Incidence Of Fatal Hemorrhage Research Articles

Cardiac, Hemorrhagic, and Coagulopathic Oncologic Emergencies

Cardiac, Hemorrhagic, and Coagulopathic Oncologic Emergencies

Warfarin Sensitivity Genotyping: A Review of the Literature and Summary of Patient Experience

The antithrombotic benefits of warfarin are countered by a narrow therapeutic index that contributes to excessive bleeding or cerebrovascular clotting and stroke in some patients. This article reviews the current literature describing warfarin sensitivity genotyping and compares the results of that review to the findings of our study in 189 patients at Mayo Clinic conducted between June 2001 and April 2003. For the review of the literature, we identified relevant peer-reviewed articles by searching the Web of Knowledge using key word warfarin-related adverse event. For the 189 Mayo Clinic patients initiating warfarin therapy to achieve a target international normalized ratio (INR) in the range of 2.0 to 3.5, we analyzed the CYP2C9 (cytochrome P450 2C9) and VKORC1 (vitamin K epoxide reductase complex, subunit 1) genetic loci to study the relationship among the initial warfarin dose, steady-state dose, time to achieve steady-state dose, variations in INR, and allelic variance. Results were compared with those previously reported in the literature for 637 patients. The relationships between allelic variants and warfarin sensitivity found in our study of Mayo Clinic patients are fundamentally the same as in those reported by others. The Mayo Clinic population is predominantly white and shows considerable allelic variability in CYP2C9 and VKORC1. Certain of these alleles are associated with increased sensitivity to warfarin. Polymorphisms in CYP2C9 and VKORC1 have a considerable effect on warfarin dose in white people. A correlation between steady-state warfarin dose and allelic variants of CYP2C9 and VKORC1 has been demonstrated by many previous reports and is reconfirmed in this report. The allelic variants found to most affect warfarin sensitivity are CYP2C9*1*1-VKORC1BB (less warfarin sensitivity than typical); CYP2C9*1*1-VKORC1AA (considerable variance in INR throughout initiation); CYP2C9*1*2-VKORC1AB (more sensitivity to warfarin than typical); CYP2C9*1*3-VKORC1AB (much more sensitivity to warfarin than typical); CYP2C9*1*2-VKORC1AB (much more sensitivity to warfarin than typical); CYP2C9*1*3-VKORC1AA (much more sensitivity to warfarin than typical); and CYP2C9*2*2-VKORC1AB (much more sensitivity to warfarin than typical). Although we were unable to show an association between allelic variants and initial warfarin dose or dose escalation, an association was seen between allelic variant and steady-state warfarin dose. White people show considerable variance in CYP2C9 allele types, whereas people of Asian or African descent infrequently carry CYP2C9 allelic variants. The VKORC1AA allele associated with high warfarin sensitivity predominates in those of Asian descent, whereas white people and those of African descent show diversity, carrying either the VKORC1BB, an allele associated with low warfarin sensitivity, or VKORC1AB or VKORC1AA, alleles associated with moderate and high warfarin sensitivity, respectively.

Acute myelogenous leukemia: implications of acute blast crisis and cardiopulmonary bypass

CUTE MYELOCYTIC leukemia (AML) is a disorder characterized by the expansion of an abnormal white blood cell line. This clonal expansion of cells may infiltrate the bone marrow and other organs, suppressing normal hematopoiesis and inducing dysfunction of the invaded organs. Clinical manifestations of this disease, therefore, result from lack of normal blood cells (primarily due to decreased production) and induced organ dysfunction (secondary to cellular infiltration and/or local hemorrhage). Although the exact incidence of coagulation abnormalities is not known, thrombohemorrhagic complications are certainly common in patients with AML (20% incidence of fatal hemorrhage), especially compared to chronic leukemias; blast crisis accentuates this potential. Although isolated case reports of thrombosis of venous and mammary artery grafts have been reported in patients requiring coronary artery bypass grafting (CABG) with concurrent stable chronic leukemia, nothing has been reported regarding potential thrombohemorrhagic events during acute blast crisis. Hence, a case is presented in which urgent CABG was performed in a patient with AML complicated by a recently diagnosed blast crisis.

Bleeding and thrombosis in acute lymphoblastic leukemia.

With the advent of modern chemotherapy schedules and the availability of adequate supportive care, the incidence of fatal hemorrhage has dramatically decreased in patients with acute leukemia, but still remains a major cause of death. Acute promyelocytic leukemia (APL) is the subtype where characteristically the highest mortality from bleeding is registered. In a retrospective analysis on 268 consecutive patients with APL collected from multiple institutions in Italy, we found that during remission induction with standard chemotherapy and routine platelet support early hemorrhagic deaths occurred in about 10% of patients, this rate being not significantly different among patients receiving or not heparin or antifibrinolytic agents.' In a study conducted by Kantarajian et al. at M.D. Anderson Hospital the incidence of fatal bleeding seemed related to the severity of thrombocytopenia, high blast and promyelocyte count, anemia, and advanced age, so that APL patients at low (5%) or high (58%) risk of early hemorrhagic death were identified.2 It is likely that death from bleeding will be reduced further with the use of all-trans retinoic acid (ATRA) in the induction phase, as ATRA is reported to rapidly correct the coagulopathy of APL with normalization of fibrinogen levels and disappearance of fibrin/fibrinogen degradation products in 4-8 days.3x4 However, it remains to be demonstrated by appropriate clinical trials whether a correction of laboratory tests is associated with a reduction of early hemorrhagic deaths. In contrast to the body of infor