Monitoring iron stores in Icelandic blood donors from 1997 through 2019.

OBJECTIVES: To estimate the frequency of iron deficiency (ID) and anaemia in blood donors in Iceland and the impact of serum ferritin (SF) testing policy change. BACKGROUND: Blood donations contribute to ID and/or anaemia in whole blood donors (WBD). SF may be used to monitor blood donor iron stores. MATERIALS AND METHODS: The study included WBD and new donors (ND) in the Icelandic Blood Bank in 1997-2019. SF was measured for ND and intermittently for WBD until October 2017, but thereafter for all WBD and ND at every visit. In January 2018, the SF threshold increased from 14 to 16 µg/L for ND and from 8 to 10 µg/L for WBD. RESULTS: The study included 85 370 SF results from 243 369 visits of 32 910 donors. Median SF was higher for males than females, both for ND (88.0 vs. 31.2 µg/L, p < 0.001) and WBD (before 2018: 43.0 vs. 22.0 µg/L, p < 0.001). After the policy change in 2018, median SF increased for both male WBD (to 45.2 µg/L, p < 0.001) and female WBD (to 25.7 µg/L, p < 0.001). ID (SF <15 µg/L) was present in 10.6% of female ND and 0.5% of male ND. After policy change, the proportion of WB donations associated with ID decreased for males (from 6.4% to 4.0%) and females (from 18.9% to 14.1%). ID anaemia was present at some time in 3.7% of female WBD and 1.2% of male WBD. CONCLUSION: This nationwide study showed that ID in WB donors is common, especially among females, but monitoring SF may improve donor management.

Rhesus D alloimmunization in pregnancy from 1996 to 2015 in Iceland: a nation-wide population study prior to routine antenatal anti-D prophylaxis.

BACKGROUND: Rhesus D (RhD) incompatibility is still the most important cause of hemolytic disease of the fetus and newborn (HDFN) worldwide. The aim of this study was to investigate the incidence, causes, and consequences of anti-D alloimmunizations in pregnancy in Iceland, prior to implementation of targeted routine antenatal anti-D prophylaxis (RAADP) in 2018. STUDY DESIGN AND METHODS: This was a nation-wide cohort study of 130 pregnancies affected by RhD alloimmunization in Iceland in the period from 1996 through 2015. Data were collected from transfusion medicine databases, medical records, and the Icelandic Medical Birth Register. RESULTS: Of 130 RhD alloimmunizations, 80 cases (61.5%) represented new RhD immunization in the current pregnancy. Sensitization was discovered in the third trimester in 41 (51.3%) and occurred in the first pregnancy in 14 cases (17.5%). The most likely causative immunization event was the index pregnancy for 45 (56.25%), a previous pregnancy/birth for 26 (32.5%), abortion for 3 (3.75%), and unknown for 6 women (7.5%). Higher anti-D titers were associated with shorter gestational length, cesarean sections, positive direct antiglobulin test (DAT), and severe HDFN. Intrauterine transfusion (IUT) was performed in five pregnancies (3.8%), and 35 of 132 (26.5%) live-born neonates received treatment for HDFN; 32 received phototherapy (24.2%), 13 exchange transfusion (9.8%), and seven simple blood transfusion (5.3%). CONCLUSION: In about half of cases, RhD alloimmunization was caused by the index pregnancy and discovered in the third trimester. Thus, the newly implemented RAADP protocol should be effective in reducing the incidence of RhD immunization in Iceland in the future.

Red blood cell alloimmunization in pregnancy during the years 1996-2015 in Iceland: a nation-wide population study.

BACKGROUND: Red blood cell (RBC) alloimmunization during pregnancy is still a major problem. Historically, anti-D antibodies are most likely to cause severe hemolysis, but other antibodies are also important. In Iceland, postnatal RhIg prophylaxis was implemented in 1969, universal RBC antibody screening was implemented in 1978, but antenatal RhIg prophylaxis is not yet routine. STUDY DESIGN AND METHODS: This nation-wide population study gathered data on alloimmunized pregnancies in Iceland between 1996 and 2015. Blood bank alloimmunization data were linked to Icelandic Medical Birth Registry data. RBC antibodies were classified as either clinically significant or clinically nonsignificant. RESULTS: In total, 912 positive antibody screens from 87,437 births were identified (1.04% prevalence). The most frequent antibodies were anti-M (19.4%), anti-E (19.0%), and anti-D (12.5%). Anti-D prevalence among D-negative mothers was 1.1%. Icelandic Medical Birth Registry data were available for 881 (96.6%) pregnancies. In the clinically significant group (n = 474), anti-E (27%) and anti-D (20%) were most common, whereas anti-M was most frequent (53%) in the clinically nonsignificant group (n = 407). Mothers in the clinically significant group were older, more often multigravidae, had more abortions and stillbirths, and had shorter gestational length. Newborns in the clinically significant group were less healthy, had lower weight and Apgar scores, and required more treatment. Among specificities in the clinically significant group, anti-D antibodies were most strongly associated with severe hemolysis. CONCLUSION: In this study, the prevalence of alloimmunization was similar to that in previous reports. Of all clinically significant antibodies, anti-D was most strongly associated with severe hemolysis, requiring phototherapy or exchange transfusions. Our data emphasize the importance of implementing an antenatal prophylactic RhIg program in Iceland in the near future.

[Positive Coomb's test in newborns; causes and clinical consequences Summary of cases diagnosed in the Blood Bank in the years 2005 to 2012].

INTRODUCTION: Hemolytic disease of the fetus and newborn (HDFN) is caused by the destruction of fetal red blood cells due to red cell antibodies produced by the mother. HDFN can cause fetal hydrops during pregnancy or neonatal jaundice after birth. Direct Antiglobulin Test (DAT) detects antibodies bound to red cells and is a valuable test aiding in the diagnosis of HDFN. In Iceland DAT is routinely performed on cord blood or newborn blood samples if the mother is Rhesus D negative or has non-A/B red cell alloantibodies. The aim of this study was to investigate the causes and consequences of positive DAT in newborns in Iceland over a period of eight years. MATERIAL AND METHODS: The study population was infants diagnosed with a positive DAT in the Blood Bank in Iceland in the years 2005-2012. Relevant data on the blood group and antibody status of mother and child, blood transfusion and DAT results were retrieved from the Blood Bank information system ProSang. Birth records provided information on birth weight, gestational age and phototherapy. Health records from the Children's Hospital provided information on the management and fate of the newborn. RESULTS: Over the study period 383 newborns had a positive DAT result at the Blood Bank. In 73.6% of cases the underlying cause was ABO blood group mismatch between mother and infant, in 20.4% of cases the mother had non-A/B red cell alloantibodies, in 3.9% both of above factors were present, while in 2.1% the cause was unclear. A total of 179 (47.6%) children had neonatal jaundice that required treatment, of which 167 (93.3%) only needed phototherapy. Eight infants required exchange transfusion, five of these had Rhesus antibodies and three ABO blood group mismatch. CONCLUSION: ABO blood group mismatch between mother and child was the most common cause for a positive DAT in neonates in Iceland in the years 2005-2012. Almost half of the neonates required treatment but usually phototherapy was sufficient. Rarely, blood transfusion or exchange transfusion was necessary in severe cases of ABO blood group mismatch or non-A/B red cell alloantibodies. KEY WORDS: Coombs test, Direct Antiglobulin Test (DAT), Hemolytic disease of the fetus and newborn (HDFN), ABO blood group mismatch, red cell alloantibodies, neonatal jaundice, exchange transfusion. Correspondence: Anna Margret Halldorsdottir, annamha@landspitali.is.

Sarcoid arthropathy and the association with the human leukocyte antigen. The Icelandic Sarcoidosis Study.

OBJECTIVES: The aim of the present study was to evaluate whether certain HLA antigens were risk factors for developing sarcoid arthritis and whether HLA antigens appear to account for the phenotype and the resolution of the arthritis condition in an unselected nationwide cohort. METHODS: The Icelandic Sarcoidosis Study (ISS) contains all tissue-verified cases of sarcoidosis in Iceland since 1981. Of a total of 234 cases, 39 patients were identified with arthritis and of those 36 delivered a biosample for the study. The patient cohort has previously been described in detail. DNA was isolated from EDTA blood and HLA antigen typing was performed. A total of 544 Icelandic stem cell donors acted as controls. RESULTS: HLA-B8 and HLA-B14 antigens were more common among those who suffered from sarcoid arthritis (24% vs. 11%, p<0.01; 6.5% vs. 2.4%, p<0.05). DRB1*03 was also found more frequently in patients with sarcoid arthritis compared to controls (28% vs. 11%, p<0.001), while DRB1*04 was less frequently reported (5.6% vs. 17%, p<0.01). No differences were found in the HLA-A distribution between the groups. A higher proportion of patients with chronic arthritis had HLA-A11 than those with resolving joint problems (60% vs. 3.8%). CONCLUSIONS: Our nationwide study of patients with sarcoid arthritis further supports the conclusion that genetics may strongly influence the development and the clinical course of the disease. Furthermore, some HLA antigens may even be protective for the disease. Thus, classification of the major histocompatibility complex may have clinical implications.

Association of Morbus Ledderhose with Dupuytren's contracture.

BACKGROUND: Fibromatous nodules in the sole of the foot are often called Ledderhose disease. It is a benign nodular formation in the plantar aponeurosis, typically at the distal medial border. A lump forms and it can be a few centimeters in diameter. It is frequently seen as an isolated disease, but a relationship to Dupuytren's has been noted in some patients. METHODS: The study was a part of a large cohort study, the Reykjavík study. Men with Dupuytren's disease (n = 122) were invited to follow-up 18 years after the initial observation. An equal number of controls, matched for age and smoking habits, were also invited. A total of 92 Dupuytren's patients and 101 control subjects attended for follow-up and were examined for plantar nodules. Statistical evaluation was carried out using chi-square test and presented as odds ratio (OR) and 95% confidence interval (95% CI). RESULTS: Ledderhose disease was identified in 14 of the 92 (15.2%) men with Dupuytren's disease, while it was only in 4 of the 101 (3.9%) matched controls (OR = 4.35, 95% CI, 1.3-16.7, P < 0.01). Men operated for Dupuytren's disease or with finger contractures were more likely to have plantar nodules than those with only nodules or strings in the palms (OR = 6.1, 95% CI, 1.8-27.1, P < 0.001). The plantar involvement was related to family history of Dupuytren's disease (OR = 3.1, 95% CI, 1.1-8.5, P = 0.02). CONCLUSION: Men with manifestations of finger contractures or who need surgery for Dupuytren's disease are more likely to also develop plantar fibromas. LEVEL OF EVIDENCE: Level III, retrospective comparative series.

Defective immunoglobulin A (IgA) glycosylation and IgA deposits in patients with IgA nephropathy.

Defective glycosylation and immune complex (IC) formation may be of primary importance in immunoglobulin A nephropathy (IgAN) pathogenesis. The aim of this study was to determine whether defective IgA1 glycosylation might support renal deposition of IgA and disease activity. IgA was isolated from the serum of 44 IgAN patients and 46 controls and glycosylation analysed by ELISA using glycan-specific lectins. IgA was measured by immunodiffusion and immune complexes by ELISA. IgA subclasses in IC deposits in kidney glomeruli were identified by immunohistochemical methods. A significant increase in N-acetylgalactosamine (GalNAc) in terminal position (p = 0.02) observed in some of the IgAN patients, became more pronounced when sialic acid was removed from IgA1, indicating enhanced expression of α-2,6-sialyltransferase in patients compared with controls (p < 0.0001). Patients with defective galactosylation had lower serum IgA than other IgAN patients (p = 0.003). IgAN patients with both IgA1 and IgA2 glomerular deposits (21.7%) had increased GalNAc in terminal position (p = 0.003). Taken together, our results show that increased IgA glycosylation in IgAN associates with low levels of IgA, concomitant IgA1 and IgA2 glomerular deposits and poor clinical outcome.

Effect of rheumatoid factor on mortality and coronary heart disease.

OBJECTIVE: An association between rheumatoid factor (RF) and increased mortality has been described in individuals with rheumatoid arthritis. The objective of this study was to determine the effect of RF on mortality and coronary heart disease (CHD) in the general population. SUBJECTS: were participants in a population-based study focused on cardiovascular disease who attended for a study visit during the years 1974-84. RF was measured and information obtained on cardiovascular risk factors, joint symptoms and erythrocyte sedimentation rate (ESR). The subjects were followed with respect to mortality and incident CHD through 2005. Adjusted comparison of overall survival and CHD event-free survival in RF-positive versus RF-negative subjects was performed using Cox proportional hazards regression models. RESULTS: Of 11 872 subjects, 140 had positive RF. At baseline RF was associated with diabetes mellitus and smoking and inversely associated with serum cholesterol. RF-positive subjects had increased all-cause mortality (HR 1.47, 95% CI 1.19 to 1.80) and cardiovascular mortality (HR 1.57, 95% CI 1.15 to 2.14) after adjusting for age and sex. Further adjustment for cardiovascular risk factors and ESR only modestly attenuated this effect. An increase in CHD among the RF-positive subjects did not reach statistical significance (HR 1.32, 95% CI 0.96 to 1.81, adjusted for age and sex). Subjects with RF but without joint symptoms also had increased overall mortality and cardiovascular mortality (HR for overall mortality 1.33, 95% CI 1.01 to 1.74, after adjustment). CONCLUSION: In a general population cohort, RF was associated with increased all-cause mortality and cardiovascular mortality after adjustment for cardiovascular risk factors, even in subjects without joint symptoms.

Increased total mortality and cancer mortality in men with Dupuytren's disease: a 15-year follow-up study.

The aim of the present study was to evaluate the mortality rate and causes of death of individuals with Dupuytren's disease. In 1981/82, as part of The Reykjavík Study, a general health survey, 1297 males were examined for clinical signs of Dupuytren's disease. Based on the clinical evaluation the participants were classified into three groups: (1) those with no signs of Dupuytren's disease were referred to as the reference cohort; (2) those with palpable nodules in the palmar fascia were classified as having stage 1; and (3) those who had contracted fingers or had been operated on due to contractures were classified as having stage 2 of Dupuytren's disease. In 1997, after a 15- year follow-up period, the mortality rate and causes of death were investigated in relation to the clinical findings from 1981/82. Information about causes of death were obtained from the National Icelandic Death Registry and the Icelandic Cancer Registry. During the follow-up period, 21.5% (225/1048) of the reference cohort were deceased compared to 29.9% (55/184) of those with stage 1 and 47.7% (31/65) of those with stage 2 of Dupuytren's disease. When adjusted for age, smoking habits and other possible confounders, individuals with stage 2 of the disease showed increased total mortality [hazard ratio (HR) = 1.6; 95% CI 1.1-2.4]. Cancer deaths were increased (HR = 1.9; CI 1.0-3.6). In contrast, participants with stage 1 of Dupuytren's disease did not show increased mortality. A moderate but non-significant increase in cancer incidence was observed among individuals with stage 2 of Dupuytren's disease (HR = 1.5; 95% CI 0.9-2.4, P = 0.15). The study showed increased total mortality of individuals with Dupuytren's disease stage 2, where 42% of the excess in mortality could be attributed to cancer deaths.