Predictive factors of bleeding and thrombosis during induction therapy in acute promyelocytic leukemia-a single center experience in 34 patients

In this retrospective study, the hemorrhagic and thrombotic events are reported at presentation and during induction in 34 consecutive acute promyelocytic leukemia (APL) patients treated in a single referral center. The most consistent hemostatic abnormality was decreased fibrinogen level (<150 mg/dL) found in 21 patients (61%), partial thromboplastin time (PTT) was normal almost in all patients. A mildly prolonged prothrombin time (PT) was observed in 14 patients (44%). Median platelet count was 30.10(9)/L (range 3-191.10(9)/L). Life-threatening bleeding manifestations occurred in 10 patients (29%). By multivariate analysis, severe bleeding complications did not correlate with hemostatic parameters but did correlate with white cell count at presentation. Four patients (12%) had severe thrombotic events, two cerebral sagital sinus thrombosis, one pulmonary embolism, and one subclavian vein thrombosis. Two other patients had pseudotumor cerebri. Three out of six patients with thrombotic events were found to have thrombophilia. These results may suggest an association between thrombophilia and thrombosis in APL patients. Two patients suffered from combined severe bleeding and thrombosis. Hemostatic parameters are not helpful in predicting neither hemorrhage nor thrombosis.     

Diencephalic tumors in children: a 30-year experience of a single institution

Purpose  

The purpose of this study is to determine the clinical behavior, treatment modalities, and outcome of different histopathological subgroups of diencephalic tumors in children.     

Validation of a rapid test (VWF-LIA) for the quantitative determination of von Willebrand factor antigen in type 1 von Willebrand disease diagnosis within the European multicenter study MCMDM-1VWD

Background

Accurate measurement of von Willebrand factor (VWF) is a critical requirement for the diagnosis of von Willebrand disease (VWD).

Aim of the study

To evaluate the diagnostic efficiency of a rapid quantitative test for the measurement of VWF antigen (VWF:Ag) in type 1 VWD.

Patients and methods

VWF:Ag was measured with an ELISA in a robotic instrument, as a reference method, and with a fully automated latex-immunoassay (LIA) on an ACL 9000 analyser in 1,716 subjects enrolled within the Molecular and Clinical Markers for Diagnosis and Management of Type 1 von Willebrand Disease (MCMDM-1VWD) Study. Among these subjects, 1,049 were healthy controls, 281 healthy family members and 386 affected members from 127 European families with type 1 VWD.

Results

The assay linearity range was 10-125 IU/dL for LIA (R² = 0.99) and 5-133 IU/dL for ELISA (R² = 0.99). The inter-assay CV for low VWF levels (∼ 30 IU/dL) was 2% for the LIA test and 8.7 % for ELISA. The sensitivity for detection of type 1 VWD affected members was 86% and the specificity 91% for LIA, 87% and 90% for ELISA. A receiver-operator (ROC) analysis disclosed only a marginal difference between the two tests, LIA having a slightly greater area under the curve (0.94 vs. 0.93, p = 0.03).

Conclusion

VWF:Ag LIA compared well to standard ELISA in this large population of patients and controls, showing better CV. However the lower detection limit for the VWF:Ag LIA compared to the VWF:Ag ELISA means that the LIA assay is less good at discriminating between type 3 VWD and moderate type 1 VWD.     

Acute disseminated encephalomyelitis in children: a single institution experience of 28 patients

The aim of this study is to describe the clinical, laboratory, and neuroimaging features, treatment and outcome of acute disseminated encephalomyelitis (ADEM) in Taiwanese children to compare with two series from United States of America and Japan. We retrospectively reviewed the medical records and magnetic resonance images of 28 children, 23 boys and 5 girls, with ADEM between January 2001 and December 2009. Their mean age at disease onset was 6 years 9 months. Twenty four children experienced a prodromal illness. There was no special seasonal distribution in our patients. They presented mostly with impaired consciousness and headache. Cerebrospinal fluid samples of 21 patients were analyzed and none showed intrathecal oligoclonal bands. Magnetic resonance imaging showed variable findings: lesions with abnormal signal changes frequently found in the subcortical white matter of frontal and parietal lobes. No patient showed cortical gray matter involvement. We also found a high rate of deep gray matter involvement including thalami and basal ganglia. Treating with steroids was usually associated with a rapid recovery and both intravenous high dose methylprednisolone and dexamethasone had the same effect. All patients survived. Twenty three patients recovered completely with only mild sequelae in the remaining five children.     

Pediatric glioblastoma: a single institution experience

Purpose

The aim of this study was to evaluate characteristics of childhood glioblastoma multiforme, effectiveness of treatment modalities, and detect factors related to outcome.

Methods

A detailed analysis was performed on a series of 15 patients treated between 2000 and 2013, based on their clinical, radiologic, pathologic, treatment, and follow-up data.

Results

Median survival time of children with glioblastoma was 13.5 months. One- and 2-year overall survival probabilities were 66.7 and 20 %, respectively. There were no significant differences in survival based on patients’ gender, age, disease presentation with or without epileptic seizures, signs/symptoms of increased intracranial pressure, or tumor location. The presence of neurological deficit initially, as well as prior to radiotherapy, which was quantified by neurologic function score (NFS), had an impact on overall survival. Children with NFS 0 lived longer compared to others (p?=?0.001). Survival of children that underwent gross total resection was longer than that of children that underwent subtotal resection (p?=?0.030). Mean survival time of children with gross total resection was 73.5 months, compared to 13 months in children with subtotal resection. There was no significant correlation between outcome and type of radiotherapy. In four patients with gigantocellular glioblastoma, we found no evidence of a better prognosis. Two long-term survivors were recorded. Both of them underwent gross total resection and were assigned a NFS 0.

Conclusions

Gross total resection is essential for longer overall survival among pediatric patients with glioblastoma and offers a possibility for long-term survival. Severity of neurologic symptoms quantified by NFS can be considered as a potential predictor of outcome.

     

Filter bleeding time: a new in vitro test of hemostasis. II. Application to the study of von Willebrand disease and platelet function inhibitors

The effect of platelet function inhibitors and von Willebrand (vW) disease on hemostasis was evaluated with a new method, the Filter Bleeding Time (FBT) test which does not require a skin incision. This method is based on the progressive slowing of blood flow associated with plugging of a woven Dacron filter by platelet clumps during passage of blood through the filter. Antiplatelet agents studied were acetyl salicylic acid (ASA), prostaglandin I₂ (PGI₂), and a thromboxane synthetase inhibitor, UK-37, 248-01 (UK). Parameters measured were FBT (time required for the drop rate interval to exceed 30 sec), bleeding volume (BV; total number of drops in FBT), initial bleeding rate (IBR; number of drops during the first minute), and percent platelet count reduction (PCR) during passage of blood through the filter. ASA (650 mg p.o. in normal human subjects) caused an increase in FBT from 4.94±2.97 ($\text{x}$±SD) to 10.28±3.27 min (p = 0.003) and BV (34±19 to 69±31 drops, p = 0.01), and a decrease in PCR (29.4±7 to 12.5±2%, p = 0.006). PGI_p (0.1 uhf added to normal human blood) caused an increase in,FBT (4.76±2.33 to 14.44±3.39, p = 0.0006) and BV (41±18 to 94±35, p = 0.001) and a decrease in PCR (29.6±6.4 to 7.1±7.8, p = 0.004). IBR did not change significantly in these studies. UK (3 mg/kg p.o. in normal dogs) caused no significant change in any of these parameters despite the drug's inhibition of platelet aggregation by ADP and collagen. Values in 4 pigs with vW disease were abnormal compared to normal pigs: FBT, 23.83±20.47 vs 5.09 min, p = 0.04; BV, 168±154 vs. 30±24 drops, p = 0.04; PCR, 7.1±1.0 vs 28.5±10.7%, p = 0.002; and IBR, 29.7±7 vs. 10±6 drops/min, p = 0.002. These studies suggest that IBR is a measure of platelet adhesion, while FBT, BV and PCR reflect the totality of platelet reactions including platelet adhesion and aggregation. FBT is considered useful in the study of the mechanisms and efficacy of platelet function inhibitors, and in the investigation of platelet disorders.     

Infant botulism: 20 years' experience at a single institution

Admissions from January 1, 1985, to December 31, 2005, with the diagnosis of infant botulism were reviewed to describe the clinical presentation, course, outcome, and changes related to the availability of botulism immune globulin treatment. Botulism diagnoses were confirmed by the finding of toxin or Clostridium botulinum organisms in stool samples (type A, 14; type B, 25; type not noted, 5). Twenty-four patients were admitted from 1985-1994 and 20 from 1995-2004. Infants in the two decades were similar in age, demographics, and presenting features. Ventilator support was needed in 13 of 24 (54%) in 1985-1994 and in 15 of 20 (75%) in 1995-2005; 43 required nasogastric feeding. Seventeen patients were treated with botulism immune globulin. Length of stay was shorter in infants treated with botulism immune globulin (13.5 vs 23 days, P = .009), with a trend toward reduced need for nasogastric feeding and in shorter duration of tracheal intubation. All patients recovered fully. Even with the availability of botulism immune globulin, meticulous supportive care remained essential for recovery.     

Intracranial tumors in infants: a single institution experience of 22 patients

Objectives  

The prognosis in infants with brain tumors has hitherto been very poor. The purpose of the study was to collect and analyze information regarding the clinical presentation, diagnosis, and management of these patients and to assess the eventual prognosis regarding survival and response to treatment.     

Five-year experience of 101 adult patients with moyamoya disease at a single institution in Eastern China

This retrospective study included 101 adult moyamoya disease (MMD) patients of whom 58 were females and 43 were males in Wenzhou, China. Clinical and diagnostic features, surgical treatment, follow-up information and outcomes constitute this review. The modified Rankin Scale (mRS) was used to determine the neurological functional outcome. The Kaplan–Meier method was used to estimate recurrent stroke and mortality risk based on drug treatment alone or in combination with revascularization. The mean age at symptom onset was 43.3 (range, 18–64) years. The initial symptom was either hemorrhage, ischemia or transient ischemic attack (TIA) in 90, 6 and 5 patients, respectively. The median follow-up time in 84 patients was 26.5 (range, 6–62) months. Ten patients were treated with revascularization. In the remaining drug-treated group, the 5-year risk of recurrent stroke and death was 8% following onset of initial symptoms, while it was 25% in the revascularization group. However, the difference between these two groups was not significant (p > 0.05). There was also no difference in mRS between these two groups upon patient discharge, but in the revascularization group was lower than that in the drug-treated group at their last follow-up (p < 0.05). Adult MMD patients were most ikely to present with hemorrhage and had a better neurological functional outcome after revascularization than from medical therapy. However, revascularization did not decrease the recurrent stroke incidence or mortality risk. These results are different from those reported by other Chinese and foreign institutions.     

Desmopressin therapy to assist the functional identification and characterisation of von Willebrand disease: Differential utility from combining two (VWF:CB and VWF:RCo) von Willebrand factor activity assays?

We performed a retrospective audit of desmopressin (DDAVP) usage to assist in the functional characterisation of von Willebrand disease (VWD). Data was evaluated for 208 patients, comprising those with VWD (Type 1 [n = 160], Type 2A [n = 19], Type 2M [n = 10]), plus 19 individuals with haemophilia or carriers of haemophilia. Laboratory testing comprised pre- and post-DDAVP evaluation of factor VIII (FVIII:C), von Willebrand factor (VWF) antigen (VWF:Ag), VWF ristocetin cofactor (VWF:RCo) activity, VWF collagen binding (VWF:CB) activity, and in one laboratory an alternate VWF activity assay. In brief, combined usage of VWF:RCo and VWF:CB appears to provide improved functional characterisation and/or ‘classification’ of VWD types, in particular better differentiation of Type 2A and 2M VWD, and clearer validation of a Type 1 VWD diagnosis. Thus, (i) Type 1 VWD displayed generally good absolute and relative rises in all test parameters, although relative rises were greatest for FVIII:C and VWF:CB, and CB/Ag ratio increases overshadowed those for RCo/Ag; (ii) Type 2A VWD patients showed good absolute and relative rises in both FVIII:C and VWF:Ag, but poor absolute rises in both VWF:CB and VWF:RCo; although small rises in both CB/Ag and RCo/Ag were also observed, both ratios tended to remain below 0.7; (iii) finally, Type 2 M VWD patients generally showed good absolute and relative rises in FVIII:C, VWF:Ag and VWF:CB, but a poor absolute and relative rise in VWF:RCo; thus, there were good rises in CB/Ag ratios but little change in RCo/Ag, which tended to remain below 0.7. Future multi-centre prospective investigations are warranted to validate these findings and to investigate their therapeutic implications.     

A family having type 2B von Willebrand disease with an R1306W mutation: Severe thrombocytopenia leads to the normalization of high molecular weight multimers

In type 2B von Willebrand disease (2B VWD), abnormal von Willebrand factor (VWF) spontaneously binds to platelets. This leads to the clearance of the high molecular weight multimers (HMWM) of VWF and results in thrombocytopenia. Herein we report a family of 2B VWD with an R1306W mutation which caused thrombocytopenia with giant platelets. The most important finding in this study is dynamic changes in VWF values in association with platelet counts. When the proband (2 years of age) had severe thrombocytopenia, his HMWM were normal, however, hematological examination showed a low level of VWF and a lack of HMWM after platelet count recovered. His affected sister also exhibited similar phenomenona. These results suggest that the severe thrombocytopenia leads to decreased clearance of VWF HMWM and restoration of VWF HMWM in plasma. We must consider 2B VWD in the case of recurrent thrombocytopenia following infection or other stress condition.     

Astrocytic tumors in children: treatment results from a single institution

Objective The aims of this study are to evaluate the patients with astrocytomas and to investigate survival rates and prognosis. Patients and methods Five hundred fourteen patients diagnosed with brain tumor between 1972 and 2003 were retrospectively analyzed. Three different chemotherapy regimens were used according to years. CCNU-based protocols were used in the early years; COPP (cyclophosphamide, oncovin, procarbazine, prednisolone) and CDDP+VP16 (cisplatinum + etoposide) were the other protocols used in the following years. Radiotherapy was used after 3 years of age according to protocols. Results Ninety-eight (19%) out of 514 patients have astrocytic histopathology. The histopathologic distribution was as follows: low grade, 55 patients; high grade, 43 patients. COPP regimen was given to 24 patients, CCNU-based regimen to 13, and CDDP+VP16 to 10 patients. We did not use any chemotherapy in 51 patients. Overall survival (OS) and event free-survival rates were 59.2 and 45.7% in whole group. OS rates were 93.3 and 22.4% for low-grade and high-grade histopathology, respectively (p=0.0001). OS for CCNU, CDDP+VP16, and COPP were 35.9, 22.8, and 30.4%, respectively. Conclusion Low-grade astrocytomas are highly responsive to the surgery, and they do not need any further treatment unless the patient has relapse or recurrence. Still, the treatment of the high-grade tumors is a problem, and it needs new treatment approaches.     

Surgical management of spinal intramedullary tumors: Ten-year experience in a single institution

Despite their rare occurrence, intramedullary spinal cord tumors can cause considerable morbidity and mortality without treatment. Timing of surgery, extent of resection and selection of favorable treatment option are important considerations for a good surgical outcome. In this clinical study, we report our patient series and convey our treatment strategy. We retrospectively reviewed 91 patients with primary intramedullary spinal cord tumors who underwent microsurgical resection at our institution between 2008 and 2018. Data were collected consisting of age, sex, location and histology of tumor, extent of resection, presenting symptoms and neurological outcomes. Modified McCormick Scale was used to assess neurological status of patients. 47 female and 44 male patients were followed-up for a mean period of 35.7 months. The most frequent pathological diagnosis was ependymoma in 56 patients, followed by astrocytoma in 21 and hemangioblastoma in 5 patients. The rest of the tumors consisted of 3 cavernomas, 3 mature cystic teratomas, 2 PNET, one epidermoid tumor. Gross total resection was achieved in 67 patients, while subtotal resection and biopsy was performed in 15 and 9 respectively. The most commonly involved localization was cervical (n = 39), followed by thoracic region (n = 24). Despite immediate postoperative worsening of neurological status, a great number of patients improved at the last follow-up. Gross total resection remains the primary goal of treatment while adjuvant radiation and/or chemotherapy may be alternative options for high grade tumors. Preoperative neurological status was the most important and the strongest predictor of functional outcome.     

An in vivo study of a new factor VIII high purity preparation

The efficacy of high purity preparations of factor VIII complex are usually lacking effect on the bleeding time in von Willebrand's disease. In this report we have studied the efficacy of a new high purity factor VIII preparation in two von Willebrand and two hemophilia A patients. The prolonged bleeding time in the patients with von Willebrand's disease was corrected after infusion of the preparation and a secondary rise in factor VIII procoagulant activity (VIII:C) demonstrated. The biological half-life time of VIII:C, in the two hemophilia A patients, was about 15hrs. The investigation shows that this particular preparation is capable of correcting the prolonged bleeding time in von Willebrand's disease.     

Outcome of children with posterior fossa medulloblastoma: a single institution experience over the decade 1994–2003

Aim While the impact of radiotherapy in the management of medulloblastoma was recognised, the introduction of chemotherapy was investigated in clinical trials and shown to confer an additional advantage. We reviewed the outcome of a series of consecutive patients to assess the impact in a population-based clinical establishment. Materials and methods A series of 38 children treated for medulloblastoma at Birmingham Children’s Hospital between 1994 and 2003 was analysed. The effect of surgery, radiotherapy, chemotherapy and metastasis on survival was analysed. Results The overall 5-year survival rate was 61.4% for the 36 patients who had resective surgery, while 2 patients had biopsy only and died within a few months. There was no operative mortality. The incidence of hydrocephalus needing permanent shunting was higher in the first 3 years of life (p = 0.007, chi-square). The 5-year survival rate of patients with total and sub-total excision of medulloblastoma was 61.1% and 61.8%, respectively. The 5-year survival rate of patients older than 3 years was 73.4% and for patients under 3 years was 36.3% (p = 0.007, log rank). Metastases at presentation did not influence survival. All deaths occurred in the first 32 months. Conclusion The contribution of chemotherapy in the improvement of the overall survival appears more evident in children younger than 3 years or presenting with metastases. The absence of significant difference in survival between patients with total or sub-total excision of medulloblastoma supports the view that total excision of medulloblastoma can be avoided when the risk for potential intra-operative damage and consequent neurological deficits is high.     

Clinical aspects and prognosis of ependymoma in infants and children A single institution experience

Thirty-two patients (22 boys and 10 girls) with a histologically confirmed diagnosis of ependymoma were treated between 1972 and 1999. A total macroscopic resection was achieved in 16 of these patients, whereas 15 resections were classified by the surgeon as subtotal. In 1 patient a ventriculostomy was created as part of a palliative strategy. All children over 3 years old were treated with postoperative radiotherapy. Chemotherapy consisted of procarbazine, ifosfamide, etoposide, methotrexate, cisplatin and cytosine arabinoside. There was 1 perioperative death. Twenty children developed a relapse of disease within 2 months to 13 years and 1 month after the initial therapy. A maximal number of five recurrences were seen in 1 patient. The value of adjuvant chemotherapy on the prognosis of children with ependymoma seems to be limited. With regard to the poor outcome, the advisability of further treatment after multiple recurrences is debatable. Received: 15 May 2000 Revised: 20 August 2000