Portal Hypertension and Myeloproliferative Neoplasms: A Relationship Revealed Patients with PMF may develop severe portal hypertension, ascites, they share certain features due to their pathophysiologic bases. November 15, ET | Source: Sequana Medical only commercial- stage product to date), the alfapump® DSR and/or any future products The forecast growth in cirrhosis and refractory ascites as a result of NASH . should only be made on the basis of information contained in the prospectus in. If you have ascites and you suddenly get a fever or new The basis of treatment includes: dates when you have taps (paracentesis).
However, there have been few investigations identifying predictors of RA development in cirrhotic patients and to our knowledge no Tunisian study has been conducted on that subject. Methods Patient characteristics This retrospective study included consecutive cirrhotic patients who were admitted to our department for the first time for controlling ascitic decompensation between January and April MELD Na score was calculated using the following formula: For patients who developed RA during the follow-up period, we specified also the type of RA and treatment modalities for RA.
Diagnosis of ascites and RA The diagnosis of ascites was made based on physical examination and ultrasonography. Accordingly, there were two types of RA: Patients with grade 3 or tense ascites were treated with initially with therapeutic paracentesis and additional albumin replacement.
After therapeutic paracentesis, patients receive the minimum dose of diuretics necessary to prevent the re-accumulation of ascites. Statistical analysis The data was summarized by descriptive statistics means and frequencies and analysed with SPSS version Data are shown as percentage, mean and standard deviation SD. Student test and Chi squared test or Fisher were used to compare quantitative and qualitative variable for univariate analysis. P value less than 0. Results Baseline characteristics Of patients hospitalized to control ascitic decompensation, 65 No patient had chylous ascites.
Two patients had hydrothorax. In case of hepatic vein occlusion, findings of various grades of hepatic failure and ascites are almost always observed. The detection of thrombosis in intra-abdominal large veins of 2 patients diagnosed with portal hypertension but the failure to detect such a mechanism in the other 2 patients suggested that not only the large vein thromboses but also the small undetected thromboses could represent a risk for portal hypertension.
Similarly, noncirrhotic portal hypertension NCPH may be a reason, which is described as follows: It has been described in association with blood coagulation disorders and myeloproliferative neoplasms, with exposure to toxic substances or to drugs and with immunological diseases. Most of the cases present with thrombosis or sclerosis of the intrahepatic portal venous system with variable involvement of the prehepatic portal system [ 21 ].
The review of similar trials in the literature revealed that the basic hematologic diagnosis was established after development of fatal portal hypertension complications such as esophageal variceal hemorrhage in some patients [ 2223 ]. Therefore, one in each 4 patients should be expected to develop thrombotic complications after 2 years. The biochemical values were within the normal limits. Serum ceruloplasmin, serum iron, total iron binding capacity were investigated, and metabolic liver diseases such as hemochromatosis or Wilson disease were ruled out.
We excluded patients with a known hepatic disease because we wanted to know the rate of portal hypertension arising solely from myeloproliferative neoplasms.
Doppler ultrasonographic examination detected portal vein thrombosis in one patient and splenic vein thrombosis in another.
This condition, which the patients were not previously aware of, shows that this group of patients may also have silent thrombosis.
Of the 29 patients participating in our study, 16 were positive for JAK2 mutation.
Management of refractory ascites in cirrhosis: Are we out of date?
Two of the four patients with PH were positive for JAK2; and those were the ones with portal and splenic vein thromboses. Splenomegaly and hepatomegaly occur as expected findings in the course of portal hypertension and myeloproliferative neoplasms both as a result of extramedullary hematopoiesis and excessive breakdown.
Because we have already excluded chronic hepatic diseases of any form, hepatomegaly found in the study group is of hematologic origin, with only increasing dimensions and without nodule formations or biochemical abnormalities of cirrhosis. Patients with esophageal varices and those with a congestion index above the normal value of 0. Anamnesis of those patients did not include alcohol addiction, and their laboratory values were normal; therefore, we thought that the cause of PH was MPN in those patients.RELATIONSHIP BASES
We detected 4 patients with PH in our trial. The ratio of those patients to the total number of patients was However, due to the fact that these are rare diseases, inadequate number of patients is a drawback. No relation was found between the types of MPN and PH generation; similarly, no relation was shown with the disease duration and the generation of PH.
The main reason for that is the small number of patient groups. For example, the small number of PMF cases falsely leads to the result that this group had a high rate of portal hypertension.
The absence of a balanced distribution between the patient groups investigated makes an intergroup comparison inappropriate. The patient can experience a complication such as portal hypertension as from the start of the disease, and we should be careful in this respect. One should also keep in mind that thrombotic episodes could occur not only in intra-abdominal veins or arteries that could lead to portal hypertension but also in intracranial veins or arteries in a patient with headache or dizziness and in cardiac arteries in a patient with exertional or resting angina.
Conclusion In conclusion, the incidence of thrombotic episodes in Ph-chromosome-negative MPN patients was found similar to those reported in the literature. The presence of portal hypertension in However, due to unbalanced distribution of patient groups, it would not be appropriate to make any comparison between the groups with respect to portal hypertension incidence. Occurrence of a complication such as portal hypertension appears to be usual in the course of these diseases.
Precautions should be taken against thrombotic episodes before they lead to fatal complications. These complications can be experienced anytime.
So, search for a complication should immediately be initiated once the hematological diagnosis is established. Recently, it has been suggested that NO plays a prominent role.
However, several in vitro studies have demonstrated variable changes in compensatory factors when NO is inhibited or promoted, suggesting that its control is not the only important factor.
In response to the release of vasodilators in the splanchnic system, there is a release of vasoconstrictors. Due to the high levels of NO and CO, these vasoconstrictors have a blunted effect on splanchnic circulation and mostly affect the kidneys and the brain[ 39 ].
Splanchnic vasodilation leads to an abnormally increased distribution of blood into the mesenteric circulation. Over time, there is an exaggerated disequilibrium of blood supply between the central and non-central volumes, characterized by a decrease in the central heart, lungs, and brain blood volume and an increase in the non-central splanchnic blood volume.
Management of refractory ascites in cirrhosis: Are we out of date?
These shifts in blood volume are not clinically significant in the early stages of cirrhosis but become more relevant as the disease worsens. With the development of non-central vasodilation and pooling of blood in the mesenteric circulation, there is an initial compensatory increase in CO and a decrease in MAP and SVR. With the activation of baroreceptors, this is accentuated over time, causing further increases in CO and heart rate.
As the sympathetic nervous system, renin-angiotensin-aldosterone system, arginine-vasopressin, and endothelin responses heighten, renal vascular resistance increases. This increase causes vasoconstriction and decreased renal blood flow leading to sodium and water retention.
Over time, as more blood volume sequestration occurs in the splanchnic system, the compensatory mechanisms are unable to sustain blood flow, leading to tissue hypoxemia and end-organ damage. This cascade of pathophysiological responses to portal hypertension is termed hyperdynamic circulatory syndrome and is generally characterized by an increase in CO and heart rate and a decrease in SVR and MAP[ 36 ]. Generally after paracentesis, there is an immediate and significant decrease in intraabdominal pressure.
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- Refractory Ascites in Cirrhosis: Prevalence and Predictive Factors
This leads to initial hemodynamic improvement, increasing CO as venous return and negative thoracic pressures improve.
In general if less than 5 L of fluid is removed, there appears to be no ill effects of paracentesis. This causes a series of complex neurohormonal responses that are not well understood. There are discrepant findings in the literature regarding the pathophysiolical cause of the decrease in SVR. However, it may be related to improved CO alone or changes in both the renin-angiotensin system and the sympathetic nervous system. The exact neurohormonal changes, sequence of events, progression over time, and impact on the cardiovascular and renal systems are also not clear.
Overall, the initial improvement in hemodynamics after paracentesis is followed by a relative hypovolemia. This constellation of events, termed PICD, is most commonly associated with hyponatremia and renal insufficiency[ 5 ]. Initial failure of diuretic therapy should be treated medically fluid restriction, sodium restriction, and diuretic therapyfollowed by serial LVP while awaiting liver transplant.
The most recent AASLD practice guideline update, published in by Runyon, made several recommendations for treating cirrhotic patients diagnosed with refractory ascites. The guidelines stated that: These are the current management guidelines to which most transplant centers in North America adhere. Research efforts in cirrhosis have since intensified, but the pathophysiology of the complications of cirrhosis remain incompletely understood.
As such, research has tended to compartmentalized each of the various complications. While many complex diseases are evaluated using this method of scientific research, cirrhosis may require a more holistic approach since cirrhosis occurs affects essentially every organ system in the body during its progression.
Our current understanding of ascites and its management seems to be based, in large measure, on evidence and observations derived from research performed decades ago. Furthermore, the evidence is based on a focused perspective rather than a global one and does not take into account the dynamic and evolving systemic nature of cirrhosis. We could not find a single study that examined the impact of variations in paracentesis volume on neuro-hormonal changes in equivalent patients.
Refractory Ascites in Cirrhosis: Prevalence and Predictive Factors
Patient volume status, fluid responses, medication doses, and many other physiological effects are based upon patient sex, height, weight, muscle mass, renal function, or body mass index BMI.
Along the same lines, one would assume that the effect, responses, and management of fluid shifts in cirrhotic patients undergoing paracentesis should be affected similarly. Although never studied, it is more likely that physiological responses after paracentesis in cirrhotic patients have a graded effect based upon variables such as milliliter of fluid removed per kilogram body weight, BMI, muscle mass, and sex. Studies conducted based upon this definition showed that PICD is associated with decreased 6-mo survival.
Another approach may be to linearly determine the effect of changes in PRA on mortality and hence determine what correctly defines LVP. Because PICD has been associated with hyponatremia and renal insufficiency, there may be some utility in proving end organ damage. However, it is not clear how this can be achieved in cirrhotic patients who already have significant multi-organ compromise.
One crude method would be to assess mixed venous oxygenation or lactate levels at different time points after paracentesis. Given this difference in disease severity, the effects of paracentesis established in previous studies may not be applicable in patients with more advanced cirrhosis. There is no published data comparing the effects of similar volumes of paracentesis with more progressive cirrhosis or higher MELD scores.
As cirrhosis progresses, most patients develop these complications and begin to exhibit hyperdynamic physiology. These patients often have refractory ascites and require more frequent paracentesis. It is likely that patients with advanced cirrhosis lack the pathophysiological reserve to compensate for paracentesis-induced fluid shifts.