Afibrinogenemia and hypobetalipoproteinemia in a kindred.

A 3-year-old boy with minor bleeding problems had no plasma fibrinogen measured by both clottable assay and immuno-precipitation. Low normal fibrinogen levels were present in the mother and father. Markedly decreased plasma cholesterol and apolipoprotein B levels were found in the father, proband's brother, and the paternal side of the kindred. The proband and his mother had normal plasma total cholesterol and apolipoprotein B levels. These findings are compatible with autosomal dominant transmission of hypobetalipoproteinemia and autosomal recessive transmission of afibrinogenemia. Two members of the father's family had plasma cholesterol levels below the fifth percentile but elevated levels of fibrinogen (6.0 and 4.4 g/L). Both have symptomatic coronary heart disease. Finding coronary heart disease with very low cholesterol but elevated fibrinogen levels is consistent with fibrinogen levels being an independent risk factor for coronary heart disease.

Effect of simulated altitude erythrocythemia in women on hemoglobin flow rate during exercise.

The effect of simulated altitude erythrocythemia on hemoglobin flow rate and maximal O2 uptake (VO2max) was determined for nine women sea-level residents. Test conditions included normoxia and normobaric hypoxia (16% O2-84% N2). Cycle tests were performed under normoxia (T1-N) and hypoxia (T1-H) at prereinfusion control and under hypoxia 48 h after a placebo infusion (T2-H) and 48 h after autologous infusion of 334 ml of erythrocytes (T3-H). Hematocrit (38.1-44.9%) and hemoglobin concentration (12.7-14.7 g.dl-1) increased from control to postreinfusion. At peak exercise, VO2max decreased from T1-N (2.40 l.min-1) to T1-H (2.15 l.min-1) then increased at T3-H (2.37 l.min-1). Maximal arterial-mixed venous O2 difference decreased from T1-N to T1-H and increased at T3-H. Cardiac output (Q), stroke volume, heart rate, and total peripheral resistance during maximal exercise were unchanged from T1-N through T3-H. Hemoglobin flow rate (Hb flow) at maximum did not change from T1-N to T1-H but increased at T3-H. When compared with submaximal values for T1-N, VO2 was unchanged at T1-H and T3-H; Q increased at T1-H and decreased at T3-H; arterial-mixed venous O2 difference decreased at T1-H and increased at T3-H; Hb flow did not change at T1-N but increased at T3-H. For young women, simulated altitude erythrocythemia increased peak Hb flow and decreased physiological altitude (227.8 m) but did not affect maximum cardiac output (Qmax).

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.

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.

Surveillance for HIV antibody and antigen in trauma patients.

Studies in a Baltimore emergency room identified the patient with penetrating trauma as having the highest incidence of Human Immunodeficiency Virus Type I (HIV-1) infection. Anonymous testing over a 15-month period of 165 victims of penetrating trauma presenting to the Medical Center Hospital Emergency Center (San Antonio, Texas) revealed a 0% incidence of HIV-1. This data suggests that HIV-1 trauma patient incidence can be expected to vary between specific geographic areas and patient populations served, independent of community-wide AIDS incidence.

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.

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.

Plasmapheresis technology.

Manual plasmapheresis is done worldwide on both paid donors, and to a much smaller extent on volunteer donors in order to generate source plasma to be fractionated into albumin, clotting factor concentrates, and gamma globulin. Automated technology has now been developed utilizing both centrifugal, and membrane separation devices (Haemonetics PCS centrifugal, Organon Teknika PLASMAPUR-membrane, HemaScience Autopheresis-C-spinning membrane) and is much faster and safer than the manual techniques with regard to the donor. The single biggest difficulty with automated technology is the high cost of the software, making the cost of producing source plasma by this type of technology, in general, not cost efficient at this time. However, fresh frozen plasma can be generated by this technology, which is cost efficient and provides a single donor source of 500 ml plasma, making the product safer for those patients that do require fresh frozen plasma by reducing the number of donor exposures to the patient.

Haemonetics V50 and Plasma Collection System: common concerns and troubleshooting.

The Haemonetics V50 and PCS are automated centrifugal systems designed for the collection of a variety of apheresis products. The microprocessor-controlled systems increase collection efficiency through many safety features and high donor and operator appeal. Troubleshooting the systems has been simplified through a systematic approach and easily understood display messages.

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.

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.

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.

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.

Effect of induced erythrocythemia on hypoxia tolerance during physical exercise.

The effect of induced erythrocythemia on hypoxia tolerance during physical exercise was determined for five male mountain climbers. Treadmill testing was performed under four conditions: 1) prereinfusion, normoxia (Pre-N); 2) prereinfusion, hypoxia (Pre-H); 3) postreinfusion, normoxia (Post-N); and 4) postreinfusion, hypoxia (Post-H). An altitude of 3,566.2 m was simulated by having subjects breath a gas mixture of 13.5% O2-86.5% N2 at normal barometric pressure. Tests were administered immediately before and 24 h after autologous transfusion of 750 ml of red blood cells. Hematocrit increased from 43.3% at prereinfusion to 54.8% at postreinfusion. Hemoglobin concentration increased from 13.80 g X 100 ml-1 at prereinfusion to 17.63 g X 100 ml-1 at postreinfusion. Maximal O2 uptake (VO2 max, 1 X min-1) increased (P less than 0.05) by 12.8% (3.28 to 3.70) from Pre-N to Post-N and 13.0% (2.62 to 2.96) from Pre-H to Post-H. Treadmill performance time (s) increased (P less than 0.05) by 15.8% (793 to 918) from Pre-N to Post-N and 8.9% (687 to 748) from Pre-H to Post-H. VO2 max decreased by 20.1% from Pre-N to Pre-H and by 9.8% from Pre-N to Post-H. Treadmill time decreased by 13.4% from Pre-N to Pre-H and 5.7% from Pre-N to Post-H. The calculated change in hypoxia tolerance following reinfusion indicated that physiological altitude was improved by 463.6 m. It was concluded that induced erythrocythemia increased hypoxia tolerance during physical exercise.

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.