Riitta Kekomäki

Prevention of alloimmunization in patients with acute leukemia by use of white cell‐reduced blood components—a randomized trial

Platelet refractoriness arising from HLA alloimmunization is a serious complication of transfusion therapy. In a prospective randomized trial, white cell (WBC)‐reduced blood components were compared to standard platelet and red cell concentrates with respect to alloimmunization, refractoriness, and platelet increments after transfusion. Sixteen of 31 adult acute leukemia patients received only WBC‐reduced platelet concentrates (PCs) and red cells (RBCs), with fewer than 106 WBCs per unit. Fifteen control patients received standard blood components with a mean of 0.1 × 109 (PCs) and 1 × 109 (RBCs) WBCs per unit. Platelet loss during cotton‐wool filtration averaged 14 percent (range, 3–32%) from fresh PCs and 24 percent (range, 9–62%) from stored PCs. Filtration did not change corrected increments (CI) measured after transfusion of fresh PCs. The Cl 1 hour after filtration of stored PCs diminished by 27 percent, but the difference was smaller after 18 hours, which suggests better survival of WBC‐reduced platelets. The number of platelet units transfused did not differ in the two groups. No patient in the WBC‐reduced group developed permanent platelet refractoriness; transient HLA antibodies of low titer developed in two patients. In the control group, one patient became refractory because of immunization and two developed transient HLA antibodies. It can be concluded that the reduction of WBCs in blood components can effectively prevent alloimmunization.

Maternal thrombocytopenia at term: a population‐based study

Background. Thrombocytopenia is a common problem during pregnancy and often inappropriately managed. This study aimed to assess the prevalence and causes of maternal thrombocytopenia at term with special attention to immune mechanisms of thrombocytopenia and the need for assessing fetal risks.

Alkali-stable blood group A- and B-active poly(glycosyl)-peptides from human erythrocyte membrane.

The study of the chemical nature of the ABH blood group antigens of the human erythrocyte membrane has been advanced in recent years by the isolation and characterization of several glycosphingolipids with blood group activity [l-3] . It has been reported that blood group ABH activity is present also in glycoproteins of the erythrocyte membrane [4-91. However, since these observations have been mainly based on serological inhibition tests, the presence of blood group-active glycolipids in the glycoprotein preparations cannot be excluded. Owing to the water solubility of the large-molecular size blood groupactive glycosphingolipids (the poly(glycosyl)ceramides), it has been suggested that these glycosphingolipids may have been regarded in some studies as glycoproteins [3]. The occurrence of protein-bound blood group ABH antigens in the erythrocyte membrane has therefore still been a matter of some controversy. In the present paper, we present direct chemical evidence for the occurrence of protein-bound blood group ABH antigens in the erythrocyte membrane. This was accomplished by the preparation of glycopeptides with pronase digestion from lipid-free membrane residues and the isolation of the blood group Aand B-active fractions using the a-galactosyland a-Nacetylgalactosaminyl-binding lectin [ 10,l l] of Bandeiraea simplicifolia (BS I lectin). The glycopeptides are composed of about 50-60 sugar residues/

Platelet alloantigens HPA-1, -2, -3, -5 and -6b in Finns.

SUMMARY. The human platelet alloantigens HPA‐1, ‐2, ‐3, ‐5 and ‐6b in the Finnish population were determined using allele specific restriction analysis (PCR‐ASRA) for HPA‐1, ‐2, ‐3 and ‐5 and monoclonal antibody immobilized platelet antigen (MAIPA) assay for HPA‐1, ‐3a, ‐5b and ‐6b. No discrepancies were observed between the results obtained with the PCR‐method and those obtained serologically. The gene frequencies obtained from 200 unrelated Finns were 0.86 and 0.14 for HPA‐1a and ‐1b, 0.91 and 0.09 for HPA‐2a and ‐2b, 0.59 and 0.41 for HPA.3a and ‐3b and 0.95 and 0.05 for HPA‐5a and ‐5b. The frequency of the HPA‐5b allele (10%) is lower in Finns than in Central‐ or South‐European populations (20–30%). The HPA‐1, ‐2 and ‐3 frequencies did not deviate from those observed in other European populations. The rare HPA‐6b antigen was observed in three of 127 individuals from south‐eastern Finland (2.4%), which suggests that the frequency of this allele in Finland is higher than previously thought.

Systematic screening for genetic polymorphism in human platelet glycoprotein Ibalpha

Glycoprotein Ibalpha (GP Ibα; CD 42b; hereafter GPIBA) is a component of the cell surface receptor for the von Willebrand factor (vWf) on platelets. Immunizations against various platelet surface antigens play a major role in neonatal alloimmune thrombocytopenia and in post-transfusion purpura. Only one antigenic polymorphism in GPIBA has thus far been established: the HPA-2 (Ko) alloantigen system. To screen other polymorphisms in GPIBA systematically, we analyzed the whole coding sequence of theGPIBA gene in 50 Finnish blood donors using the single-strand conformation polymorphism method. In addition to the known polymorphisms, we detected three others. Sequencing of the gene segments carrying the new polymorphisms revealed that none of them changed the predicted amino acid sequence. Polymorphism designatedRS was located five base pairs upstream from the initiation codon at position 3064 and had the gene frequency of 16% forR and 84% forS, respectively, in the Finnish population, and it was detectable by the restriction enzymeHae III. TheEF polymorphism was at position 3842 (Asn242) and the gene frequencies were 97% forE and 3% forF. TheKL polymorphism was at position 4142 (Arg342) and the gene frequencies were 98% forK and 2% forL. The five polymorphic positions in GPIBA formed altogether six different alleles of the gene. The data suggest that there are only a few variable amino acids in GPIBA.

Fibrinolysis, antithrombin III, and protein C in neonates during cardiac operations

Fibrinolysis and coagulation were studied in 10 neonates undergoing cardiac operations for congenital heart defects. Coagulation was activated during cardiopulmonary bypass as evidenced by highly increased prothrombin fragment 1 + 2 levels compared with preoperative values. Prothrombin fragment 1 + 2 levels remained elevated until postoperative day 3. Unlike coagulation, fibrinolysis was not activated during cardiopulmonary bypass but did show late activation on postoperative day 3, as evidenced by elevated levels of the fibrin degradation product D-dimer. Lack of fibrinolytic activation during bypass and its appearance on postoperative day 3 were partly explained by changes observed in tissue plasminogen activator and its inhibitor. During bypass, levels of tissue plasminogen activator and its inhibitor increased by 3.4-fold and 3.2-fold, respectively. In the postoperative period, levels of plasminogen activator inhibitor normalized rapidly whereas tissue plasminogen activator remained elevated, resulting in late fibrinolytic activation on postoperative day 3. In accordance with elevated prothrombin fragment 1 + 2, platelet count, antithrombin III, protein C, prothrombin, and factor VII were decreased on postoperative day 2, indicating ongoing consumptive coagulopathy. Nine patients had antithrombin III and six had protein C levels below age-specific normal ranges, consistent with an acquired deficiency state. Three had central venous thrombosis by postoperative day 4 or 5. In all three, thrombosis was preceded by antithrombin III deficiency, protein C deficiency, and highly elevated plasminogen activator inhibitor (3.7 to 37 times the mean of the other patients) on postoperative days 1 to 3. In conclusion, cardiopulmonary bypass in neonates caused rapid and profound alterations in the coagulation and fibrinolytic systems and initiated consumptive coagulopathy lasting until at least postoperative day 3. Thrombophilic abnormalities in antithrombin III, protein C, and fibrinolysis were frequently found and were associated with serious thrombotic complications.

Fetal intracranial haemorrhages caused by fetal and neonatal alloimmune thrombocytopenia: an observational cohort study of 43 cases from an international multicentre registry

Objective To characterise pregnancies where the fetus or neonate was diagnosed with fetal and neonatal alloimmune thrombocytopenia (FNAIT) and suffered from intracranial haemorrhage (ICH), with special focus on time of bleeding onset. Design Observational cohort study of all recorded cases of ICH caused by FNAIT from the international No IntraCranial Haemorrhage (NOICH) registry during the period 2001–2010. Setting 13 tertiary referral centres from nine countries across the world. Participants 37 mothers and 43 children of FNAIT pregnancies complicated by fetal or neonatal ICH identified from the NOICH registry was included if FNAIT diagnosis and ICH was confirmed. Primary and secondary outcome measures Gestational age at onset of ICH, type of ICH and clinical outcome of ICH were the primary outcome measures. General maternal and neonatal characteristics of pregnancies complicated by fetal/neonatal ICH were secondary outcome measures. Results From a total of 592 FNAIT cases in the registry, 43 confirmed cases of ICH due to FNAIT were included in the study. The majority of bleedings (23/43, 54%) occurred before 28 gestational weeks and often affected the first born child (27/43, 63%). One-third (35%) of the children died within 4 days after delivery. 23 (53%) children survived with severe neurological disabilities and only 5 (12%) were alive and well at time of discharge. Antenatal treatment was not given in most (91%) cases of fetal/neonatal ICH. Conclusions ICH caused by FNAIT often occurs during second trimester and the clinical outcome is poor. In order to prevent ICH caused by FNAIT, at-risk pregnancies must be identified and prevention and/or interventions should start early in the second trimester.

Associations among nucleated cell, CD34+ cell and colony-forming cell contents in cord blood units obtained through a standardized banking process.

Background and Objectives Nucleated cell content is one of the main components used when evaluating cord blood (CB) units for clinical use. However, other indicators of the haematopoietic potential of a CB unit, such as CD34+ cell and colony‐forming cell (CFU‐TOT) content, have also been investigated. The aim of this study was to determine whether the CD34+ cell content could be used in selecting CB collections for banking.

Clinically symptomatic central venous catheter-related deep venous thrombosis in newborns

Salonvaara M, Riikonen P, Kekomäki R, Heinonen K. Clinically symptomatic central venous catheter‐related deep venous thrombosis in newborns. Acta Pædiatr 1999; 88: 642‐6. Stockholm. ISSN 0803‐5253

Cord blood hematopoietic progenitor cell concentration and infant sex

BACKGROUND: Characterization of cord blood facilitates understanding of the factors affecting cord blood transplant quality and improvement of transplantation results. Cord blood obtained from male and female infants has not been thoroughly characterized.