Positive heparin/pf4 antibodies and high mortality rate: a retrospective case-series analysis

Abstract Introduction: Heparin-induced thrombocytopenia (HIT) is a potentially lethal complication of unfractionated or low-molecular weight heparin therapy. We aimed to determine the incidence and mortality rate of patients with positive heparin/platelet factor 4 (PF4) antibodies, which is a rapid detection test of HIT. Methods: Coronary artery bypass grafting and mitral and aortic valve surgeries were evaluated. Cardiopulmonary bypass was employed in all patients. The diagnosis of HIT was based on immunological assays. Postoperative complications, mortality rates, and the causes of death were specified in patients with positive heparin/PF4 antibodies. Results: Postoperative thrombocytopenia was detected in 257 patients. Twenty of these patients undergoing open heart surgery were included in the final analysis. Antibodies against heparin/PF4 complex were positive in 20 patients. The mean body mass index was 28.8±2.3 kg/m2, mean value of left ventricular ejection fraction was 48.3±6.7%, cardiopulmonary bypass time was 113.0±35.0 min, aortic cross-clamping time was 88.0±32.7 min, mean intensive care unit length of stay was 10.9±4.9 days, mean preoperative platelet count was 307.250±88528 platelets/microliter, and mean postoperative platelet count was 243.050±89.354 platelets/microliter. The mean duration of heparin exposure was 6.9±2.9 days. The mortality rate was 45% (nine patients) and 1.2% (three patients) in heparin/PF4 complex positive and negative patients, respectively. Conclusion: Although the incidence of HIT was low in patients undergoing open heart surgery, an increased rate of early mortality was observed in patients with positive heparin/PF4 antibodies.

Downregulation of serum CXCL4L1 predicts progression and poor prognosis in prostate cancer patients treated by radical prostatectomy / 亚洲男科学杂志(英文版)

Our previous study found that plate factor-4 variant (CXCL4L1) was downregulated in the serum of patients with prostate cancer (PCa). The aim of the present study was to investigate the prognostic value of CXCL4L1 in PCa. In total, 213 PCa patients treated with radical prostatectomy were enrolled and peripheral blood samples of all patients were collected. Expression of serum CXCL4L1 in patients with different tumor stages and grades were measured by enzyme-linked immunosorbent assay (ELISA). The Kaplan-Meier method was applied to estimate the progression to castration-resistant prostate cancer (CRPC), metastasis, biochemical recurrence (BCR)-free survival, and overall survival (OS). Prognostic factors for BCR-free survival and OS were determined by univariate and multivariate analyses using the Cox proportional hazards regression model. The expression of CXCL4L1 was significantly lower in PCa patients with advanced pathological tumor stage, high-grade Gleason score, and metastasis. Moreover, downregulation of CXCL4L1 not only strongly correlated with aggressive clinicopathological features, but also predicted tumor progression and unfavorable outcomes. Finally, multivariate Cox regression analyses identified CXCL4L1 as an independent prognostic factor for both BCR-free survival (hazard ratio [HR]: 2.03, 95% confidence interval [CI]: 1.26-3.27; P = 0.004) and OS (HR: 2.26, 95% CI: 1.07-4.79; P = 0.033). In conclusion, our results indicate that CXCL4L1 might serve as a novel and promising prognostic biomarker for patients with PCa and potential therapeutic target in the future.

Diagnostic value of two immunoassays for detecting heparin/PF4 complex antibodies in heparin-induced thrombocytopenia / 中华血液学杂志

Objectives: To assess the diagnostic values of latex immunoturbidimetric assay (LIA) and particle immunofiltration assay (PIFA) for heparin-induced thrombocytopenia (HIT) . Methods: Samples from 94 patients with suspected HIT from May 2016 to July 2018 in our hospital were prospectively analyzed by the two immunoassays. Their medical records and further follow-up data were also collected and analyzed by our hematologists to make the 4Ts scores and confirm the diagnosis of HIT, respectively. Performance characteristics of the two immunoassays were assessed, including sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) . Their post-test probabilities (PTP) were also calculated based on the 4Ts score. Results: Among 94 cases, 15 (16.0%) had a positive HIT, including 6 of 37 (16.2%) with an intermediate, and 9 of 15 (60.0%) with a high 4Ts score. PIFA operating characteristics were: sensitivity 100.0% (15/15) , specificity 51.9% (41/80) , PPV 28.3% (15/53) , NPV 100.0% (41/41) . The positive PTP in intermediate and high 4Ts score group were 28.7% and 75.7%, respectively, while negative PTP were all 0. At manufacturers' cutoffs, LIA operating characteristics were: sensitivity 66.7% (10/15) , specificity 94.9% (75/79) , PPV 71.4% (10/14) and NPV 93.8% (75/80) . The positive and negative PTP in intermediate 4Ts score group were 71.8% and 6.3%, while 95.2% and 34.4% in high 4Ts score group, respectively. Receiver operating characteristic (ROC) analysis manifested that LIA was preferable than PIFA, and combining the 2 assays together was significantly better than single test. Conclusions: 4Ts score is still an important tool for the diagnosis of HIT. Combining clinical score with heparin/PF4 antibody assay can increase the accuracy of confirming or excluding HIT. Although PIFA is inferior to LIA in the diagnostic value, its user friendliness and 100% NPV have major advantages. Combining the 2 assays together can achieve a higher diagnostic value.

Effect of sublingual immunotherapy on platelet activity in children with allergic rhinitis / Efeito da imunoterapia sublingual sobre a atividade plaquetária em crianças com rinite alérgica

Abstract Introduction: The role of platelet activation in allergic inflammation is receiving increasing attention. Sublingual immunotherapy for allergic rhinitis can modify the immunological process to an allergen, rather than simply treating symptoms. Objective: The aim of this study was to explore the role of platelet activation during sublingual immunotherapy in children with allergic rhinitis. Methods: Forty-two House Dust Mite - sensitized children with allergic rhinitis were enrolled and received House Dust Mite allergen extract for sublingual immunotherapy or placebo. Serum of different time points during treatment was collected and used for detection of Platelet Factor-4 and Beta-Thromboglobulin concentration by Enzyme-Linked Immuno Sorbent Assay. Results: Our data showed decreased expression of Platelet Factor-4 and Beta-Thromboglobulin protein after one year's sublingual immunotherapy. In addition, the decrease of symptom scores and serum Platelet Factor-4 and Beta-Thromboglobulin protein concentrations was positively related. Conclusion: During sublingual immunotherapy, platelet activation was inhibited significantly. Our results might indicate that inhibition of platelet activation within the systemic circulation is an important mechanism during sublingual immunotherapy.

Resumo Introdução: O papel da ativação de plaquetas na inflamação alérgica recebeu atenção crescente. A imunoterapia sublingual para rinite alérgica pode modificar o processo imunológico a um alérgeno, em vez de tratar os sintomas simplesmente. Objetivo: Explorar o papel da ativação plaquetária durante a imunoterapia sublingual em crianças com rinite alérgica. Método: Quarenta e duas crianças com rinite alérgica sensibilizadas por ácaros de poeira domiciliar (APD) foram inscritas e receberam extrato de alérgeno de APD para imunoterapia sublingual ou placebo. O soro de diferentes pontos no tempo durante o tratamento foi recolhido e usado para a detecção de fator 4 plaquetário e concentração de beta-tromboglobulina por ensaio imunoenzimático. Resultados: Nossos dados mostraram diminuição da expressão de fator 4 plaquetário e proteína beta-tromboglobulina após imunoterapia sublingual de um ano. Além disso, a diminuição dos escores de sintomas e o fator 4 plaquetário sérico e concentrações de proteína beta-tromboglobulina foram relacionados de maneira positiva. Conclusão: Durante imunoterapia sublingual, a ativação plaquetária foi inibida significativamente. Os nossos resultados podem indicar que a inibição da ativação de plaquetas dentro da circulação sistêmica é um mecanismo importante durante imunoterapia sublingual.

Trombocitopenia inducida por heparina: Nuevas opciones terapéuticas / Heparin-induced thrombocytopenia. New therapeutical options

La trombocitopenia inducida por heparina (TIH) es una reacción adversa inmunológica mediada por la formación de anticuerpos contra el complejo heparina-factor plaquetario 4 (FP4), caracterizada por la presencia de trombocitopenia y la asociación paradojal de trombosis arterial o venosa. Es una complicación poco frecuente pero grave del uso de cualquier tipo de heparina. En tratados con procedimientos cardiovasculares como intervención coronaria percutánea y cirugía de revascularización cardiaca, la prevalencia de anticuerpos es significativamente mayor que en otros escenarios clínicos. El reconocimiento de las características clínicas y de laboratorio permite la suspensión inmediata de la heparina y la instauración de tratamiento anticoagulante alternativo, para evitar la progresión y formación de nuevos trombos y sus complicaciones. En la presente revisión se resumen las diferentes alternativas terapéuticas para la TIH, en particular los anticoagulantes orales directos (DOACS) como el dabigatran, rivaroxaban y apixaban que pueden proporcionar una nueva opción para el tratamiento de TIH.

Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse reaction due to antibodies to a multimolecular complex of heparin and platelet factor 4 (PF4) characterized by moderate thrombocytopenia and paradoxical arterial or venous thrombosis. It is a relatively infrequent complication related to the administration of any type of heparin. In patients undergoing percutaneous coronary revascularization or coronary artery by-pass graft the prevalence of HIT is higher than in other clinical settings. Recognizing clinical and laboratory features of HIT allow immediate discontinuation of heparin and the use of alternative anticoagulants to avoid serious thrombotic complications. In this review, we summarize different therapeutic options for the treatment of HIT with special emphasis on direct oral anticoagulants (DOACS) such as dabigatran, rivaroxaban and apixaban. DOACS might represent a therapeutic alternative for HIT treatment.

Tratamiento exitoso con fondaparinux en trombocitopenia inducida por heparina y trombosis / Successful treatment with fondaparinux in heparin-induced thrombocytopenia and thrombosis

La trombocitopenia inducida por heparina (TIH) es una reacción adversa inmunológica caracterizada por trombocitopenia y la asociación paradojal de trombosis arterial o venosa. Es causada por la formación de anticuerpos IgG contra el complejo multimolecular de heparina-factor plaquetario 4 (FP4). Fondaparinux es un inhibidor selectivo del factor Xa que tiene escasa afinidad por el FP4 y posee un menor potencial para inducir una respuesta inmunológica, haciendo del mismo un agente potencialmente útil en el tratamiento de la TIH. Se presenta el caso de una mujer de 73 años con TIH asociada a fenómenos trombóticos arteriales y venosos, que recibió exitosamente fondaparinux, con normalización del recuento plaquetario y sin progresión trombótica.

Heparin induced thrombocytopenia (HIT) is an immune-mediated adverse reaction characterized by thrombocytopenia and paradoxical arterial or venous thrombosis, due to the formation IgG antibodies directed to a multimolecular complex of heparin-platelet factor 4 (PF4). Fondaparinux is a selective factor Xa inhibitor with little affinity for PF4 and thus less likely to induce an immune response, making fondaparinux a potentially useful drug for the treatment of HIT. Herein we report the case of a 73 years old woman with HIT associated with arterial and venous thrombosis that was successfully treated with fondaparinux, with normalization of the platelet countand without progression of thrombosis.

Heparin-induced thrombocytopenia in patients undergoing cardiac surgery / 中南大学学报(医学版)

OBJECTIVE@#To investigate the incidence for heparin-induced thrombocytopenia (HIT) in patients undergoing cardiac surgery and to evaluate the risk factors for the generation of HIT-antibody.
@*METHODS@#A total of 315 patients undergoing cardiac surgery in the Department of Cardiothoracic Surgery, Xiangya Hospital between December, 2013 and July, 2014 were enrolled for this study. Among them, 120, 154 and 41 were for surgery of congenital heart defect, valve and coronary artery bypass graft, respectively. There were 170 male patients and 69 patients were under 18 years old. Platelet counts, HIT-antibody and concentration of platelet factor 4 (PF4) were tested before and after the surgery. Diagnosis of HIT was based on "4Ts" (Pretest Clinical Scoring System). 
@*RESULTS@#HIT was diagnosed in 11 patients (3.5%, 11/315). And thromboembolic events occurred in 2 of 11 patients with HIT. The positive ratio for HIT-antibody was 36.5% (115/315). The coronary artery disease patients had a higher incidence of HIT than that of either the valve disease or the congenital heart defect (17.1%, 7/41 versus 1.9%, 3/154 or 0.8%, 1/120; P<0.05). The congenital heart defect patients had a higher positive ratio for HIT-antibody than that of both the valve disease and the coronary artery disease. The valve disease patients had a higher positive ratio for HIT-antibody than that of the coronary artery disease (51.7%, 62/120 versus 30.5%, 47/154 versus 14.6%, 6/41; P<0.05). Major postoperative complications occurred more frequently in HIT patients (36.4%, 4/11 versus 10.5%, 32/304; P<0.05). Age was a risk factor for HIT (P=0.030, OR=1.083, 95% CI 1.008-1.163). Cardiopulmonary bypass (CPB) (P=0.037, OR=3.113, 95% CI 1.071-9.050) and age (P<0.001, OR=0.970, 95% CI 0.959-0.982) were risk factors for HIT-antibody.
@*CONCLUSION@#The incidence of HIT is low during cardiac surgery, but HIT is a highly risk factor for the major postoperative complications. More attentions should be paid to these severe complications and the risk factors for HIT.

Platelet Activation Markers (beta-thromboglobulin and platelet factor 4) and Clopidogrel Drug Response in Patients with Myocardiac Infarction

BACKGROUND: Dual antiplatelet therapy (aspirin and clopidogrel) is used to prevent adverse cardiac events in patients undergoing percutaneous coronary intervention (PCI). Some patients do not respond adequately to clopidogrel. Beta-thromboglobulin (beta-TG) and platelet factor 4 (PF-4) can act as markers to detect platelet activation. We investigated the relationship between clopidogrel response and the dynamics of beta-TG and PF4 concentrations. METHODS: This study included 36 myocardial infarction (MI) patients, who underwent PCI and was indicated for dual antiplatelet therapy. Platelet reactivity, using the VerifyNow P2Y12 assay, was measured on the 3rd day of PCI. At the time of admission, and on the 3rd and 10th day of PCI, the plasma beta-TG and PF4 concentrations were quantified. RESULTS: Ten patients (27.8%) were clopidogrel non-responders displaying >208 P2Y12 reaction units. At the time of admission, levels of beta-TG in patients were elevated than that in the healthy controls (P<0.001). A similar trend was observed on the 3rd and 10th day of PCI (P<0.001). The beta-TG levels on the 10th day were reduced than those at the time of admission and on the 3rd day of PCI. PF4 levels were not different between patients and controls, and were not significantly reduced after PCI. Higher beta-TG levels were observed in clopidogrel non-responders on the 10th day, but not significant. CONCLUSIONS: Clopidogrel therapy in MI reduce beta-TG concentration, but the beta-TG and PF4 levels before and after therapy are not associated with the response to clopidogrel. Platelet-derived markers may not be suitable for distinguishing clopidogrel non-responders.

The Role of Platelets in Malarial Acute Lung Injury and Acute Respiratory Distress Syndrome: A World of Possibilities.

In recent decades our understanding of platelets’ role in immune response has increased. Traditionally platelets were considered as bleeding-stopping and thrombosis-causing cells. In recent years the platelets’ role in malarial innate and adaptive immune responses is being recognized. Platelets play critical role in pathogenesis of malaria infection leading to variety of outcomes. It is being realized that platelets play dual role in case of malaria (i) by preventing early stage exponential growth of parasitemia (ii) promoting exaggerated immune responses later. Platelets role in pathogenesis of severe and cerebral malaria has been widely studied. However their role in malaria related acute lung injury and respiratory distress has gained less attention. Recently the presence of active megakaryocytes and proplatelets have been explained in human lungs. Simultaneously, the platelets role in pathogenesis of acute lung injury and respiratory distress (ALI/ARDS) was also recognized. This gives a hint that there is a possible association of platelets with malaria related respiratory diseases as well. ALI/ARDS are characterized by lung edema due to increased permeability of the alveolar-capillary barrier and subsequent impairment of arterial oxygenation. In this review we have attempted to establish the importance of role of platelets in malaria related acute lungs injury and malaria acute respiratory distress syndrome and try to explain the underlying mechanism of this process. In ALI/ARDS, including those caused by malaria, platelets participate sequestration to the vascular bundle facilitating the recruitment of immune cells viz. neutrophils. Additionally, they secrete or induce the secretion of chemokines that result into vascular damage.

Heparin-induced Thrombocytopenia Type II after Free Flap Operation

Usefulness of anti-PF4/heparin antibody test for intensive care unit patients with thrombocytopenia

BACKGROUND: It is critical to differentiate heparin-induced thrombocytopenia (HIT) from disseminated intravascular coagulation (DIC) in heparinized intensive care unit (ICU) patients with thrombocytopenia because the therapeutic approach differs based on the cause. We investigated the usefulness of PF4/heparin antibody tests in these patients. METHODS: A total of 127 heparinized ICU patients whose platelet counts were 50% after 5-10 days of heparin therapy were enrolled. PF4/heparin antibodies were measured using 2 immunoassays. We assessed the probability of HIT by using Warkentin's 4T's scoring system for antibody positive patients and compared routinely performed coagulation test results between patients with and without antibodies to evaluate the ability of these tests to discriminate between HIT and DIC. RESULTS: Positive results were obtained for 14 (11.0%) and 11 (8.7%) patients in the 2 assays. The analysis performed using the 4T's scoring system revealed that 11 of 20 (15.7%) patients with antibodies in at least 1 assay had intermediate or greater probability of HIT. Patients without antibodies had significantly higher levels of D-dimer than those with antibodies. However, there were no intergroup differences in platelet counts, PT, aPTT, fibrinogen, DIC score, and rate of overt DIC. CONCLUSION: Seropositivity for PF4/heparin antibody was 8.7-11.0% in the patients with thrombocytopenia, and more than a half of them had an increased probability of HIT. Among the routine coagulation tests, only D-dimer was informative for differentiating HIT from DIC. PF4/heparin antibody test is useful to ensure appropriate treatment for thrombocytopenic heparinized ICU patients.

The Incidence, Causes, and Prognostic Significance of New-Onset Thrombocytopenia in Intensive Care Units: A Prospective Cohort Study in a Korean Hospital

This study was designed to investigate the incidence, causes, and outcomes of new-onset thrombocytopenia (NOT) in Korean intensive care units (ICUs). A prospective cohort study was conducted in medical ICUs of Samsung Medical Center between August 2010 and February 2011. All newly admitted patients were included if they stayed in the ICU for more than 48 hr and did not have thrombocytopenia upon admission. A total of 186 patients were included. NOT developed in 37.1%. Most common cause of NOT was sepsis with disseminated intravascular coagulation (66.7%), followed by drug-induced thrombocytopenia (18.8%), and heparin-induced thrombocytopenia (2.9%). IgG-specific antibody to platelet factor 4/heparin was positive in 2.4% among patients treated with heparin, and thrombosis occurred in two patients. Twenty eight-day mortality was higher in patients that developed NOT compared to those that did not develop NOT (39.1% vs 12%, P < 0.001). NOT increased the odds ratio of 28-day mortality and was an independent risk factor for mortality (OR 3.52; 95% CI 1.32-9.38; P = 0.012). In conclusion, NOT is common and is an independent risk factor for mortality in Korean ICU patients. Therefore, clinicians should make every effort to correct the causes of NOT.

The Incidence, Causes, and Prognostic Significance of New-Onset Thrombocytopenia in Intensive Care Units: A Prospective Cohort Study in a Korean Hospital

This study was designed to investigate the incidence, causes, and outcomes of new-onset thrombocytopenia (NOT) in Korean intensive care units (ICUs). A prospective cohort study was conducted in medical ICUs of Samsung Medical Center between August 2010 and February 2011. All newly admitted patients were included if they stayed in the ICU for more than 48 hr and did not have thrombocytopenia upon admission. A total of 186 patients were included. NOT developed in 37.1%. Most common cause of NOT was sepsis with disseminated intravascular coagulation (66.7%), followed by drug-induced thrombocytopenia (18.8%), and heparin-induced thrombocytopenia (2.9%). IgG-specific antibody to platelet factor 4/heparin was positive in 2.4% among patients treated with heparin, and thrombosis occurred in two patients. Twenty eight-day mortality was higher in patients that developed NOT compared to those that did not develop NOT (39.1% vs 12%, P < 0.001). NOT increased the odds ratio of 28-day mortality and was an independent risk factor for mortality (OR 3.52; 95% CI 1.32-9.38; P = 0.012). In conclusion, NOT is common and is an independent risk factor for mortality in Korean ICU patients. Therefore, clinicians should make every effort to correct the causes of NOT.

Utility of ELISA Optical Density Values and Clinical Scores for the Diagnosis of and Thrombosis Prediction in Heparin-induced Thrombocytopenia / 대한진단검사의학회지

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction caused by antibodies to the heparin/platelet factor 4 (PF4) complex, resulting in thrombocytopenia and prothrombotic state. HIT diagnosis is challenging and depends on clinical presentation and laboratory tests. We investigated the usefulness of clinical scores and heparin/PF4 ELISA optical density (OD) as a diagnostic marker and thrombosis predictor in HIT. METHODS: We analyzed 92 patients with suspected HIT. The heparin/PF4 antibody was measured using a commercial ELISA kit (GTI, USA). For each patient, the 4 T's score and Chong's score were calculated. RESULTS: Of the 92 patients, 28 were anti-heparin/PF4-seropositive. The 4 T's score and Chong's score showed good correlation (r=0.874). The 4 T's score and OD values showed good performance for diagnosis of the definite and unlikely HIT groups; however, OD levels showed better sensitivity (93.8%) than the 4 T's score used alone (62.5%). Of the 92 patients, 26 developed thrombosis. The OD values were significantly higher in patients with thrombosis than in those without thrombosis (0.52 vs. 0.22, P0.4) had an increased risk of thrombosis (adjusted odds ratio 9.44 [3.35-26.6], P<0.001) and a shorter 250-day thrombosis-free survival (32.1% vs. 54.7%, P=0.012). CONCLUSIONS: ELISA OD values in combination with clinical scoring can improve the diagnosis of and thrombosis prediction in HIT. More attention should be paid to the use of clinical scores and OD values as thrombosis predictors in HIT.

A rare case of arterial thrombosis due to heparin-induced thrombocytopenia / 中华医学杂志(英文版)

A 78-year-old man presented with an eight-hour history of chest distress. Electrocardiograph and serum cardiac enzymes were suggestive of acute inferior myocardial infarction with right ventricular infarction. The patient, who underwent emergency percutaneous coronary intervention, suffered from thrombocytopenia presenting with cerebral infarction and myocadial reinfarction during haparin exposure. The laboratory test for heparin-induced thrombocytopenia (HIT) specific antibodies (heparin-platelet factor, PF4) was positive. The case was diagnosed as arteries thrombosis due to heparin-induced thrombocytopenia; the patient died after cessation of heparin.

The Management of Heparin-induced Thrombocytopenia with Thrombosis after Open Heart Surgery: A Case Report / 대한구급학회지

Heparin-induced thrombocytopenia (HIT) is a prothrombotic, immune-mediated adverse reaction to heparin therapy. It is caused by antibodies binding to a complex of heparin and platelet factor 4, and this leads to platelet activation, excessive thrombin generation and often thrombosis. HIT with thrombosis (HITT) can lead to limb amputation, stroke, myocardial infarction and death. We report here on a case of a HITT patient who was successfully managed with argatroban therapy. Further knowledge is need about the ideal medical management for HITT.

Suppression of multiple myeloma tumor growth in vivo by transfection of platelet factor 4 or 17-70 cDNA / 中国实验血液学杂志

This study was purposed to investigate the effects of viral vector-mediated gene transfer of platelet factor 4 (PF4) or 17-70 cDNA on cell growth of multiple myeloma (MM) in vivo. Full length and p17-70 cDNA of PF4 were cloned into virapower system to transfect packing cell line 293 and produce lentiviral vectors. 3 multiple myeloma cell lines were transferred platelet factor 4 or 17-70 cDNA by lentiviral vectors. SCID-rab mice models of multiple myeloma were established by injecting U266 multiple myeloma cells selected. The human light chain proteins and VEGF in serums of mice were detected every 2 weeks. The volumes and vascular density of tumors as well as survival time of mice were observed. The results showed that the MM cells expressing foreign genes were identified and screened. There were significant difference of VEGF levels in the supernatants of MM cells between each groups (p<0.01). The SCID-rab models of U266 cells were established successfully. There were significant differences in light chain protein and VEGF in serums among three groups (p<0.01). The light chain protein and VEGF in mice serums of 17-70 cDNA groups were less than that of PF4 group (p<0.01). The light chain protein and VEGF in mice serums of PF4 group were less than that of control group (p<0.01). There were significant differences in the tumor volumes and the vascular density of tumor among 3 groups (p<0.05). The results also showed that there were significant differences of overall survival in 3 different groups of SCID-rab MM models. The overall survival in control group was shortest as compared with other groups (p<0.05). It is concluded that the cell growth of multiple myeloma is suppressed in vivo by transfection of platelet factor 4 or 17-70 cDNA and the overall survival of transfected mice will be prolonged.

Anti-heparin/platelet factor 4 antibodies and heparin-induced thrombocytopenia--review / 中国实验血液学杂志

Heparin-induced thrombocytopenia (HIT) is an antibody-mediated complication of heparin treatment that can lead to thrombosis and thromboembolism. HIT is mainly caused by immunoglobulin G (IgG) class among anti-heparin/platelet factor 4 antibodies that bind to epitopes on platelet factor 4 (PF4) released from activated platelets that developed when it forms complexes with heparin. Platelet aggregation and hypercoagulation status result from this process. Besides, the reactions between antibodies and vascular endothelial cells and monocytes are involved in HIT. Laboratory detection of anti-heparin/platelet factor 4 antibodies after heparin administration may help diagnose HIT early. Tests for detecting antibodies to the heparin/PF4 complex can be classified into functional platelet assays (which rely on the demonstration of platelet activation) and immunoassays (which detect the presence of an antibody without regard for its functional ability). But there is no simple and effective test available currently. In this article the anti-heparin/platelet factor 4 antibodies, pathogenesis of HIT, clinical laboratory assays and immunoassays are reviewed.

Effects of stromal cell-derived factor 1 and platelet factor 4 on the adhesion characteristics and chemotactic function of ex vivo expanded umbilical cord blood CD34+ cells / 中国实验血液学杂志

To investigate the effects of stromal cell-derived factor 1 (SDF-1) and platelet factor 4 (PF4) on the homing-related function of expanded ex vivo umbilical cord blood CD34(+) cells, purified cord blood CD34(+) cells were cultured in serum-free medium containing a HGF combination of FL + SCF + TPO (FST) with either 100 ng/ml SDF-1 alone, 100 ng/ml PF4 alone, or both of these 2 cytokines. The expansion rate of CD34(+) cells, colony formation, homing-related functions including expression of homing-related adhesion molecules of expanded CD34(+) cell, adhesion activity and chemotactic function of the re-selected expanded CD34(+) cells were evaluated at different time points. The results showed that expansion rate of CD34(+) cells and expansion multiple of CFU in SDF-1 groups were higher than those in control. The expression of CD49e on the expanded CD34(+) cells was remarkable up-regulated, in contrast, expression of CXCR-4 on the expanded CD34(+) cells was remarkable down-regulated in SDF-1 groups. The expression of CD49e, CD54 and CXCR-4 on the expanded CD34(+) cells were remarkably up-regulated in the PF4 groups. In all the SDF-1 group, PF4 group and SDF-1 plus PF4 group, the ability of expanded CD34(+) cells adhering to fibronectin layer were higher than those in the control on day 10. Spontaneous migration rate of expanded CD34(+) cells in SDF-1 groups were higher than those in control, while SDF-1-induced migration rate were lower than those in control on day 10. SDF-1-induced migration rate in PF4 groups were higher than those in control on day 10. Spontaneous and SDF-1-induced migration rate of expanded CD34(+) cells in the SDF-1 plus PF4 groups were higher than those in control on day 10. It is concluded that, SDF-1 and PF4 can up-regulate expression of adhesion molecules on expanded CD34(+) cells, and retain the adherent and migration ability of expanded CD34(+) cells, which is helpful for the homing of expanded CD34(+) cells. In short, SDF-1 and PF4 are helpful for the homing-related function of the expanded UCB HSPC.

Plasma markers of thrombin generation, fibrinolysis and activated platelets in sickle cell disease

Thrombotic phenomenon has an important role in the vasooclusive manifestations of sickle cell disease [SCD] that dominate its clinical spectrum. For evaluation of thrombotic activities in SCD patients, the markers of thrombin generation: thrombin anti-thrombin complex [TAT] and prothrombin fragment 1, 2 [F 1, 2], enhanced fibrinolysis markers: plasmin anti- plasmin complex [PAP] and D-dimer and platelet activation markers: platelet factor 4 [PF4] and B - thromboglobulin [BTG] were measured in 35 patients with SCD [25 during steady state and 10 during crisis], compared to 12 normal controls. The measurements were performed by enzyme-linked immunosorbent assays. The thrombotic markers [TAT and F 1, 2], fibrinolytic markers [PAP and D-dimer] and platelet activation markers [PF4 and BTG] were significantly increased in SCD patients during steady state. During vasooclusive crisis, there were marked increase in TAT, D- dimer, BTG and PF4 while there was no significant increase in the levels of PAP and F 1, 2. Also, there was significantly positive correlation among thrombin generation markers, platelet activation markers and fibrinolysis markers in SCD patients during steady state. During episodes there was significant positive correlation among markers of thrombin generation, fibrinolysis and platelet activation except PAP and F 1, 2 markers as compared with asymptomatic intervals. We concluded that, during pain episodes, there was enhanced platelet procoagulant activity, elevated fibrinolytic activity and thrombin generation. These changes may predict the frequency of pain. These findings suggested that increased their levels may increase the risk of thrombosis in these patients and establish a relationship between the laboratory determination of these parameters and clinical pain episodes in patients with SCD. The findings of platelet activation, fibrinolytic activity and thrombin generation in asymptomatic patients indicate ongoing subclinical thrombogeinc activity in patients with SCD