Management Of Coagulopathy In Patients Research Articles

Individualized Management of Coagulopathy in Patients with End-Stage Liver Disease.

Over the last decades, individualized approaches and a better understanding of coagulopathy complexity in end-stage liver disease (ESLD) patients has evolved. The risk of both thrombosis and bleeding during minimally invasive interventions or surgery is associated with a worse outcome in this patient population. Despite deranged quantitative and qualitative coagulation laboratory parameters, prophylactic coagulation management is unnecessary for patients who do not bleed. Transfusion of red blood cells (RBCs) and blood products carries independent risks for morbidity and mortality, including modulation of the immune system with increased risk for nosocomial infections. Optimal coagulation management in these complex patients should be based on the analysis of standard coagulation tests (SCTs) and viscoelastic tests (VETs). VETs represent an individualized approach to patients and can provide information about coagulation dynamics in a concise period of time. This narrative review will deliver the pathophysiology of deranged hemostasis in ESLD, explore the difficulties of evaluating the coagulopathies in liver disease patients, and examine the use of VET assays and management of coagulopathy using coagulation factors. Methods: A selective literature search with PubMed as the central database was performed with the following.

The effect of a viscoelastic-guided bleeding algorithm implementation on blood products use in adult liver transplant patients. A propensity score-matched before-after study

BackgroundPerioperative blood products transfusion is correlated with increased morbidity and mortality in liver transplantation (LTx). The objectives of our study are to assess the effect of a standardized viscoelastic test (VET)-guided bleeding management algorithm implementation on intraoperative bleeding, allogenic blood products and factor concentrates requirements and on early postoperative complications in LTx. MethodsRetrospective before-after study comparing two matched cohorts of patients undergoing LTx before (control cohort) and after (intervention cohort) the implementation of a VET-based bleeding algorithm in a single center academic hospital. ResultsAfter propensity score matching, we included 94 patients in each cohort. Patients in intervention cohort received significantly less blood products, fresh frozen plasma (FFP), and cryoprecipitate (p < 0.001 for each), while the amount of fibrinogen concentrate used was significantly higher (p < 0.001). Postoperatively, intervention cohort patients had significantly lower postoperative hemoglobin and fibrinogen levels and longer prothrombin time compared to control cohort. There were no significant differences in red blood cells transfusions, intraoperative bleeding, early postoperative complications, and short term survival. ConclusionsThe implementation of a VET-guided bleeding algorithm decreases allogenic blood products requirements, mainly FFP use and allows a more restrictive management of coagulopathy in patients with chronic liver disease undergoing LTx.

Use of prothrombin complex concentrate for management of coagulopathy after cardiac surgery: a propensity score matched comparison to plasma

BackgroundAn important cause of coagulopathy in cardiac surgery is impaired thrombin generation. While plasma is often used to correct this element of the coagulopathy, studies in vitro suggest that prothrombin complex concentrates (PCCs) might be more effective. Comparative data, however, are scant. MethodsWe compared the outcomes of those who received only plasma with those who received PCCs (with or without plasma) for management of coagulopathy in patients who underwent cardiac surgery with cardiopulmonary bypass at a single institution from 2012 to 2016. Propensity score matching was used to obtain between-group balance. Primary outcome was avoidance of perioperative red cell transfusions. Other outcomes were incidence of massive transfusion (more than nine red cell units), refractory bleeding (requiring factor VIIa), and adverse events. ResultsOf 6362 patients, 1151 (18.2%) received plasma without any PCCs, and 204 (3.2%) received PCCs, either with (n=125) or without plasma (n=79). Overall, patient risk-profile was higher in the PCCs group. In a well-balanced propensity score match that included 117 patients per group, the odds ratio (OR) for red cell avoidance was 2.4-fold [95% confidence interval (CI) 1.2–4.8] higher in the PCCs group. Massive transfusion (OR 0.58; 95% CI 0.33–1.0) and refractory bleeding (OR 0.49; 95% CI 0.24–1.03) incidences were almost significantly lower in the PCCs group. The adverse event profiles were similar. ConclusionsOur exploratory study suggests that the use of PCCs as part of a multifaceted coagulation management strategy may have blood-sparing effects. Their incorporation into clinical practice, however, must await determination of their risk-benefit profile via multicentre randomised trials.

Management of Coagulopathy in Patients with Decompensated Liver Cirrhosis

Patients with decompensated liver cirrhosis have significantly impaired synthetic function. Many proteins involved in the coagulation process are synthesized in the liver. Routinely performed tests of the coagulation are abnormal in patients with decompensated liver cirrhosis. This has led to the widespread belief that decompensated liver cirrhosis is prototype of acquired hemorrhagic coagulopathy. If prothrombin time is prolonged more than 3 seconds over control, invasive procedures like liver biopsy, splenoportogram, percutaneous cholangiography, or surgery were associated with increased risk of bleeding, and coagulopathy should be corrected with infusion of fresh frozen plasma. These practices were without any scientific evidence and were associated with significant hazards of fresh frozen plasma transfusion. Now, it is realized that coagulation is a complex process involving the interaction of procoagulation and anticoagulation factors and the fibrinolytic system. As there is reduction in both anti and procoagulant factors, global tests of coagulation are normal in patients with acute and chronic liver disease indicating that coagulopathy in liver disease is more of a myth than a reality. In the last few years, surgical techniques have substantially improved, and complex procedures like liver transplantation can be done without the use of blood or blood products. Patients with liver cirrhosis may also be at increased risk of thrombosis. In this paper, we will discuss coagulopathy, increased risk of thrombosis, and their management in decompensated liver cirrhosis.

Improving Survival in Patients with Decompensated Cirrhosis

About 60% of patients with decompensated disease have oesophageal varices. One third of these patients will experience variceal bleed. Each bleeding episode compromises the decompensated state and is associated with a 20% to 30% mortality. Bleeding from ectopic varices is rare but is generally massive and life threatening. The first two articles, “Clinicopathological features and treatment of ectopic varices with portal hypertension” and “Application of endoscopy in improving survival of cirrhotic patients with acute variceal hemorrhage” discuss the management of variceal bleeding in cirrhotic patients. “Improved survival with the patients with variceal bleed” is a review article on how new treatment modalities have improved the outlook of patients with bleeding oesophageal varices. The hepatorenal syndrome (HRS) signifies advanced liver failure and is a bad prognostic factor in patients with decompensated cirrhosis. Management of this condition is discussed in “Management of renal failure and ascites in patients with cirrhosis”. One of the features of decompensated liver disease is the occurrence of recurrent or resistant ascites. Transjugular intrahepatic portosystemic shunt (TIPS) is an effective therapy for refractory ascites and HRS at the expense of hepatic encephalopathy and may offer an effective bridge to liver transplantation, by improving short and medium term survivals, as discussed in “Role of TIPS in improving survival of patients with decompensated liver disease”. Bacterial infection is responsible for up to a quarter of the deaths of patients with decompensated liver disease. “Prevention and management of bacterial infections in cirrhosis” discuss the high index of suspicion that is needed to prevent bacterial infections in patients with decompensated cirrhosis. These patients are immunologically compromised, and prophylactic antibiotics can prevent fatal septicemia and HRS in those with gastrointestinal bleeding. Current thoughts on how to deal with the neuropsychiatric complication of cirrhosis are discussed in “Management of hepatic encephalopathy”. Cardiomyopathy, hepatopulmonary syndrome, portopulmonary hypertension and right-sided hydrothorax complications that are often overlooked in patients with decompensated liver disease are discussed in “Management of cardiopulmonary complications of cirrhosis”. Decompensated liver cirrhosis has been traditionally considered as a prototype of hemorrhagic coagulopathy, and routinely performed coagulation profile is abnormal in the majority of these patients. In “Management of coagulopathy in patients with decompensated liver disease”, the authors discussed recent thoughts on coagulation in end-stage liver disease. The related article entitled “Determination of ADAMTS13 and its clinical significance for ADAMTS13 supplementation therapy to improve the survival of patients with decompensated liver cirrhosis” reviews the role of the deficiency of the metalloproteinase ADAMTS13 in end-stage liver cirrhosis in inducing platelet clumping or thrombi and how the resulting sinusoidal microcirculatory disturbances causes further liver damage and is closely related to further deterioration of liver function, hepatic encephalopathy, hepatorenal syndrome, and intractable ascites in advanced liver cirrhosis. Fresh frozen plasma (FFP) is a source of ADAMTS13. Liver cirrhosis is the common end stage of persistent liver injury. In the Asia Pacific region, these injuries commonly result from chronic hepatitis B and C infections as well as alcohol. The following two articles, “Treatment of hepatitis B in decompensated liver cirrhosis and treatment of decompensated alcoholic liver disease” address the management of hepatitis B and alcoholic liver disease in end stage liver disease. Pharmacotherapy in patients with decompensated liver disease is not without complications and side effects and might compromise the decompensated state. The article entitled “Prescribing medications in patients with decompensated liver cirrhosis” addresses the above conundrum. A common complication of liver cirrhosis is liver cancer, and treatment of this condition is challenging in patients with liver decompensation to say the least. The paper entitled “Screening for hepatocellular carcinoma” discusses early detection of liver cancer in these patients so that appropriate management can be arranged. Finally, liver transplantation for end-stage liver failure is discussed in “Indications and contraindications for liver transplantation”. Deepak Amarapurkar Rajiv Jalan Richard Guan Paul Kwo

Recombinant factor VIIa in patients with coagulopathy secondary to anticoagulant therapy, cirrhosis, or severe traumatic injury: review of safety profile

In recent years, the hemostatic agent recombinant factor VIIa (rFVIIa) has emerged as a potentially new therapeutic agent for management of coagulopathy in patients with cirrhosis or following severe traumatic injury, a complex problem for clinicians in which standard treatment strategies are not always effective. As with other hemostatic agents, a primary safety concern of rFVIIa therapy is the theoretical possibility that systemic administration could confer an increased risk of thrombotic complications. So far, clinical experience indicates rFVIIa to be a safe treatment for currently approved indications within hemophilia. Little information is available, however, for patient populations outside this clinical setting. This article reviews critical safety data obtained from 13 Novo Nordisk-sponsored clinical trials of rFVIIa in patients with coagulopathy secondary to anticoagulant therapy, cirrhosis, or severe traumatic injury. Thrombotic adverse events were reported for 5.3 percent (23/430) of placebo-treated patients and 6.0 percent (45/748) of patients on active treatment. No significant difference was found between placebo-treated and rFVIIa-treated patients with respect to the incidence of thrombotic AEs, either on an individual trial basis or for these trial populations combined (p=0.57). An important determinant for the safety profile reported here is likely to be the specific mechanism of action of rFVIIa, shown in experimental studies to be localized to the site of vascular injury where tissue factor is exposed.

Recombinant activated factor VII (rFVIIa) as a hemostatic agent in liver disease: a break from convention in need of controlled trials.

The management of coagulopathy in patients with acute and chronic liver disease has undergone little change in many years despite advances in our understanding of the pathogenesis of this problem. In general, deficiency of clotting factors as a result of poor hepatic synthetic function accounts for most of the coagulopathy. However, other processes such as disseminated intravascular coagulation (DIC), hyperfibrinolysis, dysfibrinogenemia, hemolysis, and a decrease in number or function of platelets may be present and thus add to the complexity of the problem. Coexisting portal hypertension and the associated risks of volume expansion, renal failure, and endothelial dysfunction add even more difficulty to the management of these patients. The clinician's despair is only exacerbated by uncertainty regarding the significance of laboratory indices of coagulation and the lack of agreement between health care providers regarding how to use these indices. Simple, conventional interventions such as vitamin K or plasma administration often produce only limited amelioration, and the latter carries the potential disadvantage of volume overexpansion as well as the risk of infection and transfusion reactions. Into this complex and uncertain clinical situation has arrived the antihemophilic agent recombinant activated factor VII (rFVIIa). Its development has led to a fundamental re-evaluation of the classic understanding of the normal clotting cascade. Moreover, use of this product in liver disease patients is increasing despite the lack of definitive studies or literature to guide therapy. Herein we review the mechanism of action of this agent, report the clinical applications in patients with liver disease, address the limitations and risks associated with the drug, and discuss the issue of its cost-effectiveness.