Hematological abnormalities are common in cirrhosis and are associated with various pathophysiological mechanisms. Studies have documented a prevalence of thrombocytopenia, leukopenia, and anemia in patients with compensated cirrhosis of 77.9%, 23.5%, and 21.1%, respectively. These abnormalities carry significant clinical implications, including considerations for invasive procedures, infection risk, bleeding risk, and prognosis. Previously, cirrhosis was believed to predispose patients to bleeding due to alterations observed in classical coagulation tests such as prothrombin time, partial thromboplastin time, international normalized ratio, and thrombocytopenia. However, this understanding has evolved, and cirrhosis patients are now also acknowledged as being at a high risk for thrombotic events. Hemostasis in cirrhosis patients presents a complex phenotype, with procoagulant and anticoagulant abnormalities offsetting each other. This multifactorial phenomenon is inadequately reflected by routine laboratory tests. Thrombotic complications are more prevalent in decompensated cirrhosis and may correlate with disease severity. Bleeding is primarily associated with portal hypertension, endothelial dysfunction, mechanical vessel injury, disseminated intravascular coagulation, endotoxemia, and renal injury. This review comprehensively outlines hematologic index abnormalities, mechanisms of hemostasis, coagulation, and fibrinolysis abnormalities, limitations of laboratory testing, and clinical manifestations of bleeding and thrombosis in patients with liver cirrhosis.

Platelets (PLTs) are involved in tumor growth, metabolism and vascular activation. PLT-based models have been reported to have significant value on the recurrence of malignant hepatic tumors. The present study aimed to investigate the effect of PLT count and 18 PLT-based models on the prognosis of patients with malignant hepatic tumors. The clinical data from 189 patients with malignant hepatic tumors were retrospectively analyzed and used to calculate the scores of the 18 PLT-based models. Receiver operating characteristic curve was used to determine the suitable cut-off values of mortality and recurrence in patients with malignant hepatic tumors. The overall survival and cumulative recurrence rates of patients were calculated using Kaplan-Meier survival curves and the difference was analyzed using log-rank test. Multivariate analysis was performed to determine the independent risk factors of recurrence-free survival and overall survival. In the present study, 11 models were considered as predictors of mortality (P<0.05) and six models were considered as predictors of recurrence (P<0.05). The results from multivariate analysis demonstrated that vascular cancer embolus, uric acid >231 µmol/l, hemoglobin >144 g/l and the Lok index model >0.695 were considered as independent risk factors of mortality (P<0.05). Furthermore, vascular cancer embolus, PLT to lymphocyte ratio (PLR) >175 and fibrosis-4 (FIB-4) >4.82 were independent factors of recurrence (P<0.05). In addition, the results from this study indicated that the Lok-index could be considered as a predictor of the overall survival rate. In conclusion, the FIB-4 and PLR model may be valuable for predicting the recurrence-free rate of patients with malignant hepatic tumors.

Abnormalities in hematological indices are frequently encountered in cirrhosis. Multiple causes contribute to the occurrence of hematological abnormalities. Recent studies suggest that the presence of hematological cytopenias is associated with a poor prognosis in cirrhosis. The present article reviews the pathogenesis, incidence, prevalence, clinical significance and treatment of abnormal hematological indices in cirrhosis.

Patients with cirrhosis develop abnormal hematologic indices (HI) from multiple factors, including hypersplenism. We aimed to analyze the sequence of events and determine whether abnormal HI has prognostic significance.

We analyzed a database of 213 subjects with compensated cirrhosis without esophageal varices. Subjects were followed for approximately 9 years until the development of varices or variceal bleeding or completion of the study; 84 subjects developed varices. Abnormal HI was defined as anemia at baseline (hemoglobin, < or =13.5 g/dL for men and 11.5 g/dL for women), leukopenia (white blood cell counts, < or =4000/mm3), or thrombocytopenia (platelet counts, < or =150,000/mm3). The primary end points were death or transplant surgery.

Most subjects had thrombocytopenia at baseline. Kaplan-Meier analysis showed that leukopenia occurred by 30 months (95% confidence interval, 18.5-53.6), and anemia occurred by 39.6 months (95% confidence interval, 24.1-49.9). Baseline thrombocytopenia (P = .0191) and leukopenia (P = .0383) were predictors of death or transplant, after adjusting for baseline hepatic venous pressure gradient (HVPG), and Child-Pugh scores. After a median of 5 years, a significant difference in death or transplant, mortality, and clinical decompensation was observed in patients who had leukopenia combined with thrombocytopenia at baseline compared with patients with normal HI (P < .0001). HVPG correlated with hemoglobin and white blood cell count (hemoglobin, r = -0.35, P < .0001; white blood cell count, r = -0.31, P < .0001).

Thrombocytopenia is the most common and first abnormal HI to occur in patients with cirrhosis, followed by leukopenia and anemia. A combination of leukopenia and thrombocytopenia at baseline predicted increased morbidity and mortality.

Thrombocytopenia is a common complication of chronic liver diseases, but its pathogenesis is not clear. Although generally attributed to hypersplenism, other factors should also be considered. We investigated the relationship between the peripheral platelet count and the degree of fibrosis in patients with chronic viral hepatitis. In an effort to avoid the effects of hypersplenism, we excluded patients with splenomegaly and/or bi- or pan-cytopenia. Seven hundred eighty-four patients (265 chronic viral hepatitis C and 519 chronic viral hepatitis B) were included in the study. Univariate analysis showed that the peripheral platelet count had a negative correlation with fibrosis score, necroinflammatory activity, and age in both groups. In multivariate analysis, the peripheral platelet count had a similar correlation with the fibrosis score and age, but not with necroinflammatory activity, in both groups. The peripheral platelet count decreased more significantly in females with chronic hepatitis C but not in the chronic hepatitis B group. In conclusion, a decrease in peripheral platelet count may be a sign of an increase in the degree of fibrosis during the course of chronic viral hepatitis B and C and factors other than hypersplenism may play a role in this decrease in the peripheral platelet count.

End stage liver disease results in a complex and variably severe failure of hemostasis that predisposes to abnormal bleeding. The diverse spectrum of hemostatic defects includes impaired synthesis of clotting factors, excessive fibrinolysis, disseminated intravascular coagulation, thrombocytopenia, and platelet dysfunction. Hemostasis screening tests are used to assess disease severity and monitor the response to therapy. Correction of hemostatic defects is required in patients who are actively bleeding or require invasive procedures. Fresh frozen plasma, cryoprecipitate, and platelet transfusion remain the mainstays of therapy until larger trials confirm the safety and efficacy of recombinant factor VIIa in this population.

Portal hypertension is frequently associated with secondary hypersplenism, two common clinical manifestations of which are leukopenia and thrombocytopenia. Surgical portosystemic shunts alleviate portal hypertension but their effect on hypersplenism remains unpredictable. Transjugular intrahepatic portosystemic shunt (TIPS) is a minimally invasive procedure for portal decompression. From current reports it is not clear if TIPS improves hypersplenism in patients with portal hypertension. We present a retrospective review of our experience with TIPS to determine the effect on hypersplenism.

Sixty-five patients who had a TIPS procedure between December 1991 and June 1994 were evaluated retrospectively. The records were specifically reviewed for platelet and white blood cell counts performed before the procedure, within a week after the procedure, and then again within the subsequent 3 weeks. Hypersplenism was defined as thrombocytopenia (platelet count of <100,000/mm3), leukopenia (white blood cell count of <5,000/mm3), or both.

Thrombocytopenia alone was present in 33 patients and leukopenia alone in 4 patients before TIPS was performed. Both leukopenia and thrombocytopenia were present in 12 individuals. At least one of these indices of hypersplenism was present in 49 patients. Leukocyte count improved in 11 of 16 patients (69%) whereas platelet count improved in 34 of 45 patients (75%) within a week of the procedure. In the subsequent 3 weeks, leukopenia was relieved in 5 of 10 patients (50%) and thrombocytopenia in 21 of 28 patients (75%), respectively. Of the 12 patients who had both leukopenia and thrombocytopenia before TIPS, the indices improved in 4 patients (33%) within a week of the procedure. Thrombocytopenia was more consistently corrected as opposed to leukopenia, albeit in the short term.

The TIPS procedure is a promising, minimally invasive method of portal decompression that is effective in the treatment of complications of portal hypertension including secondary hypersplenism.

The thrombocytopenia in chronic liver disease (CLD) has been attributed mainly to hypersplenism, although other factors such as reduced mean life span with increased platelet turnover have also been demonstrated. Immunological abnormalities have been described in the pathogenesis and progression of CLD. In this sense, many studies have reported elevated levels of platelet associated IgG (PAIgG) in patients with CLD, and it has been suggested that PAIgG could represent true antiplatelet antibody. In this study we used a glycoprotein (GP)-specific immunoassay (MACE) to determine whether PAIgG or circulating antiplatelet antibodies, reacted against the GPIIb/IIIa or GPIb/IX complexes, in patients with CLD. Thirty-six patients with CLD of diverse etiology were studied (20 female, mean age 53 years, range 38-75 years). 23 out of 36 patients (64%) had anti-GP antibodies in MACE. Particularly, 12 had anti-GPIb, 4 anti-GPIIb/IIIa, and 7 had both types of autoantibodies. The existence of these anti-GP antibodies was not related with the blood platelet count or etiology of CLD. These data show that in patients with CLD of diverse origin, there is a high prevalence of autoantibodies reacting specifically with platelet membrane GP, which constitutes the first evidence of the specific nature of platelet-bound IgG in CLD. These findings suggest that in patients with CLD, an immune mechanism may participate in inducing or aggravating the thrombocytopenia.

Thrombocytopenia associated with chronic liver disease presents a difficult management issue. Most reports conclude that portocaval and distal splenorenal shunts do not improve platelet counts in this setting. The response of thrombocytopenia after transjugular intrahepatic portosystemic shunt placement has not been studied. All platelet counts of 21 patients undergoing intrahepatic shunt placement were determined retrospectively to accumulate values at one month prior to procedure, weekly for the first month after the procedure, and monthly thereafter to six months. Comparison of pre- and postshunt platelet means showed a significant increase in counts in patients with a postshunt portal pressure gradient < 12 mm Hg, with the increment evident by one week after the procedure. This response was not seen when preshunt thrombocytopenia was used as the lone variable. This study suggests that the transjugular intrahepatic portosystemic shunt may improve the thrombocytopenia associated with liver cirrhosis when these pressure gradients are attained.

The purpose of this study was to clarify the effect of orthotopic liver transplantation on hypersplenism. In a 1-year period from July 1, 1986 to June 30, 1987, 196 adult patients underwent 233 orthotopic liver transplantations. Of the 58 patients with hypersplenism who were analyzed in this study, hypersplenism was more commonly associated with postnecrotic cirrhosis than other kinds of liver disease (55.3% (47/85) vs. 14.5% (11/76); p less than 0.001). Postoperative platelet counts were statistically higher than preoperative values (p less than 0.05). The latest platelet counts were more than 100,000/mm3 in 53 patients (91.4%). Of the eight patients whose preoperative and postoperative spleen volumes could be compared, all showed the reduction in the spleen size (p less than 0.02). We conclude that orthotopic liver transplantation, which is a radical surgical procedure for portal hypertension, reverses hypersplenism.

Hypersplenism frequently accompanies cirrhosis with portal hypertension. In this series of 76 patients, 36 percent had thrombocytopenia, 41 percent had leukopenia, and 25 percent had both thrombocytopenia and leukopenia. However, hypersplenism was severe enough to necessitate splenectomy in only two patients (3 percent). Nonalcoholic cirrhotic patients exhibit hypersplenism more frequently and to a greater magnitude than do alcoholic cirrhotic patients. Fourteen and 44 percent of alcoholic and nonalcoholic cirrhotics, respectively, had both thrombocytopenia and leukopenia. Distal splenorenal shunts and nonselective shunts are equally effective in relieving preoperative hypersplenism. Approximately two thirds of the patients were relieved of thrombocytopenia or leukopenia after either of these procedures. Splenectomy invariably corrects hypersplenism associated with cirrhosis and should be included as part of the operative procedure in patients requiring surgery for control of variceal hemorrhage.

Leukopenia, thrombocytopenia, and hemolytic anemia occur commonly in advanced cirrhosis. Some investigators have reported that portacaval anastomosis (PCA) abolished hypersplenism while others have not found PCA to be uniformly beneficial. We compared the frequency of hypersplenism before and after admission to a controlled investigation of the effects of PCA in 52 unoperated control subjects and 38 patients with patent PCA. The two groups were followed for an average period of 5 1/2 years. On admission to the study leukopenia was present in about 2% of patients, thrombocytopenia in 6%, and hemolytic anemia in 4%. Splenomegaly was present in 48% and hypersplenism in 11%. After randomization splenomegaly disappeared more frequently in the shunted group. In addition, fewer patients with PCA developed splenomegaly for the first time after inclusion into the study than did unoperated control subjects. Leukopenia, thrombocytopenia, and hemolytic anemia, when present at inclusion into the study, disappeared with equal frequency in the shunted and unshunted patients, and appeared with equal frequency in both groups after randomization in previously unaffected patients. In no instance was hypersplenism clinically significant nor was splenectomy considered or carried out in any of these 90 patients. In additional uncontrolled studies we observed that therapeutic PCA did not affect hypersplenism differently from prophylactic PCA. We conclude that PCA has neither clinically nor statistically significant effects on hypersplenism.

In order to investigate the role of an immune mechanism in the pathogenesis of thrombocytopenia in hepatic patients, we measured platelet associated IgG (PAIgG) in 84 patients with various hepatic diseases. Increased PAIgG levels were found in 84% of patients with chronic active hepatitis (mean 21.32 +/- 8.45 fg/platelet) and in 75% of those with cirrhosis with hepatitis (mean 17.3 +/- 11.2 fg/platelet). In these patients there was no significant correlation between PAIgG and platelet count. Increased PAIgG amounts were also observed in some patients with inactive cirrhosis (18%). Normal PAIgG values were found in all patients with acute viral hepatitis and chronic persistent hepatitis. An immunologic mechanism may play a role in the pathogenesis of thrombocytopenia in hepatic patients. Furthermore, measurement of PAIgG may have a great usefulness in the differential diagnosis of chronic hepatic diseases.