Hemostatic Disorders: Physiology, Diagnostics, and Management.

A defect in any step of hemostasis can lead to potentially catastrophic results. The purpose of this article is to review hemostatic physiology, laboratory studies, and management of platelet and coagulation disorders to familiarize the advanced practice RN (APRN) with this often overlooked but critical system. Learning the underlying mechanisms allows for better understanding of the various disease states that can occur in the hematology and oncology settings.

Recomendaciones de consenso SEDAR-SEMICYUC sobre el manejo de las alteraciones de la hemostasia en los pacientes graves con infección por COVID-19 / SEDAR-SEMICYUC consensus recommendations on the management of haemostasis disorders in severely ill patients with COVID-19 infection

La infección por el coronavirus SARS-CoV-2, causante de la enfermedad denominada COVID-19, provoca alteraciones fundamentalmente en el sistema respiratorio. En los pacientes graves, con frecuencia la enfermedad evoluciona a un síndrome de distrés respiratorio agudo que puede predisponer a los pacientes a un estado de hipercoagulabilidad, con trombosis tanto a nivel venoso como arterial. Esta predisposición presenta una fisiopatología multifactorial, relacionada tanto con la hipoxia como con el grave proceso inflamatorio ligado a esta patología, además de los factores trombóticos adicionales presentes en muchos de los pacientes.Ante la necesidad de optimizar el manejo de la hipercoagulabilidad, los grupos de trabajo de las sociedades científicas de Anestesiología-Reanimación y Terapéutica del Dolor (SEDAR) y de Medicina Intensiva, Crítica y de Unidades Coronarias (SEMICYUC) han desarrollado un consenso para establecer unas pautas de actuación frente a las alteraciones de la hemostasia observadas en los pacientes graves COVID-19. Estas recomendaciones incluyen la profilaxis de la enfermedad tromboembólica venosa en pacientes graves y en el periparto, el manejo de los pacientes en tratamiento crónico con fármacos antiagregantes o anticoagulantes, de las complicaciones hemorrágicas en la evolución de la enfermedad y de la interpretación de las alteraciones generales de la hemostasia

The infection by the coronavirus SARS-CoV-2, which causes the disease called COVID-19, mainly causes alterations in the respiratory system. In severely ill patients, the disease often evolves into an acute respiratory distress syndrome that can predispose patients to a state of hypercoagulability, with thrombosis at both venous and arterial levels. This predisposition presents a multifactorial physiopathology, related to hypoxia as well as to the severe inflammatory process linked to this pathology, including the additional thrombotic factors present in many of the patients. In view of the need to optimise the management of hypercoagulability, the working groups of the Scientific Societies of Anaesthesiology-Resuscitation and Pain Therapy (SEDAR) and of Intensive, Critical Care Medicine and Coronary Units (SEMICYUC) have developed a consensus to establish guidelines for actions to be taken against alterations in haemostasis observed in severely ill patients with COVID-19. These recommendations include prophylaxis of venous thromboembolic disease in these patients, and in the peripartum, management of patients on long-term antiplatelet or anticoagulant treatment, bleeding complications in the course of the disease, and the interpretation of general alterations in haemostasis

Thrombocytopenia: the most frequent haemostatic disorder in the ICU.

Thrombocytopenia is the most common haemostatic disorder in patients admitted to Intensive Care Units (ICUs). The mechanisms contributing to a decrease in the platelet count in critically ill patients are multifactorial, among which sepsis and trauma are the most frequent. A differential diagnosis of profound thrombocytopenia is crucial for effective treatment. A low platelet count is a strong independent predictor of morbidity and mortality because it is associated with life-threatening bleeding or thrombosis. This article aims to outline the definition and pathophysiology of thrombocytopenia and present a three-step algorithm of the clinical management of this haemostatic disorder.

The impact of donor and recipient KIR genes and KIR ligands on the occurrence of acute graft-versus-host disease and graft survival after HLA-identical sibling hematopoietic stem cell transplantation

Background/aim: After allogeneic hematopoietic stem cell transplantation (allo-HSCT), donor natural killer (NK) cells trigger alloreactions against potential recipient cells by their killer immunoglobulin-like receptors (KIRs). This study investigated whether KIR/HLA genotypes and KIR haplotypes of donors and recipients exhibit a critical function in the prevalence of acute graft-versus-host disease (aGVHD) and persistence of the graft after HLA-identical sibling allo-HSCT for patients with hematological malignancies. Materials and methods: We studied KIR and HLA genotypes in 115 related donors and recipients (56 patients with AML and 59 patients with ALL) who had received allo-HSCT from HLA-matched sibling donors. We evaluated 17 KIR genes and some alleles, including their ligands, using the PCR-SSP assay. Results: KIR gene frequency results between donors and recipients showed that donors had more activating KIR than their recipients. Chi-square comparison of KIR genotype frequencies in donors versus recipients revealed a significant difference (P < 0.001). We found a survival association between the donor lacking and the recipient having group B KIR haplotypes, although this was not statistically significant. Conclusion: This study suggests that we could exploit NK cell alloreactivity as a part of the optimization of donor selection and potential immunotherapeutic regimens to help facilitate good engraftment and reduce the risk of aGVHD incidence after allo-HSCT.

Perioperative standards for the treatment of coagulation disorders and usage of blood products in patients undergoing liver transplantation used in the Clinic for Transplant Surgery in Wroclaw.

BACKGROUND: Coagulation system disorders in liver transplantation (ltx) patients are considered a serious issue. Liver cirrhosis leads to decreased synthesis of clotting factors and decreased elimination of waste products, including coagulation proteins. Platelet sequestration and dysfunction in an enlarged spleen additionally worsen these conditions. The resulting state, the most common pathology of the coagulation system, involves the reduction of clotting potential and hyperfibrinolysis. OBJECTIVES: Tackling the problem of impaired hemostasis is a dynamic process. Throughout the whole procedure, consisting of the preanhepatic, the anhepatic and the neohepatic phases, consecutive pathomechanisms disrupt the very balance that anesthesia aims to preserve. MATERIAL AND METHODS: Rotational thromboelastometry (ROTEM), having been introduced in the Clinic of Anesthesiology and Intensive Therapy, Wroclaw Medical University, Poland, enables the efficient and early diagnosis of clotting disorders. An additional major problem which occurs during ltx, namely blood loss, could be solved using a cell separator. RESULTS: In this study, we present the standards introduced to the Transplantology Department of the Vascular Surgery Clinic, Wroclaw Medical University, Poland, that describe blood treatment during ltx procedures. CONCLUSIONS: We conclude that thromboelastometric examination and the use of a cell separator have significantly increased the safety of ltx procedures at our clinic. The introduction of thromboelastometry (TEM) and the implementation of the cell separator recovery method have enabled us to perform the dangerous and complicated surgical procedure of ltx in a much more stable and much safer manner than in the past.

Utilization of frozen plasma, cryoprecipitate, and recombinant factor VIIa for children with hemostatic impairments: An audit of transfusion appropriateness.

BACKGROUND: Blood transfusions and fractionated products are not without risk and may lead to acute and long-term adverse events. The objective of this study was to evaluate the appropriateness of usage of frozen plasma (FP), cryoprecipitate (CRYO), and recombinant factor VIIa (rVIIa) in a pediatric setting. METHODS: All orders for FP, CRYO, and rVIIa were prospectively audited over 6 weeks. Data collected included demographics, laboratory values, indication, and adverse reactions. The appropriateness of each order was independently evaluated using adjudication criteria rated by two hematologists. RESULTS: Two hundred sixty-five products were ordered; 67% of the orders were issued to operating rooms or intensive care units. The most common indication for all products was cardiac surgery. FP was ordered as fluid replacement (15/215; 7%) to correct abnormal coagulation tests (23/215; 11%) and for patients with minor or no bleeding (111/242; 46%). FP was more likely to alter the international normalized ratio (INR) if the INR was over 2.0 (P < 0.0001). The rate of inappropriate products was judged as FP 19%, CRYO 21%, and rVIIa 91%. CONCLUSION: FP, CRYO, and rVIIa are most commonly used in the operating room and intensive care units. FP was often used for fluid resuscitation and for patients with mild to no bleeding. FP was only effective in lowering the INR when the INR was over 2.0. Use of rVIIa was rarely ordered for an appropriate indication. Results of this study inform its readers where trials of pediatric transfusion should be performed to clarify how these products should be used in clinical practice.

Management of Hemostatic Disorders in Patients With Advanced Liver Disease Admitted to an Intensive Care Unit.

Patients with liver diseases frequently acquire complex changes in their hemostatic system. Traditionally, bleeding complications in patients with liver disease were ascribed to these hemostatic changes, and liver diseases were considered as an acquired bleeding disorder. Nowadays, it is increasingly acknowledged that patients with liver diseases are in "hemostatic rebalance" due to a commensurate decline in pro- and anticoagulant drivers. Indeed, both thrombosis and bleeding may complicate liver disease. Such complications may be particularly worrisome in critically ill patients with liver disease. This review will outline knowns and unknowns in prediction, prevention, and treatment of bleeding and thrombosis in patients with liver disease admitted to an intensive care unit.

Recognition and Management of Hemostatic Disorders in Critically Ill Patients Needing to Undergo an Invasive Procedure.

Abnormal laboratory coagulation test results are frequently documented in critically ill patients, and these patients often also need to undergo invasive procedures. Clinicians have an understandable desire to minimize any perceived heightened risk of bleeding complications in those patients who require invasive procedures. In this setting, prophylactic administration of platelets or plasma is commonplace. This review explores the nature of these sequential statements and the degree to which these statements are supported by evidence. We discuss the complexity of managing the low risk of procedure-related bleeding in a setting where coagulation tests fail to reliably predict this risk. The role of prophylactic transfusion of platelets and plasma and correction of medication-induced coagulopathy is also reviewed. New strategies are required to improve the evidence base, including novel methodological approaches or the use of a clinical scoring system.

Hemostatic Disorders Associated with Hepatobiliary Disease.

The liver plays a crucial role in all aspects of coagulation because most factors that regulate procoagulation, anticoagulation, and fibrinolysis are produced, cleared, and/or activated in the liver. Establishing the coagulation status of an individual patient with hepatobiliary disease can therefore be challenging. Although, classically, patients with hepatobiliary disease were thought of as potentially hypocoagulable, hypercoagulability also occurs. The article summarizes the breadth of coagulation abnormalities that have been reported in dogs and cats with hepatobiliary disease and provides strategies to respond to bleeding and thrombotic risk.

Neonatal Hemostatic Disorders: Issues and Challenges.

Neonates form a unique cohort with distinct features associated with the hemostatic system compared with older children and adults. The development of the human hemostatic system begins around 10 weeks in utero and continues to evolve during childhood. This dynamic period termed developmental hemostasis should be taken into consideration when diagnosing a neonate with disorders of bleeding or thrombosis.

Tratamiento de la coagulopatía en la hemorragia del paciente politraumatizado / Management of bleeding and coagulopathy following major trauma

El sangrado en el paciente traumatizado representa la primera causa de muerte potencialmente prevenible. La coagulopatía aguda traumática es una entidad específica con una fisiopatología diferente a las de otras causas de sangrado masivo. Un correcto manejo del sangrado del paciente politraumatizado precisa una identificación precoz de dicha coagulopatía, con el fin de iniciar en el menor tiempo posible la llamada resucitación hemostática. Ha habido importantes novedades en el manejo de esta entidad que se están incorporando a las guías actuales. Por ejemplo, la administración de ácido tranexámico o la utilización de ratios de transfusión cercanas al 1:1:1 (plasma fresco congelado: concentrado de plaquetas:concentrado de hematíes). Estas actuaciones y otras que analizaremos a continuación han logrado mejorar el pronóstico de estos pacientes con el aval de la evidencia científica (AU)

Bleeding is the most common preventable cause of death in trauma patients. Acute traumatic coagulopathy is a specific condition with a different pathophysiology from other causes of the massive bleeding. An early identification of the coagulopathy is fundamental to implementing rapid treatment. There have been many changes in the management of massive hemorrhage, for example, the administration of the tranexamic acid and the use of balanced transfusion ratio. This review presents these practical points, some of them with scientific evidence, in order to achieve a beneficial effect for patient outcomes (AU)

Effects of transcutaneous aortic valve implantation on aortic valve disease-related hemostatic disorders involving von Willebrand factor.

BACKGROUND: Aortic valve stenosis (AVS) can be complicated by bleeding associated with acquired type 2A von Willebrand syndrome. The association of AVS and gastrointestinal bleeding from angiodysplasia is defined as Heyde syndrome. We sought to evaluate the effect of transcutaneous aortic valve implantation (TAVI) on hemostasis disorders and to assess its effectiveness to treat Heyde syndrome. METHODS: We prospectively enrolled 49 consecutive patients with severe AVS addressed for TAVI at our institution. Biological hemostasis parameters involving von Willebrand factor (vWF) were assessed at baseline and 1 week after the procedure. RESULTS: At baseline, a significant link between vWF abnormalities and the severity of AVS was evidenced: mean aortic transvalvular gradient was negatively correlated with the levels of vWF antigen (vWF:Ag) (r = -0.29; P < 0.05), vWF ristocetin cofactor activity (r = -0.402; P = 0.006), and vWF collagen-binding activity (vWF:CB; r = -0.441; P = 0.005). One week after the procedure, a significant increase of vWF:Ag, vWF ristocetin cofactor activity, and vWF:CB was evidenced in the whole cohort (respectively, 3.32 vs. 2.29 IU/mL, P < 0.001; 2.98 vs. 1.86 IU/mL, P < 0.001; and 3.16 vs. 2.16 IU/mL, P < 0.001). Patients with pre-TAVI vWF abnormalities consistent with a type 2A vWF syndrome (ratio vWF:CB/vWF:Ag < 0.7) preferentially improved their vWF function with respect to patients with a normal ratio (relative increase of vWF:CB of 63.8% vs. 3.5%). CONCLUSIONS: Hemostasis parameters involving vWF are improved after TAVI, especially in patients with pre-existing abnormalities consistent with acquired type 2A von Willebrand syndrome.

Massive transfusion in children and neonates.

Resuscitation of children and neonates with severe or refractory bleeding due to surgery or trauma often requires massive transfusion (MT). Findings from recent studies have led to a better understanding of the complex pathophysiology in massive haemorrhage and the effects of MT on haemostasis. Current management of the massively bleeding adult patient has evolved over the past few decades, shifting to early transfusion of products in a balanced ratio as part of MT protocols (MTPs). Paediatric data on successful management of MT are limited and the optimal transfusion approach is currently unknown, leading to practice variability among institutions, depending on resource availability and patients' needs. Here, we review new important concepts in the biology of massive bleeding and MT, outline important management principles and current practices, and highlight available relevant adult and paediatric data.

[The thromboelastometric criteria of hemostasis disorders correction during liver transplantation].

UNLABELLED: The purpose of the study. Optimum correction of hemostasis remains one of the unsolved problems in anesthesia maintenance during liver transplantation. Modern methods of coagulation monitoring (thromboelastography, thromboelastometry) allows to differ the increased bleeding reason. The clear criteria for the appointment of the blood components according to these methods have not developed so far. The aim of this study was to determine the criteria of hemostasis disorders correction during liver transplantation. MATERIALS AND METHODS: The study included all patients undergoing a liver transplantation in our clinic from January 2009 to December 2010. In certain intervals of time an intake of blood samples for the hemostasis study including koagulogramm, determination of the clotting factors and natural anticoagulants activity was performed. RESULTS: There is no significant correlation between the results of the standard coagulation tests and thromboelastometry Based on the international hemostasis correction recommendations, with the help of ROC-analysis the search for thromboelastometry data, which would have pointed to the need for this therapy was made. Concerning coagulation factors deficiency (INR>2, APTT> 1.5) CT-EXTEM>80 has a sensitivity of 17% and a specificity of 97%, and CT-INTEM>240 has sensitivity of 51% and specificity of 96%. Use of A10-FIBTEM for fibrinogen deficiency diagnosis, A10-FIBTEM <9 has sensitivity of 95% and specificity of 63%. A simultaneous increase of CT-EXTEM >80 and CT-INTEM more than 300 has a sensitivity of 96% and a specificity 81% in relation to diagnose thrombocytopenia (platelet count less than 50,000 per mcl). CONCLUSION: Correction of coagulation factors deficiency indicated when CT-EXTEM>80 and CT-INTEM> 240, hypofibrinogenemia when A10-FIBTEM <9, thrombocytopenia when of CT-EXTEM >80 and CT-INTEM increase simultaneously more than 300.

Patients with liver cirrhosis suffer from primary haemostatic defects? Fact or fiction?

Patients with cirrhosis can have abnormalities in laboratory tests reflecting changes in primary haemostasis, including bleeding time, platelet function tests, markers of platelet activation, and platelet count. Such changes have been considered particularly relevant in the bleeding complications that occur in cirrhosis. However, several studies have shown that routine diagnostic tests, such as platelet count, bleeding time, PFA-100, thromboelastography are not clinically useful to stratify bleeding risk in patients with cirrhosis. Moreover, treatments used to increase platelet count or to modulate platelet function could potentially do harm. Consequently the optimal management of bleeding complications is still a matter of discussion. Moreover, in the last two decades there has been an increased recognition that not only bleeding but also thrombosis complicates the clinical course of cirrhosis. Thus, we performed a literature search looking at publications studying both qualitative and quantitative aspects of platelet function to verify which primary haemostasis defects occur in cirrhosis. In addition, we evaluated the contribution of qualitative and quantitative aspects of platelet function to the clinical outcome in cirrhosis and their therapeutic management according to the data available in the literature. From the detailed analysis of the literature, it appears clear that primary haemostasis may not be defective in cirrhosis, and a low platelet count should not necessarily be considered as an automatic index of an increased risk of bleeding. Conversely, caution should be observed in patients with severe thrombocytopenia where its correction is advised if bleeding occurs and before invasive diagnostic and therapeutic procedures.