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Introduction: Rituximab, which is widely used in the treatment of B-cell lymphoma, is a chimeric monoclonal antibody directed against the CD20 antigen. Rituximab has many side effects, mainly allergic and neurological. Rituximab may cause thrombocytopenia in the long term after administration. Rare cases of rituximab-induced acute thrombocytopenia have been reported in the literature., Case Report: A 51-year-old female patient who was newly diagnosed with splenic marginal zone lymphoma received rituximab as first-line therapy. Petechiae occurred in the lower extremities on the day following rituximab administration. The blood test showed a severe drop in the platelet count from 112,000/μL to 5000/μL. Blood peripheral smear evaluation confirmed severe thrombocytopenia., Management and Outcome: There was no change in hemoglobin or white blood cell levels. After the diagnosis of rituximab-induced acute thrombocytopenia, thrombocyte suspension was administered due to the risk of bleeding. Close clinical and laboratory observations were made. The platelet count began to rise gradually in the following period. Before the second week of rituximab administration, the platelet count was 122,000/μL. No complications developed after premedication and slow rituximab administration, and subsequent treatments were continued in the same way., Discussion: Rituximab has widespread use, especially in malignancies and autoimmune diseases. Like many monoclonal antibodies, rituximab has several side effects. Thrombocytopenia is a long-term side effect associated with rituximab, and rituximab-induced severe acute thrombocytopenia has been rarely reported. Therefore, it should be kept in mind that severe acute thrombocytopenia may develop after rituximab administration.

Introduction: Pantoprazole is a proton pump inhibitor (PPI) class drug that is widely used in the treatment of SRMD (stress-related mucosal disease in critical ill patients. PPI are one class of drugs used commonly both for treatment and prophylactic therapy for stress ulcers in intensive care unit (ICU). Case: We report a case of a 51-year old male who was referred to PKU Hospital. He was admitted to ICU with diagnosis of Hyperosmolar Hyperglymic State and bronchopneumonia. Thrombocytopenia was noted in admission. There was more than 70% decrease in platelet count after initiation of pantoprazole. Patient received Thrombocyte Concentrate (TC) transfusion and corticosteroid iv for several days, but only had minor increase in platelet count. The platelets recovered after stopping pantoprazole. Discussion: In the present case report, another exposures to parenteral pantoprazole in a dose of 40 mg once daily reproduced the same adverse drug reaction. In comparison to lansoprazole, thrombocytopenia from pantoprazole is more severe that necessitate TC transfusion and corticosteroid trial. However, in the present case, TC transfusion and corticosteroid fail to escalate platelet count. This finding suggests probability of non-immune mechanism of pantoprazole-induced thrombocytopenia. Conclusion: Pantoprazole may induce thrombocytopenia with new features that were immediately developed, resulting a decrease in platelet count >70%. The mechanism found in this case may be non-immune. Drug-induced thrombocytopenia is one of the rare complications that has to be kept in mind with the use of pantoprazole.

Drug-induced immune thrombocytopenia is an isolated thrombocytopenia caused by accelerated platelet destruction from drug-dependent, platelet-reactive antibodies. Heparin-induced thrombocytopenia is the most common drug-induced immune thrombocytopenia. Common implicated antibiotics for drug-induced immune thrombocytopenia include ceftriaxone, trimethoprim-sulfamethoxazole, vancomycin, and penicillin. The platelet nadir can be less than 20 × 10 (9)/L and typically occurs within 1 to 2 weeks of exposure to the inciting drug. Although rare, drug-induced immune thrombocytopenia can be fatal. Diagnosis is made by excluding other causes of thrombocytopenia. Laboratory testing for drug-dependent antiplatelet antibodies is often helpful but not required. Thrombocytopenia typically improves within 1 to 2 days of drug discontinuation and platelet count returns to normal within a week. Identifying and discontinuing the implicated medication is key to prevention of serious complications. A patient case of drug-induced immune thrombocytopenia is described after initiation of empiric piperacillin-tazobactam for refractory right foot cellulitis in the setting of right fourth toe diabetic ulcer.

Alemtuzumab is an anti-CD52 monoclonal antibody used to treat relapsing-remitting multiple sclerosis following failure of second-line medications. It is administered intravenously in 2 treatment sequences 1 year apart. This drug is frequently associated with mild infusion reactions within days of administration, increased infection risk, and long term adverse events from secondary autoimmunity. Alemtuzumab-induced serious immune-mediated thrombocytopenia (ITP) is well-reported and occurred in 1.0-2.2% of participants in initial phase 2 and 3 trials for multiple sclerosis. Significant neutropenia, however, is rare and was only observed in 0.1% of study participants. Delayed neutropenia and/or ITP is thought to occur from secondary autoimmunity. Few case reports have described severe neutropenia occurring beyond 2 months of last alemtuzumab dose. We present an unusual case of delayed combined neutropenia and thrombocytopenia that occurred 15 months after the second infusion of alemtuzumab. The patient was asymptomatic and presented following discovery of neutropenia and thrombocytopenia during routine laboratory studies. The patient responded to steroids initially and was discharged, although outpatient cell counts subsequently revealed recurrent neutropenia and ITP. The adverse drug reaction probability (Naranjo) scale was completed and showed probable likelihood that the adverse event was alemtuzumab-related. Long term screening for delayed hematologic abnormalities, at least 4 years after initial dose, is necessary when using alemtuzumab. Greater research is needed to understand the mechanism of drug-associated neutropenia.

Background: Heparin-induced thrombocytopenia (HIT) is a common differential diagnosis in cardiothoracic surgery. The latex immunoturbidimetric assay (LIA) is an enhanced immunoassay that has recently been introduced for the detection of total HIT immunoglobulin and retains a higher specificity of 95% compared to the enzyme-linked immunosorbent assay., Objectives: To investigate if a semiquantitative relationship exists between increasing LIA levels beyond the current positivity threshold and its correlation to positive serotonin release assay results in cardiothoracic surgery., Methods: This was a multicenter, observational cohort of cardiothoracic surgery patients initiated on anticoagulation with heparin-based products. To conduct sensitivity and specificity analysis of LIA values, HIT positive was defined as a LIA value ≥1 unit/mL and HIT negative was defined as a LIA level <1 unit/mL. A receiver operating characteristic (ROC) analysis was utilized to evaluate the predictive performance of the LIA., Results: At manufactures' cutoffs of ≥1.0 unit/mL, LIA sensitivity and specificity was 93.8% and 22%, respectively, yielding a false positive rate of 78%. At a higher cutoff of 4.5 units/mL, LIA sensitivity and specificity was 75% and 71%, respectively, yielding a false positive rate of 29% and an area under the ROC curve of 0.75 ( P  = .01; 95% confidence interval: 0.621-0.889). Bivalirudin was initiated in 84.6% of false positive LIA results., Conclusion: This study suggests that the diagnostic accuracy of the LIA can be optimized by increasing the LIA positivity threshold. Proposing a higher LIA cutoff, may mitigate unwarranted anticoagulation and bleeding outcomes.

Heparin-induced thrombocytopenia (HIT) is a disorder originating from exposure to heparin and has a spectrum of presentation ranging from asymptomatic positive antibodies to thrombotic complications. When symptomatic, it is associated with morbidity and mortality. The incidence of HIT in the ESRD population is yet to be defined. End-stage renal disease (ESRD) patients are at particular risk due to constant exposure to heparin. The main treatment of HIT is to avoid heparin and pursue alternative anticoagulants. Since 1 of the main advantages of heparin in ESRD patients is the ease of its use due to non-renal clearance, the use of alternative anticoagulants poses yet another challenge for this population due to cost, availability, and adverse effects on ESRD patients. Argatroban seems like the best alternative to heparin in hemodialysis (HD) patients due to its liver clearance. Despite having limited studies in HIT, direct oral anticoagulants (DOACs) were added as a potential treatment for HIT, with apixaban favored in kidney dysfunction as it is the least dependent on kidney clearance. Other treatment modalities exist but are still being studied in ESRD patients. The presence of HIT antibodies is not always associated with clinical syndrome, and some studies suggested that heparin antibodies are transient, and the reintroduction of heparin is still being evaluated as a treatment option. Hence, HIT is a challenging diagnosis in ESRD patients, a population that has frequent exposure to anticoagulants, and a risk/benefit ratio should be weighed between the risk of progression to symptomatic HIT and the benefit of switching to a non-heparin anticoagulant bearing in mind the difficulties associated with the latter.

Background: The differential diagnosis for thrombocytopenia in critical illness is often extensive. This study was performed to determine the incidence of thrombocytopenia in septic patients undergoing continuous renal replacement therapy (CRRT) versus those not undergoing CRRT., Objective: The primary outcome of this study was to compare the development of thrombocytopenia, defined as a platelet count ≤ 100 × 10 3 /mm 3 , in septic patients within 5 days of time zero. Time zero was defined as the baseline platelet count upon hospital admission or CRRT initiation., Methods: An IRB approved, retrospective cohort study was conducted evaluating thrombocytopenia development in critically ill, septic patients who were initiated on CRRT versus those whom were not. Baseline and clinical characteristics were displayed using descriptive statistics. The primary outcome was evaluated overall and in subgroups of CRRT using Chi-square tests., Results: One hundred sixty patients, 80 per arm, were included in the study. Thrombocytopenia development within 5 days occurred more frequently in the renal replacement therapy (RRT) group compared to the control group (67.5% vs. 6.3%, p < 0.001). In the subgroup analysis of the RRT cohort, thrombocytopenia development within 5 days occurred more frequently in the continuous veno-venous hemofiltration (CVVH) group compared to the accelerated veno-venous hemofiltration (AVVH) group (76% vs. 53.3%, p = 0.049)., Conclusion: There is a high likelihood that septic patients initiated on CRRT will develop thrombocytopenia during their hospital stay. Patients receiving CVVH may develop thrombocytopenia more frequently than those receiving AVVH. Overall, CRRT should remain a differential diagnosis for thrombocytopenia development in this patient population.

Introduction: Previous studies have shown that inflammation may contribute to the interplay of endogenous glycosaminoglycans (GAGs) and anti-PF4 antibodies. In this study, we quantified the levels of anti-PF4 antibody isotypes and endogenous GAGs together with inflammatory biomarkers in pulmonary embolism (PE) patients to determine whether there is a relationship in between. Identification of this relationship may provide insight to the complex pathophysiology of PE and HIT and may also be useful for development of potential prognostic, diagnostic and therapeutic interventions., Materials and Methods: Plasma samples from PE patients (n: 210) were analyzed for anti-PF4 antibody isotypes and various thrombo-inflammatory cytokines utilizing commercially available biochip array and ELISA methods. The endogenous GAG levels in PE patients' plasma were quantified using a fluorescence quenching method. The collected data analyzed to demonstrate the relationship between various parameters., Results: The endogenous GAG levels were increased in the PE group ( P  < .05). The levels of anti-PF4 antibody isotypes were higher in varying levels in comparison to the normal group ( P  < .05). Inflammatory cytokines have shown varying levels of increase with IL-6, IL-8 and IL-10 showing the most pronounced values. Mortality outcome was related to increased GAGs and some of the cytokines., Conclusion: In this study, we demonstrated increased levels of anti-PF4 antibody isotypes, endogenous GAGs, and inflammatory biomarkers in a large patient cohort in PE. The levels of the endogenous GAGs and inflammatory biomarkers were associated with PE severity and mortality. More studies are needed to understand this complex pathophysiology.

In patients with severe aortic stenosis, the data about the incidence of acquired thrombocytopenia according to the use of balloon-expandable or self-expandable valves are limited. We investigated the relationship between the post-transcatheter aortic valve replacement (TAVR) thrombocytopenia and the balloon-expandable or self-expandable valves. A total of 127 consecutive patients who underwent TAVR were retrospectively analyzed. Among the study population, 61 (48%) patients underwent TAVR with the balloon-expandable valve and the 66 (52%) patients with the self-expandable valve. Procedural success did not differ between the groups ( P = .575). The access site complications and in-hospital mortality were the same across the groups ( P = .225 and P = .466). However, paravalvular (PV) leaks were significantly higher in the self-expandable valve group ( P = .007). Among all, 65 patients experienced thrombocytopenia, which was more frequent in the self-expandable valve group (63.6 vs 37.7%, P = .005). In multivariate analyses, admission platelet count, PV leak, and self-expandable valve deployment were the predictors of thrombocytopenia ( P = .001, P = .002, and P = .021, respectively). The present study showed a higher incidence of acquired thrombocytopenia in the self-expandable valve group. Although the procedural success was similar between the groups, postprocedural PV leaks were more common in the self-expandable valve group.

Objective: To assess whether children with autoimmune cytopenias prior to or at diagnosis of systemic lupus erythematosus (cSLE), differ phenotypically from other cSLE patients; and have a lower risk and severity of lupus nephritis (LN) as observed in prior adult studies. To assess the effect of prior immune therapy for autoimmune cytopenias on 2-year risk of LN., Methods: This was a retrospective cohort study of incident cSLE cases. We included patients aged less than 17 years at diagnosis. We excluded patients with LN at cSLE diagnosis. Our follow-up period was 2 years. We defined autoimmune cytopenias as either autoimmune hemolytic anemia, immune thrombocytopenia or Evan's syndrome., Results: Forty-three (33%) of the 130 patients had autoimmune cytopenias before or at cSLE diagnosis. Those with autoimmune cytopenias had significantly more neuropsychiatric symptoms and higher mean ESR but less arthritis, malar rash and myositis versus those without autoimmune cytopenias. They had lower 2-year incidence proportion of LN compared to other cSLE patients (7% vs 15%). Of the 16 patients who developed LN, those with autoimmune cytopenias had mostly class V (2 of 3 patients) versus mostly class III and IV in those without autoimmune cytopenias (6 of 12 patients). None of the 13 patients pre-treated for autoimmune cytopenias developed LN., Conclusion: Patients with autoimmune cytopenias before or at cSLE diagnosis have intriguing differences from other cSLE patients. They may represent a unique sub-type of cSLE patients and should be further explored.

Introduction: Proton pump inhibitors (PPIs) may rarely cause thrombocytopenia. To our knowledge, only one case of lansoprazole-induced thrombocytopenia has been reported previously., Case: We report a case of a 50-year-old South Asian male who was admitted to the intensive care unit (ICU) after cardiac arrest during general anesthesia for ureteroscopy. During ICU stay, his platelet count dropped from 315×10 3 /µL to 57×10 3 /µL after 5 days of initiation of lansoprazole for stress-ulcer prophylaxis. After excluding other causes of thrombocytopenia; lansoprazole was stopped and his platelets recovered over the next few days. Later exposure to lansoprazole resulted in another drop in his platelet count with subsequent recovery after discontinuation of lansoprazole. A review of his home medications showed that he had been taking pantoprazole prior to hospitalization., Discussion: Thrombocytopenia has been previously reported with different PPIs. In the previously reported lansoprazole-induced thrombocytopenia, the level of certainty was not high due to lack of re-exposure. In the present case, another exposure to lansoprazole, without intention of rechallenge, reproduced the same adverse drug reaction (ADR). Although platelet-reactive antibodies testing was not available to confirm causation in this case, the Naranjo score was 8 which indicated probable causation by lansoprazole. Despite probable lansoprazole-induced thrombocytopenia, our patient had been tolerating pantoprazole. This finding highlights the different effects of individual PPIs on platelet counts in the same patient., Conclusion: Lansoprazole may cause thrombocytopenia. However, patients who develop lansoprazole-induced thrombocytopenia may tolerate other PPIs.

We report a case of a Chinese neonate who was diagnosed with Noonan syndrome and had persistent, self-limited thrombocytopenia. The neonate was admitted to the Neonatology Department 20 minutes after birth because of respiratory distress. From birth until 2 months of age, platelet values fluctuated between approximately 6 and 30 × 10 9 /L. There was no intracranial hemorrhage. However, the child had a transient hypocalcemic seizure and fever. We excluded thrombocytopenia caused by perinatal asphyxia, immune thrombocytopenia, fetomaternal alloimmune thrombocytopenia, juvenile myelomonocytic leukemia, and chromosome 13, 18, and 21 trisomy syndromes. Despite treatment with anti-infective agents and transfusion of platelets and immunoglobulin, the platelet count did not return to the normal range. Genetic testing confirmed a PTPN11 gene mutation, which led to the diagnosis of Noonan syndrome. At 3 months of age, the platelet count gradually increased without intervention and returned to the normal range by 6 months. We speculate that the thrombocytopenia in this case was closely related to Noonan syndrome.

Rituximab-induced acute thrombocytopenia (RIAT) is a relatively rare complication of rituximab treatment that has been infrequently reported in a number of patients with malignant lymphoma. Most commonly encountered in mantle cell lymphoma, the extent to which RIAT occurs in splenic marginal zone lymphoma is unknown. In this report, we describe a case of RIAT in a patient with splenic marginal zone lymphoma. Rituximab was safely rechallenged with increased premedications and slowed infusion rate. While the exact mechanism of this phenomenon has yet to be elucidated, diligent monitoring of platelet counts following rituximab infusion can be considered in high-risk patients to avoid potential adverse events. Split dose rituximab for high-risk patients may provide an alternative approach to improve patient safety.

Introduction: The present study aimed to investigate the prevalence and influential factors of thrombocytopaenia in systemic lupus erythematosus (SLE) patients among the Chinese population in order to provide evidence for improving the treatment and nursing of SLE patients., Methods: A retrospective analysis of 3140 SLE patients admitted to two large tertiary hospitals was conducted in Anhui, China, from 2011 to 2018. In addition, the influential factors related to SLE with thrombocytopaenia were analysed through univariate and multivariate analysis., Results: A total of 804 SLE patients had thrombocytopaenia (25.6%). The top 5 clinical manifestations of SLE inpatients were proteinuria (51.0%), lupus nephritis (45.9%), new rash (38.4%), haematuria (36.7%) and pyuria (32.2%). The incidence of neurological manifestations, oral mucosal ulceration, pleurisy, pericarditis, hyperglycaemia, leucocytopaenia, urinary casts, haematuria, pyuria and high disease activity in the thrombocytopaenia group were higher than those in the non-thrombocytopaenia group ( p  < 0.05). Multivariate analysis showed age (odds ratio (OR) = 1.009, p  = 0.005), neurological manifestations (OR = 1.373, p  = 0.048), pericarditis (OR = 1.394, p  = 0.048), hyperglycaemia (OR = 1.717, p  < 0.001), leucocytopaenia (OR = 2.551, p  < 0.001), haematuria (OR = 1.582, p  < 0.001), serum C3 level <0.85 g/L (OR = 1.525, p  = 0.001), serum C4 concentration <0.10 g/L (OR = 1.287, p  = 0.020), serum CRP concentration <8 ng/L (OR = 1.314, p  = 0.005), prothrombin time >15.30 seconds (OR = 1.479, p  = 0.032), activated partial thromboplatin time >45 seconds (OR = 1.924, p  < 0.001) and thrombin time >21 seconds (OR = 1.629, p  = 0.015) were associated with thrombocytopaenia., Conclusion: Thrombocytopaenia has a high prevalence in SLE patients and is related to some baseline, clinical and laboratory characteristics, affecting multiple organs and systems.

Diffuse alveolar hemorrhage is a severe respiratory complication of systemic lupus erythematosus. The illness develops over hours to a few days and is the systemic lupus erythematosus-associated syndrome with highest mortality. Although no specific symptoms have been identified, a number of features are associated with diffuse alveolar hemorrhage, with a drop in blood hemoglobin the most prominent. Dyspnea, blood-stained sputum, diffuse infiltrates identified by chest imaging, elevated single breath-diffusing capacity for monoxide, thrombocytopenia and C3 hypocomplementemia are other commonly reported signs of diffuse alveolar hemorrhage. The etiology is not completely understood but many patients develop diffuse alveolar hemorrhage concomitant with lupus nephritis, suggesting immune complex-driven pathology. Biopsy studies have identified both cases with capillaritis and a bland non-inflammatory phenotype. An animal model of diffuse alveolar hemorrhage has indicated requirement of B lymphocytes and complement receptor-mediated apoptotic body phagocytosis by monocytes as part of the pathogenesis. This review will discuss considerations when diagnosing the condition and available therapies. Infections and other causes of hemorrhage have to be excluded as these require different treatment strategies. Methylprednisolone and cyclophosphamide remain the most commonly used therapies. Plasmapheresis and rituximab are other beneficial treatment options. A few studies have also considered intrapulmonary Factor VII therapy, extracorporeal membrane oxygenation and mesenchymal stem cell therapy. There is an unmet need of better definition of diffuse alveolar hemorrhages etiology and pathology for development of improved treatment strategies.

Heparin-induced thrombocytopenia (HIT) is a life and limb-threatening complication of heparin exposure. Here, we review the pathogenesis, incidence, diagnosis, and management of HIT. The first step in thwarting devastating complications from this entity is to maintain a high index of clinical suspicion, followed by an accurate clinical scoring assessment using the 4Ts. Next, appropriate stepwise laboratory testing must be undertaken in order to rule out HIT or establish the diagnosis. In the interim, all heparin must be stopped immediately, and the patient administered alternative anticoagulation. Here we review alternative anticoagulation choice, therapy alternatives in the difficult-to-manage patient with HIT, and the problem of overdiagnosis.

Heparin-induced thrombocytopenia type II (HIT) is a rare but potentially fatal antibody-mediated reaction to all forms of heparin (unfractionated heparin, low-molecular weight heparin, heparin flushes, and heparin-coated catheters), which can lead to HIT with thrombosis. Two tests commonly used to screen for HIT include the enzyme-linked immunosorbent assay (ELISA) and serotonin release assay (SRA). This is a retrospective chart review study conducted from January 1, 2013, through December 31, 2014, to estimate the rate of true HIT in critical care patients at Winthrop-University Hospital, located in Mineola, New York. Patients are classified as positive for HIT if both ELISA and SRA immunoassays are positive. We reviewed 507 heparin immunoassays, excluding 64 who had an inappropriate ELISA test sent due to no administration of heparin, enoxaparin, or heparin lock flush at this or previous hospital stays at Winthrop. Of the 443 heparin immunoassays, ELISA results were positive for 66 patients (15.1%), and only 11 (2.5%) patients had true cases of HIT with a 95% confidence interval of 1.3% to 4.4%. The 4T score for those with true HIT (median: 5.0) was statistically higher compared to those without true HIT (median: 2.0; P < .001). Despite guidelines in place, overtesting for HIT is still a prevalent issue.

Inherited thrombocytopenia is a group of hereditary diseases with a reduction in platelet count as the main clinical manifestation. Clinically, there is an urgent need for a convenient and rapid diagnosis method. We introduced a high-throughput, next-generation sequencing (NGS) platform into the routine diagnosis of patients with unexplained thrombocytopenia and analyzed the gene sequencing results to evaluate the value of NGS technology in the screening and diagnosis of inherited thrombocytopenia. From a cohort of 112 patients with thrombocytopenia, we screened 43 patients with hereditary features. For the blood samples of these 43 patients, a gene sequencing platform for hemorrhagic and thrombotic diseases comprising 89 genes was used to perform gene detection using NGS technology. When we combined the screening results with clinical features and other findings, 15 (34.9%) of 43patients were diagnosed with inherited thrombocytopenia. In addition, 19 pathogenic variants, including 8 previously unreported variants, were identified in these patients. Through the use of this detection platform, we expect to establish a more effective diagnostic approach to such disorders.

We audited the diagnostic accuracy of ROTEM® (TEM Innovations, GmbH, Munich, Germany) measurements of hypofibrinogenaemia (fibrinogen <1.5 g/l) and thrombocytopenia (platelet count <100 x 10 9 /l) in 200 adult non-transplant patients during cardiopulmonary bypass (CPB). Blood samples were obtained for FIBTEM (assay for the fibrin part of the clot), PLTEM (calculated platelet-specific component), and laboratory measurements simultaneously. Our thresholds for FIBTEM and PLTEM were A10 (clot firmness 10 minutes after clotting time) ≤8 mm, and <35 mm respectively. We also calculated the accuracy of smaller thresholds and earlier indices. We found that FIBTEM A10 ≤8 mm had low sensitivity (0.62) for hypofibrinogenaemia. With the 13% hypofibrinogenaemia prevalence in our sample, the positive predictive value (PPV) was 0.47. In contrast, FIBTEM A10 ≤8 mm had higher specificity (0.90) (negative predictive value [NPV] 0.94). Of the other FIBTEM values analysed, only A5 ≤6 mm had similar or superior accuracy. The PLTEM results were less encouraging (sensitivity 0.81, specificity 0.62). With our prevalence of thrombocytopenia (also 13%), the PPV was only 0.24. However, the NPV was high (0.96). Of the other PLTEM values analysed, only A5 <25 mm had similar or superior accuracy. These findings indicate that during CPB FIBTEM A10 ≤8 mm and PLTEM A10 <35 mm have greater accuracy in identifying the absence of hypofibrinogenaemia and thrombocytopenia respectively than their presence. On the basis of these results we would be reassured by FIBTEM A10 values >8 mm and PLTEM A10 values ≥35 mm, but would continue to use laboratory measurements for confirmation. We would not use FIBTEM A10 ≤8 mm or PLTEM A10 <35 mm values alone to guide replacement therapy unless clinical conditions warranted an immediate decision before laboratory measurements were available.

Heparin-induced thrombocytopenia (HIT) remains diagnostically challenging. Immunoassays including PF4/heparin enzyme-linked immunosorbent assay (ELISA) have high sensitivity but low specificity. Whether the heparin neutralization assay (HNA) improves the diagnostic accuracy of the PF4/heparin ELISA for HIT is uncertain. In this study, to assess its clinical utility and evaluate whether it improves the diagnostic accuracy for HIT, we implemented HNA in conjunction with PF4/heparin ELISA over a 1-year period. A total of 1194 patient samples were submitted to the laboratory for testing from December 2015 to November 2016. Heparin neutralization assay alone is a poor predictor for HIT, but it has high negative predictive value (NPV): Cases with %inhibition <70% are always negative for serotonin release assay. It improves the diagnostic positive predictive value (PPV) of ELISA without compromising sensitivity: ELISA optical density (OD) ≥1.4 alone has a sensitivity of 88% (14/16) and a PPV of 61% (14/23); with HNA %inhibition ≥70%, the sensitivity remains 88% (14/16) and PPV is 82% (14/17). 4Ts score correlates with ELISA OD and predicts HIT; the predictive accuracy of 4Ts score is further improved by HNA. Interestingly, HNA %inhibition of <70% correlates with low 4Ts scores. Based on its high NPV, HNA has the potential to facilitate more timely and accurate HIT diagnosis.

Background: Thrombocytopenia and hypofibrinogenemia during neonatal cardiopulmonary bypass (CPB) contribute to bleeding and morbidity. Rotational thromboelastometry (ROTEM) is a viscoelastic assay with a rapid turnaround time. Data validating ROTEM during neonatal cardiac surgery remain limited. This study examined perioperative hemostatic trends in neonates treated with standardized platelet and cryoprecipitate transfusion during CPB. We hypothesized that ROTEM would predict thrombocytopenia, hypofibrinogenemia, and the correction thereof., Methods: Forty-four neonates undergoing CPB were included in this prospective observational study. Blood samples were obtained at Baseline, On CPB, Post-CPB, and Postoperative. The ROTEM analysis included extrinsically activated (Extem) and fibrinogen-specific (Fibtem) assays. Platelet-specific thromboelastometry (Pltem) values were calculated. Platelet and cryoprecipitate transfusion was initiated prior to termination of CPB., Results: Platelet count and Extem amplitude decreased significantly On CPB ( P < .0001), increased significantly Post-CPB ( P < .0001), and Postoperative values were not significantly different from Baseline. Extem amplitude at 10 minutes (A10) > 46.5 mm (AUC = 0.941) and Pltem A10 > 37.5 mm [area under curve (AUC) = 0.960] predicted platelet count > 100 × 10 3 /μL, and they highly correlated with platelet count ( R = 0.89 and R = 0.90, respectively). Fibrinogen concentration and Fibtem amplitude decreased significantly On CPB ( P ≤ .0001) and normalized after cryoprecipitate transfusion. Fibtem A10 > 9.5 mm predicted fibrinogen >200 mg/dL (AUC = 0.817), but it correlated less well with fibrinogen concentration ( R = 0.65)., Conclusions: ROTEM analysis during neonatal cardiac surgery is sensitive and specific for thrombocytopenia and hypofibrinogenemia, identifying deficits within 10 minutes. Platelet and cryoprecipitate transfusion during neonatal CPB normalizes platelet count, fibrinogen level, and ROTEM amplitudes.

Drug-induced immune thrombocytopenia (D-ITP) typically occurs after the patient has been receiving the implicated drug for at least 1 week, due to newly forming drug-dependent antibodies ("typical-onset" D-ITP). A "rapid-onset" form of D-ITP can occur when previous sensitization has occurred, where antibodies have thus already been formed, and a precipitous platelet count fall occurs upon reexposure. Typical-onset D-ITP has been reported after levofloxacin, but the rapid-onset form with a well-documented previous exposure has not been described. We report a 76-year-old male treated with levofloxacin for acute exacerbation of chronic obstructive pulmonary disease. After a single 750 mg oral dose of levofloxacin, his platelet count fell from 187 to 5 × 10 9 /L (nadir) over 4 days. Other causes of thrombocytopenia were ruled out. He had received a previous course of levofloxacin 6 months earlier. Discontinuation of levofloxacin and treatment with intravenous immunoglobulin and dexamethasone resulted in platelet count recovery. Levofloxacin-dependent antibodies were not detectable, consistent with the known low sensitivity of laboratory tests for drug-dependent antibodies, presumably indicating antibodies against levofloxacin metabolites, as is indirectly supported by the abrupt but relatively slow platelet count decline observed. This case illustrates a rapid-onset presentation of levofloxacin-induced D-ITP in the setting of previous drug exposure.

Monitoring of direct thrombin inhibitors (DTIs) in patients with heparin-induced thrombocytopenia (HIT) is primarily performed using the activated partial thromboplastin time (aPTT). This assay is poorly standardized, reagent dependent, and not DTI specific. We compared aPTT, thrombin time (TT), and prothrombin time (PT) to drug levels obtained by the ecarin chromogenic assay (ECA). We analyzed 495 samples of patients with confirmed or suspected HIT on treatment with either argatroban (n = 37) or lepirudin (n = 80). Mean DTI levels ± standard deviation (SD) were 0.41 ± 0.36 µg/mL for argatroban and 0.20 ± 0.21 µg/mL for lepirudin. Results of aPTT were highly variable: 67 ± 22 seconds for argatroban and 55 ± 20 seconds for lepirudin. Significant correlations ( P < .01) were found between ECA-based DTI level and TT (argatroban, r = .820 and lepirudin, r = .830), PT (argatroban, r = -.544), and aPTT (lepirudin, r = .572). However, there was no correlation of aPTT with argatroban or PT with lepirudin concentration. Multiple regression analyses revealed that the TT predicted 54% of argatroban and 42% of lepirudin levels, but no significant impact was seen for PT or aPTT. The aPTT-guided monitoring of DTI therapy leads to a high percentage of patients with inaccurate plasma levels, hence resulting to either undertreatment or overtreatment. Knowledge of baseline values prior to DTI therapy and inclusion of clinical settings are essential for dosing DTIs when using aPTT. However, due to several limitations of aPTT, monitoring according to exact plasma concentrations as obtained by specific tests such as ECA may be more appropriate.

Purpose TAFRO syndrome is a novel disorder manifesting as fever, anasarca, thrombocytopenia, renal insufficiency and organomegaly, and its etiology has not been clarified. The aim of this study was to elucidate similarities and differences between systemic lupus erythematosus (SLE) and TAFRO syndrome. Methods We examined 46 consecutive patients diagnosed with SLE and determined whether they meet the proposed diagnostic criteria for TAFRO syndrome (2015 version). Results Of the 46 patients with SLE, four (8.7%) also met the TAFRO syndrome criteria (TAFRO-like group). All patients in the TAFRO-like group were males, and their mean age was significantly higher than that of the non-TAFRO group (67.5 ± 8.7 vs. 39.3 ± 18.1 years, p = 0.004). C-reactive protein and γ-glutamyl transpeptidase levels were significantly higher, and frequencies of anti-dsDNA and anti-Sm antibodies were significantly lower in the TAFRO-like than non-TAFRO group. Elder cases (onset age ≥ 50 years) met significantly more categories of the diagnostic criteria for TAFRO syndrome than did those with younger cases. Conclusions Several patients with SLE, especially elder cases, showed features similar to those of TAFRO syndrome. Although exclusion of SLE is needed in the diagnostic criteria for TAFRO syndrome, TAFRO syndrome-like SLE should be considered.

Objective The objective of this study was to assess outcomes of childhood systemic lupus erythematosus (cSLE) in three different age groups evaluated at last visit: group A early-onset disease (<6 years), group B school age (≥6 and <12 years) and group C adolescent (≥12 and <18 years). Methods An observational cohort study was performed in ten pediatric rheumatology centers, including 847 cSLE patients. Results Group A had 39 (4%), B 395 (47%) and C 413 (49%). Median disease duration was significantly higher in group A compared to groups B and C (8.3 (0.1-23.4) vs 6.2 (0-17) vs 3.3 (0-14.6) years, p < 0.0001). The median Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI) (0 (0-9) vs 0 (0-6) vs 0 (0-7), p = 0.065) was comparable in the three groups. Further analysis of organ/system damage revealed that frequencies of neuropsychiatric (21% vs 10% vs 7%, p = 0.007), skin (10% vs 1% vs 3%, p = 0.002) and peripheral vascular involvements (5% vs 3% vs 0.3%, p = 0.008) were more often observed in group A compared to groups B and C. Frequencies of severe cumulative lupus manifestations such as nephritis, thrombocytopenia, and autoimmune hemolytic anemia were similar in all groups ( p > 0.05). Mortality rate was significantly higher in group A compared to groups B and C (15% vs 10% vs 6%, p = 0.028). Out of 69 deaths, 33/69 (48%) occurred within the first two years after diagnosis. Infections accounted for 54/69 (78%) of the deaths and 38/54 (70%) had concomitant disease activity. Conclusions This large multicenter study provided evidence that early-onset cSLE group had distinct outcomes. This group was characterized by higher mortality rate and neuropsychiatric/vascular/skin organ damage in spite of comparable frequencies of severe cumulative lupus manifestations. We also identified that overall death in cSLE patients was an early event mainly attributed to infection associated with disease activity.

Background: The prognosis in patients after acute coronary syndromes (ACS) is significantly burdened by coexisting anaemia, leukocytosis and low glomerular filtration rate (GFR). Hyperglycaemia in the early stages of ACS is a strong predictor of death and heart failure in non-diabetic subjects. This study aimed to evaluate the effect of hyperglycaemia, anaemia, leukocytosis, thrombocytopaenia and decreased GFR on the risk of the failure of cardiac rehabilitation (phase II at the hospital) in post-ST-segment elevation myocardial infarction (STEMI) patients., Methods: The study included 136 post-STEMI patients, 96 men and 40 women, aged 60.1 ± 11.8 years, admitted for cardiac rehabilitation (phase II) to the Department of Internal Medicine and Cardiac Rehabilitation, WAM University Hospital in Lodz, Poland. On admission fasting blood cell count was performed and serum glucose and creatinine level was determined (GFR assessment). The following results were considered abnormal: glucose ⩾ 100 mg/dl, GFR < 60 ml/min/1, 73 m², red blood cells (RBCs) < 4 × 106/μl, white blood cells (WBCs) > 10 × 103/μl; platelets (PLTs) < 150 × 10³/ml. In all patients an exercise test was performed twice, before and after the completion of the second stage of rehabilitation, to assess its effects., Results: Based on logistic regression analysis and the results of an individual odds ratio (OR) of the tested parameters, their prognostic impact was determined on the risk of failure of cardiac rehabilitation. This risk has been defined on the basis of the patient's inability to tolerate workload increment >5 Watt in spite of the applied program of cardiac rehabilitation. As a result of building a logistic regression model, the most statistically significant risk factors were selected, on the basis of which cardiac rehabilitation failure index was determined. leukocytosis and reduced GFR determined most significantly the risk of failure of cardiac rehabilitation (respectively OR = 6.42 and OR = 3.29, p = 0.007). These parameters were subsequently utilized to construct a rehabilitation failure index., Conclusions: Peripheral blood cell count and GFR are important in assessing the prognosis of cardiac rehabilitation effects. leukocytosis and decreased GFR determine to the highest degree the risk of cardiac rehabilitation failure. Cardiac rehabilitation failure index may be useful in classifying patients into an appropriate model of rehabilitation. These findings support our earlier reports.

Background: Previous studies have demonstrated optimized diagnostic accuracy in utilizing higher antiheparin-platelet factor 4 (PF4) enzyme-linked immunosorbent assay (ELISA) optical density (OD) thresholds for diagnosing heparin-induced thrombocytopenia (HIT). We describe the incidence of positive serotonin release assay (SRA) results, as well as performance characteristics, for antiheparin-PF4 ELISA thresholds ≥0.4, ≥0.8, and ≥1.0 OD units in the diagnosis of HIT at our institution., Methods: Following institutional review board approval, we conducted a single-center retrospective chart review on adult inpatients with a differential diagnosis of HIT evaluated by both antiheparin-PF4 ELISA and SRA from 2012 to 2014. The major endpoints were to assess incidence of positive SRA results, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy at antiheparin-PF4 ELISA values ≥0.4 OD units when compared to values ≥0.8 and ≥1.0 OD units. Clinical characteristics, including demographics, laboratory values, clinical and safety outcomes, length of stay, and mortality, were collected., Results: A total of 140 patients with 140 antiheparin-PF4 ELISA and SRA values were evaluated, of which 23 patients were SRA positive (16.4%) and 117 patients were SRA negative (83.6%). We identified a sensitivity of 91.3% versus 82.6% and 73.9%, specificity of 61.5% versus 87.2% and 91.5%, PPV of 31.8% versus 55.9% and 63.0%, NPV of 97.3% versus 96.2% and 94.7%, and accuracy of 66.4% versus 86.4% and 88.6% at antiheparin-PF4 ELISA thresholds ≥0.4, ≥0.8, and ≥1.0 OD units, respectively., Conclusion: Our study suggests an increased antiheparin-PF4 ELISA threshold of 0.8 or 1.0 OD units enhances specificity, PPV, and accuracy while maintaining NPV with decreased sensitivity.

Objective To determine the overall prevalence of autoimmune hemolytic anemia (AIHA), and to compare clinical and laboratory features in a large population of children and adult lupus patients at diagnosis. Methods This retrospective study evaluated the medical charts of 336 childhood-onset systemic lupus erythematosus (cSLE) and 1830 adult SLE (aSLE) patients followed in the same tertiary hospital. Demographic data, clinical features and disease activity were recorded. AIHA was defined according to the presence of anemia (hemoglobin <10 g/dL) and evidence of hemolysis (reticulocytosis and positive direct antiglobulin test (DAT)/Coombs test) at SLE diagnosis. Evans syndrome (ES) was defined by the combination of immune thrombocytopenia (platelet count <100,000/mm 3 ) and AIHA. Results The frequency of AIHA at diagnosis was significantly higher in cSLE patients compared to aSLE (49/336 (14%) vs 49/1830 (3%), p = 0.0001), with similar frequency of ES (3/336 (0.9%) vs 10/1830 (0.5%), p = 0.438). The median of hemoglobin levels was reduced in cSLE vs aSLE patients (8.3 (2.2-10) vs 9.5 (6.6-10) g/dL, p = 0.002) with a higher frequency of multiple hemorrhagic manifestations (41% vs 7%, p = 0.041) and erythrocyte transfusion due to bleeding (24% vs 5%, p = 0.025). cSLE patients also had more often constitutional involvement (84% vs 31%, p < 0.001), fever (65% vs 26%, p < 0.001), weight loss > 2 kg (39% vs 6%, p < 0.001), reticuloendothelial manifestations (48% vs 8%, p < 0.001), hepatomegaly (25% vs 2%, p < 0.001) and splenomegaly (21% vs 2%, p = 0.004). Other major organ involvements were common but with similar frequencies in cSLE and aSLE ( p > 0.05). Median systemic lupus erythematosus disease activity index 2000 (SLEDAI-2 K) was comparable in cSLE and aSLE (p = 0.161). Conclusions We identified that AIHA was not a common condition in cSLE and aSLE, with distinct features characterized by a higher prevalence/severity in children and concomitant constitutional symptoms in the majority of them.

The relationship between primary hematologic disease and rheumatologic manifestations is well known, especially acute lymphocytic leukemia, lymphomas, plasma cell dyscrasias and myelodysplastic syndrome (MDS). Currently, more has been described about autoimmune manifestations in chronic myelomonocytic leukemia (CMML). Many different clinical scenarios may lead a patient with MDS/CMML initially to seek a rheumatological unit. Autoimmune features such as polymyalgia rheumatic symptoms, myositis, neutrophilic dermatosis, cutaneous vasculitis and positive antinuclear antibodies (ANA) are some examples of clinical presentation of MDS/CMML. Moreover, peripheral cytopenias are a common initial presentation both for systemic lupus erythematous (SLE) and MDS/CMML. The aim of this study was to describe a case of an elderly woman with thrombocytopenia and positivity of antibodies to anti-extractable nuclear antigens (anti-ENA) as initial manifestation of CMML mimicking SLE, and to present some clues that encourage the clinician to perform a bone marrow study in such a clinical scenario.

We present an 82-year-old man with a history of hairy cell leukemia, having an 11-cm abdominal aortic aneurysm, who also had severe thrombocytopenia (about 20 000 platelets/μL) and splenomegaly at presentation. The patient had unfavorable anatomy for endovascular aneurysm repair, and therefore, an open procedure was planned. To reduce risk for perioperative bleeding and optimize patient preoperative status, a staged approach was employed. Initially, several sessions of embolization of 2 splenic artery branches were performed with the intent to decrease spleen size and to increase platelet count thus decreasing the perioperative bleeding risk. Then, after successfully increasing platelet count (280 000 PLT/μL), open repair of the aneurysm was conducted. This case demonstrates that selective splenic embolization in patients with hypersplenism and subsequent thrombocytopenia who are in need for major surgery may achieve a significant rise in platelet count and optimize patient's preoperative status in order to avoid bleeding complications., (© The Author(s) 2016.)

A 6-year-old child developed heparin-induced thrombocytopenia while on extracorporeal life support. Hours after a difficult transition from heparin to argatroban for anticoagulation therapy, the child underwent heart transplantation. Intraoperative management was plagued with circuit thrombus formation while on cardiopulmonary bypass and subsequent massive hemorrhage after bypass. We review the child's anticoagulation management, clinical challenges encountered, and review current literature related to the use of argatroban in pediatric cardiac surgery., (© The Author(s) 2015.)

Trauma patients are at a high risk of both bleeding and thromboembolism. This study assessed whether conventional coagulation blood tests were reliable predictors of an increased in vitro thrombotic and bleeding tendency of trauma and non-trauma patients. Conventional coagulation blood tests and thromboelastographs of 63 trauma and 63 randomly selected, critically ill non-trauma patients were compared. Increased in vitro thrombotic and bleeding tendencies were defined by a maximum amplitude>72 mm or an angle>74° on the thromboelastograph and a maximum amplitude<54 mm or an angle<47°, respectively. In vitro thrombotic tendency was more common than bleeding tendency and this was not different between the critically ill trauma and non-trauma patients (59% versus 67% with thrombotic tendency, P=0.461; 11% versus 10% with bleeding tendency, respectively, P=0.999). Thrombocytopenia (<150x10(9)/l) and low fibrinogen concentrations (<2 g/l) were the only two factors associated with an increased in vitro bleeding tendency (both P=0.001) and thrombocytopenia was the only factor associated with a lower risk of in vitro thrombotic tendency (21% versus 75%, P=0.001). Platelet counts (Pearson's correlation coefficient [r]: 0.59, P=0.001) and fibrinogen concentrations (r 0.61, P=0.001) both had a relatively linear association with maximum amplitude of the thromboelastograph. Prolonged International Normalized Ratio (>1.5) and activated Partial Thromboplastin Time (>40 seconds) were, however, not significantly associated with an increased in vitro thrombotic or bleeding tendency. In conclusion, in vitro thrombotic tendency was more common than bleeding tendency in critically ill trauma and non-trauma patients. Platelet counts and fibrinogen concentrations were better predictors of increased in vitro thrombotic and bleeding risks than International Normalized Ratio or activated Partial Thromboplastin Time.

Bortezomib treatment requires four visits to a chemotherapy unit in each 21-day cycle. Analysis of the Day 1 full blood count could allow clinicians to predict the risk of Grade 4 thrombocytopenia, thus negating the need to review the full blood count prior to each dose. The freedom to administer bortezomib without reviewing full blood count results on each treatment day could minimise appointment times and be a step toward home administration. A prospective study of treatment authorisation following a full toxicity assessment and full blood count results from the previous treatment day was undertaken. The full blood count results from 27 patients, receiving 381 doses revealed 12 treatment episodes where bortezomib was administered in the presence of Grade 4 thrombocytopenia. One instance of bleeding and two episodes of neutropenic sepsis were detected during toxicity assessments and treatment was not administered. Only one instance of Grade 4 thrombocytopenia was reported on any other treatment day when the Day 1 platelet count was greater than 75 × 10(9) units/l. From this data, Day 1 full blood count parameters were derived, which minimise the risk of Grade 4 haematological toxicity on subsequent treatment days, allowing clinicians to identify suitable patients for administration of bortezomib prior to reviewing full blood count results. When platelet counts on Day 1 are greater than 75 × 10(9) units/l and neutrophil counts are greater than 1.0 × 10(9) units/l, the administration of bortezomib can be authorised without the need for review of the full blood count on subsequent days of that cycle., (© The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Background: Enzyme-linked immunosorbent assay (ELISA) for antiplatelet factor 4 (anti-PF4)/heparin antibodies is expressed in terms of optical density (OD). Previous studies have shown correlation between OD and heparin-induced thrombocytopenia (HIT) diagnosis. However, these were mainly laboratory based., Objective: Retrospective correlation of clinical HIT to ELISA OD., Patients/methods: We conducted a retrospective study involving 104 patients with a positive ELISA for anti-PF4/heparin antibodies between 2008 and May 2012. For each patient, a clinical diagnosis was adjudicated based on different features including "4T scores," laboratory results, and a 3-month clinical follow-up., Results: In this study, 28.8% of the patients were HIT positive, and 71.2% HIT negative. Patients with positive diagnosis had significantly higher mean OD (2.15 ± 0.76 vs 0.83 ± 0.62). Patients with OD <1.0 only had 3.4% positive diagnosis versus 45.5% for OD 1.0 to 2.0 and 78% for >2.0 units., Conclusion: This study is a clinical confirmation that ELISA OD results are correlated with the probability of a clinical diagnosis of HIT.

Guidelines for the diagnosis and management of heparin-induced thrombocytopenia (HIT) vary between hospitals. Recent guidelines recommend initiating alternative anticoagulant therapy in patients with suspected HIT while awaiting laboratory test results confirming the presence of heparin-PF-4 antibodies (PF-4). This retrospective chart review was designed to assess the current state of management of patients with thrombocytopenia suspected to be due to HIT at 26 US hospitals. Most hospitals (25 of 26; 96.2%) had guidelines in place for the management of suspected HIT, with 7 (26.9%) having a "halt heparin, test, and await results" (ie, "test and wait") policy. One-third of hospitals had a wait time for obtaining PF-4 antibodies of 3 days or more. Hospital guidelines for the management of HIT may actually discourage the use of optimal HIT management strategies.

Licorice originates from the root of Glycyrrhiza glabra, which has a herbal ingredient, glycyrrhizic acid, and has a mineralocorticoid-like effect. Chronic intake of licorice induces a syndrome similar to that found in primary hyperaldosteronism. Excessive intake of licorice may cause a hypermineralocorticoidism-like syndrome characterized by sodium and water retention, hypertension, hypokalemia, metabolic alkalosis, low-renin activity, and hypoaldosteronism. In this case report, an association of hypokalemia, edema, and thrombocytopenia that is developed due to the excessive intake of licorice is presented. There are case reports in the literature, which suggest that toxicity findings may emerge with hyperaldosteronism-like manifestations such as hypokalemia, edema, and hypertension. However, any knowledge of thrombocytopenia as a resultant was not encountered among these reported toxic effects. Our case is important because it shows that the excessive intake of licorice may cause a toxic effect in the form of thrombocytopenia. This report is the first presented case to show thrombocytopenia due to licorice syrup consumption.

The widespread usage of blood count autoanalyzers has led to a major improvement in cellular hematology because of quick and accurate results found in most instances. However, spurious test results also can be observed like pseudothrombocytopenia (PTCP). In our study, we aimed to evaluate the clinical and laboratory factors associated with PTCP. Forty-six patients with PTCP and 69 healthy volunteers were enrolled in the study. Sex distribution was similar between the groups. Hospitalization, infection, the use of low-molecular-weight heparin and pregnancy increased the incidence of PTCP. Atherosclerosis and some drugs such as warfarin and calcium channel blockers were associated with PTCP, but the coincidence was not statistically significant. Antinuclear antibody positivity was higher in PTCP group (18.8% vs 7.2%; P=0.033) but anticardiolipin positivity rates were similar when compared to controls. Pseudothrombocytopenia was frequently misdiagnosed, which led to inappropiate treatments. Therefore, this situation should be kept in mind.

A 57-year-old man with metastatic melanoma developed grade 4 thrombocytopenia during treatment with ipilimumab (anti-CTLA-4 antibody). Bone marrow examination confirmed increased megakaryocytes, which supported a diagnosis of drug-induced, immune-mediated thrombocytopenia and he received 1 mg/kg prednisolone and 1 g/kg intravenous immunoglobulin. There was a delayed response to treatment, with the first evidence of rise in platelet count seen after 9 days. This was followed by a complete and sustained resolution of thrombocytopenia. Hematological toxicity has rarely been associated with ipilimumab and to our knowledge this is the first report of isolated grade 4 thrombocytopenia. This case demonstrates the importance of monitoring full blood count in all patients receiving ipilimumab.

Objective: The objective of this study was to determine the role of thrombocytopenia in terms of disease manifestations, disease activity and prognostic impact in a cohort of Tunisian systemic lupus erythematosus (SLE) patients., Methods: The charts of 182 SLE patients diagnosed between 1996 and 2009 were retrospectively reviewed. The clinical manifestations, immunological profiles, disease activity, SLE relapses and survival rate at the time of follow-up were recorded., Results: Thrombocytopenia (<100,000/mm(3)) and severe thrombocytopenia (<20,000/mm(3)) was observed in 19.2% and 4.4%, respectively. Hemorrhagic manifestations were observed in 11 patients (31.4%). Thrombocytopenia was significantly associated with splenomegaly, renal disorders, neurologic manifestations, arterial thrombosis, leucopenia, low C3 level at SLE diagnosis, SLE relapses and infectious complications. Using multivariate logistic regression, thrombocytopenia was independently associated with splenomegaly (odds ratio [OR] = 9.36, p = 0.001), neurologic manifestations (OR = 4.6, p = 0.006) and renal disease (OR = 4.15, p = 0.02). By multivariable Cox proportional hazard regression analyses, thrombocytopenia was associated with the occurrence of mortality after adjusting for variables known to influence it (hazard ratio [HR] = 1.79, p = 0.045). The cause of death was unrelated to hemorrhagic complications in all patients., Conclusion: Our results, concerning North-African SLE patients, confirm the findings of previous studies which suggest that thrombocytopenia correlates with more severe disease and has a negative impact on the survival of lupus patients.

Pseudothrombocytopenia (PTCP) is a laboratory event of platelet clustering related to drugs used for anticoagulation. This condition is engendered by autoantibodies against platelets in usually EDTA-anticoagulated blood. Pseudothrombocytopenia has no clinical significance but when evaluated as true thrombocytopenia, this misconception may lead to unnecessary diagnostic procedures. Heparin-induced thrombocytopenia with thrombosis (HITT) is a complication of heparin treatment caused by heparin platelet factor 4 (HPF-4) antibodies, leading to platelet activation and hypercoagulability. In our study, 48 patients with PTCP and 36 healthy volunteers were included. Heparin platelet factor 4 antibody positivity was detected in 12 patients from PTCP group; nobody from control group had. Citrated serum samples and peripheral blood smears showed normal platelet count. Of the 4 patients using heparin derivative, 1 (2.1%) had antibody positivity but without any bleeding symptoms. In conclusion, HPF-4 antibody positivity might be a risk factor for PTCP. Clinicians should be aware of this kind of condition.

We describe a patient who experienced immediate onset severe thrombocytopenia as part of a hypersensitivity reaction to oxaliplatin, following substantial relatively uncomplicated previous exposure to the drug. We review other reports of acute hematological toxicity from oxaliplatin. We draw attention to the important need for vigilance when patients develop unusual acute symptoms during or shortly after oxaliplatin infusion.

During baseline evaluation prior to a preclinical safety study, a 10-month-old male pure-bred Beagle dog was found to have marked thrombocytopenia (6 × 10(3) platelets [PLT]/µL) associated with a mean platelet volume (MPV) of 17.9 fL. Tests for Rickettsia rickettsii, Ehrlichia canis, and Borrelia burgdorferi were negative. Buccal bleeding time was normal. Over 3 months, PLT were 4 to 141 × 10(3) PLT/µL, and MPV was 11.4 to 25.1 fL; however, PLT were <50 × 10(3) PLT/µL and MPV was >16 fL during most of this period. Antinuclear antibody (ANA) and anti-PLT antibody tests were negative. Genotyping for the presence of a beta 1-tubulin mutation demonstrated the normal wild-type gene. Treatment with prednisone resulted in normal values after only 3 days. Ultrastructure of enlarged PLT was consistent with that of immature PLT, characterized by reduced numbers of peripheral microtubules and the presence of rough endoplasmic reticulum, free ribosomes, Golgi apparatus, and a prominent canalicular system. PLT ultrastructure and glucocorticoid responsiveness supported a diagnosis of immune-mediated thrombocytopenia that was masked by the cyclic nature of PLT decreases and lack of clinical signs. Inclusion of such a dog in a preclinical safety study could result in misinterpretation of clinical pathology findings.

A 19-year-old male was admitted because of the trauma due to sepsis-induced disseminated intravascular coagulation (DIC) and multiple organ failure (MOF). We treated with antibiotics, danaparoid, and continuous hemodiafiltration (CHDF). Once he recovered, but after several days, he had septic shock and MOF again. With treatment, the inflammation and MOF improved but the platelet count was less than 1.0 × 10( 4)/μL. Because of the usage of heparin, we suspected heparin-induced thrombocytopenia (HIT) and measured the HIT antibody and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13). Heparin-induced thrombocytopenia antibody was positive in the second sepsis but negative in the first sepsis. ADAMTS13 activity was low in both sepses. After stopping CHDF and the usage of heparin, his platelet count improved. Thrombocytopenia is the common and occasional condition for DIC. Heparin-induced thrombocytopenia and thrombotic thrombocytopenic purpura is rare but they must be ruled out in thrombocytopenia with nontypical clinical course, and the assays for HIT antibody and ADAMTS13 activity are useful tools.