The effect of total plasma exchange on fulminant hepatic failure.

Total plasma exchange (TPE) corrects coagulopathy in patients with liver disease and removes hepatotoxins/cytokines. This improvement is transient but can be used as a bridge until an organ is identified for liver transplantation (LTx) or the liver itself regenerates. Our aim was to retrospectively assess the efficacy of TPE in fulminant hepatic failure (FHF) and its impact on liver function tests. Between 1995-2001, 39 patients with FHF who had undergone TPE were reviewed. FHF was defined according to the O'Grady criteria based on the duration of encephalopathy as well as jaundice. TPE was performed using the Cobe Spectra TPE (Gambro) in Liver Intensive Care Unit, continued on a daily basis, until either adequate clinical response was achieved, the patient expired, or transplantation occurred. INR, PTT, Fibrinogen, ALT, AST, GGT, BUN, Ammonia, and Total Bilirubin were analyzed before and after TPE. Student's t-test and chi-square test and ANOVA were used for statistical analysis. Thirty-nine patients with FHF (31 females, 8 males with mean age of 32.3, range: 7-64) underwent TPE. Coagulopathy, hyperbilirubinemia, hyperammonemia were significantly improved (P < 0.05). Twenty-one patients survived (54%), 12 required LTx, and 18 patients (including one after LTx) expired. TPE was found to be significantly effective for correction of coagulopathy and improvement of liver tests. This intervention can be considered for temporary liver support until recovery or liver transplantation.

First year donation patterns predict long-term commitment for first-time donors.

BACKGROUND AND OBJECTIVES: Converting first-time donors to become regular donors continues to be a challenge facing blood centres. We examined whether first-time donors with frequent return in the first 12 months were more likely to become regular donors. SUBJECTS AND METHODS: The donation histories of 179 409 community whole-blood donors, whose first-time donation in 1991 was negative on donor screening tests, were evaluated. Donors were categorized by the number of donations made in the 12 months after (and including) their first donation. The donor return pattern in the subsequent 6 years, and its association with first-year donation frequency and demographics, was evaluated by using logistic regression analysis. A 'regular donor' was defined as one who returned to donate in at least 4 of the 6 years of follow-up. RESULTS: First-year donation frequency was significantly correlated with long-term donor return (P < 0.0001). Among those giving 1, 2, 3, 4 and > or = 5 donations in the first year, 4%, 11%, 21%, 32% and 42%, respectively, became regular donors (P < 0.0001). Similar associations between donation pattern and donor return behaviour were observed after adjusting for demographic variables (P < 0.0001). CONCLUSIONS: Strategies aimed at encouraging current donors to donate more frequently during the first year may help to establish a regular donation behaviour.

The impact of total plasma exchange on early allograft dysfunction.

INTRODUCTION: Early allograft dysfunction (EAD) is a rare but serious complication encountered among patients undergoing liver transplant surgery. Total plasma exchange (TPE) in EAD has been suggested, but its role is still considered investigational. We retrospectively assessed the efficacy of TPE in EAD and its impact on other parameters of liver function. MATERIALS AND METHODS: Between 1995 and 2001, 25 orthotopic liver transplant recipients developed EAD, which was defined as early postoperative prothrombin time (PT) >17 seconds, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >2500 IU/L, and/or the presence of hepatic encephalopathy, and development of renal failure. Daily TPE was performed using the Cobe Spectra TPE (Gambro) for 4 hours until an adequate clinical response, the patient underwent retransplantation, or the patient died. International normalizing ratio (INR), partial thromboplastin time (PTT), fibrinogen, ALT, AST, gamma-glutanyl transpeptidase (GGT), blood urea nitrogen (BUN), ammonia, and total bilirubin were analyzed before and after TPE. Student t and chi-square tests were used for statistical analysis. RESULTS: Twenty-five patients with EAD included 13 females, 12 males of mean age 42.3 years (range, 1-63 years). Coagulopathy and hyperbilirubinemia significantly improved with TPE. Nineteen patients (76%) survived and 2 required retransplantation. Mean number of TPE sessions was 4.3. CONCLUSION: TPE was effective to correct coagulopathy and improve liver function. These results suggest the benefit of potential temporary liver support until recovery or retransplantation, in the absence of sepsis or multi-system organ failure.

Unintentional platelet removal by plasmapheresis.

Therapeutic plasmapheresis may remove platelets as well as plasma. Unintentional platelet loss, if not recognized, may lead to inappropriate patient assessment and treatment. A patient with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is reported in whom persistent thrombocytopenia was interpreted as continuing active disease; thrombocytopenia resolved only after plasma exchange treatments were stopped. This observation prompted a systematic study of platelet loss with plasmapheresis. Data are reported on platelet loss during 432 apheresis procedures in 71 patients with six disease categories using three different instruments. Comparing the first procedure recorded for each patient, there was a significant difference among instrument types (P<0.001); platelet loss was greater with the Fresenius AS 104 (17.5%, N = 21) than with the COBE Spectra (1.6%, N = 26) or the Haemonetics LN9000 (2.6%, N = 24). With all procedures, platelet loss ranged from 0 to 71%. Among disease categories, platelet loss was greater in patients with dysproteinemias who were treated for hyperviscosity symptoms. Absolute platelet loss with the first recorded apheresis procedure, in the 34 patients who had a normal platelet count before the procedure, was also greater with the AS 104 (2.23 x 10(11) platelets) than with the Spectra (0.29 x 10(11) platelets) or the LN9000 (0.37 x 10(11) platelets). In 39 patients in whom data were collected on consecutive days, platelet removal by plasmapheresis correlated with a decreased patient platelet count (r = 0.40, P = 0.011). In these 39 patients, the platelet counts were significantly decreased at 24 hours (P = 0.002).

Prevalence, donation practices, and risk assessment of blood donors with hemochromatosis.

CONTEXT: Despite changes in eligibility policies, practical barriers limit blood donations from individuals with hemochromatosis. Increased knowledge of hemochromatosis donor characteristics may help foster further changes that will promote more donations. OBJECTIVES: To estimate the prevalence of donors diagnosed as having hemochromatosis and to compare rates of unreported deferrable risks for transfusion-transmissible viral infections (TTVIs), positive screening test results for TTVIs, and donation patterns between hemochromatosis patient donors and donors reporting no medical conditions necessitating phlebotomy (non-health-related donors). DESIGN: An anonymous mail survey conducted in 1998 as part of the ongoing Retrovirus Epidemiology Donor Study. SETTING AND PARTICIPANTS: Among a stratified probability sample of 92 581 blood donors from 8 geographically diverse US blood centers, 52 650 (57%) responded. MAIN OUTCOME MEASURES: Prevalence of hemochromatosis among blood donors; prevalence of unreported deferrable risks and positive screening test results for TTVIs among hemochromatosis patient donors vs non-health-related donors. RESULTS: One hundred ninety-seven respondents (0.4%) identified themselves as hemochromatosis patients and 50 079 (95.1%) as non-health-related donors. An estimated 0.8% of all donations were from hemochromatosis patients, 45.8% of whom reported that they had donated blood to treat their illness. The proportion of repeat donors was higher in hemochromatosis patients than in non-health-related donors (83.5% vs 76.5%; P =.03). Among repeat donors, 68.7% of hemochromatosis patients reported donating at least 3 times in the past year compared with 49.1% of non-health-related donors (P<.001). The prevalence of unreported deferrable risks for TTVIs was similar in hemochromatosis patients (2.0%) and non-health-related donors(3.1%) as was the overall prevalence of positive screening test results (1.3% of hemochromatosis patients vs 1.6% of non-health-related donors). CONCLUSIONS: Although significant numbers of hemochromatosis patients reported donating blood for therapeutic reasons, our findings suggest that this population does not present a greater risk to blood safety than other donors.

Leukoreduction of sickle cell trait blood: an unresolved issue.

With the increasing demand for leukoreduction of blood components and the implementation of universal leukoreduction in several countries, the problems associated with leukocyte filtration of sickle cell trait blood have been revisited. Currently, there is no unified standard practice for sickle cell trait donors. Different blood centers adopt different policies. While some defer these donors from red cell component donation, some do not. Some screen all ethnic African donors for hemoglobin S (Hb S), others do not. Furthermore, there are differences in views of whether sickle cell trait red cells should be considered as equivalent to non-sickle cell trait red cells. Some blood centers do not give red cells from a sickle cell trait donor to the newborn or patients undergoing general anesthesia as a preventative measure. In this presentation, we discuss the epidemiology of the sickle gene, the sickling process, problems associated with leukoreduction of sickle cell trait whole blood and red cells, and some unresolved issues concerning donor referral and the usage of sickle cell trait blood.

In vitro bleeding time test can diagnose thrombotic thrombocytopenia purpura and can possibly monitor therapeutic plasma apheresis.

Thrombotic thrombocytopenia purpura (TTP) is perplexing, mainly because of its difficult diagnosis and dramatic clinical presentations, high mortality rates, and the effectiveness of empirical plasma infusions and plasma exchanges. Scientific evidence supports the hypothesis that TTP results from platelet hyperagglutination. To support this, a new in vitro bleeding time (Platelet-Stattrade mark) test was used. Eleven patients had a mean in vitro bleeding time of 7.3 +/- 2.1 seconds prior to plasma exchange and eight patients had a mean of 13.6 +/- 4.7 seconds after the plasma exchange procedure. Normal controls were 14 +/- 2 seconds. The test was used to monitor plasma exchanges in two patients. At the time the platelet count and LDH returned to normal, the Platelet-Stattrade mark remained shortened. The two patients relapsed and required continued plasma exchanges until Platelet-Stattrade mark corrected to normal. These results suggest that plasma exchanges may be effectively monitored by Platelet-Stattrade mark rather than the traditional parameters, i.e., LDH. Therefore, the Platelet-Stattrade mark test may be a useful test to diagnose TTP and monitor therapy in this disease.

Complications of plasma exchange in 71 consecutive patients treated for clinically suspected thrombotic thrombocytopenic purpura-hemolytic-uremic syndrome.

BACKGROUND: With the increased frequency of diagnosis and improved survival of thrombotic thrombocytopenic purpura-hemolytic-uremic syndrome (TTP-HUS), the morbidity of plasma exchange (PE) treatment has become more important. STUDY DESIGN AND METHODS: Data were prospectively collected on 71 consecutive patients referred to the Oklahoma Blood Institute (OBI) for PE treatment for clinically suspected TTP-HUS from mid-1996 to mid-1999. Complications were defined as major or minor, and distinguished between those related to central venous catheter access or to the plasma. RESULTS: Twenty-one patients (30%) had 27 major complications, which caused two deaths. The major complications included 2 episodes of hemorrhage after subclavian line insertion (1 death), 1 pneumothorax requiring a chest tube, 12 systemic infections (1 death), 7 episodes of catheter thrombosis requiring removal of the central venous catheter, 2 episodes of venous thrombosis requiring anticoagulant treatment, 2 episodes of hypoxemia and hypotension, and 1 episode of serum sickness. Minor complications occurred in 22 additional patients (31%). Twenty-eight patients (39%) had no complications. CONCLUSIONS: The morbidity and mortality of catheter placement and PE are important considerations when PE treatment for clinically suspected TTP-HUS is anticipated.

Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: diagnosis and management.

Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is a clinical syndrome defined by the presence of thrombocytopenia and microangiopathic hemolytic anemia without a clinically apparent etiology. Patients may also have multiple other symptoms and signs including neurologic and renal abnormalities and fever. In the era prior to effective therapy with plasma exchange, most patients developed multisystem abnormalities and the syndrome was more easily recognized. Now, since there is urgency to begin treatment, sufficient diagnostic criteria for TTP-HUS are only thrombocytopenia and microangiopathic hemolytic anemia without a clinically apparent cause; patients may have no neurologic symptoms, renal abnormalities, or fever. This has lead to an apparent increased incidence because of both the increased importance of early recognition and the decreased specificity of the diagnostic criteria. Effective treatment has also revealed new aspects of the clinical course of TTP-HUS following the initial response to plasma exchange treatment: prompt exacerbations, which are common when plasma exchange is diminished in frequency or discontinued, and later relapses, which may occur many years after the initial episode. This review describes the evolution of the syndrome of TTP-HUS in the current era of effective treatment, and describes the management and clinical outcomes among patients treated by the Oklahoma Blood Institute.

A method for estimating hepatitis B virus incidence rates in volunteer blood donors. National Heart, Lung, and Blood Institute Retrovirus Epidemiology Donor Study.

BACKGROUND: Calculations of the incidence of hepatitis B virus (HBV) infections in the blood donor setting that are based solely on data for seroconversion to hepatitis B surface antigen (HBsAg) will underestimate the incidence due to the transient nature of antigenemia. Estimates based on antibody to hepatitis B core antigen will overestimate the incidence due to false-positive results caused by the nonspecificity of the test. STUDY DESIGN AND METHODS: Serologic test results were obtained from multiple-time volunteer donors at five United States blood centers from January 1991 through December 1993. The observed HBsAg seroconversion rate was multiplied by an adjustment factor, derived from the weighted average probability of a positive HBsAg test for HBV-infected donors who become chronic carriers, for donors with a primary antibody response without detectable antigenemia, and for donors who develop transient antigenemia. RESULTS: Among 586,507 multiple-time donors giving 2,318,356 donations and observed for 822,426 person-years, the HBsAg incidence rate was 4.01 per 100,000 person-years. On the basis of prior reports of the duration of HBsAg positivity and the observed distribution of interdonation intervals among the study group, there was an estimated 53-percent chance that an HBV-infected donor with transient antigenemia would have a positive HBsAg test result. If 70 percent of newly HBV-infected adults have transient antigenemia, 25 percent have a primary antibody response without primary antigenemia, and 5 percent become chronic carriers, the overall chance of being detected by the HBsAg test was 42 percent, for an adjustment factor of 2.38. The total HBV incidence rate, therefore, was estimated to be 9.54 per 100,000 person-years. CONCLUSION: The crude HBV incidence rate observed from HBsAg test results will underestimate the true rate. The adjusted HBV incidence rate should be used in applications such as estimations of residual HBV risk to the blood supply and projections of the benefits of screening for HBV DNA.

Loss of volunteer blood donors because of unconfirmed enzyme immunoassay screening results. Retrovirus Epidemiology Donor Study.

BACKGROUND: Blood donors who test repeatably reactive on enzyme immunoassay (EIA) and are not confirmed as positive are a continuing problem for blood banks. Units are discarded and donors are deferred, in spite of multiple studies indicating that such donors are very rarely infected with the transmissible agents. Few data are available, however, with which to evaluate whether the discarded units are more likely to come from particular demographic subgroups. STUDY DESIGN AND METHODS: The Retrovirus Epidemiology Donor Study database of over 2 million allogeneic whole-blood donations collected in the years 1991 through 1993 was utilized. The prevalence of false-positive and indeterminate test results within demographic subgroups was computed for antibodies to human immunodeficiency virus, hepatitis C virus, and human T-lymphotropic virus (anti-HIV, anti-HCV, anti-HTLV, respectively) and hepatitis B surface antigen (false-positive only) as the proportion of donations that were repeatably reactive on EIA but negative or indeterminate on the confirmatory or supplemental test. RESULTS: Several demographic groups with increased prevalence of false-positive and indeterminate anti-HIV results were the same females, younger age groups, blacks, and first-time donors. Likewise, many of the demographic subgroups with increased prevalence of false-positive and indeterminate anti-HCV results were similar: older age groups, non-whites, lower education levels, first-time donors, donors making directed donations, and donors who had received transfusions. For anti-HTLV, by contrast, the oldest group had the highest prevalence of false-positive results but the lowest prevalence of indeterminate results: blacks had the lowest prevalence of false positive results but the highest prevalence of indeterminate results. CONCLUSION: If units that test repeatably reactive on EIA but that are not confirmed as positive are almost always from individuals not infected with the virus in question, then these results indicate that there may be sex-, race-, and/or age-linked proteins cross-reacting with the test kit materials. Elucidation of these antigenic determinates and their subsequent removal should be a priority.

Demographic determinants of hepatitis C virus seroprevalence among blood donors.

OBJECTIVE: To measure demographic determinants of hepatitis C virus (HCV) seroprevalence among blood donors in the United States. DESIGN: Cross-sectional epidemiological study. SETTING: Five blood centers in different regions of the United States. SUBJECTS: A total of 862,398 consecutive volunteer blood donors with one or more nonautologous donations from March 1992 through December 1993. METHODS: Demographic data collection, serological screening with second-generation anti-HCV enzyme immunoassay, and confirmation with anti-HCV recombinant immunoblot. RESULTS: There were 3126 donors with at least one blood donation confirmed HCV-seropositive, for a crude prevalence of 3.6 per 1000. Age-specific HCV seroprevalence rose from 0.5 per 1000 donors younger than 20 years to a maximum of 6.9 per 1000 in donors aged 30 to 39 years and declined in older age groups. There was interaction between age and educational attainment, with 30- to 49-year-olds with less than a high school diploma at highest risk of HCV infection (odds ratio [OR], 33.0; 95% confidence interval [CI], 23.0 to 47.2 compared with those younger than 30 years with a bachelor's degree or higher degree). Other independent risk factors for HCV seropositivity included male sex (OR, 1.9; 95% CI, 1.8 to 2.1), black race (OR, 1.7; 95% CI, 1.6 to 1.9), Hispanic ethnicity (OR, 1.3; 95% CI, 1.1 to 1.5), previous blood transfusion (OR, 2.8; 95% CI, 2.5 to 3.1), and first/only time donor status (OR, 4.2; 95% CI, 3.9 to 4.5 compared with repeat donors). Seropositivity for human T-lymphotropic virus types I and II, human immunodeficiency virus, or hepatitis B core antigen was highly associated with HCV seropositivity (OR, 10.4; 95% CI, 9.6 to 11.4 for one vs no marker). CONCLUSIONS: Despite a low overall HCV prevalence in blood donors in the United States, there is a marked variation in HCV seroprevalence by demographic subgroup, even after controlling for prior blood transfusion, a recognized risk factor for HCV. Further study of the prevalence of other parenteral risk factors such as past injection drug use among blood donors is needed.

Relationship between antibody to hepatitis B core antigen and retroviral infections in blood from volunteer donors.

BACKGROUND: The value of the test for antibody to hepatitis B core antigen (anti-HBc) as a surrogate screening assay in the time before sensitive, virus-specific screening tests were available has been well established. There is significant debate, however about the residual value of anti-HBc screening after the implementation of human immunodeficiency virus (HIV)-, human T-lymphotrophic virus (HTLV)-, and hepatitis C virus (HCV)-specific assays and, in particular, about its utility as a lifestyle marker to identify persons at risk for retrovirus infections. STUDY DESIGN AND METHODS: Screening tests for antibodies to HIV, HTLV, and HBc, as well as confirmatory or supplemental test results for anti-HIV and anti-HTLV, were obtained from approximately 2.8 million donations collected from 1991 through 1993 by five blood centers within the United States. The sensitivity, positive predictive value, and relative prevalence of anti-HBc for each retrovirus were calculated and compared among demographic subgroups. RESULTS: The overall relationship between anti-HBc and anti-HIV was similar to that between anti-HBc and anti-HTLV. When calculated from the measured endpoint of the prevalence of anti-HIV-positive and anti-HTLV-positive donations, the sensitivities were 31.1 and 26.2 percent, the positive predictive values were 0.18 and 0.21 percent, and the relative prevalences were 30.1 and 23.8, respectively. Among 27 anti-HIV-seroconverting donors and 9 anti-HTLV-seroconverting donors, the sensitivities were 7.4 percent (95% CI: 0.9-24.3%) and 0 percent (95% CI: 0.0-28.3%), respectively. It was estimated that for each HIV-infected window-period donation detected by anti-HBc, from 19,000 to 81,000 HIV-noninfected donations are discarded. Similarly, more than 33,000 HTLV-noninfected donations are likely to be discarded for each HTLV-infected donation detected by anti-HBc. CONCLUSION: Although anti-HBc-reactive donations are more likely to be seropositive for a retrovirus than are anti-HBc-nonreactive donations, the low positive predictive value limits the test's effectiveness. If the anti-HBc test is retained in the blood donor setting, efforts should be focused on reducing the number of false-positive results.

Comparison of two second-generation anti-hepatitis C virus ELISA on 21431 US blood donor samples.

We have compared two different second-generation (2.0) enzyme-linked immunosorbent assays (ELISA) for the presence of antibodies to hepatitis C virus (anti-HCV) in blood from volunteer, unpaid donors. At two separate blood centres, a total of 21,431 donor samples were tested with Abbott Anti-HCV 2.0 ELISA and Ortho Anti-HCV 2.0 ELISA. Samples found to be repeatedly reactive were tested by supplemental/investigational assays. MATRIX HCV (Abbott) and anti-HCV RIBA II (Ortho/Chiron), to 'confirm' the presence of anti-HCV. Discordant ELISA samples were additionally tested by the polymerase chain reaction (PCR) for the presence of HCV RNA. The Abbott anti-HCV assay had a repeatedly reactive rate of 0.59% (127/21,431) and the Ortho anti-HCV assay 0.51% (110/21,431). Overall agreement between assays was 99.76%, 72/127 (56.7%) of Abbott repeatedly reactive samples confirmed on MATRIX and 61/127 (48.0%) on RIBAII; 70/110 (63.6%) of Ortho repeatedly reactivate samples confirmed on MATRIX and 61/110 (55.5%) on RIBA II. Discordant ELISA samples tested by PCR yielded negative results. Hence the two ELISA had equal sensitivity, as defined by detection of true positive samples; the slightly lower specificity of the Abbott Anti-HCV 2.0 ELISA may be owing to culling of donors with a false positive test by Ortho's Anti-HCV 1.0 and 2.0 ELISA tests (the routine tests in place at each blood centre). A sample found to be repeatedly reactive by two different ELISA tests for anti-HCV is likely to be a true positive and may not require further 'confirmatory' testing.

Type 2 cryoglobulinemia and hepatitis C virus: its recognition and treatment.

Type 2 mixed cryoglobulinemia is a relatively common although rarely recognized consequence of chronic hepatitis C virus infection. Its detection should be pursued in individuals with lower extremity vasculitis which occurs in association with other signs of systemic disease such as proteinuria or a peripheral neuropathy. Importantly, HCV-associated cryoglobulinemia can occur in individuals with clinical evidence for cryoglobulinemia but without any evidence of detectable liver injury. Two cases recently seen in Oklahoma demonstrating these points are reported.

An anti-EnaTS detected in the serum of an MiI homozygote.

The serum of EH reacted with all red cells (RBCs) except her own, ficin- or trypsin-treated red cells, and En(a-) red cells. This reactivity defined an anti-EnaTS specificity. The red cells of the proposita typed as M-N+S-S+, Vw+Mur-Hil-Hut-Anek-Lane-, Wr(a-b+), EnaKT+. Red cells of five relatives were Vw+ and positive with her serum. Titration studies suggest that EH is genetically an MiI homozygote and that her Vw+ relatives are MiI heterozygotes. There is no history of consanguinity. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting studies have agreed with the serologic observations. A variant sialoglycoprotein of faster mobility than normal glycoprotein A, but no normal glycoprotein A, was detected on her red cells. Treatment with N-glycanase did not alter the mobility, which indicated that there was no N-glycosylation of residue 26. These findings are in agreement with the reported properties of the Mi.I-specific glycoprotein A. The relatives' Vw+ red cells showed the variant sialoglycoprotein and normal glycoprotein A. EH appears to be the first reported MiI homozygote.