Identification of a Novel Gene Mutation in a Chinese Pedigree with X-linked Thrombocytopenia.

BACKGROUND: X-linked thrombocytopenia (XLT) is a milder form of Wiskott-Aldrich syndrome (WAS), characterized predominantly by thrombocytopenia with small-sized platelets. Mutations in the WAS gene are responsible for the disease. We herein detected a new mutation in the WAS gene responsible for XLT in a 3-generation Chinese pedigree. METHODS: Peripheral blood samples were collected from 7 members in the family. WAS gene was amplified from genomic DNA isolated from leucocytes, and then direct sequencing was performed. RESULTS: Three male members of this family (the proband, his younger brother and maternal uncle) had thrombocytopenia and decreased mean platelet volume. A homozygous mutation (T>C) was found at nucleotide position 319 in exon 3, causing the amino acid Tyr (T) to be abnormally changed to His (H) at position 107. Two female members (the proband's mother and grandmother) were carriers of the mutation. CONCLUSIONS: XLT is easy to misdiagnose as immune thrombocytopenic purpura (ITP). The diagnosis of XLT should be considered in any male with congenital microthrombocytopenia or early onset of microthrombocytope-nia (< 7 fL). This article adds to the growing number of known mutations associated with XLT.

Hematologic Manifestations of Brucellosis in Children.

BACKGROUND: Brucellosis is a common zoonosis in the Bedouin population of southern Israel. Limited data exist for the rate and risk factors of hematologic complication of brucellosis in children. We assessed anemia, leukopenia, thrombocytopenia and pancytopenia in childhood brucellosis in southern Israel. METHODS: Our medical center is the sole hospital in southern Israel. All medical files of brucellosis, 2005-2014, identified through positive blood cultures or International Classification of Diseases 9th revision coding with positive serology, were reviewed retrospectively. RESULTS: Overall, 511 brucellosis episodes were identified; 42% (N = 214) with ≥1 cytopenia, including 13% (N = 68) anemia, 28% (N = 144) leukopenia, 14% (N = 74) thrombocytopenia and 2% (N = 9) pancytopenia. Overall, 99.8% of episodes were in Bedouin children and 70% in males. In 79% of episodes, blood culture was positive for Brucella melitensis. Acute infections comprised 84% of all episodes. In univariate analysis, older age (10.49 ± 4.81 vs. 9.25 ± 4.89 years), fever (92% vs. 78%), positive blood culture (84% vs. 75%) and IgM ≥1:640 levels (50% vs. 39%) were associated with cytopenia. In contrast, arthralgia was associated with noncytopenic episodes. In multivariate analyses, older age (odds ratio = 1.063) and fever (odds ratio = 3.127) were associated with cytopenia. CONCLUSIONS: Brucellosis is commonly presented with cytopenia, especially in bacteremic episodes with fever. However, pancytopenia is uncommon and its finding should alert the physician to look for other possible etiologies.

A comparison of TAFRO syndrome between Japanese and non-Japanese cases: a case report and literature review.

TAFRO syndrome was first described as a variant of multicentric Castleman's disease with thrombocytopenia, anasarca, fever, renal dysfunction, and organomegaly. We report the case of a 25-year-old Caucasian male with diagnosis of TAFRO syndrome and present a literature review. The objective of the study was to compare TAFRO syndrome between Japanese and non-Japanese patients. Cases were included by searching the term "TAFRO" in the Medline database using PubMed between 2010 and 2016. The Student t test and Mann-Whitney U test were used to compare continuous variables. Fisher's exact test was used for categorical variables. Statistical significance was set at p < 0.05. Forty-four cases were included. Thirty-two patients (73%) were of Japanese origin. Japanese patients were significantly older than non-Japanese ones (52.0 ± 13.6 years versus 36.9 ± 19.8 years, p = 0.0064) but there was no difference in gender. Creatinine level on admission was significantly higher in the non-Japanese group (1.87 ± 0.84 mg/dL versus 1.32 ± 0.57 mg/dL, p = 0.0347). There were no significant differences concerning lymphadenopathy, elevated number of megakaryocytes on bone marrow aspiration, autoimmune abnormalities, and the following parameters on admission: platelet count, hemoglobin, albumin, alkaline phosphatase (ALP). Corticotherapy was always used on induction for Japanese patients while it was only used in 75% of the cases on induction in non-Japanese patients (p = 0.0166). Our study was the first to compare TAFRO syndrome according to ethnicity. Japanese patients were significantly older and had a significantly lower creatinine level on admission than non-Japanese patients.

Congenital Amegakaryocytic Thrombocytopenia: A Case Series Indicating 2 Founder Variants in the Mississippi Band of Choctaw Indians.

Congenital amegakaryocytic thrombocytopenia is a rare disorder causing thrombocytopenia that progresses to pancytopenia and bone marrow failure if untreated. It is caused by variants in the MPL gene which encodes the thrombopoeitin receptor. In this report, we review 5 cases of congenital amegakaryocytic thrombocytopenia, all of whom belong to the Mississippi Band of Choctaw Indians. There are 2 common variants in these cases: R90X and R537W. One variant was previously reported only once and had unclear significance at that time. With these variants identified, we hope to improve screening that results in earlier diagnosis in the Choctaw population in the future.

Variability in the Use of Platelet Transfusion in Patients with Intracerebral Hemorrhage: Observations from the Ethnic/Racial Variations of Intracerebral Hemorrhage Study.

BACKGROUND: We examined platelet transfusion (PTx) in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study, hypothesizing that rates of PTx would vary among hospitals and depend on whether patients were on an antiplatelet therapy or underwent intracerebral hemorrhage (ICH) surgical treatment. METHODS: The ERICH study is a prospective observational study evaluating risk factors for ICH among whites, blacks, and Hispanics. We identified factors associated with PTx, examined practice patterns of PTx across the United States, and explored the association of PTx with mortality and poor outcome (modified Rankin Scale score 4-6). RESULTS: Nineteen centers enrolled 2572 ICH cases; 11.7% received PTx. Factors significantly associated with PTx were antiplatelet use before onset (odds ratio [OR], 5.02; 95% confidence interval [CI], 3.81-6.61, P < .0001), thrombocytopenia (OR, 13.53; 95% CI, 8.43-21.72, P < .0001), and ventriculostomy placement (OR, 1.85; 95% CI, 1.36-2.52, P < .0001). Blacks were less likely (OR, .57; 95% CI, .41-0.80) to receive PTx. Among patients who received PTx, 42.4% were not on an antiplatelet therapy before onset. Twenty-three percent of patients on antiplatelet therapy received PTx, but percentages varied from 0% to 71% across centers. There was no difference in mortality or poor outcome at 3 months between patients receiving PTx and those who did not. CONCLUSIONS: The frequency of PTx for ICH varies across academic centers. Thrombocytopenia, antiplatelet use, vascular risk factors, and ventriculostomy placement were associated with PTx. PTx was not associated with improved outcomes. We anticipate reduced PTx use over time given recent clinical trial data suggesting its use could be harmful; however, the issue of whether surgical management warrants PTx remains.

[Mutation analysis for a large Chinese family affected with MYH9-related thrombocytopenia].

OBJECTIVE: To analyze the clinical manifestations and mutation of MYH9 gene in a large Chinese family affected with MYH9-related thrombocytopenia. METHODS: After informed consent was obtained; clinical examination and history investigation was performed on 29 members of the family. DNA was extracted using a standard method, then exons 1 to 40 and their corresponding exon-intron junctions of the MYH9 gene were amplified with PCR and subjected to Sanger sequencing. The results were compared to reference sequence from the University of California, Santa Cruz (UCSC) to screen the mutation. PCR and Sanger sequencing was performed on genome DNA of all family members to confirm the identified mutation. RESULTS: The clinical manifestations of family members were prominently heterogeneous. Four affected members showed hearing loss or deafness, two affected members showed nephritis or kidney failure, and other affected members was only characterized by mild bleeding or with no obvious symptoms. A heterozygous missense mutation c.4270G>A (p.Aspl841Asn) in exon 30 of the MYH9 gene was identified in all affected members from this family, which also co-segregated with the phenotype. CONCLUSION: A missense mutation c.4270G>A (p.Aspl841Asn) within the exon 30 of the MYH9 gene was identified to be associated with MYH9-related thrombocytopenia in a Chinese family.

The platelet derived growth factor-B polymorphism is associated with risk of severe fever with thrombocytopenia syndrome in Chinese individuals.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus named SFTS virus (SFTSV). We hypothesize that host genetic variations may contribute to susceptibility to SFTS. RESULTS: Compared with the rs1800818 AA genotype, AG + GG genotypes were significantly associated with increased susceptibility to SFTS (odds ratio, 1.66, 95% confidence interval = 1.28-2.16; P < 0.001). By using the ELISA assay, we observed that PDGF-BB concentration was significantly reduced in acute phase of patients than in the controls (P < 0.001) and recovered patients at 6 month (P = 0.007) and 12 month (P = 0.003). A persistently reduced PDGF-BB was also revealed from the SFTSV-infected C57BL/6J mice (P < 0.001). The rs1800818 G allele was associated with decreased serum PDGF-BB levels in SFTS patients at their early infection (P = 0.015). In accordance, the relative mRNA levels of the at-risk G allele of 1800818 were lower than those of the A allele in heterozygous cell from acute phase of SFTS patients. PDGF-B rs1800818 conferred no susceptibility to severe or fatal outcome in SFTS patients. MATERIALS AND METHODS: An initially small-scale case-control association study guided the selection of platelet derived growth factor-B (PDGF-B) rs1800818 in 1020 SFTS patients and 1353 controls. Functional analyses were conducted to verify the biological significance of rs1800818 polymorphism. CONCLUSIONS: Our findings suggest that the PDGF-B rs1800818 polymorphism might play a role in mediating the susceptibility to SFTS.

Features associated with hematologic abnormalities and their impact in patients with systemic lupus erythematosus: Data from a multiethnic Latin American cohort.

OBJECTIVE: To examine hematological manifestations' correlates and their impact on damage accrual and mortality in SLE patients from the multiethnic, Latin American, GLADEL cohort. METHODS: In patients with recent SLE diagnosis (≤2 years), the association between follow-up hematological manifestations (per ACR criteria) and socio-demographic and clinical variables was examined by univariable and multivariable logistic regressions; their impact on damage accrual and mortality was examined by Poisson and Cox proportional-hazards regression analyses, respectively. RESULTS: Of 1437 patients, 948 (66.0%) developed ≥1 hematological manifestation [5.5% hemolytic anemia (AHA), 16.3% thrombocytopenia, and 56.4% lymphopenia] over 4.3 (3.3) follow-up years. Younger age, Mestizo ethnicity, hematologic disorder (at/or before SLE diagnosis), and first damage recorded were associated with hematological manifestations while antimalarials were negatively associated. AHA (at/or before SLE diagnosis), anti-Sm, and anti-RNP antibodies were associated with subsequent AHA occurrence while musculoskeletal involvement was negatively associated. Thrombocytopenia (at/or before SLE diagnosis), AHA, anti-phospholipid antibodies (aPLs), anti-SSA/Ro, anti-SSB/La antibodies, and first damage recorded were associated with later thrombocytopenia occurrence. Lymphopenia (at/or before SLE diagnosis), younger age at diagnosis, Mestizo ethnicity, having medical insurance, and first damage recorded were associated with subsequent lymphopenia occurrence while antimalarials and azathioprine treatment were negatively associated. AHA was associated with damage accrual and mortality after adjusting for variables known to affect these outcomes. CONCLUSIONS: Mestizo ethnicity and early hematological manifestations are risk factors for their subsequent occurrence while antimalarials have a protective effect. The associations between AHA and aPLs and thrombocytopenia were corroborated. AHA contributes independently to damage accrual and diminished survival.

Deleterious mutation in the FYB gene is associated with congenital autosomal recessive small-platelet thrombocytopenia.

BACKGROUND: The FYB gene encodes adhesion and degranulation-promoting adaptor protein (ADAP), a hematopoietic-specific protein involved in platelet activation, cell motility and proliferation, and integrin-mediated cell adhesion. No ADAP-related diseases have been described in humans, but ADAP-deficient mice have mild thrombocytopenia and increased rebleeding from tail wounds. PATIENTS AND METHODS: We studied a previously reported family of five children from two consanguineous sibships of Arab Christian descent affected with a novel autosomal recessive bleeding disorder with small-platelet thrombocytopenia. Homozygosity mapping and exome sequencing were used to identify the genetic lesion causing the disease phenotype on chromosome 5. Bone-marrow morphology and platelet function were analyzed. Platelets were characterized by scanning electron microscopy. RESULTS: We identified a homozygous deleterious nonsense mutation, c.393G>A, in FYB. A reduced percentage of mature megakaryocytes was found in the bone marrow. Patients' platelets showed increased basal expression of P-selectin and PAC-1, and reduced increments of activation markers after stimulation with ADP, as detected by flow cytometry; they also showed reduced pseudopodium formation and the presence of trapped platelets between the fibrin fibers after thrombin addition, as observed on scanning electron microscopy. CONCLUSIONS: This is the first report of a disease caused by an FYB defect in humans, manifested by remarkable small-platelet thrombocytopenia and a significant bleeding tendency. The described phenotype shows ADAP to be important for normal platelet production, morphologic changes, and function. It is suggested that mutation analysis of this gene be included in the diagnosis of inherited thrombocytopenia.

Related factors of fetal loss in Chinese women with systemic lupus erythematosus: data from Chinese SLE Treatment and Research Group registry IV.

OBJECTIVE: To study the factors associated with fetal loss in Chinese women with systemic lupus erythematosus (SLE) in a large cohort of SLE patients in the CSTAR (Chinese SLE Treatment and Research Group) registry. METHODS: We compared the clinical characteristics and auto-antibody profiles between SLE patients with fetal loss and SLE patients with normal pregnancies. The relationship between selected variables and fetal loss was examined by univariate analysis and binary logistic regression analysis. RESULTS: A total of 992 patients with 2026 pregnancies were recruited. Fifty women experienced fetal loss, including 49 spontaneous abortion, eight stillbirths and three neonatal deaths. The overall fetal loss rate was 3.0% (60/2026). Arthritis and serositis were observed significantly more frequently (P < 0.05) in normal pregnancy women. The rate of thrombocytopenia was significantly increased in patients with fetal loss (30.0% vs. 16.1%, P = 0.010), while there was no statistically significant difference in the frequency of nephropathy, central nervous system involvement between the normal pregnancy group and fetal loss group. Factors that associated with fetal loss included anti-phospholipid antibodies (aPL) (OR 2.299; 95% CI 1.058-4.993; P = 0.035) and anti-Sjögren syndrome antigen A (SSA) antibody (OR 2.283; 95% CI 1.275-4.088; P = 0.005), and thrombocytopenia (OR 2.241; 95% CI 1.192-4.213; P = 0.012). However, arthritis (OR 0.544, 95% CI 0.307-0.965, P = 0.037) was associated with favorable fetal outcome. CONCLUSIONS: Both univariate analysis and binary logistic regression analysis suggest that thrombocytopenia, aPL antibodies and anti-SSA antibody are associated with fetal loss in Chinese SLE women, while arthritis may be a possible factor related to favorable pregnancy outcome.

Population pharmacokinetic/pharmacodynamic modelling of eltrombopag in healthy volunteers and subjects with chronic liver disease.

AIMS: To characterize the pharmacokinetics (PK)/pharmacodynamics (PD) of eltrombopag in chronic liver disease (CLD). METHODS: The PK/PD model was developed using data from 79 CLD patients using nonlinear mixed-effects modelling. RESULTS: The PK of eltrombopag were described by a two-compartment model with dual sequential first-order absorption. Gender, race and severity of CLD were predictors of the apparent clearance of eltrombopag. The PD of eltrombopag in CLD were adequately described by a four-compartment lifespan model, in which eltrombopag stimulated platelet precursor production rate. East Asian CLD patients were less sensitive to the stimulatory effect of eltrombopag. Following a daily dose regimen of 50 mg eltrombopag, the time to achieve peak platelet counts was longer for the CLD population compared with patients who had immune thrombocytopenic purpura, but was comparable to patients with hepatitis C. Likewise, it took a longer time for platelet counts to rebound back to baseline once eltrombopag treatment was discontinued. CONCLUSIONS: The time course of the platelet response in CLD was different from that in immune thrombocytopenic purpura but comparable to that in hepatitis C.

Helicobacter pylori and thrombocytopenia in the pregnant hispanic population.

OBJECTIVE: An association between Helicobacter pylori (H. pylori) and thrombocytopenia has been demonstrated in the literature in a non-pregnant population. The purpose of this study was to determine whether or not there is a similar association in the third trimester of pregnancy in a Hispanic population. METHODS: This is a secondary analysis of 82 pregnant Hispanic women with and without hyperemesis gravidarum who underwent serologic evaluation for H. pylori IgG. Results of complete blood counts obtained in the third trimester were analysed for thrombocytopenia. RESULTS: Of the 82 subjects who had H. pylori testing, 54 subjects had both serum H. pylori IgG results and third trimester platelet levels. The prevalence of thrombocytopenia was 11.1% (6/54). Thirty-six subjects were seropositive for H. pylori IgG and 18 subjects were seronegative. Of the 36 subjects who were H. pylori seropositive, four (11.1%) developed thrombocytopenia compared to three of 18 (16.7%) H. pylori seronegative subjects (P = 0.67). There was no difference between the groups in their mean platelet values (205 K/cu mm vs. 212 K/cu mm, P = 0.69). CONCLUSIONS: In this limited study, we found no association between H. pylori and thrombocytopenia in the pregnant Hispanic population.

Dosing patterns and outcomes in African American, Asian, and Hispanic patients with heparin-induced thrombocytopenia treated with argatroban.

We retrospectively evaluated dosing patterns and 37-day outcomes in argatroban-treated African American (n = 52), Asian (n = 13), and Hispanic (n = 14) patients with heparin-induced thrombocytopenia (HIT). The Asians required a lesser median dose (1.0 microg/kg/min) than the other groups (1.9 microg/kg/min, each) to achieve comparable activated partial thromboplastin times (medians: 61-69 s). Durations of therapy were similar (medians: 4.0-5.5 days). New thrombosis occurred in 11 (21%) African Americans, 1 (8%) Asian, and 1 (7%) Hispanic; of these 13 patients, 9 (69%) had baseline HIT-related thrombosis. Amputation occurred in 6 (12%) African Americans and 3 (21%) Hispanics; of these nine patients, 6 (67%) had diabetes. One (2%) African American and 1 (7%) Hispanic died from thrombosis. The composite of death due to thrombosis, amputation due to ischemic complications of HIT, or new thrombosis occurred in 14 (27%) African Americans, 1 (8%) Asian, and 4 (29%) Hispanics. Two (4%) African Americans and none others (0%) had major bleeding. These findings suggest that despite argatroban anticoagulation, African Americans and Hispanics may have worse outcomes in HIT than Asians. In minority patients with adverse HIT outcomes, baseline HIT-related thrombosis or diabetes is often present.

Features associated with, and the impact of, hemolytic anemia in patients with systemic lupus erythematosus: LX, results from a multiethnic cohort.

OBJECTIVE: To examine the clinical and genetic correlates of hemolytic anemia and its impact on damage accrual and mortality in systemic lupus erythematosus (SLE) patients. METHODS: SLE patients (American College of Rheumatology [ACR] criteria) of Hispanic (Texan or Puerto Rican), African American, and Caucasian ethnicity from the LUMINA (LUpus in MInorities, NAture versus nurture) cohort were studied. Hemolytic anemia was defined as anemia with reticulocytosis (ACR criterion). The association between degrees of hemolytic anemia and socioeconomic/demographic, clinical, pharmacologic, immunologic, psychological, and behavioral variables was examined by univariable and multivariable (proportional odds model) analyses. Genetic variables (FCGR and Fas/Fas ligand polymorphisms) were examined by 2 degrees of freedom test of association and Cochran-Armitage trend tests. The impact of hemolytic anemia on damage accrual and mortality was examined by multivariable linear and Cox regression analyses, respectively. RESULTS: Of 628 patients studied, 90% were women, 19% were Texan Hispanic, 16% were Puerto Rican Hispanic, 37% were African American, and 28% were Caucasian. Sixty-five (10%) patients developed hemolytic anemia at some time during the disease course, 83% at or before diagnosis. Variables independently associated with degrees of hemolytic anemia were African American ethnicity, thrombocytopenia, and the use of azathioprine. Hemolytic anemia was associated with damage accrual after adjusting for variables known to affect this outcome; however, hemolytic anemia was not associated with mortality. CONCLUSION: The association of hemolytic anemia with thrombocytopenia suggests a common mechanism in their pathophysiology. Hemolytic anemia is an early disease manifestation and is associated with African American ethnicity and the use of azathioprine; it appears to exert an impact on damage but not on mortality.

New mutations on platelet GPIIb in Sub-Saharan African populations revealed by genotyping discrepancies.

BACKGROUND: Previous studies of platelet allele frequencies in Sub-Saharan African populations enabled us to identify discrepancies in HPA-3 typing, suggesting the presence of new mutations and of a greater polymorphism than so far described in other populations. OBJECTIVES: To analyze these discrepancies and to assess the factors leading to potential alloimmunization in these populations. SAMPLES: Maternal samples from a Beninese woman following in utero death and panels of blood donors from Benin, Cameroon, Congo, and Pygmies from Central Africa. TECHNIQUES: Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), PCR-sequence specific primers (PCR-SSP) and sequencing techniques. RESULTS: Three new mutations were found on GPIIb gene: exon 26 a) 2614C>A situated between HPA-3 and HPA-9w, b) 2645C>T downstream of HPA-3, c) intron 26 IVS26+89G>A. These mutations may lead to discrepant DNA typing results, due either to a localization in the complementary sequence recognized by the primer or to the appearance of a new enzyme restriction site. Furthermore, a bilateral linkage << deletion (Delta9 bp) intron 21 and the HPA-3b allele (exon 26) >> found in Caucasian, Asian, and Oceanian populations is not found in African populations, suggesting that its appearance was prior to HPA-3. CONCLUSION: Three new mutations have been identified, two of them potentially immunogenic through their position. Furthermore, the polymorphism found on intron 26, localized in the complementary sequence of the PCR primer, may lead to a false typing assignation. It is therefore important to diversify techniques, both genomic (PCR-RFLP and PCR-SSP), and proteomic monoclonal antibody-specific immobilization of platelets antigen (MAIPA) to ensure accurate HPA antigenic system typing.

Clinical features of Thai male lupus: an age-matched controlled study.

To study the prevalence, and clinical and laboratory manifestations of male lupus, and compare these findings with their age-matched female lupus in Thai patients. The medical records of patients with diagnosed Systemic lupus erythematosus (SLE) were reviewed. The clinical and laboratory manifestations were determined. There were 37 males in 508 patients with SLE (7.3%). There was no difference in mean +/- SD age and disease duration between male patients and their 74 female age-matched controls. When compared with females, male lupus patients had a significantly lower prevalence of alopecia (13.6 vs. 44.6%, P = 0.001), arthralgia (2.7 vs. 17.6%, P = 0.032), Raynaud's phenomenon (0.0 vs. 12.2%, P = 0.027), and psychosis (0.0 vs. 13.5%, P = 0.029), but they had a significantly higher prevalence of thrombocytopenia (32.4 vs. 12.2%, P = 0.019) and renal insufficiency (40.5 vs. 16.4%, P = 0.006). Our study showed several existing sex-related differences in the clinical manifestations in Thai SLE patients.

National survey of heparin-induced thrombocytopenia in the haemodialysis population of the UK population.

BACKGROUND: Heparin-induced thrombocytopoenia (HIT) type II is an antibody-mediated, drug-induced thrombocytopenia which is associated with significant morbidity and mortality. Several case reports and small series have described the occurrence of HIT type II in the haemodialysis population and the challenges associated with it. Some of these reports raise the possibility of a recent increase in prevalence of this condition. But to date, there has never been a large study to estimate the prevalence, demography or treatment options for this syndrome in the haemodialysis population. METHODS: The renal units in the UK were surveyed to establish the prevalence of HIT type II syndrome in the haemodialysis population. Demographic data for haemodialysis patients with HIT type II syndrome were gathered and current treatments assessed. RESULTS: Fifty responses from the 81 UK renal units surveyed were received. The combined population for these units was 13 682 patients on dialysis of whom 10 564 were on maintenance haemodialysis. The prevalence and incidence of HIT type II syndrome in the UK haemodialysis population were 0.26 and 0.32 per 100 patients, respectively. The mean age of the patients with HIT type II syndrome was 62 years (range 22-86), 52% were females and 92% were Caucasians. Only 17% of patients have had complications of HIT syndrome. Thirty-six percent of renal units use danaparoid as anticoagulant of choice for patients on haemodialysis with HIT type II syndrome. CONCLUSION: This is the largest survey of HIT type II in the haemodialysis population to date. The prevalence is considerably lower (0.26 per 100 patients) than previous estimates, with only a minority of patients developing complications of the condition. Haemodialysis patients with HIT type II in the UK are predominantly treated with danaparoid.

Systemic lupus erythematosus in a multiethnic US cohort: XLIII. The significance of thrombocytopenia as a prognostic factor.

OBJECTIVE: To examine the clinical correlates of thrombocytopenia and the value of thrombocytopenia as a predictor of disease activity, damage accrual, and mortality in patients with systemic lupus erythematosus (SLE). METHODS: SLE patients participating in a longitudinal multiethnic cohort were studied. Thrombocytopenia was defined as a platelet count <100,000/mm(3) at or before enrollment (baseline). Patients were categorized by the presence and absence of thrombocytopenia. The impact of thrombocytopenia as well as severe thrombocytopenia (platelet count <50,000/mm(3)) on disease activity, damage accrual, and mortality was examined by multivariable analyses. RESULTS: A total of 616 patients were studied; 121 of the patients (20%) had thrombocytopenia, of whom 30 had severe thrombocytopenia. By univariable analyses, those with thrombocytopenia had more pulmonary, neurologic, renal, and hematologic involvement, worse disease activity and damage, and higher mortality rates. By multivariable analyses, thrombocytopenia was associated with higher disease activity over the disease course (P = 0.018), but not with the accrual of damage either at baseline (P = 0.543) or at the last visit (P = 0.086); however, severe thrombocytopenia was associated with damage accrual at the last visit (P = 0.020). When poverty was not included in the models, thrombocytopenia (<100,000/mm(3) or <50,000/mm(3)) was strongly associated with mortality (P < 0.001 for each comparison); however, the level of significance decreased some when poverty was included in the models. CONCLUSION: Thrombocytopenia early in the course of SLE is indicative of more severe and active disease. Severe thrombocytopenia is an independent predictor of damage accrual at the last visit. Thrombocytopenia is also an independent predictor of mortality, albeit of a lesser magnitude than that predicted by poverty. Patients with thrombocytopenia need close monitoring for possible undesirable outcomes.