International normalized ratio versus plasma levels of coagulation factors in patients on vitamin K antagonist therapy.

CONTEXT: The key question when managing patients on warfarin therapy who present with life-threatening bleeding is how to use the international normalized ratio (INR) to best direct corrective therapy. The corollary question for the clinical laboratory is at what level will the INR reflect a critical value that requires notifying the clinician. OBJECTIVE: To determine the levels of vitamin K-dependent factors over a range of INR values. DESIGN: Evaluation of the vitamin K-dependent coagulation factor levels on plasma remnants from patients in whom a prothrombin time and INR was ordered to monitor warfarin therapy. There were a total of 83 specimens evaluated with an INR range from 1.0 to 8.26. RESULTS: The mean activity levels of all 4 factors remained near or above 50% when the INR was less than 1.5. The average factor X level was 23% when the INR range was 1.6 to 2.5, but levels of factors II, VII, and IX did not drop below the hemostatic range until the INR was greater than 2.5. At an INR of 3.6 or more, the activity levels of all 4 factors were less than 30% in more than 90% of the specimens. CONCLUSION: Levels of factors II, VII, IX, and X declined with increasing INR but not at the same rate and not to the same level at a given INR. However, most of the values were below the hemostatic value once the INR was 3.6 or more, the level that was also considered critical for physician notification.

Optimism, social support, and adjustment in African American women with breast cancer.

Past studies show that optimism and social support are associated with better adjustment following breast cancer treatment. Most studies have examined these relationships in predominantly non-Hispanic White samples. The present study included 77 African American women treated for nonmetastatic breast cancer. Women completed measures of optimism, social support, and adjustment within 10-months of surgical treatment. In contrast to past studies, social support did not mediate the relationship between optimism and adjustment in this sample. Instead, social support was a moderator of the optimism-adjustment relationship, as it buffered the negative impact of low optimism on psychological distress, well-being, and psychosocial functioning. Women with high levels of social support experienced better adjustment even when optimism was low. In contrast, among women with high levels of optimism, increasing social support did not provide an added benefit. These data suggest that perceived social support is an important resource for women with low optimism.

Increased von Willebrand factor antigen and high molecular weight multimers in sickle cell disease associated with nocturnal hypoxemia.

We evaluated vWF profiles in children and adolescents with SCD and sleep hypoxemia. Mean vWF:Ag levels were significantly elevated in the SCD-hypoxemia group when compared with SCD-normoxia and control groups (p=0.007); and correlated inversely with pulse oximetry (r=-0.54, p=0.01). Densitographic analyses of vWF multimer distribution also showed an inverse correlation between %HMW-multimers and oxygen saturation (r=-0.62, p=0.03). The previously reported association between nocturnal desaturation and SCD vascular complications, including stroke, may be influenced by hypoxemic modulation of vWF as noted in this study.

Reproducibility of platelet function testing.

Platelet aggregation and release studies aid in the diagnosis of bleeding disorders. However, variability in normal individuals has not been established. We evaluated the variation in platelet aggregation and release testing over a period of 2 years with 59 observations among 5 subjects. In addition, the intra-run variation for specific agonists and the adenosine triphosphate standard was determined. The average coefficients of variation (CV) for aggregation with each agonist, except the lower 2 concentrations of ristocetin, were less than 17%. The CV for the 1.0 mg/mL ristocetin aggregation for each subject ranged from 42% to 160%. The average CVs for all the release tests were greater than 30%; with 5 and 10 muM adenosine diphosphate, 56% and 42%, respectively. Decreased adenosine triphosphate release with epinephrine as the sole abnormality occurred in only one of the 59 separate studies. The significance of an abnormal result in initial testing of a patient will depend on understanding this variation.

Clinical perspectives of emerging pathogens in bleeding disorders.

As a result of immunological and nucleic-acid screening of plasma donations for transfusion-transmissible viruses, and the incorporation of viral reduction processes during plasma fractionation, coagulation-factor concentrates (CFC) are now judged safe in terms of many known infectious agents, including hepatitis B and C viruses, HIV, and human T-cell lymphotropic virus. However, emerging pathogens could pose future threats, particularly those with blood-borne stages that are resistant to viral-inactivation steps in the manufacturing process, such as non-lipid-coated viruses. As outlined in this Review, better understanding of infectious diseases allows challenges from newly described agents of potential concern in the future to be anticipated, but the processes of zoonotic transmission and genetic selection or modification ensure that plasma-derived products will continue to be subject to infectious concerns. Manufacturers of plasma-derived CFC have addressed the issue of emerging infectious agents by developing recombinant products that limit the need for human plasma during production. Such recombinant products have extended the safety profile of their predecessors by ensuring that all reagents used for cell culture, purification steps, and stabilisation and storage buffers are completely independent of human plasma.

Standardized versus open-ended assessment of psychosocial and medical concerns among African American breast cancer patients.

Standardized quality of life measures have been developed and used primarily with Caucasian and middle-class cancer patients. This study assessed the ability of several widely used standardized measures to capture the concerns and problems of 89 African American breast cancer patients. Concerns and problems were assessed using both an open-ended format and standardized measures. The degree of overlap in responses from these two formats was examined. The most frequently reported problems in the open-ended format included physical (43%), financial (40%), and worry about others (30%). Overall, standardized measures had significant overlap with open-ended concerns and problems. The Cancer Rehabilitation Evaluation System-Short Form subscales/items were associated with corresponding open-ended physical, financial, and social problems (R2 change = 0.07-0.16, p's < or = 0.02), the Interpersonal Support Evaluation List-Short Form was associated with open-ended social problems (R2 change = 0.11, p = 0.004), and the Mental Health Inventory was associated with open-ended psychological distress problems (R2 change = 0.08, p = 0.01). One category of open-ended problems, worry about others, was not captured by standardized measures. With the exception of associations between open-ended physical problems and psychological distress measures, there were few significant correlations between standardized measures and dissimilar problem categories. These findings suggest that the standardized measures in this study reflected the concerns and problems of African American breast cancer patients. Additional studies are needed to evaluate the utility of other widely used standardized measures that have not been developed or standardized among non-white samples.

Psychological adjustment among African American breast cancer patients: one-year follow-up results of a randomized psychoeducational group intervention.

The effectiveness of support group interventions for cancer patients has been established among White patients but has been virtually unstudied among minority patients. The current study represents the 1st randomized support group intervention targeted to African American women with breast cancer. Participants (N = 73) with nonmetastatic breast cancer were randomly assigned to an 8-week group intervention or an assessment-only control condition At 12 months, the intervention resulted in improved mood as well as improved general and cancer-specific psychological functioning among women with greater baseline distress or lower income. Subsequent research is needed to address effective methods of enrolling and following women with fewer psychosocial and financial resources, as they were the most likely to benefit from this particular intervention.

Treatment regimen, sexual attractiveness concerns and psychological adjustment among African American breast cancer patients.

BACKGROUND: Among a sample of African American women recently diagnosed with breast cancer, we assessed the consequences of different treatment regimens on sexual attractiveness concerns, and the impact of sexual attractiveness concerns on current and subsequent psychological adjustment. PATIENTS AND METHODS: The sample included 91 African American women with breast cancer; 90% had Stage I or II disease, 48% had chemotherapy, 47% had a lumpectomy, and 53% received a mastectomy. Feelings of sexual attractiveness and psychological adjustment were assessed an average of 3 months following surgery and again 4 months post-baseline. RESULTS: Regression analyses revealed that chemotherapy was associated with greater concerns about sexual attractiveness among lumpectomy patients (p<0.05), but not among mastectomy patients (p>0.20). The interaction also suggested that chemotherapy equalized the impact of types of surgery, as there was no difference on sexual attractiveness between surgery groups among women who had received chemotherapy (p>0.20). However, among women who had not received chemotherapy, mastectomy patients reported greater sexual attractiveness concerns (p<0.01). Finally, regression analyses revealed that feelings of sexual attractiveness were an important component of psychological well-being, both cross-sectionally (p<0.001) and longitudinally (p<0.001). CONCLUSION: Assessment of the combined impact of different treatment regimens on feelings of sexual attractiveness is particularly important given the current consensus that all breast cancer patients should receive chemotherapy, regardless of nodal status. Further, concerns about sexual attractiveness should be considered for inclusion as one component of psychosocial support programs for African American women with breast cancer, as our results suggested that they played a significant role in psychological adjustment.