Objective To study the incidence of leukocytosis and retinoic acid （RA） syndrome in newly diagnosed and relapsed acute promyelocytic leukemia （APL） patients treated with arsenic trioxide （ATO）. Methods Thirty pa...Objective To study the incidence of leukocytosis and retinoic acid （RA） syndrome in newly diagnosed and relapsed acute promyelocytic leukemia （APL） patients treated with arsenic trioxide （ATO）. Methods Thirty patients with newly diagnosed or relapsed APL received ATO for remission induction at the dose of 10 mg/d. RA syndrome was defined when patient was with one or more of the following signs or symptoms： fever, dyspnea, serous cavity effusion, muscular pain, pulmonary infiltration, weight gain, or pulmonary infiltration on chest X-ray. Results Twenty-three （77%） patients achieved complete remission, mean time to remission was 37. 1 days. Leukocytosis was observed in 14 （47%） patients, mean time to leukocytosis was 12. 7 days, median baseline leukocyte count for patients with leukocytosis was 3.1 x 109/L, which was higher than that for patients who did not de,.＇elop leukocytosis （2.6 × 10^9/L, z = - 2. 635, P = 0. 008）. No other cytotoxic therapy was administered, and the leukocytosis resolved in all cases. The RA syndrome was observed in 9 （30%） patients, mean time to diagnose of RA syndrome was 13.9 days, median baseline leukocyte count for patients with RA syndrome was 3.6 × 10^9/L, which was higher than that for patients who did not develop RA syndrome （2. 6 × 10^9/L, z = - 1. 909, P =0. 046）. No patient died of RA syndrome. Conclusion Leukocytosis and RA syndrome are associated with ATO and baseline leukocyte count respectively, and there is distinct link between leukocytosis and RA syndrome.展开更多
Objective To study the effects of constantly slow intravenous arsenic trioxide （As2O2） infusion regimen on decreasing leukocytosis in vivo and in vitro. Methods Three kinds of leukemia cells, NB4, K562, and acute p...Objective To study the effects of constantly slow intravenous arsenic trioxide （As2O2） infusion regimen on decreasing leukocytosis in vivo and in vitro. Methods Three kinds of leukemia cells, NB4, K562, and acute promyelocyfic leukemia （APL） cells, were cultured in the media with constant concentration and varying concentrations of As2O3 respectively for 24 hours. Seventyfive patients were enrolled in two groups randomly. In trial group, 37 patients received continuously slow intravenous As2O3 infusion regimen for 24 hours with an infusion rate of 8 drips per minute and total infusion duration of about 18- 21 hours daily. In control group, 38 patients received routine regimen with an infusion rate of 45-55 drips per minute and total infusion duration of about 2-3 hours daily for 24 hours. The daily As2O3 dosage was 0. 16 mg/kg. The intracellular arsenic concentration was measured by atomic fluorescence assay. The apoptosis rate of cells, CD33 ^- CD11b ^＋ cells, and CD33^ ＋ CD11b^ - cells were monitored by flow cytometry. Results The apoptosis rates of NB4, K562, and APL leukemia cells in the media with constant As2O3 concentration were 56.6% ±2.4%, 27.6% ±3.1%, and 52.2% ±2. 8%, respectively, which were significantly higher than those with changing As2O3 concentration （23.2% ±2. 1%, 11.0% ±2.5%, and 21.0% ±2.5%, respectively, P〈 0.01）. The apoptosis rates of APL, M2 type acute myeloid leukemia （AML-M2）, and chronic myeloid leukemia （CML） patients in the trial group （28.5% ±1.9%, 9.5% ±0.6%, and 12.5% ±1.8% ） were also significantly higher than those in control group （8.5% ± 2. 2%, 2. 9% ± 0. 8%, and 4. 5% ± 1.2% ; P 〈 0.05 ）. The ratios of CD33 ~ CD11b^- and CD33^- CD11b^＋ cells in control group were significantly higher than those in trial group. Conclusion The continuously slow intravenous As2O3 infusion regimen can obtain high efficiency of apoptosis and low differentiation proportion, relieve leukocytosis, and gain maximal therapeutic benefit.展开更多
AIM: To investigate the effects of exercise on healthy individuals of both genders. METHODS: This study lasted 6 years and involved about 800 healthy people. Individuals were divided into females and males and further...AIM: To investigate the effects of exercise on healthy individuals of both genders. METHODS: This study lasted 6 years and involved about 800 healthy people. Individuals were divided into females and males and further sub-divided into two groups; in the first group individuals run(or skied in the winter time) and then rested for 3 h, whereas individuals in the second group intensely cycled for 5 min. The status of health was determined by measuring the sedimentation rate and the intensity of exercises by measuring the heart rate. Blood samples were collected before and after exercise. RESULTS: We observed that in the first group a significant increase of the total white blood cells, segmented neutrophils, band neutrophils, eosinophils and to a lesser extent lymphocytes but not monocytes in the blood circulation. However, all cell types were increased in the circulation after 5 min intense exercise. No differences in the pattern of cell increase were observed among the genders. Activated partial thromboplastin time(APTT) and D-dimer were also measured in the blood of individuals who cycled intensely for 5 min to determine the coagulation and fibrinolytic activities in the blood. APTT is reduced and D-dimer values significantly increased after intense exercise. However, APTT was statistically lower in males than females, whereas no differences in the D-dimer values were observed among the genders. CONCLUSION: Our results indicate that exercise whether leisure or strenuous affects leukocytosis and hemostasis in both genders. A major advantage of this study is the high numbers of individuals involved and the inclusion of both females and males values.展开更多
Background and Objectives: Search for inexpensive laboratory markers have identified associations between blood counts and lung cancer outcomes. In this study, we evaluated the prognostic value of paraneoplastic leuko...Background and Objectives: Search for inexpensive laboratory markers have identified associations between blood counts and lung cancer outcomes. In this study, we evaluated the prognostic value of paraneoplastic leukocytosis(p-Leukocytosis) and paraneoplastic thrombocytosis(p-Thrombocytosis) in patients with non-small cell lung cancer(NSCLC). We also studied their relation to the expression of commonly detected molecular markers. Methods: We conducted a retrospective chart review on 571 consecutive NSCLC patients over a 10 year period. Blood counts were recorded at the time of cancer diagnosis. Kaplan-Meier survival curves were used to compare overall survival(OS) between patients with and without p-Leukocytosis(or) p-Thrombocytosis(p-Leuko/Thrombocytosis). Cox regression was used to determine if leukocytosis/thrombocytosis was a predictor of OS in NSCLC.Results: Patients with p-Leukocytosis and p-Thrombocytosis had a significantly poorer survival compared patients with normal blood counts(P<0.001). In a multivariate survival analysis, both continued to correlate even when adjusted for histology, gender, stage and chemotherapy(P<0.01, 0.03 respectively). Stage I and II NSCLC with p-Leuko/Thrombocytosis did not perform poorly compared to stage I/II NSCLC patients without paraneoplasia. Patients with the combined leukothrombocytosis syndrome did not have worse outcomes compared to those with either paraneoplastic syndrome alone. Conclusions: p-Leuko/Thrombocytosis is an accessible laboratory parameter of prognostic value in NSCLC. Evidence of p-Leuko/Thrombocytosis portends poor survival. The role of various cytokines in tumor pathobiology provides a rationale for identifying cytokine factors responsible for the paraneoplasia and administering anti-cytokine therapies alongside traditional chemotherapy in an attempt to improve survival outcomes in these subset of patients.展开更多
Driver mutations in patients with non-small cell lung cancer(NSCLC)can lead to distinct behaviors and patterns of metastasis.Mutations in the proto-oncogene B-raf(BRAF)occur in approximately 3%of NSCLC cases.In the li...Driver mutations in patients with non-small cell lung cancer(NSCLC)can lead to distinct behaviors and patterns of metastasis.Mutations in the proto-oncogene B-raf(BRAF)occur in approximately 3%of NSCLC cases.In the literature,reports of patients with lung adenocarcinomas metastasizing to the duodenum are rare,and most of the only 21 cases reported were from before the advent of next-generation sequencing.We present here a case involving a 57-year-old female who had a lytic lesion in her lesser trochanter.Biopsy showed metastatic adenocarcinoma of lung origin.Chest X-ray showed a large left upper lobe mass.Next-generation sequencing analysis confirmed the presence of BRAF V600 Q mutation.The patient presented with persistent anemia and melena.Esophagogastroduodenoscopy confirmed the presence of duodenal metastasis.She also had suspected paraneoplastic leukemoid reaction.To our knowledge,this is only the second well-documented case of gastrointestinal metastasis from BRAF-mutated lung cancer.展开更多
BACKGROUND Pregnancy is a complex physiological process.Physiological leukocytosis occurs often and is mainly associated with increased neutrophil counts,especially in the third trimester of pregnancy.Non-congenital l...BACKGROUND Pregnancy is a complex physiological process.Physiological leukocytosis occurs often and is mainly associated with increased neutrophil counts,especially in the third trimester of pregnancy.Non-congenital leukocytosis with white blood cell counts above 20×109/L lasting 13 wk during pregnancy is rare and has been reported occasionally.Herein,we present a case of pregnancy-induced leukocytosis.CASE SUMMARY We present the case of a 33-year-old Chinese woman at 27 wk of gestation who had a leukocytosis complication.No abnormalities were detected in the examinations before pregnancy or in the first trimester.From the third trimester of pregnancy,the patient began to suffer from asymptomatic leukocytosis.We administered antibiotics to treat the patient;however,the complication persisted until the patient underwent a cesarean section after 40+3 wk of gestation.One day after the cesarean section,the patient’s neutrophil count returned to normal.After 2 years of follow-up,we found that the patient and baby were healthy.CONCLUSION Pregnancy-induced leukocytosis seems to be associated with immunoregulation and pregnancy termination may be the most effective treatment approach for pregnancies complicated with malignant leukocytosis.展开更多
Lung cancer is the most common cancer-related death in both men and women in the world. Approximately 25% of all cancer deaths are attributable to lung carcinoma. Moreover, about one-half of patients with lung cancer ...Lung cancer is the most common cancer-related death in both men and women in the world. Approximately 25% of all cancer deaths are attributable to lung carcinoma. Moreover, about one-half of patients with lung cancer have metastases at the time of initial diagnosis, most frequently of lymph nodes, adrenals, liver, bone and brain. However metastasis to the colon is very rare. Over the past 25 years about 13 cases of symptomatic colonic metastases from lung malignancies of all types have been reported in the literature. Hypercalcemia and leukocytosis are two of the most common paraneoplastic syndromes associated with various malignancies. However, concomitant manifestation of hypercalcemia and leukocytosis are occasionally observed in the same cancer patients. Here, we present a rare case of colonic metastasis from a squamous cell carcinoma of the lung associated with paraneoplastic syndromes of hypercalcemia and leukocytosis.展开更多
Myelofibrosis (MF) represents the major long-term complication of essential thrombocythemia (ET). There is evidence that leukocytosis at diagnosis is associated with poorer survival in patients with ET. In this study,...Myelofibrosis (MF) represents the major long-term complication of essential thrombocythemia (ET). There is evidence that leukocytosis at diagnosis is associated with poorer survival in patients with ET. In this study, we retrospectively evaluated 143 patients with ET, diagnosed in agreement with WHO criteria, followed in a single centre over >10 years. Nine of them transformed into MF (post-essential thrombocythemia-myelofibrosis PET-MF). We compared PET-MF data at diagnosis with that of the remaining 134 patients (ET-1) and with a selected sub-group of ET-1 (ET-2, 19 pats) sex, age and follow-up duration matched to PET-MF. The PET-MF evolution rate was 4.6 per 1000 person-years;white blood cells count (WBC) count, haemoglobin levels and hematocrit were higher in PET-MF than in ET-1 (P = 0.01) while only WBC was higher than in ET-2 (P = 0.01). With multivariate analysis, only WBC count retained its signifi-cance. Our study highlights the prognostic relevance of leukocytosis on myelofibrotic transformation of ET.展开更多
Leukocytosis or hyperleukocytosis occurs during ATRA or arsenic trioxide differentiation therapy, which is related to the RA syndrome. The number of WBC often increased by ten or more times as high as that of pretreat...Leukocytosis or hyperleukocytosis occurs during ATRA or arsenic trioxide differentiation therapy, which is related to the RA syndrome. The number of WBC often increased by ten or more times as high as that of pretreatment, around 7 to 20 days after treatment with ATRA or arsenic trioxide. Usually, when number of WBC tended to peak, there was concomitance with down-regulation of promyelocytes, up-regulation of myelocytes and more mature neutrophils. The same trend of classification of BM was observed in most of the patients with APL to whom leukocytosis happened. Although the mechanism of leukocytosis has not been demonstrated clearly, so far the proliferation hypothesis by cytokines and rheological hypothesis by adhesion molecules were taken into consideration. Otherwise, hypothesis about more divisions of differentiated myelocytes induced by ATRA or arsenic trioxide remains unclear. Usually, this kind of leukocytosis or hyperleukocytosis itself requires no additional cytotoxic treatment.展开更多
Objective To explore the mechanism of leukocytosis Methods Enzyme linked immunosorbent assay (ELISA) method was used for detecting levels of serum granulocyte colony stimulating factor (G CSF) in 47 cases of acu...Objective To explore the mechanism of leukocytosis Methods Enzyme linked immunosorbent assay (ELISA) method was used for detecting levels of serum granulocyte colony stimulating factor (G CSF) in 47 cases of acute promyelocytic leukemia (APL) during the treatment with all trans retinoic acid (ATRA) Results The peak of increased serum G CSF level occurred on the 9th day, and WBC number was the highest on the 11th day After ATRA treatment, both serum G CSF level and WBC number increased in 68 1% of the cases In 19 2% of the cases treated, serum G CSF level was increased but without obvious change in WBC number, and the reverse was true in 12 7% of the cases Conclusion Serum G CSF level was statistically correlated to the number of WBC, promyelocytes and its late stage by Spearman's rank order correlation coefficient展开更多
AIM： To investigate acute transient hepatocellular injury in patients with cholelithiasis and cholecystitis but no evidence of choledocholithiasis.METHODS： The medical records of patients with cholelithiasis who und...AIM： To investigate acute transient hepatocellular injury in patients with cholelithiasis and cholecystitis but no evidence of choledocholithiasis.METHODS： The medical records of patients with cholelithiasis who underwent cholecystectomy between July 2003 and June 2007 were retrospectively reviewed. Imaging studies to detect common bile duct （CBD） stones were performed in 186 patients, who constituted the study population. Biochemical liver tests before and after surgery, and with the presence or absence of CBD stones were analyzed.RESULTS： In 96 patients with cholelithiasis and cholecystitis without evidence of CBD stones, 49 （51.0%） had an alanine aminotransferase level elevated to 2-3 times the upper limit of normal, and 40 （41.2%） had an elevated aspartate aminotransferase level. Similar manifestations of hepatocellular injury were, as would be expected, even more obvious in the 90 patients with CBD stones. These markers of hepatocellular injury resolved almost completely within 2 wk to 1 mo after cholecystectomy. Compared to 59 patients with histologically less severe cholecystitisin the group undergoing urgent surgery （total 74 patients）, the 15 patients with a gangrenous gallbladder had a higher mean level of total bilirubin （2.14 ± 1.27 mg/dL vs 2.66 ± 2.97 mg/dL, P 〈 0.001） and white cell count （9480 ± 4681/μL vs 12840 ± 5273/μL, P = 0.018）.CONCLUSION： Acute hepatocellular injury in cholelithiasis and cholecystitis without choledocholithiasis is mild and transient. Hyperbilirubinemia and leukocytosis may predict severe inflammatory changes in the gallbladder.展开更多
AIM: To investigate the prognostic significance of perioperative leukopenia in patients with resected gastric cancer.METHODS: A total of 614 eligible gastric cancer patients who underwent curative D2 gastrectomy and a...AIM: To investigate the prognostic significance of perioperative leukopenia in patients with resected gastric cancer.METHODS: A total of 614 eligible gastric cancer patients who underwent curative D2 gastrectomy and adjuvant chemotherapy were enrolled in this study. The relationship between pre- and postoperative hematologic parameters and overall survival was assessed statistically, adjusted for known prognostic factors.RESULTS: The mean white blood cell count(WBC) significantly decreased after surgery, and 107/614(17.4%) patients developed p-leukopenia, which was defined as a preoperative WBC ≥ 4.0 × 109/L and postoperative WBC < 4.0 × 109/L, with an absolute decrease ≥ 0.5 × 109/L. The neutrophil count decreased significantly more than the lymphocyte count. P-leukopenia significantly correlated with poor tumor differentiation and preoperative WBC. A higher preoperative WBC and p-leukopenia were independent negative prognostic factors for survival [hazard ratio(HR) = 1.602, 95% confidence interval(CI): 1.185-2.165; P = 0.002, and HR = 1.478, 95%CI: 1.149-1.902; P = 0.002, respectively] after adjusting for histology, Borrmann type, p TNM stage, vascular or neural invasion, gastrectomy method, resection margins, chemotherapy regimens, and preoperative WBC count. The patients with both higher preoperative WBC and p- leukopenia had a worse prognosis compared to those with lower baseline WBC and no p-leukopenia(27.5 mo vs 57.3 mo, P < 0.001). CONCLUSION: Preoperative leukocytosis alone or in combination with postoperative leukopenia could be independent prognostic factors for survival in patients with resectable gastric cancer.展开更多
Interstitial lung and liver disease(ILLD) is caused by biallelic mutations in the methionyl-tRNA synthetase(MARS) gene. To date, no genetic changes other than missense variants were reported in the literature. Here, w...Interstitial lung and liver disease(ILLD) is caused by biallelic mutations in the methionyl-tRNA synthetase(MARS) gene. To date, no genetic changes other than missense variants were reported in the literature. Here, we report a five-month old female infant with typical ILLD(failure to thrive, developmental delay, jaundice, diffuse interstitial lung disease, hepatomegaly with severe steatosis, anemia, and thrombocytosis) showing novel phenotypes such as kidney stones, acetabular dysplasia, prolonged fever, and extreme leukocytosis. Whole exome sequencing revealed a novel truncating variant(c.2158 C>T/p.Gln720 Stop) together with a novel tri-nucleotide insertion(c.893_894 insTCG that caused the insertion of an arginine at amino acid position 299) in the MARS gene.展开更多
BACKGROUND Acute mesenteric venous thrombosis(AMVT)can cause a poor prognosis.Prompt transcatheter thrombolysis(TT)can achieve early mesenteric revascularization.However,irreversible intestinal ischemia still occurs a...BACKGROUND Acute mesenteric venous thrombosis(AMVT)can cause a poor prognosis.Prompt transcatheter thrombolysis(TT)can achieve early mesenteric revascularization.However,irreversible intestinal ischemia still occurs and the mechanism is still unclear.AIM To evaluate the clinical outcomes of and to identify predictive factors for irreversible intestinal ischemia requiring surgical resection in AMVT patients treated by TT.METHODS The records of consecutive patients with AMVT treated by TT from January 2010 to October 2017 were retrospectively analyzed.We compared patients who required resection of irreversible intestinal ischemia to patients who did not require.RESULTS Among 58 patients,prompt TT was carried out 28.5 h after admission.A total of 42(72.4%)patients underwent arteriovenous combined thrombolysis,and 16(27.6%)underwent arterial thrombolysis alone.The overall 30-d mortality rate was 8.6%.Irreversible intestinal ischemia was indicated in 32(55.2%)patients,who had a higher 30-d mortality and a longer in-hospital stay than patients without resection.The significant independent predictors of irreversible intestinal ischemia were Acute Physiology and Chronic Health Evaluation(APACHE)II score(odds ratio=2.368,95% confidence interval:1.047-5.357,P=0.038)and leukocytosis(odds ratio=2.058,95% confidence interval:1.085-3.903,P=0.027).Using the receiver operating characteristic curve,the cutoff values of the APACHE II score and leukocytosis for predicting the onset of irreversible intestinal ischemia were calculated to be 8.5 and 12×10^9/L,respectively.CONCLUSION Prompt TT could achieve a favorable outcome in AMVT patients.High APACHE II score and leukocytosis can significantly predict the occurrence of irreversible intestinal ischemia.Therefore,close monitoring of these factors may help with the early identification of patients with irreversible intestinal ischemia,in whom ultimately surgical resection is required,before the initiation of TT.展开更多
BACKGROUND Following the global outbreak of coronavirus disease 2019(COVID-19),unlike other vaccines,COVID-19 vaccines were developed and commercialized in a relatively short period of time.The large-scale administrat...BACKGROUND Following the global outbreak of coronavirus disease 2019(COVID-19),unlike other vaccines,COVID-19 vaccines were developed and commercialized in a relatively short period of time.The large-scale administration of this vaccine in a short time-period led to various unexpected side effects,including severe cytopenia and thrombosis with thrombocytopenia syndrome.Despite many reports on adverse reactions,vaccination was necessary to prevent the spread of COVID-19;thus,it is essential to understand and discuss various cases of adverse reactions after vaccination.CASE SUMMARY A 77-year-old woman was administered the second dose of Pfizer mRNA COVID-19 vaccine.After vaccination she experienced fever,myalgia,and weakness.Antibiotics were subsequently administered for several days,but there was no improvement in the symptoms.The patient showed severe thrombocytopenia and leukocytosis.Thoracic and abdominopelvic computed tomography showed no infection related findings,but splenomegaly and cirrhotic liver features were observed.A large number of immature cells were observed in the peripheral blood smear;thus,bone marrow examination was performed for acute leukemia.However,there were no abnormalities.The patient recovered after administration of hepatotoxins and transfusion treatment for cytopenia and was diagnosed with an adverse reaction to COVID-19 vaccination.CONCLUSION Adverse reactions of vaccination could be mistaken for hematologic malignancies including leukemia.We report a patient with leukocytosis following COVID-19 vaccination.展开更多
Rationale:COVID-19 usually presents with flu-like symptoms and signs,but some rare presentations like leukemoid symptoms cannot be ignored.Patient’s concerns:A 37-year-old female presented to the outpatient departmen...Rationale:COVID-19 usually presents with flu-like symptoms and signs,but some rare presentations like leukemoid symptoms cannot be ignored.Patient’s concerns:A 37-year-old female presented to the outpatient department with flu-like symptoms.Diagnosis:The RT-PCR test for SARS-CoV-2 infection was positive,while complete blood cell and peripheral blood smear showed leukemoid reaction.Intervention:Paracetamol and fexofenadine for flu-like symptoms and leukemoid presentation.Outcomes:On the 10th day,the patient was asymptomatic and RT-PCR was negative.So the patient was discharged and leukemoid presentation subsided after clearance of viral disease.Lessons:COVID-19 has a myriad of presentations,and unusual symptoms/signs especially in this pandemic could be induced by COVID-19 infection.展开更多
BACKGROUND: Pyogenic and amoebic liver abscesses are rare, potentially lethal conditions. In this study, we aimed to examine the clinical and pathological differences between them. METHODS: Patients with confirmed liv...BACKGROUND: Pyogenic and amoebic liver abscesses are rare, potentially lethal conditions. In this study, we aimed to examine the clinical and pathological differences between them. METHODS: Patients with confirmed liver abscesses were divided into two groups: the pyogenic (n = 47) and amoebic group (n = 21), which were analyzed for differences in clinical and laboratory findings. RESULTS: Amoebic liver abscesses presented most frequently in young adults (14 - 30 years;71%), whereas pyogenic liver abscesses were most commonly observed in adults 41 - 50 years (49%). Indirect hemagglutination test revealed a 100% positive response in the amoebic group, whereas 68% of the pyogenic group presented with blood/pus culture. Multiple abscesses were observed in 66% and 24% of patients in the pyogenic and amoebic group, respectively. CONCLUSIONS: Pyogenic abscesses were commonly observed in older patients, and were associated with features such as markedly deranged liver function test, higher prothrombin time, and multiple abscesses, compared to amoebic abscess. Early and improved diagnoses and differentiation between the two conditions, followed by the correct treatment, can help prevent serious complications and lead to an overall improved mortality rate.展开更多
Neutrophilic leukocytosis above 50 × 109/l exclude leukemia, defines a leukemoid reaction (LR). It is associated with several diseases. Although it simulates leukemia, most of the causes are benign. Tumor-related...Neutrophilic leukocytosis above 50 × 109/l exclude leukemia, defines a leukemoid reaction (LR). It is associated with several diseases. Although it simulates leukemia, most of the causes are benign. Tumor-related LR is more common. It is associated with ranulocyte colony-stimulating factor (G-CSF) secreted by the tumor cells. A 38-year-old woman, presented with advanced breast cancer and leukocytosis (79.9 × 103/uL) was found. After completion of MRM, the condition of leukocytosis subsided. Two months later, tumor local relapse was found and white blood cells (WBC) rose again. After completion of wide excision, the condition of leukocytosis subsided again. We think this case was associated with leukemoid reaction.展开更多
Migration of polymorphonuclear leukocytes from bloodstream to the site of inflammation is an important event required for surveillance of foreign antigens.This trafficking of leukocytes from bloodstream to the tissue ...Migration of polymorphonuclear leukocytes from bloodstream to the site of inflammation is an important event required for surveillance of foreign antigens.This trafficking of leukocytes from bloodstream to the tissue occurs in several distinct steps and involves several adhesion molecules.Defect in adhesion of leukocytes to vascular endothelium affecting their subsequent migration to extravascular space gives rise to a group of rare primary immunodeficiency diseases(PIDs)known as Leukocyte Adhesion Defects(LAD).Till date,four classes of LAD are discovered with LAD I being the most common form.LAD I is caused by loss of function of common chain,cluster of differentiation(CD)18 of β2 integrin family.These patients suffer from life-threatening bacterial infections and in its severe form death usually occurs in childhood without bone marrow transplantation.LAD II results from a general defect in fucose metabolism.These patients suffer from less severe bacterial infections and have growth and mental retardation.Bombay blood group phenotype is also observed in these patients.LAD III is caused by abnormal integrin activation.LAD III patients suffer from severe bacterial and fungal infections.Patients frequently show delayed detachment of umbilical cord,impaired wound healing and increased tendency to bleed.LAD IV is the most recently described class.It is caused by defects in β2 and α4β1 integrins which impairs lymphocyte adhesion.LAD IV patients have monogenic defect in cystic-fibrosis-transmembraneconductance-regulator(CFTR)gene,resulting in cystic fibrosis.Pathophysiology and genetic etiology of all LAD syndromes are discussed in detail in this paper.展开更多
文摘Objective To study the incidence of leukocytosis and retinoic acid （RA） syndrome in newly diagnosed and relapsed acute promyelocytic leukemia （APL） patients treated with arsenic trioxide （ATO）. Methods Thirty patients with newly diagnosed or relapsed APL received ATO for remission induction at the dose of 10 mg/d. RA syndrome was defined when patient was with one or more of the following signs or symptoms： fever, dyspnea, serous cavity effusion, muscular pain, pulmonary infiltration, weight gain, or pulmonary infiltration on chest X-ray. Results Twenty-three （77%） patients achieved complete remission, mean time to remission was 37. 1 days. Leukocytosis was observed in 14 （47%） patients, mean time to leukocytosis was 12. 7 days, median baseline leukocyte count for patients with leukocytosis was 3.1 x 109/L, which was higher than that for patients who did not de,.＇elop leukocytosis （2.6 × 10^9/L, z = - 2. 635, P = 0. 008）. No other cytotoxic therapy was administered, and the leukocytosis resolved in all cases. The RA syndrome was observed in 9 （30%） patients, mean time to diagnose of RA syndrome was 13.9 days, median baseline leukocyte count for patients with RA syndrome was 3.6 × 10^9/L, which was higher than that for patients who did not develop RA syndrome （2. 6 × 10^9/L, z = - 1. 909, P =0. 046）. No patient died of RA syndrome. Conclusion Leukocytosis and RA syndrome are associated with ATO and baseline leukocyte count respectively, and there is distinct link between leukocytosis and RA syndrome.
基金Supported by National Natural Science Foundation (30370507) Heilongjiang Excellent Youth Foundation (2003AA9CS188-12).
文摘Objective To study the effects of constantly slow intravenous arsenic trioxide （As2O2） infusion regimen on decreasing leukocytosis in vivo and in vitro. Methods Three kinds of leukemia cells, NB4, K562, and acute promyelocyfic leukemia （APL） cells, were cultured in the media with constant concentration and varying concentrations of As2O3 respectively for 24 hours. Seventyfive patients were enrolled in two groups randomly. In trial group, 37 patients received continuously slow intravenous As2O3 infusion regimen for 24 hours with an infusion rate of 8 drips per minute and total infusion duration of about 18- 21 hours daily. In control group, 38 patients received routine regimen with an infusion rate of 45-55 drips per minute and total infusion duration of about 2-3 hours daily for 24 hours. The daily As2O3 dosage was 0. 16 mg/kg. The intracellular arsenic concentration was measured by atomic fluorescence assay. The apoptosis rate of cells, CD33 ^- CD11b ^＋ cells, and CD33^ ＋ CD11b^ - cells were monitored by flow cytometry. Results The apoptosis rates of NB4, K562, and APL leukemia cells in the media with constant As2O3 concentration were 56.6% ±2.4%, 27.6% ±3.1%, and 52.2% ±2. 8%, respectively, which were significantly higher than those with changing As2O3 concentration （23.2% ±2. 1%, 11.0% ±2.5%, and 21.0% ±2.5%, respectively, P〈 0.01）. The apoptosis rates of APL, M2 type acute myeloid leukemia （AML-M2）, and chronic myeloid leukemia （CML） patients in the trial group （28.5% ±1.9%, 9.5% ±0.6%, and 12.5% ±1.8% ） were also significantly higher than those in control group （8.5% ± 2. 2%, 2. 9% ± 0. 8%, and 4. 5% ± 1.2% ; P 〈 0.05 ）. The ratios of CD33 ~ CD11b^- and CD33^- CD11b^＋ cells in control group were significantly higher than those in trial group. Conclusion The continuously slow intravenous As2O3 infusion regimen can obtain high efficiency of apoptosis and low differentiation proportion, relieve leukocytosis, and gain maximal therapeutic benefit.
基金Supported by The Faculty of Medicine at the University of Oslo
文摘AIM: To investigate the effects of exercise on healthy individuals of both genders. METHODS: This study lasted 6 years and involved about 800 healthy people. Individuals were divided into females and males and further sub-divided into two groups; in the first group individuals run(or skied in the winter time) and then rested for 3 h, whereas individuals in the second group intensely cycled for 5 min. The status of health was determined by measuring the sedimentation rate and the intensity of exercises by measuring the heart rate. Blood samples were collected before and after exercise. RESULTS: We observed that in the first group a significant increase of the total white blood cells, segmented neutrophils, band neutrophils, eosinophils and to a lesser extent lymphocytes but not monocytes in the blood circulation. However, all cell types were increased in the circulation after 5 min intense exercise. No differences in the pattern of cell increase were observed among the genders. Activated partial thromboplastin time(APTT) and D-dimer were also measured in the blood of individuals who cycled intensely for 5 min to determine the coagulation and fibrinolytic activities in the blood. APTT is reduced and D-dimer values significantly increased after intense exercise. However, APTT was statistically lower in males than females, whereas no differences in the D-dimer values were observed among the genders. CONCLUSION: Our results indicate that exercise whether leisure or strenuous affects leukocytosis and hemostasis in both genders. A major advantage of this study is the high numbers of individuals involved and the inclusion of both females and males values.
文摘Background and Objectives: Search for inexpensive laboratory markers have identified associations between blood counts and lung cancer outcomes. In this study, we evaluated the prognostic value of paraneoplastic leukocytosis(p-Leukocytosis) and paraneoplastic thrombocytosis(p-Thrombocytosis) in patients with non-small cell lung cancer(NSCLC). We also studied their relation to the expression of commonly detected molecular markers. Methods: We conducted a retrospective chart review on 571 consecutive NSCLC patients over a 10 year period. Blood counts were recorded at the time of cancer diagnosis. Kaplan-Meier survival curves were used to compare overall survival(OS) between patients with and without p-Leukocytosis(or) p-Thrombocytosis(p-Leuko/Thrombocytosis). Cox regression was used to determine if leukocytosis/thrombocytosis was a predictor of OS in NSCLC.Results: Patients with p-Leukocytosis and p-Thrombocytosis had a significantly poorer survival compared patients with normal blood counts(P<0.001). In a multivariate survival analysis, both continued to correlate even when adjusted for histology, gender, stage and chemotherapy(P<0.01, 0.03 respectively). Stage I and II NSCLC with p-Leuko/Thrombocytosis did not perform poorly compared to stage I/II NSCLC patients without paraneoplasia. Patients with the combined leukothrombocytosis syndrome did not have worse outcomes compared to those with either paraneoplastic syndrome alone. Conclusions: p-Leuko/Thrombocytosis is an accessible laboratory parameter of prognostic value in NSCLC. Evidence of p-Leuko/Thrombocytosis portends poor survival. The role of various cytokines in tumor pathobiology provides a rationale for identifying cytokine factors responsible for the paraneoplasia and administering anti-cytokine therapies alongside traditional chemotherapy in an attempt to improve survival outcomes in these subset of patients.
文摘Driver mutations in patients with non-small cell lung cancer(NSCLC)can lead to distinct behaviors and patterns of metastasis.Mutations in the proto-oncogene B-raf(BRAF)occur in approximately 3%of NSCLC cases.In the literature,reports of patients with lung adenocarcinomas metastasizing to the duodenum are rare,and most of the only 21 cases reported were from before the advent of next-generation sequencing.We present here a case involving a 57-year-old female who had a lytic lesion in her lesser trochanter.Biopsy showed metastatic adenocarcinoma of lung origin.Chest X-ray showed a large left upper lobe mass.Next-generation sequencing analysis confirmed the presence of BRAF V600 Q mutation.The patient presented with persistent anemia and melena.Esophagogastroduodenoscopy confirmed the presence of duodenal metastasis.She also had suspected paraneoplastic leukemoid reaction.To our knowledge,this is only the second well-documented case of gastrointestinal metastasis from BRAF-mutated lung cancer.
基金Supported by Scientific Research Seed Fund of Peking University First Hospital to Xi Wang,No.2020SF30。
文摘BACKGROUND Pregnancy is a complex physiological process.Physiological leukocytosis occurs often and is mainly associated with increased neutrophil counts,especially in the third trimester of pregnancy.Non-congenital leukocytosis with white blood cell counts above 20×109/L lasting 13 wk during pregnancy is rare and has been reported occasionally.Herein,we present a case of pregnancy-induced leukocytosis.CASE SUMMARY We present the case of a 33-year-old Chinese woman at 27 wk of gestation who had a leukocytosis complication.No abnormalities were detected in the examinations before pregnancy or in the first trimester.From the third trimester of pregnancy,the patient began to suffer from asymptomatic leukocytosis.We administered antibiotics to treat the patient;however,the complication persisted until the patient underwent a cesarean section after 40+3 wk of gestation.One day after the cesarean section,the patient’s neutrophil count returned to normal.After 2 years of follow-up,we found that the patient and baby were healthy.CONCLUSION Pregnancy-induced leukocytosis seems to be associated with immunoregulation and pregnancy termination may be the most effective treatment approach for pregnancies complicated with malignant leukocytosis.
文摘Lung cancer is the most common cancer-related death in both men and women in the world. Approximately 25% of all cancer deaths are attributable to lung carcinoma. Moreover, about one-half of patients with lung cancer have metastases at the time of initial diagnosis, most frequently of lymph nodes, adrenals, liver, bone and brain. However metastasis to the colon is very rare. Over the past 25 years about 13 cases of symptomatic colonic metastases from lung malignancies of all types have been reported in the literature. Hypercalcemia and leukocytosis are two of the most common paraneoplastic syndromes associated with various malignancies. However, concomitant manifestation of hypercalcemia and leukocytosis are occasionally observed in the same cancer patients. Here, we present a rare case of colonic metastasis from a squamous cell carcinoma of the lung associated with paraneoplastic syndromes of hypercalcemia and leukocytosis.
文摘Myelofibrosis (MF) represents the major long-term complication of essential thrombocythemia (ET). There is evidence that leukocytosis at diagnosis is associated with poorer survival in patients with ET. In this study, we retrospectively evaluated 143 patients with ET, diagnosed in agreement with WHO criteria, followed in a single centre over >10 years. Nine of them transformed into MF (post-essential thrombocythemia-myelofibrosis PET-MF). We compared PET-MF data at diagnosis with that of the remaining 134 patients (ET-1) and with a selected sub-group of ET-1 (ET-2, 19 pats) sex, age and follow-up duration matched to PET-MF. The PET-MF evolution rate was 4.6 per 1000 person-years;white blood cells count (WBC) count, haemoglobin levels and hematocrit were higher in PET-MF than in ET-1 (P = 0.01) while only WBC was higher than in ET-2 (P = 0.01). With multivariate analysis, only WBC count retained its signifi-cance. Our study highlights the prognostic relevance of leukocytosis on myelofibrotic transformation of ET.
文摘Leukocytosis or hyperleukocytosis occurs during ATRA or arsenic trioxide differentiation therapy, which is related to the RA syndrome. The number of WBC often increased by ten or more times as high as that of pretreatment, around 7 to 20 days after treatment with ATRA or arsenic trioxide. Usually, when number of WBC tended to peak, there was concomitance with down-regulation of promyelocytes, up-regulation of myelocytes and more mature neutrophils. The same trend of classification of BM was observed in most of the patients with APL to whom leukocytosis happened. Although the mechanism of leukocytosis has not been demonstrated clearly, so far the proliferation hypothesis by cytokines and rheological hypothesis by adhesion molecules were taken into consideration. Otherwise, hypothesis about more divisions of differentiated myelocytes induced by ATRA or arsenic trioxide remains unclear. Usually, this kind of leukocytosis or hyperleukocytosis itself requires no additional cytotoxic treatment.
文摘Objective To explore the mechanism of leukocytosis Methods Enzyme linked immunosorbent assay (ELISA) method was used for detecting levels of serum granulocyte colony stimulating factor (G CSF) in 47 cases of acute promyelocytic leukemia (APL) during the treatment with all trans retinoic acid (ATRA) Results The peak of increased serum G CSF level occurred on the 9th day, and WBC number was the highest on the 11th day After ATRA treatment, both serum G CSF level and WBC number increased in 68 1% of the cases In 19 2% of the cases treated, serum G CSF level was increased but without obvious change in WBC number, and the reverse was true in 12 7% of the cases Conclusion Serum G CSF level was statistically correlated to the number of WBC, promyelocytes and its late stage by Spearman's rank order correlation coefficient
文摘AIM： To investigate acute transient hepatocellular injury in patients with cholelithiasis and cholecystitis but no evidence of choledocholithiasis.METHODS： The medical records of patients with cholelithiasis who underwent cholecystectomy between July 2003 and June 2007 were retrospectively reviewed. Imaging studies to detect common bile duct （CBD） stones were performed in 186 patients, who constituted the study population. Biochemical liver tests before and after surgery, and with the presence or absence of CBD stones were analyzed.RESULTS： In 96 patients with cholelithiasis and cholecystitis without evidence of CBD stones, 49 （51.0%） had an alanine aminotransferase level elevated to 2-3 times the upper limit of normal, and 40 （41.2%） had an elevated aspartate aminotransferase level. Similar manifestations of hepatocellular injury were, as would be expected, even more obvious in the 90 patients with CBD stones. These markers of hepatocellular injury resolved almost completely within 2 wk to 1 mo after cholecystectomy. Compared to 59 patients with histologically less severe cholecystitisin the group undergoing urgent surgery （total 74 patients）, the 15 patients with a gangrenous gallbladder had a higher mean level of total bilirubin （2.14 ± 1.27 mg/dL vs 2.66 ± 2.97 mg/dL, P 〈 0.001） and white cell count （9480 ± 4681/μL vs 12840 ± 5273/μL, P = 0.018）.CONCLUSION： Acute hepatocellular injury in cholelithiasis and cholecystitis without choledocholithiasis is mild and transient. Hyperbilirubinemia and leukocytosis may predict severe inflammatory changes in the gallbladder.
基金Supported by The National Natural Science Foundation of China,No.81301896the Natural Science Foundation of the Colleges and Universities in Jiangsu Province,China,No.13KJB320011+2 种基金the Program for Development of Innovative Research Teams,Jiangsu Province Clinical Science and Technology Projects(Clinical Research Center,BL 2012008)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)Provincial Initiative Program for Excellency Disciplines,Jiangsu Province,China
文摘AIM: To investigate the prognostic significance of perioperative leukopenia in patients with resected gastric cancer.METHODS: A total of 614 eligible gastric cancer patients who underwent curative D2 gastrectomy and adjuvant chemotherapy were enrolled in this study. The relationship between pre- and postoperative hematologic parameters and overall survival was assessed statistically, adjusted for known prognostic factors.RESULTS: The mean white blood cell count(WBC) significantly decreased after surgery, and 107/614(17.4%) patients developed p-leukopenia, which was defined as a preoperative WBC ≥ 4.0 × 109/L and postoperative WBC < 4.0 × 109/L, with an absolute decrease ≥ 0.5 × 109/L. The neutrophil count decreased significantly more than the lymphocyte count. P-leukopenia significantly correlated with poor tumor differentiation and preoperative WBC. A higher preoperative WBC and p-leukopenia were independent negative prognostic factors for survival [hazard ratio(HR) = 1.602, 95% confidence interval(CI): 1.185-2.165; P = 0.002, and HR = 1.478, 95%CI: 1.149-1.902; P = 0.002, respectively] after adjusting for histology, Borrmann type, p TNM stage, vascular or neural invasion, gastrectomy method, resection margins, chemotherapy regimens, and preoperative WBC count. The patients with both higher preoperative WBC and p- leukopenia had a worse prognosis compared to those with lower baseline WBC and no p-leukopenia(27.5 mo vs 57.3 mo, P < 0.001). CONCLUSION: Preoperative leukocytosis alone or in combination with postoperative leukopenia could be independent prognostic factors for survival in patients with resectable gastric cancer.
基金Supported by the National Natural Science Foundation of China,No.81570468
文摘Interstitial lung and liver disease(ILLD) is caused by biallelic mutations in the methionyl-tRNA synthetase(MARS) gene. To date, no genetic changes other than missense variants were reported in the literature. Here, we report a five-month old female infant with typical ILLD(failure to thrive, developmental delay, jaundice, diffuse interstitial lung disease, hepatomegaly with severe steatosis, anemia, and thrombocytosis) showing novel phenotypes such as kidney stones, acetabular dysplasia, prolonged fever, and extreme leukocytosis. Whole exome sequencing revealed a novel truncating variant(c.2158 C>T/p.Gln720 Stop) together with a novel tri-nucleotide insertion(c.893_894 insTCG that caused the insertion of an arginine at amino acid position 299) in the MARS gene.
基金Supported by National Natural Science Foundation of China,No.81770532Jiangsu Province Medical Foundation for Youth Talents,China,No.QNRC2016901.
文摘BACKGROUND Acute mesenteric venous thrombosis(AMVT)can cause a poor prognosis.Prompt transcatheter thrombolysis(TT)can achieve early mesenteric revascularization.However,irreversible intestinal ischemia still occurs and the mechanism is still unclear.AIM To evaluate the clinical outcomes of and to identify predictive factors for irreversible intestinal ischemia requiring surgical resection in AMVT patients treated by TT.METHODS The records of consecutive patients with AMVT treated by TT from January 2010 to October 2017 were retrospectively analyzed.We compared patients who required resection of irreversible intestinal ischemia to patients who did not require.RESULTS Among 58 patients,prompt TT was carried out 28.5 h after admission.A total of 42(72.4%)patients underwent arteriovenous combined thrombolysis,and 16(27.6%)underwent arterial thrombolysis alone.The overall 30-d mortality rate was 8.6%.Irreversible intestinal ischemia was indicated in 32(55.2%)patients,who had a higher 30-d mortality and a longer in-hospital stay than patients without resection.The significant independent predictors of irreversible intestinal ischemia were Acute Physiology and Chronic Health Evaluation(APACHE)II score(odds ratio=2.368,95% confidence interval:1.047-5.357,P=0.038)and leukocytosis(odds ratio=2.058,95% confidence interval:1.085-3.903,P=0.027).Using the receiver operating characteristic curve,the cutoff values of the APACHE II score and leukocytosis for predicting the onset of irreversible intestinal ischemia were calculated to be 8.5 and 12×10^9/L,respectively.CONCLUSION Prompt TT could achieve a favorable outcome in AMVT patients.High APACHE II score and leukocytosis can significantly predict the occurrence of irreversible intestinal ischemia.Therefore,close monitoring of these factors may help with the early identification of patients with irreversible intestinal ischemia,in whom ultimately surgical resection is required,before the initiation of TT.
文摘BACKGROUND Following the global outbreak of coronavirus disease 2019(COVID-19),unlike other vaccines,COVID-19 vaccines were developed and commercialized in a relatively short period of time.The large-scale administration of this vaccine in a short time-period led to various unexpected side effects,including severe cytopenia and thrombosis with thrombocytopenia syndrome.Despite many reports on adverse reactions,vaccination was necessary to prevent the spread of COVID-19;thus,it is essential to understand and discuss various cases of adverse reactions after vaccination.CASE SUMMARY A 77-year-old woman was administered the second dose of Pfizer mRNA COVID-19 vaccine.After vaccination she experienced fever,myalgia,and weakness.Antibiotics were subsequently administered for several days,but there was no improvement in the symptoms.The patient showed severe thrombocytopenia and leukocytosis.Thoracic and abdominopelvic computed tomography showed no infection related findings,but splenomegaly and cirrhotic liver features were observed.A large number of immature cells were observed in the peripheral blood smear;thus,bone marrow examination was performed for acute leukemia.However,there were no abnormalities.The patient recovered after administration of hepatotoxins and transfusion treatment for cytopenia and was diagnosed with an adverse reaction to COVID-19 vaccination.CONCLUSION Adverse reactions of vaccination could be mistaken for hematologic malignancies including leukemia.We report a patient with leukocytosis following COVID-19 vaccination.
文摘Rationale:COVID-19 usually presents with flu-like symptoms and signs,but some rare presentations like leukemoid symptoms cannot be ignored.Patient’s concerns:A 37-year-old female presented to the outpatient department with flu-like symptoms.Diagnosis:The RT-PCR test for SARS-CoV-2 infection was positive,while complete blood cell and peripheral blood smear showed leukemoid reaction.Intervention:Paracetamol and fexofenadine for flu-like symptoms and leukemoid presentation.Outcomes:On the 10th day,the patient was asymptomatic and RT-PCR was negative.So the patient was discharged and leukemoid presentation subsided after clearance of viral disease.Lessons:COVID-19 has a myriad of presentations,and unusual symptoms/signs especially in this pandemic could be induced by COVID-19 infection.
文摘BACKGROUND: Pyogenic and amoebic liver abscesses are rare, potentially lethal conditions. In this study, we aimed to examine the clinical and pathological differences between them. METHODS: Patients with confirmed liver abscesses were divided into two groups: the pyogenic (n = 47) and amoebic group (n = 21), which were analyzed for differences in clinical and laboratory findings. RESULTS: Amoebic liver abscesses presented most frequently in young adults (14 - 30 years;71%), whereas pyogenic liver abscesses were most commonly observed in adults 41 - 50 years (49%). Indirect hemagglutination test revealed a 100% positive response in the amoebic group, whereas 68% of the pyogenic group presented with blood/pus culture. Multiple abscesses were observed in 66% and 24% of patients in the pyogenic and amoebic group, respectively. CONCLUSIONS: Pyogenic abscesses were commonly observed in older patients, and were associated with features such as markedly deranged liver function test, higher prothrombin time, and multiple abscesses, compared to amoebic abscess. Early and improved diagnoses and differentiation between the two conditions, followed by the correct treatment, can help prevent serious complications and lead to an overall improved mortality rate.
文摘Neutrophilic leukocytosis above 50 × 109/l exclude leukemia, defines a leukemoid reaction (LR). It is associated with several diseases. Although it simulates leukemia, most of the causes are benign. Tumor-related LR is more common. It is associated with ranulocyte colony-stimulating factor (G-CSF) secreted by the tumor cells. A 38-year-old woman, presented with advanced breast cancer and leukocytosis (79.9 × 103/uL) was found. After completion of MRM, the condition of leukocytosis subsided. Two months later, tumor local relapse was found and white blood cells (WBC) rose again. After completion of wide excision, the condition of leukocytosis subsided again. We think this case was associated with leukemoid reaction.
文摘Migration of polymorphonuclear leukocytes from bloodstream to the site of inflammation is an important event required for surveillance of foreign antigens.This trafficking of leukocytes from bloodstream to the tissue occurs in several distinct steps and involves several adhesion molecules.Defect in adhesion of leukocytes to vascular endothelium affecting their subsequent migration to extravascular space gives rise to a group of rare primary immunodeficiency diseases(PIDs)known as Leukocyte Adhesion Defects(LAD).Till date,four classes of LAD are discovered with LAD I being the most common form.LAD I is caused by loss of function of common chain,cluster of differentiation(CD)18 of β2 integrin family.These patients suffer from life-threatening bacterial infections and in its severe form death usually occurs in childhood without bone marrow transplantation.LAD II results from a general defect in fucose metabolism.These patients suffer from less severe bacterial infections and have growth and mental retardation.Bombay blood group phenotype is also observed in these patients.LAD III is caused by abnormal integrin activation.LAD III patients suffer from severe bacterial and fungal infections.Patients frequently show delayed detachment of umbilical cord,impaired wound healing and increased tendency to bleed.LAD IV is the most recently described class.It is caused by defects in β2 and α4β1 integrins which impairs lymphocyte adhesion.LAD IV patients have monogenic defect in cystic-fibrosis-transmembraneconductance-regulator(CFTR)gene,resulting in cystic fibrosis.Pathophysiology and genetic etiology of all LAD syndromes are discussed in detail in this paper.
