. The aim of this case report was to present the situation in which one asymptomatic patient who tested positive for COVID-19 developed severe immune thrombocytopenia.

Orthopedic surgery in hemophilic patients with musculoskeletal disorders: A systematic review.

Hemophilia is a hereditary coagulopathy caused by factor VIII (hemophilia type A) or by coagulation factor IX (hemophilia type B) dysfunction, characterized by an increased bleeding predisposition, which is either spontaneous or secondary to minimal trauma. Currently, hemophilia may also be considered an 'orthopedic' condition, due to the fact that it affects the musculoskeletal system of most hemophilic patients. In recent years, constant prophylaxis using coagulation factors has led to a significant improvement in the hemophilic patient's quality of life, by reducing both life-threatening hemorrhagic phenomena, as well as the occurrence of chronic complications. Nevertheless, progressive joint bleeding remains unavoidable in this category of patients, and the onset of chronic arthropathy with secondary motor deficiency remains the main complication with an invalidating character. In such cases, orthopedic management is imperative; osteoarticular complications being managed most often with the help of conservative or surgical techniques. The purpose of this review is to provide an overview of modern orthopedic practices which are useful in the management of hemophilic patients suffering from osteoarticular disorders.