The prognostic role of pre-cystectomy thrombocytosis in invasive bladder cancer.

PURPOSE: We aim to evaluate the impact of preoperative thrombocytosis on oncological outcomes in patients with bladder cancer (BC) who undergo radical cystectomy (RC). METHODS: Retrospective data collection of 1092 patients managed by RC for BC from 2 tertiary-care centers was performed. Elevated platelet count (PLT) was defined as > 450 × 109/L. Univariable and multivariable logistic regression analyses were used to investigate the impact of thrombocytosis on oncological outcomes. These outcomes were also compared using Kaplan-Meier survival analysis. RESULTS: The median follow-up was 50 months (32-64 months). Thrombocytosis was detected in 18.6% of the patients. The 3-year cancer-specific survival (CSS) for patients with normal PLT count was 92% which was higher than those with elevated PLT count (55%, P < 0.001). Similar results were found for the 6-year CSS with 82% for the no thrombocytosis group and 27% for the thrombocytosis group. Thrombocytosis was still significantly associated with poor prognosis for overall survival and recurrence-free survival (P < 0.001). In the multivariate analysis, CSS was significantly lower in patients with thrombocytosis (HR = 1.71, 95% CI = 1.22-2.39, P = 0.002). Patients with elevated PLT counts were also significantly more likely to receive adjuvant chemotherapy, to have a T stage > pT2b (P = 0.024), to have a positive lymph node, to have variant histology and positive resection margins, and to have concomitant carcinoma in situ (CIS) on final pathology (all P < 0.001). CONCLUSIONS: Preoperative thrombocytosis was valuable for predicting the oncological outcomes of patients undergoing RC for BC.

Reactive Thrombocytosis in Non-aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: The role of reactive thrombocytosis in non-aneurysmal subarachnoid hemorrhage (NA-SAH) is largely unexplored to date. Therefore, the impact of a quantitative thrombocyte dynamic in patients with NA-SAH and its clinical relevance were analyzed in the present study. METHODS: In this retrospective analysis, 113 patients with nontraumatic and NA-SAH treated between 2003 and 2015 at our institution were included. World Federation of Neurosurgical Societies admission status, cerebral vasospasm, delayed infarction, hydrocephalus, need for ventriculoperitoneal (VP) shunt, and Fisher grade were analyzed for their association with reactive thrombocytosis. RESULTS: Reactive thrombocytosis was not associated with hydrocephalus (p ≥ 0.05), need for VP shunt implantation (p ≥ 0.05), cerebral vasospasm (p ≥ 0.05), or delayed cerebral ischemia (p ≥ 0.05). CONCLUSION: Our study is the first to investigate the role of thrombocyte dynamics, reactive thrombocytosis, and the clinical course of NA-SAH patients. Our analysis showed no significant impact of thrombocyte count on NA-SAH sequelae.

Thrombocytosis in splenic trauma: In-hospital course and association with venous thromboembolism.

INTRODUCTION: Thrombocytosis is common following elective splenectomy and major trauma. However, little is known about the in-hospital course of platelet count (PC) and incidence of thrombocytosis after splenic trauma. Extreme thrombocytosis (PC>1000×109) is associated with increased risk of venous thromboembolism (VTE) in primary thrombocytosis leading to the use of acetylsalicylic acid (ASA) for risk reduction, but the need for this agent in splenic trauma is undefined. METHODS: Retrospective cohort study of all patients with splenic trauma between April 1, 2010 and March 31, 2014. The in-hospital course of PC was assessed based on splenic injury management type. The association of management type with thrombocytosis was evaluated using a multivariable logistic regression model adjusting for potential confounders. The association of thrombocytosis, extreme thrombocytosis, and ASA use for the outcome of VTE was explored. RESULTS: 156 patients were eligible, PC initially increased in all patients with the highest peak after total splenectomy. The incidence of thrombocytosis was 41.0% (64/156). Thrombocytosis was more likely following splenectomy compared with spleen preserving strategies independent of length of stay, injury grade, ISS, age and transfusion (OR 7.58, 95% CI: 2.26-25.45). Splenectomy was associated with extreme thrombocytosis (OR 10.39, 95% CI: 3.59-30.07). CONCLUSIONS: Thrombocytosis in splenic trauma is more likely after splenectomy than with spleen preserving strategies. Splenectomy is associated with extreme thrombocytosis. There was insufficient data in our study to determine the use of ASA as primary prevention of VTE after splenic trauma.

Acute Retroperitoneal Hematoma After Psoas Catheter Placement in a Patient with Myeloproliferative Thrombocytosis and Aspirin Therapy.

Retroperitoneal hematoma is a rare complication of psoas catheter placement, typically occurring several days after placement and in the setting of anticoagulation. We present the case of a patient with a history of myeloproliferative thrombocytosis receiving aspirin therapy who underwent total hip arthroplasty with preoperative psoas catheter placement complicated by immediate development of a large retroperitoneal hematoma. It is likely that the combination of aspirin therapy and thrombocytosis paradoxically placed the patient at increased risk for hemorrhagic complications. Regional techniques should be used cautiously in patients with myeloproliferative disorders, even in the presence of supraphysiologic platelet counts.

Thrombocytosis in asplenia syndrome with congenital heart disease: a previously unrecognized risk factor for thromboembolism.

BACKGROUND: Thrombocytosis and thromboembolic complications occur after splenectomy. However, there is no previous report investigating the presence of thrombocytosis and its association with thromboembolic events in patients having asplenia syndrome with congenital heart disease. METHODS: Enrolled were 161 consecutive patients with functionally single ventricle who underwent cardiac catheterization between 1997 and 2010. They were divided into two groups: patients having asplenia (Group A, n=46) and patients having no asplenia (Group B, n=115). Aspirin therapy was employed in all patients after surgical interventions except for pulmonary artery banding. We retrospectively reviewed the platelet counts at each seven stage of cardiac catheterization (for pre- and postoperative evaluation of the first palliation, Glenn operation, and Fontan operation, and for late evaluation after Fontan operation), incidence of thromboembolic events, and other possible risk factors for thromboembolism. RESULTS: The median platelet counts in Group A were consistently higher than those in Group B at any of the seven stages of cardiac catheterizations (p<0.002). The incidence of thromboembolic complications was also higher in Group A than that in Group B (28% vs. 10%, p=0.030). Univariate and multivariate logistic regression analyses showed that a platelet count of more than 550 × 10(9)/L at the first cardiac catheterization was associated with thromboembolic complications (Odds ratio 3.17; p=0.046). CONCLUSIONS: Persistent thrombocytosis is present in patients with asplenia syndrome. It may greatly contribute to the development of thromboembolism during the management of congenital heart disease than expected.

Tumor-platelet interactions: glioblastoma growth is accompanied by increasing platelet counts.

OBJECTIVES: We have recently shown that pre-operative thrombocytosis is associated with significantly shorter survival in patients with glioblastoma (GBM). The interaction between platelets and growth of GBM is not clear yet. One hypothesis suggests that platelet-released growth factors support growth and migration of malignant glioma and endothelial cells and thus may increase angiogenesis in these tumors. Another hypothesis would be that larger tumors are associated with poorer survival and produce more factors inducing thrombocytosis. In this study we investigate whether GBM growth induces thrombocytosis. PATIENTS AND METHODS: We compared pre-operative platelet counts of 24 patients with GBM with platelet counts taken 46.3+/-29.2 months (mean+/-1S.D.) prior to diagnosis of GBM. RESULTS: We found immediate pre-operative platelet counts to be significantly higher than the older platelet counts (p=0.02). Furthermore, patients with GBM at time of diagnosis presented with increased platelet counts (314+/-86 platelets/nl) compared to the normal population. CONCLUSION: Our results suggest that elevation of platelet counts in glioblastoma patients is caused by growth and development of GBM. Whether tumor secreted cytokines are the underlying mechanism for this finding, remains to be elucidated.

Sclerodermatous graft-versus-host disease: clinical spectrum and therapeutic challenges.

Sclerodermatous graft-versus-host disease (GVHD) is a rare complication of bone marrow transplantation. While GVHD is often associated with the beneficial graft vs. tumour effect, it also contributes towards significant morbidity and mortality. No reliably effective treatment has yet been established. We present 10 patients with haematological malignancies who underwent an allogeneic stem cell transplant and developed sclerodermatous GVHD. Donor lymphocyte infusion administered for relapse or reducing donor T-cell chimerism was a known trigger for sclerodermatous GVHD in four of the patients. Treatment with immunosuppressants, psoralen plus ultraviolet A (PUVA) and extracorporeal photopheresis has been largely unsuccessful in their management. Intensive immunosuppression including the use of anti-CD20 monoclonal antibody may have contributed to relapse of leukaemia in one patient 10 years after her transplant. Sclerodermatous GVHD may occur without a preceding lichenoid stage. Clinical heterogeneity is common, although sclerodermatous GVHD has a predilection for the limbs. Treatment options are largely unsatisfactory if conventional immunosuppression fails. PUVA may give some symptomatic benefit and extracorporeal photopheresis seems to be less efficacious than previously published work suggests.

Topical use of tranexamic acid to control perioperative local bleeding in gynaecology patients with clotting disorders: two cases.

Operating on patients with abnormal coagulation is a challenge frequently faced by surgeons. Achieving haemostasis perioperatively can involve bleeding points that would not ordinarily present a problem with intact clotting function. Here we present two women with localised wound bleeding following a gynaecological surgery in the presence of a clotting disorder. Haemostasis was successfully achieved with tropical use of tranexamic acid. These two cases illustrate a novel use for this antifibrinolytic agent. We suggest that there is a role for topical use of tranexamic acid in perioperative haemostasis in patients with clotting disorders.

Thrombocythemia and hemoperitoneum after transvaginal oocyte retrieval for in vitro fertilization.

OBJECTIVE: To present the first report of massive hemoperitoneum in a case of essential thrombocythemia after transvaginal oocyte retrieval for IVF and review the relevant literature related to the management of patients with this condition. DESIGN: Case report. SETTING: Assisted conception unit of a tertiary care university hospital in the United Kingdom. PATIENT(S): A 37-year-old woman with essential thrombocythemia who developed massive intra-abdominal bleeding after transvaginal oocyte retrieval for IVF. INTERVENTION(S): Emergency laparotomy and right salpingoophorectomy. RESULT(S): Resuscitation of the patient. MAIN OUTCOME MEASURE(S): Overall management of the patient is discussed. CONCLUSION(S): The management of patients with essential thrombocythemia at the childbearing period poses a difficult problem. Fertility may be reduced, and an adverse outcome of pregnancy due to thrombotic or bleeding complications is a matter of concern. A multidisciplinary approach with close and early cooperation with the hematologists before initiation of IVF therapy for patients with essential thrombocythemia is essential. Efforts should be made to reduce the platelet count and assess the platelet function before embarking on IVF, keeping in mind the double jeopardy from bleeding and thrombosis in these cases.

Aortic valve replacement for a patient with essential thrombocythemia: a case report.

A 51-year-old male patient with 3+ aortic insufficiency, hepatitis C, osteomyelitis right foot, and a preoperative platelet count 1.3 million/mm3 required cardiopulmonary bypass (CPB). Essential thrombocythemia is a relatively unknown entity with the utilization of CPB. After consulting with the surgeon, an anesthesiologist and another perfusionist, a team approach was used to discuss treatment for this patient during CPB. The treatment consisted of exchange transfusions, autotransfusion techniques, and current protocol for blood gas management. No incidence of hypercoagulability was observed during this procedure or postoperatively. Based on current knowledge of pathophysiology and review of the literature, plateletpheresis should be the current management of essential thrombocythemia.

Circulating thrombopoietin in reactive conditions behaves like an acute phase reactant.

In a recent study we found elevated thrombopoietin (TPO) levels along with a trend toward correlation between serum TPO and some acute phase reactants (APR) in patients with reactive thrombocytosis. In order to further clarify the behaviour of TPO in reactive conditions and to highlight the eventual drawbacks of serum TPO (sTPO) against plasma TPO (pTPO) measurements, serial measurements were made of sTPO, pTPO, interleukin (IL)-6, C-reactive protein (CRP), fibrinogen (FBG), and erythrocyte sedimentation rate (ESR) in 12 patients before and at the 3rd, 7th, 14th, 45th day after hip replacement surgery. Platelet count, sTPO and pTPO were also measured in 30 healthy donors. As expected sTPO were significantly higher than pTPO levels (approximately 30% on average) both in controls (P < 0.00001) and in patients (P < 0.00001). Overall a very good correlation (r = 0.975, P < 0.00001) was found between serum and plasma TPO, whereas no correlation was found between platelet count and the sTPO/pTPO ratio indicating that the difference between sTPO and pTPO is independent from platelet count. So both serum and plasma seem to be suitable samples for TPO measurement if it is taken into account that sTPO are about 30% higher than pTPO. All the parameters we measured in our patients increased during the post-surgery period and returned to the basal value at the 45th day. pTPO levels peaked at the 3rd day, preceding by 11 days the peak in platelet count. A significant correlation was found between pTPO and ESR (P = 0.012), pTPO and FBG (P = 0.044), pTPO and CRP (P = 0.033), and a nearly significant correlation between pTPO and IL-6 (P = 0. 054). These results indicate that, in the course of reactive conditions, an early rise in TPO precedes and probably induces a later increase in platelet count. Moreover, the significant correlations along with the similarity in the chronological variations between TPO and some APRs suggest that TPO behave like an APR.

Thrombocytosis after major lower extremity trauma: mechanism and possible role in free flap failure.

Microvascular thrombosis and free flap failure are complications of free tissue transfer for coverage of lower extremity soft-tissue and bony defects despite appropriate vessel selection and adherence to meticulous technique. Increased rates of flap failure have been associated with reconstruction performed between 3 days and 6 weeks after injury, as well as in patients with thrombocytosis. We have found that serum platelet levels rise significantly after lower extremity injury. It is our theory that a circulating mediator or cytokine is released in response to injury, inducing the thrombocytosis. Twenty-one patients with Gustilo grade IIIb and IIIc injuries were studied prospectively. Serum was collected throughout the postinjury period. Platelet count, leukocyte count, hemoglobin concentration, and hematocrit were determined. Samples were also subjected to a platelet aggregation study as well as enzyme-linked immunosorbent assay for interleukin-3, interleukin-6, interleukin-11, and granulocyte macrophage-colony-stimulating factor. Megakaryocyte growth and development factor enzyme-linked immunosorbent assay and a myleoproliferative leukemia virus-transfected cell line assay for thrombopoietin were performed. Bone marrow was studied with flow cytometric analysis. Mean initial platelet count was 196,000 per cubic millimeter. There was an initial 26% decline to 140,000 per cubic millimeter, followed by an increase to 361% of baseline on day 16. No significant variations in serum leukocyte count or hemoglobin concentration were seen. Spontaneous and induced platelet aggregation responses were normal. Interleukin-6 was detected at elevated levels. However, interleukin-3, interleukin-11, granulocyte macrophage-colony-stimulating factor, and thrombopoietin were not measurable. Marked megakaryocytosis was seen on bone marrow analysis. Interleukin-6 may, therefore, play a role in the mechanism of thrombocytosis. We suggest that because patients with complex bony injuries of the leg experience platelet elevations that peak approximately 2 weeks after injury, microvascular free flap reconstructions should be considered high risk during this time period.

[Cerebral space-occupying lesion in thrombocytosis]. / Cerebrale Raumforderung bei Thrombozytose.

We report a case of venous thrombosis presented as ischemic intracranial expanding lesion localized in the parietal lobe of a young man with essential thrombocytosis. As surgical intervention became necessary we were able to investigate the morphological changes by histology and immunocytochemistry. The almost exclusive venous manifestation of thrombosis most probably initiated by elevated amounts of platelets suggests altered blood flow conditions as the predominant factor. Surgical interventions in such conditions are rare and might only proceed in space-occupying lesions with clinical symptoms. Treatment with inhibitors of platelet aggregation under strict control of the patient is the therapy of choice.