Primary Hemostasis in Chronic Liver Disease and Cirrhosis: What Did We Learn over the Past Decade?

Changes in primary hemostasis have been described in patients with chronic liver disease (CLD) and cirrhosis and are still subject to ongoing debate. Thrombocytopenia is common and multifactorial. Numerous studies also reported platelet dysfunction. In spite of these changes, primary hemostasis seems to be balanced. Patients with CLD and cirrhosis can suffer from both hemorrhagic and thrombotic complications. Variceal bleeding is the major hemorrhagic complication and is mainly determined by high portal pressure. Non portal hypertension-related bleeding due to hemostatic failure is uncommon. Thrombocytopenia can complicate management of invasive procedures in CLD patients. Recently, oral thrombopoietin agonists have been approved to raise platelets before invasive procedures. In this review we aim to bundle literature, published over the past decade, discussing primary hemostasis in CLD and cirrhosis including (1) platelet count and the role of thrombopoietin (TPO) agonists, (2) platelet function tests and markers of platelet activation, (3) von Willebrand factor and (4) global hemostasis tests

Challenges of biological monitoring in a hemophilia A patient without inhibitors on emicizumab undergoing major orthopedic surgery: a case report.

A man with severe hemophilia A (HA) without factor VIII (FVIII) inhibitors was admitted for total arthroplasty of his elbow. The patient was being treated with emicizumab, with his last administration given 8 days before surgery. Preoperatively, he received a bolus of 4000 international units (IU) of recombinant (r)FVIII. Throughout the operation, a continuous infusion of 4 IU/kg/h was administered and maintained over 24 hours. On the first postoperative day, the FVIII infusion rate was reduced to 225 IU/h for 4 days and stopped on the fifth day. Under this treatment, no bleeding complications occurred. Emicizumab is known to interfere with a wide range of coagulation assays, thereby challenging replacement therapy monitoring before, during, and after surgery. In this case study, we report on the assessment of FVIII levels at different time points using various reagents. We conclude that for both hematologists and non-hematology clinicians, it is crucial to be aware of emicizumab interferences with routine coagulation tests so as to avoid misinterpretation. In addition, laboratory specialists must be familiar with this treatment in order to select appropriate coagulation tests and provide rapid and reliable result interpretations

Anti-GPVI (HY101) activates platelets in a multicolor flow cytometry panel

The platelet transmembrane receptor GPVI can be assessed together with other platelet membrane markers in a whole blood multicolor flow cytometry panel. The advantage of combining multiple antibodies in a single tube is the possibility of distinguishing multiple platelet subgroups. In this short communication, we describe an activation problem encountered with anti-GPVI, clone HY101. Activation of platelets was seen after the addition of anti-GPVI in a flow cytometry panel, highlighted by the expression of the activation markers CD62P, PAC-1, CD63, and CD107a. This was also confirmed by platelet aggregation studies

A rare presentation of homozygous factor X deficiency in a pregnant patient: A case report and review of the literature.

Dear Editor, Congenital factor X (FX) deficiency is an extremely rare, autosomal recessive inherited condition with an estimated incidence of 1:1 000 000 with an eightfold to 10‐fold increase in frequency in populations with consanguineous marriages.1 It is a heterogeneous bleeding disorder that, dependent on the residual FX level, can be asymptomatic or present with grade I (minor provoked), grade II (minor spontaneous; eg, epistaxis) to grade III (severe spontaneous) bleeding (eg, haematomas, haemarthrosis, central nervous, umbilical cord and gastrointestinal bleeding). [...

A rare presentation of homozygous factor X deficiency in a pregnant patient: A case report and review of the literature

status: publishe

Analytical performances and biological variation of PIVKA-II (des-y-carboxy-prothrombin) in European healthy adults.

BACKGROUND: PIVKA-II (DCP) is increasingly used for the diagnosis and the surveillance of hepatocellular carcinoma (HCC) in at-risk populations. However, to date, few data are available concerning the intra- and inter-individual variability of this marker, which makes the interpretation of serial measurements difficult in the context of monitoring. METHODS: 19 European healthy volunteers (HVs) were taken each week during five consecutive weeks. Samples were analyzed in duplicate on the Lumipulse® analyzer (Fujirebio, Gent, Belgium). Analytical variation (CVA), within-subject biological variation (CVI) and between-subject biological variation (CVG) were calculated using nested ANOVA following normality assessment, outlier exclusion, and homogeneity of variance analysis. RESULTS: No significant difference was observed for the mean values (p = 0.23) between men (mean: 30.66 mAU/mL) and women (mean: 33.90 mAU/mL) subgroups. CVA was 2.82% while sex-independent CVI and CVG were 13.35% and 16.05%, respectively. Taking these values, the calculated reference change value (RCV) and index of individuality were 37.70% and 0.85, respectively. CONCLUSION: We reported for the first-time biological variation data for PIVKA-II in a cohort of European HVs. We believe that our results can be used to set analytical specification goals as well as to improve the interpretation of serial measurements of PIVKA-II for monitoring purposes

Vitamin K May Be A-OK, in Kids and Cholestatic Patients.

Comment on Routine Use of Vitamin K in the Treatment of Cirrhosis-Related Coagulopathy: Is it A-O-K? Maybe Not, We Say

Streptococcus Pneumoniae Bacteremia with Acute Kidney Injury and Transient ADAMTS13 Deficiency

A 43-year-old woman with a medical history of splenectomy for immune thrombocytopenic purpura was diagnosed with Streptococcus pneumoniae bacteremia. Her initial complaints were fever and more importantly painful extremities that appeared cyanotic. During her hospitalisation, she never developed cardiocirculatory failure but presented acute kidney injury (AKI) with oliguria. Laboratory investigations confirmed AKI with serum creatinine 2.55 mg/dL which peaked at 6.49 mg/dL. There was also evidence for disseminated intravascular coagulation (DIC) with decreased platelet count, low fibrinogen levels, and high D-dimer levels. There were no signs of haemolytic anaemia. The initial ADAMTS13 activity was low (17%) but slowly recovered. Renal function progressively improved with supportive therapy, as opposed to the progressing skin necrosis. The association of DIC and low ADAMTS13 activity may have contributed to the severity of microthrombotic complications, even in the absence of thrombotic microangiopathy as thrombotic thrombocytopenic purpura (TTP) or pneumococcal-associated haemolytic uremic syndrome (pa-HUS)

Characterization of Candida spp. interference on the Sysmex XN-1000 body fluid mode

Sir, The body fluid (BF) module on the XN-1000 (Sysmex Corporation, Kobe, Japan) represents a convenient platform for accurate and fast quantification of white blood cells (WBC) by flow cytometry in multiple types of BF. Despite their well-known advantages in comparison with light microscopy, analyzers with BF mode can be affected by different types of interference leading to spurious results and potential clinical misinterpretations [...

The use of prothrombin complex concentrate in chronic liver disease: A review of the literature

Patients with chronic liver disease (CLD) and cirrhosis present a rebalanced hemostatic system in the three phases of haemostasis. This balance is however unstable and can easily tip towards bleeding or thrombosis. Management of both spontaneous bleeding and bleeding during invasive procedures remains a challenge in this patient population. Transfusion of blood products can result in circulatory overload and thereby worsen portal hypertension. As an alternative to fresh frozen plasma (FFP), prothrombin complex concentrates (PCC) may have merit in patients with liver disease because of their low volume. The impact of PCC in in-vitro spiking experiments of cirrhotic plasma is promising, but also warrants cautious use in light of thromboembolic risk. The majority of existing studies carried-out in CLD patients are retrospective or do not have an adequate control arm. A prospective study (the PROTON trial) was set up in 2013 to investigate the utility of PCC in patients undergoing liver transplantation. However, the study has never recruited the planned number of patients. Robust data on PCC safety in CLD is also required. The limited existing evidence does not seem to indicate an excessive thromboembolic risk. Currently, the utilisation of PCC in CLD cannot be routinely recommended but can provide an option for carefully selected cases in which other measures were not sufficient to control bleeding and after delicately weighing risks and benefits