• After splenectomy, patients with ITP have a higher risk of venous thrombosis and sepsis than patients with ITP who do not undergo splenectomy.Patients with immune thrombocytopenia (ITP) who relapse after an initial trial of corticosteroid treatment present a therapeutic challenge. Current guidelines recommend consideration of splenectomy, despite the known risks associated with surgery and the postsplenectomy state. To better define these risks, we identified a cohort of 9976 patients with ITP, 1762 of whom underwent splenectomy. The cumulative incidence of abdominal venous thromboembolism (AbVTE) was 1.6% compared with 1% in patients who did not undergo splenectomy; venous thromboembolism (VTE) (deep venous thrombosis and pulmonary embolus) after splenectomy was 4.3% compared with 1.7% in patients who did not undergo splenectomy. There was increased risk of AbVTE early (<90 days; hazard ratio [HR] 5.4 [confidence interval (CI), 2.3-12.5]), but not late ( ‡90 days; HR 1.5 [CI, 0.9-2.6]) after splenectomy. There was increased risk of VTE both early (HR 5.2 [CI, 3.2-8.5]) and late (HR 2.7 [CI, 1.9-3.8]) after splenectomy. The cumulative incidence of sepsis was 11.1% among the ITP patients who underwent splenectomy and 10.1% among the patients who did not. Splenectomy was associated with a higher adjusted risk of sepsis, both early (HR 3.3 [CI, 2.4-4.6]) and late (HR 1.6 or 3.1, depending on comorbidities). We conclude that ITP patients post splenectomy are at increased risk for AbVTE, VTE, and sepsis. (Blood. 2013;121(23):4782-4790)

OBJECTIVE To assess subclinical haemostatic activation and clinical variables to predict bleeding during radical retropubic prostatectomy (RP), as haemostatic activation is common in cancer and might be useful for predicting outcomes, but routine coagulation screening does not correlate with bleeding. PATIENTS AND METHODS Clinical data and blood samples were collected from 153 patients (median age 63 years; prostate‐specific antigen, PSA, level 5.92 ng/mL) before RP and lymph node dissection. Plasma was assayed for d‐dimer and thrombin‐antithrombin complex (TAT). Univariable then multivariable analyses were used to identify associations between plasma markers and clinical variables for bleeding and thrombosis. RESULTS Most patients (77%) were stage T1c and most (76.5%) had organ‐confined cancer (≤pT2). Pathological Gleason scores were ≤6 in 68 (44.4%) and ≥8 in 14 (9%) of the patients. The median (range) estimated blood loss (EBL) was 400 (50–3000) mL, the median decrease in haemoglobin level 3.5 (−0.1, 6.6) g/dL, and eight men (5.2%) required a transfusion. In the univariable analysis, a lower TAT before RP (P < 0.001) and d‐dimer level (P = 0.023) correlated with a greater decline in haemoglobin level. The platelet count, international normalised ratio, and activated partial thromboplastin time (aPTT) did not predict the EBL nor change in haemoglobin level; the eight transfused patients had lower platelet counts before RP (P = 0.004). Higher surgical volume predicted a lower EBL (P < 0.001) and lower decrease in haemoglobin (P < 0.05). Multivariable linear regression showed that TAT remained significant for the decrease in haemoglobin, and surgical volume for EBL and decrease in haemoglobin. CONCLUSIONS Haemostatic activation before RP was associated with significantly less bleeding when assessed by objective measures, predicting the decrease in haemoglobin level better than prothrombin time, aPTT or platelet counts. Current surgeon volume might also predict both subjective and objective bleeding variables.

This study quantified architectural and population changes in the rat retinal vasculature after proton irradiation using stereology. A 100 MeV conformal proton beam delivered 8, 14, 20 and 28 Gy as single and split doses to the whole eye. The vascular networks were prepared from retinal digests. Stereological methods were used to obtain the area of the retina and unbiased estimates of microvessel/artery/vein endothelial, pericyte and smooth muscle population, and vessel length. The retinal area increased progressively in the unirradiated, age-matched controls and in the retinas irradiated with 8 and 14 Gy, indicating uniform progressive retinal growth. No growth occurred after 20 and 28 Gy. Regression analysis of total endothelial cell number in all vessels (arteries, veins and capillaries) after irradiation documented a progressive time- and dose-dependent cell loss occurring over 15 to 24 months. The difference from controls was significant (P<0.01) after 28 Gy given in single and split doses and after 20 Gy given as a split dose (P<0.05). Total vessel length in microvessel was significantly shortened at 20 and 28 Gy compared to that of controls (P<0.05). No evident dose recovery was observed in the endothelial populations after split doses. At 10 Gy, the rate of endothelial cell loss, a dose parameter used to characterize the time- and dose-dependent loss of the endothelial population, was doubled.

Patients undergoing vascular surgery frequently develop PF4/heparin antibodies, with platelet-activating antibodies detected in up to 11% of these individuals. However, thrombocytopenia and vascular graft thrombosis both appear to be an uncommon consequence.

Background: While symptomatic venous thromboemboli (VTE) clearly have an adverse impact on survival among cancer patients, the outcome of cancer patients with unsuspected pulmonary emboli (PE) found on routine cancer staging multi-row detector CT (MDCT) scans is unknown. In order to evaluate survival among cancer patients with unsuspected PE, we expanded on a previous study (O’Connell, JCO2006; 24:4928) of such patients. Methods: We performed a retrospective chart review of cancer patients with unsuspected PE found on routine cancer staging MDCT scans between May, 2003 and August, 2006. Two patients matched for age, cancer type and stage (“controls”) were identified for each patient with unsuspected PE (“cases”). Patients with known VTE, patients already receiving anticoagulation for any reason and patients with multiple active cancers were excluded. We recorded cancer characteristics, signs and symptoms typical of PE, risk factors, presence of PE on subsequent staging scans, time to death, and cause of death. We used conditional logistic regression analysis to compare the baseline characteristics. To evaluate the impact of unsuspected PE and other covariates on survival, we used stratified Cox proportional hazard analysis and the logrank test. Results: Seventy patients with unsuspected PE and 137 matched controls were evaluated. There were no significant differences between the groups in terms of matching factors, gender, or sites of metastases. Cases were more likely to have had prior VTE and to have had surgery within the previous 2 months than were controls (p=0.008, p=0.0002, respectively). There were no differences in the time from cancer diagnosis to the index MDCT scan, use of erythropoietin, exposure to chemotherapy, presence of central lines, hormonal therapy or use of antiplatelet medication between cases and controls. As previously reported in the smaller series, cases were more likely to actually have complained to someone on the medical team of shortness of breath and fatigue than were control patients (p =0.0009, p=0.001, respectively); case patients were also more likely than control patients to complain of cough (p=0.019). There were no statistically significant differences in other signs or symptoms such as hypoxia, fever, limb pain or swelling, chest pain or tachycardia. Of the 70 patients with unsuspected PE, 17 (24.3%) had isolated subsegmental clots and 53 (75.7%) had more proximal clots. Fifty-nine of the 70 patients (84.3%) with PE received some form of anticoagulation as treatment. Using a stratified analysis adjusting for the presence of brain, liver and lung metastases and for use of erythropoietin we found that proximal unsuspected PE conferred a hazard ratio for death of 1.79 (95% CI 1.10–2.90, p =0.018) (Kaplan-Meier curves, Figure 1). Symptomatic patients with unsuspected proximal PE, in particular, had poorer overall survival than matched controls (5 months vs. 14 months, p=0.009, logrank test). Use of erythropoietin, metastases to lung, liver or lymph nodes, gender, and active treatment with chemotherapy had no significant impact on survival; brain metastases, however, conferred poorer overall survival (20.5 vs. 61 months, p=0.003) independent of PE. Conclusion: These data support our previous findings in the smaller series that patients with unsuspected PE detected on routine staging MDCT scans are more likely to be symptomatic than are matched control patients, particularly with shortness of breath, fatigue and cough. Unsuspected PE have a significant adverse impact on overall survival among cancer patients; this impact is more pronounced among those patients reporting PE-related symptoms. Figure SEQ Figure \* ARABIC 1. Overall survival among cancer patients with unsuspected PE and matched controls Figure. SEQ Figure \* ARABIC 1. Overall survival among cancer patients with unsuspected PE and matched controls