Hematological disorders underlie a small proportion of all ischemic strokes. The association of these coagulation abnormalities with ischemic stroke is not always clear. The etiology of stroke still remains uncertain in a large number of cases and proper screening for coagulation abnormalities and the discovery of new coagulation disorders will probably increase the rate of strokes attributable to these causes. Since large case-control studies with unselected and consecutive stroke patients from different ethnic origins have not yet been performed to determine the role of coagulation abnormalities in ischemic stroke, our knowledge is dependent on case reports and small series of mostly younger patients. Extensive hematologic evaluation of unselected stroke patients will likely yield little useful information and be too expensive. Every stroke patients needs a careful evaluation, and in selected cases, this should include coagulation parameters. Patients with unexplained strokes after a careful evaluation, previous thrombotic episodes, or a positive family history for thrombosis, are good candidates for further coagulation studies. As long as the hypercoagulable state persists, both arterial and venous thromboembolic recurrences can be expected. Many of these patients may benefit from anticoagulants. In patients with hereditary coagulation disorders, studies should be extended to close relatives. Since some coagulation tests are fairly expensive, provide only equivocal data, and are not widely available, we advise a step-by-step approach starting with the patient and family history.

Twenty-two patients with previously untreated metastatic breast cancer and nineteen patients with refractory metastatic breast cancer were treated with trimetrexate (TMTX). Patients received TMTX 8 mg/m2/day if previously treated or 12 mg/m2/day if previously untreated, both given by intravenous bolus days 1-5, every 21 days. None of the patients previously treated for metastatic disease responded to TMTX. There was one partial responder among the 22 patients with previously untreated metastatic disease. The primary toxicity was hematologic and occurred more frequently in patients with a pleural effusion, low serum protein or albumin, or poor performance status. There were three toxic deaths. The study for previously untreated patients required cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) after 4 cycles of TMTX. This study design for previously untreated patients allows the Cancer and Leukemia Group B (CALGB) to prospectively evaluate the activity of new agents in "chemotherapy-sensitive" metastatic breast cancer.