Background-Long-term low-molecular-weight heparin (LMWH) is the current standard for treatment of venous thromboembolism (VTE) in cancer patients. Whether treatment strategies should vary according to individual risk of VTE recurrence remains unknown. We performed a retrospective cohort study and a validation study in patients with cancer-associated VTE to derive a clinical prediction rule that stratifies VTE recurrence risk. Methods and Results-The cohort study of 543 patients determined the model with the best classification performance included 4 independent predictors (sex, primary tumor site, stage, and prior VTE) with 100% sensitivity, a wide separation of recurrence rates, 98.1% negative predictive value, and a negative likelihood ratio of 0.16. In this model, the score sum ranged between Ϫ3 and 3 score points. Patients with a score Յ0 had low risk (Յ4.5%) for recurrence and patients with a score Ͼ1 had a high risk (Ն19%) for VTE recurrence. Subsequently, we applied and validated the rule in an independent set of 819 patients from 2 randomized, controlled trials comparing low-molecular-weight heparin to coumarin treatment in cancer patients. Conclusions-By identifying VTE recurrence risk in cancer patients with VTE, we may be able to tailor treatment, improving clinical outcomes while minimizing costs. (Circulation. 2012;126:448-454.)

475 Background: Current guidelines suggest that all cancer patients with venous thromboembolism be treated with long-term low molecular weight heparin (LMWH). However, whether treatment strategies should vary according to patient and malignancy characteristics, in particular whether patients with low risk of VTE recurrence can be identified, remains unknown. Methods: We performed a single centre retrospective cohort study conducted at the Thrombosis Unit of the Ottawa Hospital. The charts of patients with cancer and VTE followed from 2002 to 2004 and from 2007 to 2008 were reviewed to assess the feasibility of derivation of a clinical prediction rule that stratifies VTE recurrence risk in patients with cancer—associated venous thrombosis through identification and evaluation of characteristics of malignancy and other clinical characteristics. We analysed only the patients who had a recurrent VTE within the first 6 months of anticoagulation. A univariate analysis determined the strength of association between each potential predictor and VTE recurrence. All potential predictor variables (p<0.25) were evaluated in a logistic regression model. Result: Of 543 patients 55 (10.1%) presented with a VTE recurrence during the first 6 months of anticoagulation. At VTE recurrence 19 (9.5%) patients were using VKA and 36 (10.5%) patients were using LMWH. The relative risk for VTE recurrence was not significantly different between patients who used VKA or LMWH [RR= 1. 13 (95%CI, 0.743 – 1.711; p= 0.565)]. A multivariate analysis suggested that gender, primary tumour site, tumour stage and history of prior VTE were significant variables to include in the clinical prediction rule. The final model included female gender, lung cancer and prior history of VTE as increasing risk and breast cancer and stage I disease as lowering risk. Patients with a score equal or less than 0 have low risk (4.5%) for VTE recurrence and this represented 48% of our patients. Patients with a score equal or above 1 have high risk (> 19%) for VTE recurrence (Tables 1 and 2). Conclusion: We were able to derive a simple and easy scoring system that stratifies patients with cancer-associated thrombosis into low or high risk of recurrent VTE. Future prospective validation of the model is warranted and may be very relevant to better tailor anticoagulation treatment in this heterogeneous population. Disclosure: No relevant conflicts of interest to declare.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder characterized by heparindependent antibodies that activate platelets (PLTs) via PLT FcγIIa receptors. "Autoimmune" HIT (aHIT) indicates a HIT subset where thrombocytopenia progresses or persists despite stopping heparin; aHIT sera activate PLTs strongly even in the absence of heparin (heparin-independent PLTactivating properties). Affected patients are at risk of severe complications, including dual macro-and microvascular thrombosis leading to venous limb gangrene. High-dose intravenous immunoglobulin (IVIG) offers an approach to interrupt heparin-independent PLT-activating effects of aHIT antibodies. CASE REPORT:A 78-year-old male who underwent cardiopulmonary bypass for aortic dissection developed aHIT, disseminated intravascular coagulation, and deep vein thrombosis; progression to venous limb gangrene occurred during partial thromboplastin time (PTT)-adjusted bivalirudin infusion (underdosing from "PTT confounding"). Thrombocytopenia recovered with high-dose IVIG, although the PLT count increase began only after the third dose of a 5-day IVIG regimen (0.4 g/kg/day × 5 days). We reviewed case reports and case series of IVIG for treating HIT, focusing on various IVIG dosing regimens used. RESULTS: Patient serum-induced PLT activation wasinhibited in vitro by IVIG in a dose-dependent fashion; inhibition of PLT activation by IVIG was much more marked in the absence of heparin versus the presence of heparin (0.2 U/mL). Our literature review indicated 1 g/kg × 2 IVIG dosing as most common for treating HIT, usually associated with rapid PLT count recovery. CONCLUSION:Our clinical and laboratory observations support dose-dependent efficacy of IVIG for decreasing PLT activation and thus correcting thrombocytopenia in aHIT. Our case experience and literature review suggests dosing of 1 g/kg IVIG × 2 for patients with severe aHIT. ABBREVIATIONS: aHIT = autoimmune heparin-induced thrombocytopenia; DIC = disseminated intravascular coagulation; DVT = deep vein thrombosis; HIT = heparin-induced thrombocytopenia; ITP = idiopathic thrombocytopenic purpura; PE = pulmonary embolism; PF4 = platelet factor 4; POD = postoperative day; PTT(s) = partial thromboplastin time(s); SRA = serotonin release assay; UFH = unfractionated heparin. From the

Patients with cancer-associated venous thromboembolism (VTE) should be treated with low molecular weight heparin. The ideal duration of anticoagulation in this population is unknown. It is important to evaluate whether there is variation in susceptibility for recurrent VTE according to malignancy characteristics. In this systematic review we sought to evaluate cancer characteristics that may influence the risk for VTE recurrence and the success of anticoagulation in patients with cancer-associated VTE. A systematic literature search strategy identified potential studies on MEDLINE, Embase, the Cochrane Register of Controlled Trials, MEDLINE In-Process and other nonindexed citations using the Ovid interface. There was no restriction to study design or language. No randomized controlled trials fulfilled our inclusion criteria. We included four retrospective and six prospective studies. VTE recurrence rate according to tumour stage suggested an increased risk for patients with metastatic malignancy compared with patients with localized disease (relative risk 1.36; 95% confidence interval 1.06-1.74, P = 0.01). We were unable to pool data to evaluate VTE recurrence according to tumour site and histology. The isolated evaluation of the included studies suggested that younger patients with adenocarcinoma, lung or gastrointestinal malignancy have the highest risk. There is paucity of data regarding detailed malignancy characteristics in patients with cancer-associated VTE. It appears that metastatic malignancy, or adenocarcinoma, or lung malignancy confers a higher risk of VTE recurrence than patients with localized malignancy, nonadenocarcinoma or breast cancer.

Overall, although antepartum anticoagulant prophylaxis has the potential to reduce placenta-mediated pregnancy complications in women with and without identifiable thrombophilia, the data generated by these trials are methodologically limited and inadequate. Hence, we conclude that further trials are required prior to adopting the use of antepartum anticoagulant prophylaxis to prevent placenta-mediated pregnancy complications in routine clinical practice.

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Colorectal cancer is the third most common cancer and the second leading cause of death from cancer worldwide. In Vietnam, the disease is the fifth leading cancer (8.9%), with 14 733 new cases in 2018. In recent years, the mFolfox6 regimen has been indicated commonly as the adjuvant chemotherapy after curative resection for patients with colorectal cancer. However, the efficacy of the regimen in Vietnamese patients has not been assessed and reported. In this retrospective study, we reviewed medical records of 83 patients with stage II or stage III colorectal cancer who received mFOLFOX6 regimen in order to investigate simultaneously survival and safety of this chemotherapy regimen. Three-year overall and disease-free survival were 84.3% and 79.5%, respectively. Our data revealed that postoperative Carcinoma Embryonic Antigen (CEA) level was a significant prognostic factor for survival, with hazard ratio of 3.83 and 3.67, respectively ( P < .05), for overall survival and disease-free survival in the elevated CEA level group when compared to the normal CEA level group. The regimen also demonstrated to be well tolerated and can be used in routine practice as an adjuvant chemotherapy.

Background: Outcomes of unselected adult ALL patients (pts) have not been well studied at a population level. Whether such pts behave differently to those in formal clinical trials is unclear. We developed a uniform therapeutic protocol as the provincial standard of care in Manitoba, a province with 1.2 million people, for adult pts since 1989 (“ALL89-1”). The aim of this retrospective study was: to ascertain the local epidemiology of adult ALL; to analyze the efficacy and toxicity of the ALL89-1 regimen and any other regimens given to pts in a population-based setting. Methods: All pts aged ≥18 years (yrs) diagnosed with ALL in Manitoba between 01/1989 and 11/2004 were identified via the provincial cancer registry. A review of computerized and paper charts was conducted. We focused on demographics, diagnostic clinical characteristics, therapy, treatment related toxicities, and whether stem cell transplantation (SCT) was performed. Results: There were 81 pts with a median age of 44yrs (range, 18–90). 53 (65%) pts were male. 58 pts received ALL89-1, 12 received other regimens and 11 patients received palliation only. Thirteen pts were Philadelphia chromosome positive (Ph+). Complete remission (CR) rate after one cycle of induction therapy was 74% for all pts, and 74% for ALL89-1 pts. At a median follow-up of 56 months (range 7–265), estimated overall survival (OS) and leukemia free survival (LFS) at 5 years was 26% (95% Confidence interval [C.I.], 15–36) and 24%( 95% C.I. 14–35). The 5 year OS and LFS for the ALL89–1 group was 23% (95% C.I. 11–35) and 20% (95% C.I. 8–32). There were 13 treatment related deaths in the 58 ALL 89-1 pts, 4 of whom died post SCT. In multivariate analysis for all 81 pts, attainment of CR post induction chemotherapy independently predicted improved survival (hazard ratio 0.23, 95% C.I. 0.11–0.5). In contrast, age > 55yrs, Ph+ status, and high WBC at diagnosis were not significant survival predictors. Palliative pts survived for a median of 10 days (range, 0–53) from diagnosis. Conclusions: This comprehensive province-wide study of adult ALL pts treated at a single cancer centre shows that durable leukemia free survival is possible, but for only a small subgroup. These results appear inferior to results of published clinical trials. The reasons for the relatively poor outcomes require further analysis in this and other jurisdictions.