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Many perpetrators of Munchausen syndrome by proxy present bloodstained materials as counterfeit evidence of proxy hemorrhage. Although blood grouping may show that the blood is not the proxy's, DNA typing may specifically identify the blood's source. A mother claimed that she alone had witnessed gastrointestinal bleeding of her son and presented bloodstrained towels as evidence. Several clinical investigations had failed to reveal a bleeding source. I compared the DNA types of the bloodstains and the child's buccal cells. The bloodstain and epithelial cells differed at 4 of 8 microsatellite loci and at the amelogenin locus. The blood and buccal cells shared 1 allele at every locus, suggesting that their sources were closely related. The probability that the source of the blood was maternal was 0.9915 (prior probability, 0.5). I recommend DNA matching in suspected cases of Munchausen syndrome by proxy whenever blood is presented as evidence. [ABSTRACT FROM AUTHOR]

Pregnancies, including ones that follow sexual assaults, occasionally produce hydatidiform moles. The alleged fathers (AFs) of moles have been tested for paternity by identifying the mole's locus phenotype-the one or two visible paternal obligate alleles (POAs) per locus. The probability that the mole inherited the POAs from the AF was divided by the probability that the mole inherited the POAs from a random man. This likelihood ratio (LR) would increase if the mole's specific genotype was known. Moles are generated in five different ways that produce five distinct genotypes. Examining a mole's multilocus STR profile reveals a mole's pathogenesis, determines locus genotypes, and increases paternity LRs., (© 2021 American Academy of Forensic Sciences.)

We were presented with the STR (short tandem repeat) profiles from two separate paternity trios. Each trio consisted of a mother, an alleged father, and products of conception (POC) that contained a hydatidiform mole but no visible fetus. In both cases, antecedent pregnancies had followed alleged sexual assaults. Mole classification and pathogenesis are described in order to explain the analyses and statistical reasoning used in each case. One mole exhibited several loci with two different paternal alleles, indicating it was a dispermic (heterozygous) mole. Maternal decidua contaminated the POC, preventing the identification of paternal obligate alleles (POAs) at some loci. The other mole exhibited only one paternal allele/locus at all loci and no maternal alleles, indicating it was a diandric and diploid (homozygous) mole. In each case, traditional calculations were used to determine paternity indices (PIs) at loci that exhibited one paternal allele/locus. PIs at mole loci with two different paternal alleles/locus were calculated from formulas first used for child chimeras that are always dispermic. Combined paternity indices in both mole cases strongly supported the paternity of each suspect., (© 2020 American Academy of Forensic Sciences.)

Background: Chimeras are organisms composed of cells derived from two or more zygotes. Clinicians, blood group serologists, and cytogeneticists have recognized natural human chimeras for more than 60 years and molecular biologists are now able to recognize them using more sensitive and definitive tests., Study Design: Human chimeras are divided into two major classes, man-made and natural. Man-made chimeras include transplanted patients and several kinds of iatrogenic chimeras including those that develop after in vitro fertilization (IVF). Natural chimeras have historically included twin chimeras and fusion chimeras. Recently described microchimeras are primarily natural ones as well. Updated terminology and classification are suggested to account for information gleaned from natural and experimental animal chimeras., Conclusions: Many human chimeras remain undetected. The states of health and disease of human chimeras remain largely unknown. Of four ways to detect human chimeras, molecular typing is the most sensitive and specific. Before systematic and temporal studies can be undertaken, improved cell sampling and better analytical detection methods are necessary. Chimeras may be sought among dizygotic twins and children born after IVF procedures., (© 2018 AABB.)

Background: Older and younger siblings occasionally attempt to impersonate parent and child to expedite immigration under US family-based visa policies. The rate with which full siblings escape detection by current relationship tests is unknown., Study Design and Methods: Retrospective study of full-sibling immigrant pairs was undertaken to determine the proportion that show insufficient genetic evidence to exclude parentage. Sibship and parentage indices (SI and PI) were compared/case in unexcluded sibling cases and true parent-child cases. Alleles shared per short-tandem-repeat locus were compared in sibling and parent-child pairs. The proportion of successful parentage fraud by siblings was estimated from the parentage exclusion rate among immigrants and the proportion of sibships without genetic inconsistencies (GIs)., Results: When 11 to 25 independent loci were tested per two-sibling case to verify or refute parentage, tests failed to demonstrate any GI in 9% and PI was greater than SI in seven of 10 of these cases. Another 29% of full-sibling pairs demonstrated insufficient evidence (fewer than two GIs) to exclude parentage. Thus, 0.4% of sibling pairs could falsely claim a parent-child relationship and show no GIs. Another 1.4% could make that false claim and not present sufficient evidence to be excluded., Conclusion: At present, with no evidence of parentage exclusion in a full-sibling pair, the relative magnitudes of PI and SI are misleading relationship indicators because too few loci are examined and rates of sharing one and two alleles/locus vary greatly in parentage and sibling pairs. Only evidence of exclusion ascertains false parentage claims by siblings. Nevertheless, the expected rate of successful fraud is quite low., (© 2013 American Association of Blood Banks.)

Background: In sibship analysis, the usual comparison of an alleged (test) sibling's short tandem repeat (STR) types with those of a reference sibling may prove inconclusive. Increasing the number of examined STR loci may not change sibship probabilities very much. We increased the number of verified reference siblings to resolve problematic cases of alleged sibship., Study Design and Methods: (A) Ten paternity cases were chosen in which there were three highly probable children of each alleged father. Pairs of the alleged father's children were analyzed for full sibship. The test sib with the lowest likelihood of sibship was reanalyzed by a comparison with two reference siblings combined. (B) Five problematic sibship cases are presented to demonstrate how two-person reference pedigrees can improve diagnosis over tests using one reference person., Results: (A) Two-person pedigrees exponentially increased sibship probabilities of true siblings above those produced by one reference person. (B) In problem cases, reference pedigrees provided data that: (1) statistically verified some alleged sibships in which analyses using one reference person yielded inconclusive results, (2) allowed exclusion of some alleged sibships, or (3) suggested alternate blood relationships to the alleged one., Conclusions: Use of reference pedigrees often resolves sibship questions left unsettled by tests using reference individuals. Adding reference relatives is a far more powerful analytical strategy than adding test loci. Whenever possible, verified blood relatives should be incorporated into a reference pedigree to retest an alleged sibling whose initial results were unclear., (© 2012 American Association of Blood Banks.)

Relationship testing laboratories provide genetic evidence to support or refute claims of kinship between U.S. citizen petitioners and potential immigrant beneficiaries. One female beneficiary presented a male amelogenin type and alleles at 15 autosomal loci that were identical to an alleged brother's. Laboratory records showed that her alleged father had petitioned to have 15 children emigrate from Ghana. The petitioner's 15 paternity indices exceeded 10⁵, but the children shared only four short tandem repeat (STR) profiles, suggesting fraudulent reuse of genotypes in this alleged pedigree (AP). To determine the extent of this "genotype recycling," I examined the laboratory's 555 APs from Ghana and 532 control APs from Nigeria. Seventeen Ghanaian APs (3.1%) but no Nigerian APs showed genotype recycling. Of 90 tested people in the 17 APs, 56 shared identical STR profiles with others in their AP. Of these 56 people, 10 were petitioners with unexpectedly high parentage indices. Seven of 56 had amelogenin types that disagreed with their declared genders. Database searches for identical multilocus genotypes in allegedly different people would best detect this fraud., (© 2010 American Academy of Forensic Sciences.)

Antibodies of apparent D specificity may be found in D+ patients. We report a D+, multi-transfused Caucasian woman with myelodysplasia who exhibited several alloantibodies. One antibody was a moderately strong (2+) anti-D that persisted for 9 months, until the woman died. Molecular analysis of the patient's RHD gene identified the rare weak D type 21 (938C > T) allele. D alloantibodies do not occur in patients with most weak D types, but some patients with a weak D phenotype, including those with type 21, can produce antibodies to nonself epitopes of the wild-type D antigen.

Background: Almost all relationship analysts now use molecular (DNA) tests to obtain necessary genetic information, yet older blood group tests remain valid. Circumstances may provide blood test results from old reports to avoid trying to sample DNA from inaccessible sources., Case Study: A mother recently claimed that a deceased man (alleged father [AF]) sired her child. Insurance investigation recovered two paternity test reports from an AABB-accredited laboratory. The 16- and 18-year-old reports employed blood groups and protein polymorphisms to exonerate two different men. One report contained the multilocus phenotypes of the AF and the other contained the phenotypes of the mother and child at the same loci. A new case was synthesized from the old reports., Results: Genetic inconsistencies (three direct and one indirect) were demonstrated among the nine loci that had been typed in both the AF and the mother-child pair., Conclusion: New relationship tests may be reconstructed from phenotypes reported before the molecular test era. This approach avoids exhumation and other problematic methods of specimen retrieval.

Background: Suspected incestuous paternity is encountered infrequently and investigation may be complicated by absence of the suspected father. Incest indices (IIs) can be calculated from microsatellite (STR) types of only a mother and child, but could be misleading. Therefore, the method was evaluated., Study Design and Methods: Combined incest indices (CIIs) of 50 randomly mated (RM) mothers and their children were compared with those of 50 simulated incestuous (SI) mothers and their children. Each CII was calculated from 18 individual locus IIs. Combined indices were categorized as "diagnostic" (<0.010 and >100 for RM and SI cases, respectively), "indicative" (CII was directionally correct but not erroneously diagnostic), and "misleading" (>1.0 in RM and <0.01 in SI). The relative importance was determined of each of the three variables contributing to the CII., Results: In 41 cases (41%), CIIs attained diagnostic values. Fifty-two CIIs were indicative. CIIs were misleading in 3 RM cases and 4 SI cases. The number of mother-child (M-C) STR genotype similarities was the most important determinant of CIIs. Infrequent alleles in M-C similarities were important in raising CIIs in SI. The kind of M-C genotype similarity was the least important variable., Conclusions: Study of 18 STR loci produces diagnostic CIIs in only two of five suspected incest cases. Study of approximately 33 independent STRs would assure that greater than 97.5 percent of cases will have diagnostic CIIs if incest occurred. Study of loci that are more informative than typical STRs would be advantageous.

Neonatal screening for hemoglobinopathies occasionally results in the detection of novel hemoglobin (Hb) variants. Two heterozygous infants were found with different beta chain mutations, neither of which produced obvious clinical or laboratory abnormalities on routine examinations. The variants were characterized by cation exchange high performance liquid chromatography (HPLC), reversed phase HPLC, and sequencing of amplified beta-globin genes. Functional studies could not be performed at this time.

Background: The contribution of maternal typing to paternity analysis was evaluated to determine how many additional loci to study in one-parent cases., Study Design and Methods: Four groups underwent paternity analyses with an eight-locus test battery. Files of 25 case trios were retrieved, in which alleged fathers had achieved paternity indices of greater than 100 ("included trios"). Maternal types were omitted and the cases were reanalyzed ("included duos"). Mother-child pairs of the cases were then coupled with unrelated men ("excluded trios"), and the cases were analyzed. Maternal types were omitted from the excluded trios and cases were reanalyzed ("excluded duos")., Results: Paternity indices of men in included duos were markedly reduced when compared to included trios; odds were sufficiently low in 9 of 25 men that paternity remained in doubt. After omission of maternal phenotypes, excluded duos exposed 33 percent fewer genetic inconsistencies than excluded trios; 5 of 25 men in excluded duos demonstrated less than two genetic inconsistencies and 1 man had none. The specific probabilities of paternity exclusion in motherless cases averaged 61 percent per locus of those in case trios. One random man in 52 duos was not excluded by the eight tests versus 1 in 417 trios., Conclusions: Omission of maternal typing from eight common microsatellite paternity tests reduced conclusive evidence for or against paternity by 30 to 40 percent. False inclusion of random men is an important failing of tests in motherless cases. Cases involving one parent and child (e.g., in immigration) would require examination of an additional five similar loci to compensate for absent maternal data. A change in standards is suggested.

Background: The impersonation of parent and child by two other blood relatives is an important problem in parentage analysis involving potential immigrants., Study Design and Methods: A statistic (AR) is proposed, based on the specific power of exclusion of paternity, which describes the ability of a child's test results to demonstrate evidence of nonparentage under the hypothesis that an ostensible parent is actually an older sibling. A case illustrates the value of A(R): a woman and her two alleged children were typed at 3 variable number of tandem repeat (VNTR) loci after 18 short tandem repeat (STR) loci initially showed strong evidence of the woman's maternity of one child and her exclusion from parentage of the second. AR and 1 - AR were calculated from the STR types of the first child., Results: The woman was excluded from maternity of both children with the additional VNTR tests. Given the 18 STR test findings of the first child, the probability was 12 percent that there would be no inconsistencies with parentage in a sibling pretending to be a parent., Conclusion: The value 1 - AR, siblings not excluded from parentage, explains how a seemingly large number of examined loci can fail to reveal even one genetic inconsistency if two siblings have posed as parent and child. Approximately 25 STR loci appear necessary to achieve 95 percent confidence of detecting at least one genetic inconsistency indicative of nonparentage.

Purpose of Review: Parentage analyses are of interest to workers in health care, law enforcement, immigration and other fields. This review describes recent applications, technical advances, and quality improvements., Recent Findings: Mutations at short tandem repeat sequence loci confound interpretations of genetic data used to assess all blood relationships. Rates of the usual mutation type (change in repeat number) are probably related to specific alleles at each locus as well as to allele length, locus, and gender. Short tandem repeat sequences have relatively limited information content per locus. Intermediate tandem repeat sequence loci may be better. In immigration proceedings, probabilities can be calculated for excluding parentage in blood relatives who might impersonate the biologic parent. Unrelated immigrants from a subpopulation may appear to be related, but it is now possible to statistically determine the effect of population substructure on kinship determinations. In forensic analyses, sex chromosomal (X and Y) short tandem repeat sequences and mitochondrial DNA sequence variations have helped identify the parental lineages of human remains. Recent laboratory quality improvements include a way to estimate the frequency of common mother-child specimen mislabeling in routine paternity cases. In prenatal testing there are now methods for avoiding erroneous assignment of contaminant maternal alleles to the fetus. False paternity exclusions can be avoided by adhering to a standard of the American Association of Blood Banks requiring duplicate DNA isolation and retesting of excluded men., Summary: Laboratory technology and quality have advanced, but genetic tests with greater information content are needed. Better communication is highly desirable between persons requesting tests and parentage laboratories.

Background: Units of frozen S/D-treated plasma (SDP) must be transfused within 24 hours after thawing. To avoid waste, an attempt was made to determine how long SDP could be therapeutically effective after thawing and storing it at 20 degrees C., Study Design and Methods: The microbiologic safety and the activity of labile coagulation factors were evaluated in units stored at 20 degrees C of thawed SDP units and FFP within 24 hours of collection (FFP24). Five SDP and FFP24 samples of each ABO blood group were cultured and assayed for coagulation factors daily over 5 days. Assays included FV, FVII, FVIIa, FVIII, F IX, FXI, protein S, antiplasmin, fibrinogen, prothrombin times (PTs), and activated partial thromboplastin times (aPTTs)., Results: None of the 80 bacterial cultures demonstrated growth under either aerobic or anaerobic conditions. FV, FVIII, F IX, FXI, fibrinogen, and the aPTT appeared to be stable in both thawed FFP24 and SDP. The PT increased slightly in thawed FFP24 and insignificantly in SDP. FVII decreased slightly in FFP24 but remained in the normal range, and FVIIa was low and constant. FVII was increased in SDP and FVIIa was markedly increased. Protein S decreased from initial normal values in FFP24 to very low values. Protein S was very low immediately after thawing in the SDP and continued to decline. Antiplasmin was normal and stable in thawed FFP24 but was low in SDP and remained constant after thawing., Conclusion: Sterile SDP that is stored at 20 degrees C provides sufficient coagulant activity of labile FV and FVIII to transfuse it for up to 5 days after thaw. Caution is warranted by decreases in Protein S and antiplasmin, clinical evidence of coagulopathy in some recipients of SDP, and a recent manufacturer's warning.

A woman with end-stage renal disease underwent peritoneal dialysis. On initiation of treatment, there was turbid peritoneal dialysis fluid, which proved to be of chylous rather than inflammatory origin. A low-fat and medium-chain triglycerides diet induced visible clearing of the fluid and a decrease in its triglyceride concentration. Challenge with a high-fat diet produced two early recurrences. After 8 months, dietary fat no longer induced chyloperitoneum. The patient was able to continue peritoneal dialysis at home without a recurrence.

Isolated cases of malaria are increasing in frequency in nonendemic countries. Blood film examination remains a mainstay of diagnosis of these sporadic cases because immunologic and molecular methods are unavailable, expensive, and problematic. Two tertian malarial species, Plasmodium vivax and Plasmodium ovale, may appear to be similar morphologically. Plasmodium ovale infection is infrequent, and misdiagnosis of this species is common. Plasmodium vivax infection can be ruled out, however, if a patient's erythrocytes phenotype as Fy(a-b-), because these cells completely resist entry by the latter species.

Background: Full siblings were compared with half-siblings to observe how well the two relationships could be distinguished by informative tests. STUDY AND DESIGN METHODS: Parentage analysis ascertained 25 pairs of full siblings and 25 pairs of half-siblings. The pairs were then examined for the sharing of alleles at three independent variable number of tandem repeat (VNTR) loci. A sibling index (SI) and a half-sibling index (HSI) were calculated for each pair, and an SI:HSI ratio was determined., Results: The SI:HSI ratio favored full siblings in 18 of 25 full sibling pairs. The SI:HSI ratio exceeded 100 in 8 of those 25 pairs. Although the ratio favored half-siblings in 23 of 25 half-sibling pairs, as was expected with the use of only 3 loci, it exceeded 0.1 in all 25 pairs., Conclusion: Study of more than three highly informative loci is required to improve the identification of full siblings and might well permit the identification of half-siblings.

Risk managers should consider misidentifications as causes of otherwise unexplained diagnostic and process errors. Genetic tests are powerful tools that can resolve problem cases and indicate ways to improve patient-sample identification. Genetic typing, especially for DNA markers, has provided evidence of patient or sample identity in 21 of 22 hospital and laboratory cases of accidental or intentional patient misidentification, specimen mislabeling, and sample contamination. Identity is established with very high probability if infrequent genetic markers are observed in both unknown and reference specimens. The odds of a match of markers express both the infrequency of finding the match by chance (in specified populations) and the adequacy of testing. Genetic tests establish nonidentity with virtual certainty.

Laboratory samples from two different patients produced false-positive results. Investigations indicated that the errors were produced by a combination of miniscule preanalytical contamination of disposables, suboptimal systems design, and very sensitive analytical systems. The errors may be avoidable by changing the configuration of workstations.

We evaluated the efficacy of prolonged plasma exchange (PEX) for attaining durable remissions in thrombotic thrombocytopenic purpura (TTP). A recent review using steroids or PEX in initial management showed an 80% response rate but produced a relapse rate of 67-84%. Records of 50 patients starting PEX treatment for TTP/HUS were reviewed to identify and select those whose course of treatment had ended over 1 year earlier, whether or not the result was satisfactory. Records were evaluated for outcome, especially remission associated with treatment by "prolonged" plasma exchange. "Prolonged" was defined as continuing PEX beyond the stage where a normal platelet count was attained and until evidence of hemolysis was "minimal or at least compensated." If disease activity as judged by the criteria of hemolysis became accelerated or resumed, PEX was increased by volume of FFP (e.g., from 3 to 4 L) or rate (from less than daily to daily). Of 50 consecutive patients treated by PEX for TTP/HUS there were 40 cases after which at least one year had passed since the end of treatment. These 40 patients were evaluated for the results of treatment by PEX. Eight failed to achieve remission, dying in hospital within 1 month of admission. Twenty-eight achieved remission, sustained for 1 year or more in all. These are the reasons for our enthusiasm about this report. Four achieved remission lasting less than 1 year. Splenectomy was performed to obtain a sustained remission in one patient following administration of three 2 mg doses of vincristine and two relapses.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To determine if microwave heating of dialysis solutions to 37 degrees C produced focal overheating (hot spots) and caramelization of dextrose., Design: In vitro determination of conditions for controlling time, temperature, and procedures. Bags had been stored at ambient room temperature., Main Outcome Measures: Solution and external bag surface temperature determinations. Dextrose degradation products determined spectrophotometrically. Microscopy for potential caramel precipitates., Results: A microwave oven with no rotation tray produced uneven heating of bags of two commercially available concentrations of dialysis solutions. The greatest hot spots were evident in spike ports. External bag surface temperatures were within 0.20 degrees C of reservoir temperatures. Initial solution temperatures correlated with temperatures of the solutions after microwave heating (r = 0.895). No statistically significant differences were found between dextrose degradation product concentrations of unheated and heated solutions, including hot spots. No precipitates were observed microscopically., Conclusions: Despite the presence of solution hot spots in bag infusion ports, 37 degrees C temperatures were achievable in the bag reservoirs with no evidence of increased glucose degradation. This outcome is assured if the initial temperature and the microwave conditions (procedure, time, mixing of solution) are held constant, and the external bag temperatures are measured after heating.

At the turn of the 20th century, Mendel's laws were found to be applicable to human blood groups. Within two decades, blood group genetics were applied to problems of parentage. Expansion of immunohematology into leukocyte antigen identification produced the single most informative, expressed polymorphism. About the same time, analysis of a great number of soluble protein polymorphisms followed advances in electric separation methods, enzymology, and immunochemistry. As new, independent loci were discovered, the power to exclude the falsely accused increased, and it became possible to apply Bayesian principles to determined probabilities of biologic relationships. The revolution in nucleic acid technology has dramatically improved analysis and statistical inferences. By the turn of the 21st century, laboratories should be able to determine biologic parentage with virtual certainty.

Alpha-fetoprotein (AFP) is produced in the gut and liver during fetal life and appears to act like albumin in the adult. Because AFP appears in the maternal circulation during pregnancy, interest has been focused on its measurement in maternal serum to predict fetal abnormality. In addition, AFP, as an embryonic product, is elevated in certain malignant states. This article provides a summary of current clinical knowledge of AFP and its applications.